TEST BANK for The Immune System 5th Edition by Peter Parham.

Name: ___________________________ Class: _________________ Date: __________

Chapter 01 1. The last cases of smallpox were reported in the a. 1950s. b. 1960s. c. 1970s. d. 1980s. e. 1990s.

2. The first line of defense against microorganisms that infect the body is referred to as __________ immunity. a. opportunistic b. innate c. adaptive d. primary e. central

3. Select the correct statement about innate and adaptive immunity. a. Innate immunity involves cells bearing receptors that are highly specific for a pathogen. b. The first response to a pathogen involves immunological memory. c. Hematopoiesis occurs in the lymph node. d. Phagocytosis involves the uptake and killing of microbes. e. Once lymphocytes mature, they remain in lymphoid organs and do not reenter the blood.

4. Which of the following are chemical barriers of innate immunity? a. lactic acid and lysozyme b. lactic acid, lysozyme, and the normal microbiota c. skin and mucous membranes

d. neutrophils and macrophages e. All of these answers are correct.

5. When macrophages secrete __________, an inflammatory response ensues. a. lysozyme b. defensins c. lymph d. sebum e. cytokines

6. The thin layer of cells that makes up the interior lining of the blood vessels is called the a. mucosa. b. epithelium. c. endothelium. d. connective tissue. e. lymphoid tissue.

7. Identify the incorrect statement regarding hematopoiesis. a. Hematopoiesis is a continuous process that occurs throughout one’s lifetime. b. The location for hematopoiesis differs with age. c. Self-renewal is necessary to replenish the supply of hematopoietic stem cells. d. Most hematopoiesis occurs in the bone marrow after birth. e. Leukocytes, but not erythrocytes, must go through hematopoiesis to develop.

8. The progenitors of macrophages are a. megakaryocytes. b. dendritic cells. c. monocytes. d. neutrophils.

e. M cells.

9. __________ act as cellular messengers by delivering degraded pathogens to lymphoid organs. a. Plasma cells b. Dendritic cells c. Large granular lymphocytes d. Mast cells e. Basophils

10.Another name for a large granular lymphocyte is a a. plasma cell. b. helper T cell. c. monocyte. d. natural killer cell. e. eosinophil.

11.Effector cells that secrete antibodies are known as __________ cells. a. natural killer b. cytotoxic T c. helper T d. M e. plasma

12.Spherical regions in lymph nodes containing areas that are packed densely with proliferating B cells are called a. efferent vessels. b. germinal centers. c. red pulp zones. d. periarterial lymphoid sheaths. e. medullary sinuses.

13.The __________ is/are the lymphoid organ(s) that filter(s) the blood. a. spleen b. tonsils c. Peyer’s patches d. appendix e. adenoids

14.__________ cells persist long after an individual has been vaccinated. a. Neutrophil b. Plasma c. Memory d. M e. Mast

15.During an infection, __________ are mobilized in large numbers from the bone marrow. a. dendritic cells b. memory cells c. macrophages d. neutrophils e. B cells

16.In most cases, the adaptive immune response relies on the initial activation of CD4 T cells by the antigen-presenting __________ that have entered a secondary lymphoid tissue through the afferent lymph. a. macrophages b. CD8 T cells c. B cells d. dendritic cells e. epithelium

17.Select the statement that is characteristic of a secondary immune response.

a. Secondary immune responses are activated when primary immune responses fail to completely eradicate an infection. b. Secondary immune responses occur in both innate and adaptive immune responses. c. Memory cells are activated rapidly during a secondary immune response. d. Secondary immune responses are orders of magnitude smaller than primary immune responses. e. All of these answers are correct.

18.A bacterium that causes a common disease in a population that has been previously exposed to it is called a. opportunistic. b. resistant. c. commensal. d. endemic. e. attenuated.

19.An example of an antimicrobial substance that protects epithelial surfaces from pathogens by degrading the bacterial cell wall is a. glycoprotein. b. complement. c. proteoglycan. d. lysozyme. e. sebum.

20.Which of the following is characteristic of innate immunity? a. inflammation b. improvement in recognition of the pathogen during the response c. slow response d. highly specific for a particular pathogen e. All of these answers are correct.

21.Which statement about neutrophils is NOT true?

a. Neutrophils are mobilized from the bone marrow to sites of infection when needed. b. Neutrophils are active only in aerobic conditions. c. Neutrophils are phagocytic. d. Neutrophils form pus, which comprises dead neutrophils. e. Dead neutrophils are cleared from sites of infection by macrophages.

22.Primary lymphoid tissues are the sites where lymphocytes __________, whereas secondary lymphoid tissues are the sites where lymphocytes __________. a. are stimulated; develop and mature b. encounter pathogens; undergo apoptosis c. develop and mature; become stimulated d. undergo clonal selection; differentiate from hematopoietic stem cells e. die; are phagocytosed after death.

23.The spleen differs from other secondary lymphoid organs in which of the following ways? a. It does not contain T cells. b. It filters blood as well as lymph. c. It is populated by specialized cells called M cells. d. It receives pathogens via afferent lymphatic vessels. e. It has no connection with the lymphatics.

24.Examples of pathogens that cause human disease include a. bacteria. b. viruses. c. fungi. d. parasites (protozoans and worms). e. All of these are examples of pathogens that cause human disease.

25.Which of the following is NOT associated with mucosal surfaces? a. mucus-secreting goblet cells

b. lysozyme c. M cells d. white pulp e. beating cilia

26.A term generally used to describe all white blood cells is __________. a. hematopoietic cells b. myeloid progenitor c. dendritic cells d. monocytes e. leukocytes

27.The most abundant type of leukocyte in human peripheral blood is the a. eosinophil. b. basophil. c. neutrophil. d. monocyte. e. lymphocyte.

28.Which of the following statements is correct? a. Macrophages are granulocytes. b. Macrophages derive from neutrophils. c. Macrophages are non-phagocytic. d. Macrophages reside in the tissues. e. All of these statements are false.

29.Select the correct statement about hematopoiesis. a. During human development, hematopoiesis takes place at different anatomical locations. b. The hematopoietic stem cell gives rise to white blood cells, but a different stem cell is the progenitor of red blood cells. c. Hematopoietic stem cells are able to differentiate but not divide.

d. Platelets differentiate from red blood cells. e. Megakaryocytes are small cells lacking a nucleus.

30.Which of the following describes the flow of lymph through a lymph node draining an infected tissue? a. efferent lymphatic vessel > lymph node > afferent lymphatic vessel b. venule > lymph node > efferent lymphatic vessel c. afferent lymphatic vessel > lymph node > efferent lymphatic vessel d. artery > lymph node > efferent lymphatic vessel e. afferent lymphatic vessel > lymph node > artery

31.Immune cells within the lymphatic circulation are directly deposited into which of the following anatomical sites so that the cells may reenter the bloodstream? a. right aorta b. left subclavian vein c. left carotid artery d. high endothelial venule e. hepatic vein

32.Which of the following is the predominant route by which pathogens are brought from a site of infection into a lymph node? a. efferent lymphatics b. artery c. vein d. afferent lymphatics e. high endothelial venule

33.Vaccination is best described as prevention of severe disease by a. the deliberate introduction of a virulent strain of an infectious agent. b. prior exposure to an infectious agent in a related, but weakened form. c. prophylactic treatment with antibiotics. d. stimulating effective innate immune responses.

e. using effective public-health isolation regimens such as quarantine.

34.Which statement explains why immunity to influenza may appear to be relatively short-lived? a. Effective immunological memory fails to develop. b. Immune responses to influenza involve innate immune mechanisms only. c. The primary and secondary immune responses are equivalent. d. Influenza virus targets memory cells. e. New influenza variants able to escape previous immunity appear regularly.

35.Select the correct statement concerning the gut-associated lymphoid tissue.

a. Number 1 refers to the cell that transports antigen from the lumen across the mucosa. b. Number 2 highlights the B cell–rich region of the gut-associated lymphoid tissue. c. Number 3 identifies the afferent lymphatics. d. Number 4 identifies the germinal center, which is the site of resting B cells that have not yet been activated by antigen. e. All of these answers are correct.

36.Select the correct statement concerning the gut-associated lymphoid tissue (GALT). a. Antigen enters the GALT via the afferent lymphatic vessels.

b. T cells do not recirculate to the GALT. c. Tonsils, Peyer’s patches, and the appendix are all part of the GALT. d. The GALT is a primary lymphoid tissue. e. All of these answers are correct.

37.Which of the following would likely occur during an effective immune response to the SARS-CoV-2 virus? a. MHC class I would present SARS-CoV-2 viral peptides. b. Epitopes located on the SARS-CoV-2 surface would be bound by antibodies. c. A neutralizing antibody response would be generated. d. B cells would undergo clonal selection and clonal expansion. e. All of the these answers are correct.

38.State the location where monocytes and neutrophils develop in adults.

39.Compare how B and T cells recognize antigen.

40.Why does it take approximately a week after infection for the benefits of an adaptive immune response to start to be felt?

41.Compare granulocytes to monocytes, including physical features and their functions.

42.Identify the different anatomical locations where hematopoiesis occurs in embryonic, fetal, and adult life.

43.What are clonal selection and clonal expansion in the context of an adaptive immune response? Describe how they shape the adaptive immune response.

44.What would be the consequence of a bioterrorist attack that released smallpox virus into a city?

45.Phagocytosis of either microbes or microbial constituents by macrophages is followed by the activation of macrophages and the secretion of cytokines. What are the main effects of these cytokines?

46.Identify the four classes of pathogens that provoke immune responses in our bodies and give an example of each.

47.Identify the two major progenitor subsets of leukocytes and the types of cells that differentiate from each progenitor.

48.How can antibiotics upset the barrier function of intestinal epithelia? Give a specific example.

49.Describe the characteristics commonly associated with inflammation and what causes them.

50.Describe the three main ways in which epithelia function as a barrier to infection, giving details of the mechanisms employed and the sites of the body protected.

51.Describe three distinct mechanisms by which antibodies eradicate infection.

52.What are the main differences between innate immunity and adaptive immunity?

Answer Key Chapter 01 1. Answer: C 2. Answer: B 3. Answer: D 4. Answer: A 5. Answer: E 6. Answer: C 7. Answer: E 8. Answer: C 9. Answer: B 10.Answer: D 11.Answer: E 12.Answer: B 13.Answer: A 14.Answer: C 15.Answer: D 16.Answer: D 17.Answer: C 18.Answer: D 19.Answer: D 20.Answer: A

21.Answer: B 22.Answer: C 23.Answer: E 24.Answer: E 25.Answer: D 26.Answer: E 27.Answer: C 28.Answer: D 29.Answer: A 30.Answer: C 31.Answer: B 32.Answer: D 33.Answer: B 34.Answer: E 35.Answer: A 36.Answer: C 37.Answer: E 38.Answer: In adults, all leukocytes originate in the bone marrow and are derived from pluripotent hematopoietic stem cells.

39.Answer: Both B and T cells have antigen receptors with variable regions that bind with

high specificity to a region of the antigen.

The antigen-binding site of immunoglobulin is made up of the tips of two variable regions, whereas the T-cell receptor has one antigen-binding site. The B-cell receptor can recognize carbohydrates, glycoproteins, proteoglycans, and glycolipids on the surface of microbial pathogens. B-cell receptors and antibodies recognize the native conformation, or three-dimensional structure, of the antigen. In contrast, the epitope recognized by a T-cell receptor is a short peptide of 8–16 amino acids in length that is presented by an MHC molecule on the surface of another cell.

40.Answer: Before the establishment of an effector population of lymphocytes, several events must occur: (1) specific recognition of pathogen by lymphocyte receptors (clonal selection); (2) proliferation of pathogen-specific lymphocytes to expand responding populations (clonal expansion); and (3)

differentiation into effector lymphocytes with the resulting establishment of an organized adaptive immune response.

41.Answer: The granulocytes are defined by prominent granules containing molecules that kill microbes and enhance inflammation and irregularly shaped nuclei. The granulocytes include neutrophils, basophils, and eosinophils.

Neutrophils are phagocytic cells; eosinophils provide protection against helminth worms; and basophils initiate the anti-parasite response and function as regulatory cells. In comparison, monocytes are larger than granulocytes and have a more uniform appearance including a distinctive indented nucleus. Monocytes circulate in the blood and are recruited to tissues where they differentiate into macrophages.

Monocytes and macrophages are both phagocytic.

42.Answer: The yolk sac and the liver produce blood cells in the embryo and early fetus through the first three months of gestation.

The fetal spleen takes over this function from the third to the seventh months. Once developed, the bone marrow is the site of hematopoiesis from the fourth month of gestation throughout the remainder of fetal development and into adulthood.

43.Answer: In an adaptive immune response to a pathogen, the term clonal selection describes the fact that only those lymphocytes that can recognize that particular pathogen and respond to it are selected to participate in the immune response. Clonal expansion describes the proliferation and subsequent differentiation of these few original lymphocytes to provide large numbers of effector lymphocytes. Clonal selection ensures that the adaptive response will be tailored specifically for the particular type of pathogen involved in the infection. Clonal expansion ensures that the few original lymphocytes specific for the pathogen produce a large population of effector lymphocytes that can make an effective

immune response against the pathogen.

44.Answer: The last case of smallpox was reported in the 1970s. As a result, children are no longer vaccinated routinely as was the case before smallpox was eradicated. A large proportion of any given population today would be unvaccinated, and thus susceptible to smallpox infection.

The mortality rate would be high (30–50 percent) among those not protected by vaccination.

45.Answer: The cytokines released by activated macrophages have three principal effects.

Some cytokines act as chemoattractants and recruit other leukocytes into the infected tissue, for example, neutrophils, which efficiently phagocytose and kill bacteria, forming pus.

Cytokines increase the adhesive properties of the blood endothelium, allowing cells such as neutrophils to adhere and leave the blood to enter tissues. Other cytokines act on the endothelial cells of local blood vessels to increase vascular permeability and

vasodilation, thus initiating inflammation of the infected tissue.

46.Answer: The four classes of pathogens are bacteria, viruses, fungi, and parasites (protozoa and worms).

47.Answer: The two major progenitor subsets of leukocytes are the common lymphoid progenitor and the myeloid progenitor.

The common lymphoid progenitor differentiates into three cell types: B cells, T cells, and natural killer (NK) cells. The myeloid progenitor differentiates into six main cell types: basophils, eosinophils, neutrophils, mast cells, dendritic cells, and monocytes.

Monocytes are circulating leukocytes that enter tissues, where they then differentiate into macrophages.

48.Answer: Antibiotics attack the microbiological barriers of intestinal epithelia. The normal microbiota sensitive to the antibiotics are killed off, and the intestine can then be recolonized and overgrown by microorganisms that in normal circumstances

are present in very small numbers and thus do not cause a problem. An example is a condition called pseudomembranous colitis caused by the overgrowth of Clostridium difficile.

The toxin produced by Clostridium leads to diarrhea and bleeding, and may cause death, particularly in elderly patients.

49.Answer: The hallmarks of inflammation are heat, redness, pain, and swelling (edema).

These are caused by a combination of vasodilation (causing redness and heat), increased vascular permeability, and the consequent infiltration of fluid and leukocytes from the blood into the infected site (causing swelling and pain as a result of the increased pressure on local nerve endings).

50.Answer: (1) Mechanical (physical) barriers.

The tough outer barrier of layers of keratinized cells on the skin help make it impenetrable. On ciliated epithelial surfaces, such as those of the respiratory tract, the formation of a layer of mucus that is kept in continual movement

by the beating cilia inhibits colonization and invasion by microorganisms.

(2) Chemical barriers.

The epithelium produces a variety of chemical substances that interfere with the adherence of microorganisms to epithelium and their replication. The skin produces fatty acids in sebaceous glands, which helps to create an acid environment inhibitory to the growth of many bacteria.

Lysozyme, an enzyme that inhibits cell-wall formation in bacteria, is secreted in tears, saliva, and sweat. The acidic environments of the stomach, vagina, and skin prevent microbial growth.

(3) Microbiological barriers. A microbiota of non-pathogenic commensal microorganisms colonizes many epithelial surfaces and provides an additional barrier to infection.

They compete with pathogenic microbes for space and nutrients, and sometimes produce antibacterial proteins that further inhibit attachment to epithelium. For example, Escherichia coli in the large intestine produce colicins, which prevent

colonization by other bacteria. The sites protected are the skin, mucosal epithelium of the gastrointestinal tract, mucosal epithelium of the respiratory tract, and the mucosal epithelium of the urinogenital tract.

51.Answer: (1) Neutralization. By binding to the surface of a pathogen, antibodies interfere with the ability of the pathogen to grow and replicate. Antibody binding to a pathogen or a bacterial toxin can also inhibit its binding to receptors on host cells and therefore prevent its entry into cells.

(2) Opsonization.

Antibody coating the surface of a pathogen or toxin can promote phagocytosis of the antibody-covered particle. Antibodies acting in this way are known as opsonins.

The antibody-bound material interacts with Fc receptors on the surface of phagocytic cells such as macrophages and neutrophils, which bind the constant region (the stem) of the antibody.

Stimulation of Fc receptors in this way stimulates the engulfment and degradation of antibody-coated

material by the phagocyte.

(3) Complement activation.

IgG or IgM antibody bound to a pathogen stimulates activation of the complement system, leading to the deposition of complement proteins on the surface of the pathogen. Certain of these act as opsonins and bind to complement receptors on phagocytic cells to stimulate the phagocytosis and destruction of the pathogen.

52.Answer: Innate immune responses are initiated almost immediately after infection, whereas adaptive immunity takes longer to develop. Innate immunity uses generalized and invariant mechanisms to recognize pathogens. Examples of these are the receptors on phagocytes that recognize surface molecules shared by many different pathogens and stimulate phagocytosis, and serum proteins such as complement.

Innate immunity is often unable to eradicate the pathogen completely, and even when it does, it does not

produce immunity to reinfection. An adaptive immune response, in contrast, involves specific recognition of the particular pathogen by highly specific receptor on a subset of lymphocytes, which are selected from a pool of millions of lymphocytes each bearing receptors specific for different molecules. Adaptive immunity is often powerful enough to eradicate the infection and provides longterm protective immunity through immunological memory.

Name: ___________________________ Class: _________________ Date: __________

Chapter 02 1. Soluble effector molecules a. are effective when encountering pathogens in both extracellular spaces and the cytosol. b. are not effective against viruses at any stage of infection. c. often provide protection during the late stages of the immune response. d. include the pentraxins. e. All of these answers are correct.

2. Which of the three complement pathways becomes activated soonest after an initial infection? a. the classical pathway b. the lectin pathway c. the alternative pathway

3. All of the following complement proteins help form a pore in the pathogen’s membrane except a. C3b. b. C5b. c. C6. d. C7. e. C8. f. C9.

4. The importance of CD59 (also known as protectin) is to a. promote the speed of complement activation by protecting C3 convertase C3bBb from proteolytic degradation. b. prevent the recruitment of C9. c. dissociate the components of the alternative C3 convertase. d. prevent the attachment of C3b to host cell surfaces.

e. inhibit the anchoring of C5b, C6, and C7 to host cell surfaces.

5. __________ are soluble complement fragments that mediate localized and systemic inflammatory responses. a. cryptdins b. defensins c. anaphylatoxins d. selectins e. c-reactive proteins

6. Alpha2-macroglobulin a. binds covalently to its target via a disulfide bond. b. is not found in the circulation until several hours after microbial infection. c. possesses protease activity to cleave microbial targets. d. binds its target and is cleared from the circulation by cells bearing receptors specific for the complex. e. targets the membrane-attack complex on human cells.

7. Which of the following is the soluble form of C3 convertase of the alternative pathway of complement activation? a. iC3 b. iC3b c. C3b d. iC3Bb e. C3bBb

8. Which of the following does not accurately describe complement components? a. soluble proteins b. made by the spleen c. located in extracellular spaces d. some function as proteases once activated e. activated by a cascade of enzymatic reactions

9. Which of the following is the membrane-bound form of C3 convertase of the alternative pathway of complement activation? a. iC3 b. C3a c. C3b d. iC3Bb e. C3bBb

10.The plasma proteins that counteract the activity of factor P by inactivating C3 convertase through the cleavage of C3b are a. factor B and factor H. b. factor H and factor I. c. factor B and factor I. d. decay-accelerating factor and factor H. e. decay-accelerating factor and membrane cofactor protein.

11.The membrane-bound proteins on human cells that dissociate and inactivate alternative C3 convertase to avoid complement activation are a. factor B and factor H. b. factor H and factor I. c. factor B and factor I. d. decay-accelerating factor and factor H. e. decay-accelerating factor and membrane cofactor protein.

12.Which of the following complement components is an opsonin that binds to complement receptor 1 (CR1) on macrophages? a. C3b b. C3a c. Bb d. Ba e. C3bBb.

13.Which of the following polymerizes to form a transmembrane channel that compromises the integrity of cell membranes? a. C5 b. C6 c. C7 d. C8 e. C9

14.Which of the following are important in anchoring the membrane-attack complex to the membrane? a. C3 and C5 b. C5 and C6 c. C6 and C7 d. C7 and C8 e. C8 and C9

15.In an individual lacking the enzyme to produce a glycosylphosphatidylinositol (GPI) lipid tail, which of the following proteins will still be expressed normally? a. decay-accelerating factor (DAF) b. homologous restriction factor (HRF) c. membrane cofactor protein (MCP) d. protectin (CD59) e. None of these answers are correct.

16.The ligand for CR3 and CR4 formed by the cleavage of C3b by the combined action of factors H and I is called a. C3bBb. b. C3a. c. C3b2Bb. d. iC3b. e. C5b.

17.Which of the following does not describe the actions of the coagulation system? a. blood clot formation b. enhancement of dissemination of microbes into lymphatics and bloodstream c. decrease in blood loss and fluid into interstitial spaces in tissues d. release of inflammatory mediators by platelets e. wound healing

18.Damage to tissues triggers a cascade of plasma proteins involving bradykinin and is known as a. the alternative pathway of complement. b. the coagulation system. c. the kinin system. d. receptor-mediated endocytosis. e. the acute-phase response.

19.Which of the following does not accurately describe the defensins? a. They are highly conserved with few variants. b. They contain a large proportion of arginine residues. c. They contain three intra-chain disulfide bonds. d. They are amphipathic, with hydrophobic and hydrophilic regions. e. They disrupt pathogen membranes by penetrating them and disrupting their integrity.

20.The microbiota a. triggers the immune system to stop developing after birth. b. refers to pathogenic bacteria that invade during infection. c. competes with pathogens for nutrients. d. is composed of ten key bacterial species. e. is absent in germ-free mice.

21.Select the correct response concerning the three lines of immune defense.

a. Low pH in the stomach and the antimicrobial enzymes of tears are part of the induced innate immune response. b. Factors that increase in activity or concentration following pathogen detection are part of the induced innate immune response. c. The adaptive immune response peaks within the first 96 hours of infection. d. All of these answers are correct. e. None of these answers are correct.

22.Which of the following provide immune defense against viruses in the extracellular phase? a. pentraxins b. defensins c. complement d. All of these answers are correct. e. None of these answers are correct.

23.Select the correct statement about complement and macrophages.

a. The bacterial cell is opsonized by C3a, which is bound by CR1 leading to endocytosis by the macrophage. b. The bacterial cell is opsonized by C3bBb, which is bound by CR1 leading to endocytosis by the macrophage. c. Opsonization is due to the formation of a covalent bond between the microbial surface and CR1. d. Opsonization is prevented by the activity of decay accelerating factor. e. Opsonization occurs in the alternative pathway of complement activation, but not in the classical pathway.

24.Clostridium difficile

a. is a commensal organism that benefits its human host. b. outcompetes resident commensals to cause illness following antibiotic treatment. c. is an example of a viral infection. d. is part of the microbiological barrier protecting us from infection.

25.Extracellular pathogens a. replicate within the host cell. b. are cleared when the host cell is killed. c. are targets of soluble molecules such as complement or antibodies. d. are found only on the skin. e. None of these answers are correct.

26.In the complement pathway, regulatory proteins a. decrease complement activity by stabilizing membrane-bound C3b. b. decrease complement activity by preventing C3b degradation by proteases. c. decrease complement activity by disrupting the alternative C3b convertase. d. increase complement activity by allowing C3b to be fixed on the surface of human cells. e. increase complement activity by preventing C3bBb degradation by proteases.

27.Pentraxins a. circulate in the blood, but not in the lymph. b. are classified as part of the adaptive immune response. c. function to generate the alternative C3 convertase. d. simultaneously bind pathogens and receptors on phagocytes. e. are made only by the liver cells.

28.Select the correct statement concerning defensins. a. Each bacterial toxin requires one unique defensin protein to inactivate it. b. Defensins are similar to chaperone proteins as they aid proper folding and function of other proteins.

c. Bacterial toxins are thermodynamically stable and structurally rigid, enabling their inactivation by defensins. d. Defensins are large proteins composed of three subunits. e. Human proteases aid the defensins in inactivating bacterial toxins.

29.Select the statement that is accurate concerning plasma proteins. a. The key function of the coagulation system is to promote blood vessel dilation leading to elimination of pathogens and repair of tissues. b. Platelets release factors that recruit immune-system cells and lead to tissue repair. c. The coagulation and kinin systems both lead to the production of blood clots. d. The α2-macroglobulin proteins activate the classical complement pathway, thus helping to clear pathogens.

30.Which of the following best describes the innate immune system? a. Epithelial tight junctions are considered a chemical barrier. b. The mechanical barrier of the skin likely acts to prevent infection before induced innate mechanisms of immunity. c. Complement proteins are not present prior to infection and must be produced following infection with a pathogen. d. Following a first exposure to a pathogen, an individual does not need the innate immune system if they produce a strong adaptive response within 24 hours.

31.Although activation of the three different pathways of complement involves different components, the three pathways converge on a common enzymatic reaction referred to as complement fixation. Describe this reaction.

32.Compare the C3 convertase generated by the three different pathways of complement.

33.Explain the steps that take place when a bacterium is opsonized via C3b:CR1

interaction between the bacterium and a resident macrophage in tissues.

34.In the early stages of the alternative pathway of complement activation there are complement control proteins that are both soluble (factors H and I) and associated with the cell surface (DAF and MCP). Identify the (i) soluble and (ii) cell surface–associated complement control proteins that operate in the terminal stages of the alternative pathway of complement activation, and describe their activities.

35.Why is it important to expose the hydrophobic sites of C7 and C8 during the formation of the membrane-attack complex?

36.Explain the similarities between membrane cofactor protein and factor H in terms of their complement control properties.

37.Identify proteins A, B, and C of the complement pathway.

38.Identify the three effector mechanisms of complement that help clear a microbial infection.

39.Review the differences between the three pathways of complement (alternative, lectin, and classical) in terms of how they are activated.

40.Distinguish which complement pathways contribute to both innate and adaptive immunity, and explain why.

41.Explain why a genetic deficiency of C3 leads to a type of immunodeficiency characterized by recurrent and severe infections.

42.Explain how the alternative C3 convertase on pathogen cell surfaces is formed and stabilized.

43.Explain how the anaphylatoxins C3a and C5a contribute physiologically to inflammation during complement activation.

Answer Key Chapter 02 1. Answer:

D

2. Answer:

C

3. Answer:

A

4. Answer:

B

5. Answer:

C

6. Answer:

D

7. Answer:

D

8. Answer:

B

9. Answer:

E

10.Answer:

B

11.Answer:

E

12.Answer:

A

13.Answer:

E

14.Answer:

D

15.Answer:

C

16.Answer:

D

17.Answer:

B

18.Answer:

C

19.Answer:

A

20.Answer:

E

21.Answer:

B

22.Answer:

D

23.Answer:

D

24.Answer:

B

25.Answer:

C

26.Answer:

E

27.Answer:

D

28.Answer:

E

29.Answer:

B

30.Answer:

B

31.Answer:

The cleavage of C3 into C3a and C3b and the covalent bonding of C3b to the pathogen surface is called complement fixation and is the reaction on which the alternative, lectin, and classical pathways of complement activation converge.

32.Answer:

The enzyme responsible for cleaving C3 into C3a and C3b is called C3 convertase, and it differs in composition depending on the particular complement pathway. The classical and lectin pathways use the classical C3 convertase (C4b2a), whereas the alternative pathway uses the alternative convertase (C3bBb).

33.Answer:

The CR1 on the macrophage can bind to C3b that is coating a bacterial surface after complement activation, and the macrophage then engulfs the bacterium through receptor-mediated endocytosis. The macrophage membrane invaginates and forms an intracellular vesicle called a phagosome. The phagosome fuses with a lysosome to form a phagolysosome, where toxic mediators and degradative enzymes are localized. The bacterium is destroyed.

34.Answer:

The soluble proteins include S protein, clusterin, and factor J, which all inhibit C5b, C6, and C7 from binding to cell membranes. The cell surface-associated proteins include homologous restriction factor (HRF) and CD59 (protectin),

which both prevent the recruitment of C9 and thus block C9 polymerization.

35.Answer:

The hydrophobic sites of C7 and C8 enable anchoring of these two complement components into the membrane of the pathogen. Once anchored in the membrane, the hydrophobic site of C8 facilitates C9 polymerization, which completes the formation of the membrane-attack complex.

36.Answer:

MCP and factor H both bind to C3b and render it susceptible to proteolytic cleavage by factor I. They both contain complement control protein (CCP) modules and are therefore considered regulators of complement activation (RCA).

37.Answer:

Protein “A” is the complement protein C3, which is cleaved to form protein “B” or C3b and protein “C” or C3a.

38.Answer:

C3 is the most abundant complement component in the plasma and circulates as a zymogen, an inactive enzyme.

When cleaved into C3a and C3b, three different effector mechanisms are armed: (1) C3b binds to and tags pathogens for destruction by phagocytes through binding to a C3b receptor, CR1; (2) C3b contributes to a multicomponent enzyme, C5 convertase, that catalyzes the assembly of the terminal complement components and the formation of the membrane-attack complex leading to pathogen lysis; and (3) C3a is an inflammatory mediator that serves as a chemoattractant and recruits inflammatory cells to the infection site.

39.Answer:

(1) The classical pathway is activated in two ways, either by the presence of antibody bound to the surface of the microorganism (for example IgM bound to lipopolysaccharide of Gram-negative bacteria) or by the presence of C-reactive protein bound to a bacterium. (2) The lectin pathway requires the presence of mannosebinding lectin, an acute-phase protein made by the liver in response to interleukin-6 (secreted by activated macrophages), which accumulates in plasma during infection. (3) The alternative pathway requires an activating surface of a pathogen, which stabilizes complement components.

40.Answer:

Only the classical pathway is considered part of the adaptive immune response because of the requirement for antibody. However, the classical pathway is also considered part of innate immunity because of the ability of C-reactive protein, an acute-phase protein, to activate it.

The other two pathways are considered part of innate immunity because they are initiated independently of antibody.

41.Answer:

C3 is a key element in the initiation of the complement cascade in all three pathways of complement activation, namely the alternative, lectin, and classical pathways. Its cleavage into C3a and C3b occurs early in the complement cascade. C3a acts as an inflammatory mediator and recruits inflammatory cells to the site of infection. C3b becomes fixed to the pathogen surface and facilitates the opsonization of pathogens by phagocytes and the assembly of complement components for perforation of the pathogen membrane. In the absence of C3, all three pathways of complement activation would be arrested, and extracellular pathogens would escape immune detection until adaptive immune mechanisms develop fully many days later.

42.Answer:

Spontaneous hydrolysis of C3 without cleavage exposes its highly reactive thioester bond, forming iC3. Factor B binds to iC3, is cleaved by factor D, and consequently releases a small fragment called Ba. The larger fragment, Bb, remains associated with iC3 to form iC3Bb, a soluble C3 convertase, which cleaves C3 into C3a and C3b. The reactive thioester bond of C3b is attacked by R–OH and R–NH2 groups on the surface of the pathogen, where it becomes anchored and binds to factor B. Factor D then cleaves factor B, releasing fragment Ba and forming C3bBb, the C3 convertase, on the pathogen surface.

Factor P (properdin) binds to C3 convertase (C3bBb) bound to the pathogen surface and inhibits the proteolytic degradation of C3bBb. This stabilizes the C3 convertase and enhances the rate of C3b deposition on the pathogen surface.

43.Answer:

G-protein-coupled receptors for the anaphylatoxins C3a and C5a are found on phagocytes, mast cells, and the endothelial cells of blood vessel walls. Anaphylatoxin bound to mast cells causes them to degranulate, releasing inflammatory mediators such as histamine and leading to increased vascular permeability. Through their action on endothelial cells, anaphylatoxins exert vasoactive effects on blood vessels, contributing to increased vascular permeability and increased blood flow, which facilitate the extravasation of plasma proteins, such as complement proteins and antibodies, and the recruitment of cells to infected tissues through increased adherence and chemotaxis. Phagocytic activity is enhanced by

anaphylatoxins, which bring about increased levels of CR1 and CR3 and microbicidal activity. All these activities enhance inflammation.

Name: ___________________________ Class: _________________ Date: __________

Chapter 03

1.

This figure shows the interaction of natural killer cells with activated macrophages. Is the following statement true or false? The macrophage must be infected with the virus to form a synapse with the NK cell. a. True b. False

2.

This figure shows the interaction of natural killer cells with activated macrophages. Is the following statement true or false? The macrophage secretes IL-12 and IL-15 to activate the NK cell. a. True

b. False

3.

This figure shows the interaction of natural killer cells with activated macrophages. Is the following statement true or false? The interferon-gamma secreted by the NK cell kills the activated macrophage. a. True b. False

4.

This figure shows the interaction of natural killer cells with activated macrophages. Is the following statement true or false? The interferon-gamma secreted by the NK cell kills the activated macrophage. a. True b. False

5.

This figure shows the interaction of natural killer cells with activated macrophages. Is the following statement true or false? NK cells exit the bone marrow unable to undergo further proliferation. a. True b. False

6.

This figure shows the interaction of natural killer cells with activated macrophages. Is the following statement true or false? Both the NK cell and the macrophage express receptors for IL-15. a. True b. False

7. C-type lectins are so called because of the role of __________ in facilitating receptor–ligand interactions.

a. carbohydrate b. CR1 c. calcium d. chemokines e. caspases

8. Lectins recognize microbial a. phosphate-containing lipoteichoic acids. b. nucleic acids. c. carbohydrates. d. flagellin. e. sulfated polysaccharides.

9. Scavenger receptors do not recognize a. lipopolysaccharides. b. lipoteichoic acid. c. phosphatidyl serine. d. CpG-rich bacterial DNA. e. mannose.

10.Macrophages bear on their surface receptors for all of the following EXCEPT a. mannose. b. glucans. c. C3b. d. lipopolysaccharide. e. CpG-rich bacterial DNA.

11.__________ is a soluble protein. a. TLR4 b. CD14 c. lipopolysaccharide-binding protein (LBP) d. CXCR1

e. MARCO

12.__________ belong to a family of structurally similar membrane-bound proteins that aid in the adhesion between various types of human cell. a. Interferons b. Integrins c. GTP-binding proteins d. Pyrogens e. Scavengers

13.All of the following induce fever EXCEPT a. IL-12. b. IL-6. c. IL-1. d. TNF-alpha.

14.Which of the following is NOT associated with mobilization of neutrophils to infected tissue? a. TNF-alpha production by macrophages b. upregulation of selectins on blood vessel endothelium c. interferon response d. generation of a CXCL8 gradient e. proteolysis of basement membrane

15.Which of the following pairs is mismatched? a. primary granules: azurophilic granules b. secondary granules: unsaturated lactoferrin c. azurophilic granules: myeloperoxidase d. gelatinase: iron sequestration e. tertiary granules: natural killer cells.

16.The pH of the phagosome increases following phagocytosis because

a. the microbe delivers a significant number of hydroxyl ions in its cytosol that are released upon membrane disruption. b. hydrogen ions are consumed by the activity of NADPH oxidase and superoxide dismutase. c. azurophilic granules deliver alkaline substances. d. catalase consumes hydrogen ions once activated.

17.C-reactive protein binds to a. phosphorylcholine. b. mannose-containing carbohydrates. c. lipoteichoic acid. d. flagellin. e. MASP-1/MASP-2.

18.The C3 convertase that functions in the lectin pathway of complement activation consists of a. C3bBb. b. C3b2a. c. C4b2a. d. C4b2b. e. C3b2Bb.

19.Which of the following cleaves C2? a. Factor B b. C1r c. MASP-2 d. C4b2a e. C4b

20.With which of the following complement proteins does C-reactive protein interact? a. factor D b. C1

c. factor P d. C4 e. C2

21.All of the following are true of MyD88 EXCEPT a. it binds to the TIR domains of all Toll-like receptors except TLR3. b. it binds to IRAK4, a protein kinase, causing the kinase to phosphorylate itself. c. it is an adaptor protein with similar function to TRIF. d. a genetic deficiency of MyD88 causes the disease X-linked ectodermal dysplasia and immunodeficiency.

22.The name given to cytokines that recruit cells to move toward areas of inflammation is a. chemokines. b. caspase-recruitment domains (CARDs). c. inflammakines. d. adhesion molecules. e. pyrogens.

23.In common with Toll-like receptors, NOD-like receptors also contain __________ that is/are used for pathogen-recognition of microbial ligands. a. caspase-recruitment domains (CARD) b. Toll interleukin 1 receptor (TIR) domain c. variable extracellular domain d. leucine-rich repeat regions (LRRs) e. C-type lectin domain (CTLD)

24.Identify which of the following receptors lead to nuclear translocation of NF\kappaB through an activated IKK intermediates. a. TLR4 b. IL-1 receptor c. NOD1

d. NOD2 e. All of these receptors culminate in nuclear translocation of NF\kappaB through an activated IKK intermediate.

25.Which of the following is most similar in its activity to that of IRF3? a. IRAK4 b. NF\kappaB c. TRAF6 d. I\kappa\kappa e. GTP-binding (G) protein

26.__________ help to prevent systemic bacterial dissemination by producing chromatin structures loaded with antimicrobial substances. a. Inflammasomes b. Neutrophil extracellular traps c. RIG-1-like helicases d. Granulomas e. Plasmacytoid dendritic cells

27.__________ is/are needed to minimize the damaging effects to neighboring host cells during a respiratory burst. a. Catalase activity b. Complement control proteins c. NADPH oxidase activity d. Neutrophil mobilization e. C reactive protein

28.Measurement of which of the following is commonly used when monitoring patients for infection or inflammation? a. IL-1RA b. cryopyrin c. C-reactive protein d. proIL-1\beta

e. IL-15

29.All of the following characterize serum amyloid protein EXCEPT a. it can activate cells to produce inflammatory cytokines. b. it interacts with CD36 scavenger receptor. c. it increases in concentration by 25 percent or more in response to infection. d. it associates with high-density lipoprotein particles. e. it activates the classical pathway of complement activation.

30.__________ is not an opsonin. a. Mannose-binding lectin b. IFN-\alpha c. C-reactive protein d. Surfactant protein-A (SP-A) e. Surfactant protein-D (SP-D)

31.Toll-like receptors are located a. only on the plasma membrane. b. on the plasma membrane and the mitochondrial outer membrane. c. on the plasma membrane and endosomal membranes. d. only in the cytoplasm. e. inside inflammasomes.

32.Toll-like receptors differ from scavenger receptors in that they a. bind to common repetitive arrays on microbial surfaces. b. stimulate a pathway that causes enzymatic degradation of the microbe to which they bind. c. are soluble receptors that bind to microbes in extracellular spaces. d. mediate signal transduction pathways, causing cytokine production.

33.The Toll-like receptor that is able to signal through both the TRIF and MyD88 pathways is

a. TLR3. b. TLR4. c. TLR7. d. TLR8. e. TLR9.

34.Unlike inflammatory cytokines, Toll-like receptors a. are never secreted. b. participate only in adaptive immune responses. c. are expressed only by dendritic cells. d. stimulate the production of acute-phase proteins. e. induce fever.

35.All of the following statements regarding Toll-like receptors are true EXCEPT a. they exist as either transmembrane homodimers or heterodimers. b. the extracellular domain detects the microbial component. c. they facilitate changes in gene expression. d. they sense molecules not found in or on human cells. e. the cytoplasmic signaling domain contains a variable number of leucine-rich repeat regions (LRRs).

36.__________ binds to and retains NFκB in the cytosol. a. MyD88 b. TRAF6 c. I\kappaB d. I\kappa\kappa e. IRAK4

37.Plasmacytoid dendritic cells a. detect viral infection by using TLR4. b. produce large amounts of the type I interferons when activated. c. are found exclusively in the blood.

d. make up 10 percent of circulating leukocytes. e. have a cytoplasmic morphology resembling that of a resting B cell.

38.All of the following are correct in reference to type I interferons EXCEPT a. type I interferons inhibit the replication of viruses. b. in the presence of type I interferons, virus-infected cells undergo cellsurface changes that render them more susceptible to attack by NK cells. c. not only can most cells synthesize type I interferons, but they can also respond to them. d. the receptor for type I interferons is abundant in the cytosol and absent on the cell surface. e. type I interferons promote NK-cell proliferation and differentiation into cytotoxic cells.

39.The following cytokines activate NK cells early in the course of a viral infection with the exception of a. IFN-\alpha. b. IFN-\beta. c. IFN-\gamma. d. IL-12. e. IL-15.

40.The function of uterine NK cells (uNK) is to a. kill virus-infected cells. b. secrete growth factors that promote blood vessel growth to supply the placenta. c. activate resident macrophages by secreting inflammatory cytokines. d. secrete 1,000 times more type I interferon than other cells to protect the fetus from viral infection.

41.NK cells express each of the following proteins either on endosome membranes or on their cell surface with the exception of a. CD3.

b. type I interferon receptor. c. CD56. d. LFA-1.

42.Natural killer cells a. express either activating or inhibitory receptors on the cell surface, but not both. b. lack receptors for IL-12, thus preventing host tissue damage. c. perform the same function in the blood and in tissues such as the uterus. d. express Toll-like receptors allowing them to respond to viral RNA. e. All of these answers are correct.

43.Which of the following describes a safety mechanism to ensure that only infected cells are attacked by NK cells? a. The default state for NK cells is one of activation, which is overcome by the binding of inhibitory ligands. b. NK cells are able to secrete cytotoxic enzymes and proteins, thus killing multiple infected cells from a distance. c. No single receptor–ligand interaction induces cytotoxicity, but instead many combinations of receptor–ligand interactions influence the decision to kill or not to kill a target cell. d. NK cells express the receptor NKG2C, which limits NK cell activation.

44.Which of the following does NOT describe a feature observed when a target cell is induced to commit apoptosis by an NK cell? a. DNA fragmentation by target cell nucleases b. target cell shrinkage c. shedding of membrane-enclosed vesicles by the target cell d. chromatin extrusion in the form of decondensed DNA by the target cell e. macrophage disposal of apoptotic remains of the target cell.

45.Which of the following set of Toll-like receptors are expressed in NK cells? a. TLR3, TLR7, TLR8

b. TLR2, TLR4, TLR5, c. TLR2, TLR4, TLR9 d. TLR7 and TLR8 e. NK cells express all 10 Toll-like receptors

46.Immediately after engagement of NK-cell Toll-like receptors, the NK cell a. discharges cytotoxic granules. b. ligates IL-12R\beta1 and IL-12R\beta 2. c. synthesizes and secretes IL-15. d. synthesizes and secretes IL-12. e. synthesizes and secretes type I interferons.

47.Stimulation of NK cells by IL-12 a. is sufficient to cause the NK cell to produce large amounts of IFN-gamma. b. skews their differentiation into effector NK cells. c. induces the synthesis and secretion of IL-15 by NK cells. d. turns off type I interferon production by NK cells. e. induces the NK cell to undergo programmed cell death.

48.__________ is a cytokine produced by both macrophages and dendritic cells that promotes the proliferation, differentiation, and survival of NK cells. a. IL-15 b. IL-1\beta c. CXCL8 d. TNF-\alpha e. IL-6

49.Virally infected myeloid dendritic cells a. are not able to be detected or killed by NK cells. b. may release IL-15, activating macrophages to kill the virally infected cells. c. may outnumber NK cells and migrate to secondary lymphoid tissues. d. are unable to migrate to secondary lymphoid tissues.

e. secrete cytokines that allow the migration of NK cells to secondary lymphoid tissue.

50.After recognizing its ligand, a NOD receptor interacts with a signaling protein called __________, which is a serine–threonine kinase that phosphorylates TAKI. a. CARD b. NLRP3 c. RIPK2 d. MARCO e. SR-A

51.An adaptor protein in the inflammasome is required to link __________ to the NOD-like receptor NLRP3. a. MyD88 b. procaspase-1 c. RIPK2 d. TAKI e. IKK

52.Chemokine receptors form complexes with __________ after binding to their ligands. a. inflammasome components b. pro-IL-1\beta c. potassium channels d. GTP-binding proteins e. tertiary granules

53.All of the following acute-phase proteins increase in concentration in the plasma during inflammation with the exception of a. albumin. b. serum amyloid A protein. c. fibrinogen. d. C3.

e. mannose-binding lectin.

54.The ligands of endosomal Toll-like receptors are a. lipids of Gram-negative bacteria. b. flagellin proteins of bacteria. c. lipids of Gram-positive bacteria. d. zymosan of fungi. e. nucleic acids of viruses and bacteria.

55.Of the following Toll-like receptors, which is the most highly conserved and displays the smallest amount of allelic polymorphism? a. TLR1 b. TLR8 c. TLR10 d. TLR6 e. TLR4

56.Sensors for viral nucleic acid in the cytoplasm, called RLRs, possess domains that bind to a. GTP-binding proteins. b. type 1 interferons. c. the 5’ cap of messenger RNA (mRNA). d. oligomerized procaspase-1. e. CARD domains of MAVS.

57.What is the name given to the earliest intracellular vesicle that contains material opsonized by macrophages? a. opsonome b. membrane-attack complex c. lysosome d. phagosome e. phagolysosome

58.Which of the following activities are most closely associated with natural killer cells? a. production of TNF-α b. lysis of virus-infected cells c. phagocytosis of bacteria d. release of reactive oxygen intermediates e. formation of extracellular traps

59.The lectin pathway of complement activation is induced by a. C-reactive protein. b. antibodies bound to pathogens. c. mannose-binding lectin. d. iC3Bb. e. terminal components of the complement pathway.

60.Which of the following is NOT a characteristic of mannose-binding lectin? a. acts as an opsonin by binding to mannose-containing carbohydrates of pathogens b. synthesized by hepatocytes c. induced by elevated IL-6 levels d. triple helix of protein-forming, multiple ligand-binding sites e. triggers the alternative pathway of complement activation

61.Which of the following is NOT a characteristic of C-reactive protein? a. acts as an opsonin by binding to phosphorylcholine of pathogens b. synthesized by spleen c. induced by elevated IL-6 levels d. a member of the pentraxin family e. triggers the classical pathway of complement activation

62.Which of the following TLRs do not use a signal transduction cascade involving

MyD88? a. TLR1:TLR2 b. TLR3 c. TLR4 d. TLR2:TLR6 e. TRL7

63.Which of the following adaptor proteins participates in the activation pathway induced through either TLR3 or TLR4 that culminates in the synthesis of type I interferons? a. C-reactive protein b. MyD88 c. LPS-binding protein d. TRIF e. NF-κB

64.Which of the following properties is common to macrophages and neutrophils in an uninfected individual? a. life-span b. anatomical location c. ability to phagocytose d. morphology e. formation of pus

65.Which of the following best describes an endogenous pyrogen? a. cytokines made by pathogens that decrease body temperature b. pathogen products that decrease body temperature c. pathogen products that increase body temperature d. cytokines made by the host that decrease body temperature e. cytokines made by the host that increase body temperature

66.Which of the following is an acute-phase protein that enhances complement fixation?

a. TNF-\alpha b. mannose-binding lectin c. fibrinogen d. LFA-1 e. CXCL8

67.Inflammation a. is dependent on antibodies activating complement. b. can lead to fever and swelling. c. may result in damage to host tissue. d. may occur when a pathogen bypasses the protective epithelial surfaces and immediate immune defenses. e. includes the recruitment of white blood cells to site of infection.

68.Select the correct response using the information shown in the figure.

a. The cell labeled “A” is most likely recognizing a viral glycoprotein on the infected cell’s surface. b. The cell labeled “B” is categorized as “non-self.” c. The bacterial components labeled “C” likely resemble “self” molecules and

are thus able to be recognized by the macrophage. d. The molecules labeled “D” are categorized as “altered-self.” e. None of these answers are correct.

69.Pro-IL-1β a. is secreted by activated macrophages. b. is produced by neutrophils after TLR activation. c. is cleaved by procaspase 1. d. is cleaved and may lead to pyroptosis. e. All of these answers are correct.

70.The common lymphocyte precursor cell a. gives rise to lymphocytes involved in adaptive immunity only. b. gives rise to both the ILCs and NK cells. c. is located in the lymph nodes. d. is not needed for the development of NK cells. e. gives rise to cells that are able to fight viral infections, but not bacterial infections.

71.During an infection in the gut with large multicellular parasites a. NK cells would first respond followed by ILCs. b. ILC1 cells would respond. c. ILC2 cells would respond. d. ILC cells secreting IL-17 would respond.

72.Which of the following statements is INCORRECT concerning the process of neutrophils accessing infected tissues? a. Neutrophils respond to a chemokine gradient at the site of infection. b. Neutrophils move between blood endothelial cells via diapedesis. c. LFA-1 on neutrophils binds ICAM-1 in a process of rolling adhesion, and this interaction is followed by selectin binding to addressins. d. Neutrophils that have entered the tissues may activate NADPH oxidase.

e. In the absence of infection, neutrophils remain in the blood.

73.Match the term with its correct description. a. interferon response b. apoptosis c. extravasation d. respiratory burst e. acute-phase response 1. __________ a notable rise or reduction of plasma proteins in response to IL-6 2. __________ stimulates inhibition of viral replication 3. __________ temporary rise in oxygen consumption and toxic oxygen species production 4. __________ cellular suicide characterized by DNA fragmentation 5. __________ migration of neutrophils into inflamed tissues

74.Match the condition/disease with its correct description. a. X-linked hypohidrotic ectodermal dysplasia and immunodeficiency (NEMO deficiency) b. septic shock c. chronic granulomatous disease d. increased susceptibility to herpesvirus infections 1. __________ insufficient superoxide production in neutrophils compromises the respiratory burst 2. __________ failure to translocate NF\kappaB and activate macrophages due to deficiency in IKK/gamma subunit 3. __________ allelic polymorphism of TLR4 with glycine at position 299 causing reduced responsiveness to LPS of Gram-negative bacteria 4. __________ natural killer cell deficiency

75.Match the term with its correct description. a. oligoadenylate synthetase b. plasmacytoid dendritic cell (PDC) c. RIG-I-like helicase d. protein kinase R (PKR) e. NK-cell synapse

1. __________ activates endoribonucleases that degrade viral RNA 2. __________ facilitates adhesion and information exchange between cells undergoing surveillance via activating and inhibitory receptors 3. __________ synthesizes 1,000 times more interferon than do other cells 4. __________ inhibits protein synthesis by phosphorylating eIF-2 5. __________ contains domains that bind to viral RNA and mitochondrial antiviral signaling proteins

76.Match the innate immune receptor with its ligand(s). Use each ligand once. a. lectin receptor b. scavenger receptor c. CR1 d. TLR4:TLR4 e. TLR5 f. TLR3 1. __________ carbohydrates (for example mannose or glucan) 2. __________ lipopolysaccharide (LPS) 3. __________ heat-shock proteins and other stress or damage markers 4. __________ C3b 5. __________ flagellin 6. __________ RNA

77.Match the letter in the figure with the correct description. Use each letter once.

a. A b. B c. C d. D e. E 1. __________ exits the cell through a gasdermin D pore 2. __________ contains Leucine Rich Repeats (LRRs) 3. __________ lacks a typical signal sequence required for secretion 4. __________ is synthesized as an inactive enzyme 5. __________ contains active caspase

78.Match the labels in the figure to the correct cytokine. Use each cytokine once.

a. A b. B c. C d. D e. E 1. CXCL8 2. IL-12 3. IL-6 4. TNF-α 5. CCL2

79.Other than their ligand specificity, what is a key difference between TLR5, TLR4, TLR1:TLR2, and TLR2:TLR6 compared to TLRs 3, 7, 8, and 9?

80.Explain why TLRs can detect many different species of microbes despite the limited number of different TLR proteins.

81.Describe the two different domains of TLRs and their respective functions.

82.Explain the consequence of engagement of the TLR4, CD14, and MD2 complex with LPS in macrophages.

83.During inflammation, host tissue may be damaged owing to the release of toxic oxygen derivatives produced by activated macrophages and neutrophils. Explain what cellular mechanisms limit these damaging bystander effects.

84.Describe the different functions performed by the NK cells in the blood and the NK cells found in the uterus.

85.What is NF\kappaB, and what is its role in mediating signals through TLRs?

86.Discuss the mechanisms by which type I interferons exert their antiviral effects.

87.An individual experiences recurrent systemic inflammation over a period of years with symptoms including fever and rashes. They are tested and found to have a mutation that results in overactivation of an inflammasome. Evaluate whether treatment with colchicine and an IL-1 receptor antagonist may provide relief for this individual or whether an alternative therapy would be more effective.

Answer Key Chapter 03 1. Answer:

B

2. Answer:

A

3. Answer:

B

4. Answer:

B

5. Answer:

B

6. Answer:

A

7. Answer:

C

8. Answer:

C

9. Answer:

D

10.Answer:

E

11.Answer:

C

12.Answer:

B

13.Answer:

A

14.Answer:

C

15.Answer:

E

16.Answer:

B

17.Answer:

A

18.Answer:

C

19.Answer:

C

20.Answer:

B

21.Answer:

D

22.Answer:

A

23.Answer:

D

24.Answer:

E

25.Answer:

B

26.Answer:

B

27.Answer:

A

28.Answer:

C

29.Answer:

E

30.Answer:

B

31.Answer:

C

32.Answer:

D

33.Answer:

B

34.Answer:

A

35.Answer:

E

36.Answer:

C

37.Answer:

B

38.Answer:

D

39.Answer:

C

40.Answer:

B

41.Answer:

A

42.Answer:

D

43.Answer:

C

44.Answer:

D

45.Answer:

A

46.Answer:

E

47.Answer:

B

48.Answer:

A

49.Answer:

C

50.Answer:

C

51.Answer:

B

52.Answer:

D

53.Answer:

A

54.Answer:

E

55.Answer:

B

56.Answer:

E

57.Answer:

D

58.Answer:

B

59.Answer:

C

60.Answer:

E

61.Answer:

B

62.Answer:

B

63.Answer:

D

64.Answer:

C

65.Answer:

E

66.Answer:

B

67.Answer:

A

68.Answer:

A

69.Answer:

D

70.Answer:

B

71.Answer:

C

72.Answer:

C

73.Answer:

1. E 2. A 3. D 4. B 5. C

74.Answer:

1. C 2. A 3. B 4. D

75.Answer:

1. A 2. E 3. B 4. D 5. C

76.Answer:

1. A 2. D 3. B

4. C 5. E 6. F 77.Answer:

1. E 2. A 3. C 4. B 5. D

78.Answer:

1. C 2. E 3. B 4. A 5. D

79.Answer:

TLR5, TLR-4, TLR1:TLR2, and TLR2:TLR6 are transmembrane receptors anchored in the plasma membrane on the surface of human cells that interact with pathogens located in extracellular locations. In contrast, TLRs 3, 7, 8, and 9 are anchored in endosomal membranes located in the cytosol, where the intracellular degradation of pathogens takes place.

80.Answer:

Because many pathogens possess features that are common to different groups of pathogens, for example LPS in Gramnegative bacteria, only a small number of TLRs are required to act as sensors of molecular patterns shared by pathogens.

81.Answer:

The first domain of the TLR is an extracellular domain, also known as the pathogen-recognition domain, which contains a hydrophobic, leucine-rich repeat region (LRR) forming a horseshoe-shaped structure that binds specifically to arrays on microbial surfaces. The second domain of the TLR is the cytoplasmic signaling domain, also known as the Toll/interleukin-1 receptor (TIR) domain, which facilitates the transmission of information to the nucleus.

82.Answer:

When TLR4 on the surface of macrophages is bound to its LPS ligand, a signal transduction cascade is initiated that

mediates signaling between the cell surface and the nucleus, resulting in the entry of the transcription factor NF\kappaB into the nucleus. The macrophage in turn begins to express particular genes encoding cytokines and adhesion molecules that are needed to induce a state of inflammation in the infected tissue.

83.Answer:

Toxic oxygen species including superoxide, hydrogen peroxide, singlet oxygen, hydroxyl radical, hypohalite, and nitric oxide are produced during the respiratory burst in macrophages and neutrophils. Simultaneous extraphagosomal production of enzymes that neutralize these compounds occurs. Specifically, superoxide dismutase metabolizes superoxide to hydrogen peroxide, which is further metabolized by catalase to innocuous water and molecular oxygen.

84.Answer:

(i) 90 percent of the NK cells in the blood are differentiated cytotoxic effector cells that express lower levels of the CD56 marker on their cell surface (CD56dim). These NK cells are committed to killing virus-infected cells so as to interfere with virus replication and intercellular spread. In the uterus, there exists a specialized subpopulation of NK cells called uterine NK cells (uNK), which comprise the predominant leukocytes in this tissue and are CD56bright. They do not kill cells and they do not induce inflammation. Instead they provide growth factors needed for expansion of maternal blood vessels to ensure that the placenta and fetus are supplied adequately with oxygen during pregnancy. They are also able to secrete non-inflammatory cytokines.

85.Answer:

NF\kappaB is a transcription factor, and some TLRs signal through an intracellular pathway that involves the activation of NF\kappaB. In the absence of stimulation of the TLR, NF\kappaB is found in an inactive form in the cytoplasm bound by an inhibitor (I\kappaB). Signaling through the TLR results in a phosphorylation cascade that converts NF\kappaB to its active form, which is then able to translocate into the nucleus and direct the transcription of specific genes that promote the cell’s response to the infection, such as the genes for inflammatory cytokines.

86.Answer:

Type I interferon genes (for interferons-\alpha and -\beta) are transcribed as a result of the presence of double-stranded RNA. Type I interferons (IFN-\alpha and -\beta) block virus replication in infected cells and protect uninfected cells nearby from becoming infected. This is accomplished by: (1) inducing cellular genes that destroy viral RNA through endonuclease attack; and (2) inhibiting protein synthesis of

viral mRNA by modifying the initiation factors required for protein synthesis. In addition, IFN-\alpha and -\beta activate natural killer (NK) cells. NK cells kill virus-infected cells by releasing cytotoxic granules through a mechanism that involves the engagement of activating and inhibitory receptors; if inhibitory signals predominate, the target cell is not killed; however, if activating signals predominate, the target cell is killed.

87.Answer:

This individual likely has an autoinflammatory disease. The mutation that causes overactivation of the inflammasome results in the release of too much IL-1\beta, which results in the fever and also rashes due to the influx of neutrophils. The IL-1 receptor antagonist blocks the binding of IL-1\beta to the receptors, thus preventing and terminating macrophage activation. Colchicine may be helpful because it prevents the formation of inflammasomes.

Name: ___________________________ Class: _________________ Date: __________

Chapter 04 1. The immunoglobulin heavy- and light-chain loci are encoded on the same chromosome. a. True b. False

2. Light chains contain V and J segments, whereas heavy chains contain V, D, and J segments. a. True b. False

3. All immunoglobulin loci include a leader sequence. a. True b. False

4. On the heavy-chain locus, V rearranges to D first, and then J joins the combined VD sequence. a. True b. False

5. Immunoglobulin heavy-chain loci undergo two rounds of somatic recombination, whereas light-chain loci undergo only one. a. True b. False

6. B-cell antigen receptors are both membrane-bound and secreted. a. True b. False

7. B-cell antigen receptors consist of a variable region and a constant region. a. True b. False

8. B-cell antigen receptors lack specificity and can bind to several different antigens. a. True b. False

9. B-cell antigen receptors undergo affinity maturation as a consequence of somatic hypermutation. a. True b. False

10.With reference to immunoglobulin structure, the antibody secreted by a plasma cell has a different specificity for antigen than the immunoglobulin expressed by its B-cell precursor. a. True b. False

11.In reference to immunoglobulin structure, the amino-terminal regions of heavy and light chains of the B-cell antigen receptor located on different naive B cells all differ in amino acid sequence. a. True b. False

12.In reference to immunoglobulin structure, a flexible hinge region holds the heavy chain and light chain together. a. True b. False

13.In reference to immunoglobulin structure, the heavy-chain constant region is responsible for the effector function of immunoglobulins. a. True b. False

14.In reference to immunoglobulin structure, λ and κ light chains have different functions. a. True b. False

15.Individuals with mutations in the activation-induced cytidine deaminase (AID) enzyme can produce B cells expressing both IgM and IgD on the cell surface. a. True b. False

16.Isotype switching occurs after a mature B cell’s exposure to foreign antigen. a. True b. False

17.Individuals with mutations in the AID enzyme can produce antibodies that trigger mast-cell degranulation. a. True b. False

18.The AID enzyme targets recombination signal sequences (RSSs) during the process of isotype switching. a. True b. False

19.Individuals with mutations in the AID enzyme would have low levels of secreted IgM antibody.

a. True b. False

20.The five classes (isotypes) of human immunoglobulins comprise are a. IgA, IgD, IgE, IgG, IgM. b. IgA, IgC, IgD, IgE, IgG. c. IgA, IgD, IgE, IgH, IgM. d. IgA, IgD, IgE, IgG, IgK. e. IgA, IgD, IgE, IgG, IgS.

21.The name given to a fully activated and differentiated B cell that secretes antibody is __________ cell. a. T b. antigen-presenting c. hematopoietic d. secretory e. plasma

22.The heavy-chain isotypes of human immunoglobulin include a. α, β, γ, δ, and ε. b. α, β, γ, δ, and λ. c. α γ, δ, κ, and μ. d. α, γ, δ, ε, and μ.

23.Which statement regarding immunoglobulin light chains is true? a. κ associates with only particular heavy-chain isotypes. b. There is no functional difference between κ and λ. c. A given antibody may contain just κ, or just λ, or both. d. Most antibodies in humans contain λ light chains. e. Light chains possess only framework regions, not hypervariable regions.

24.__________, __________, and __________ are the three most abundant

antibodies in blood. a. IgA; IgD; IgE b. IgA; IgE; IgG c. IgA; IgG; IgM d. IgE; IgG; IgM e. IgD; IgE; IgM

25.The five isotypes of immunoglobulin differ from each other in their __________ regions. a. light-chain constant b. heavy-chain constant c. light-chain variable d. heavy-chain variable e. heavy-chain variable and constant

26.Which one of these features renders all IgG antibodies less susceptible to proteolysis than the other antibody classes? a. length of the hinge region b. ability to exchange chains with other IgG antibodies c. presence of additional disulfide bonds d. capacity to activate complement e. degree of accessibility for binding to C1

27.Which of the following statements about immunoglobulin domains is true? a. They are 100–110 amino acids in length. b. They are present in the variable, but not the constant region of the immunoglobulin molecule. c. They are unique to antibodies and are not found in other proteins. d. They are present in the heavy chain, but not the light chain of antibodies.

28.The __________ contribute to antigen specificity of immunoglobulins, and __________ make up the more conservative flanking regions.

a. hypervariable loops; framework regions b. constant domains; variable domains c. heavy chains; light chains d. variable gene segments; joining gene segments e. antigenic determinants; complementarity determining regions

29.The immunoglobulin heavy-chain gene consists of __________ segments, whereas the immunoglobulin light-chain gene consists of __________ segments a. κ; λ b. VDJ; VJ c. VJ; VDJ d. P; N e. RAG-1; RAG-2

30.On the heavy-chain immunoglobulin gene locus, recombination signal sequences flank __________ of the V segment, __________ of the D segment, and __________ of the J segment. a. the 5′ side; both sides; the 3′ side b. the 5′ side; the 5′ side, the 5′ side c. the 3′ side; both sides; the 3′ side d. both sides; both sides; both sides e. the 3′ side; both sides; the 5′ side

31.Which of the following describes two recombination signal sequences required for a permitted somatic recombination event? a. VH 7-12-9: 9-23-7 JH b. Vλ7-23-9: 9-23-7 Jλ c. DH 7-12-9: 9-23-7 JH d. Vκ7-12-9: 7-23-9 Jκ e. VH 9-23-7: 7-12-9 DH

32.The enzyme complex responsible for recombining V, D, and J segments during

somatic recombination is called a. V(D)J recombinase. b. terminal deoxynucleotidyl transferase. c. exonuclease. d. DNA polymerase. e. DNA ligase.

33.The component of the V(D)J recombinase involved in recognition of the recombination signal sequences is a. activation-induced cytidine deaminase. b. terminal deoxynucleotidyl transferase. c. RAG-1/RAG-2. d. DNA ligase IV.

34.Which of the following corresponds to the antigen-binding site of immunoglobulins? a. VH:CH b. VH:VL c. VL:CL d. CH:CL e. VH:CL

35.Another term commonly used to describe hypervariable loops is a. multivalency. b. framework regions. c. hinge region. d. complementarity-determining regions. e. signal joint.

36.An epitope a. is recognized by the Fc region of an antibody.

b. is recognized by the complementarity-determining region of an antibody. c. must be a contiguous sequence of amino acids. d. is part of the framework region of the antibody.

37.All of the following are utilized in the binding of antibodies to antigens EXCEPT a. interchain disulfide bonds. b. hydrogen bonding. c. hydrophobic interactions. d. electrostatic forces (salt bridges). e. van der Waals interactions.

38.Production by the patient of antibodies against therapeutic mouse monoclonal antibodies is the major limitation for their use in humans. These human antiantibodies are directed primarily against the __________ of the mouse antibody. a. V regions b. D regions c. C regions d. J regions e. MC regions

39.Identify the INCORRECT statement regarding flow cytometry. a. Samples must be incubated with fluorescent molecules (such as fluorescent antibodies) before analyzing. b. It is possible to label samples with two fluorescent tags and determine whether cells are negative or positive for either one tag or the other, or both. c. A one-dimensional histogram measures the amount of fluorescence versus cell number. d. Samples must consist of a single cell type and cannot be composed of multiple cell types. e. A laser is required to detect labeled cells. f. A stream of cells in single file is generated by a nozzle.

40.With the exception of B cells, all other cells of the body have the immunoglobulin genes in the a. germline configuration. b. monoclonal form. c. recombined configuration. d. expressed configuration. e. chimeric form.

41.Membrane-coding (MC) exons of immunoglobulin genes a. code for amino acids that anchor and stabilize the light chain to the membrane of B cells. b. specify hydrophilic amino acids that associate with the B-cell membrane. c. are included in the primary RNA transcripts of secreted antibodies. d. are targets for somatic hypermutation.

42.In what way does the κ light chain differ from the λ light chain? a. κ performs a different function from λ when bound to the immunoglobulin heavy chain. b. κ, but not λ, is encoded on the same chromosome as the heavy-chain locus. c. κ contains a VJ region, whereas λ contains a VDJ region. d. The κ locus encodes a single C segment, whereas the λ locus has more than one. e. κ contains a transmembrane domain but λ does not.

43.In contrast to leader peptides and the C regions, the V regions in immunoglobulin heavy-chain genes a. encode hydrophobic amino acids that anchor the immunoglobulin chains to B-cell membranes. b. comprise the smallest number of gene segments in the human immunoglobulin loci. c. are not subject to allelic exclusion. d. do not undergo somatic hypermutation. e. are composed of V, D, and J gene segments that must undergo gene

rearrangement to generate a transcribable exon.

44.The enzyme responsible for adding N nucleotides is a. V(D)J recombinase. b. terminal deoxynucleotidyl transferase. c. uracil-DNA-glycosylase (UNG). d. DNA ligase. e. activation-induced cytidine deaminase (AID).

45.Which of the following enzymes facilitates the process of affinity maturation? a. DNA ligase b. V(D)J recombinase c. terminal deoxynucleotidyl transferase d. activation-induced cytidine deaminase (AID) e. exonuclease

46.The process of gene rearrangement in immunoglobulin and T-cell receptor genes is called a. somatic hypermutation. b. isotype switching. c. somatic recombination. d. apoptosis. e. clonal selection.

47.Junctional diversity during gene rearrangement results from the addition of a. switch region nucleotides. b. P and N nucleotides. c. V, D, and J nucleotides. d. recombination signal sequences. e. mutations in complementarity-determining regions.

48.Which of these genetic defects would result in a lack of somatic recombination

between V, D, and J segments? a. lack of a functional activation-induced cytidine deaminase gene b. lack of a functional RAG1 gene c. lack of a functional terminal deoxynucleotidyl transferase gene d. lack of a functional exonuclease

49.A circulating B cell that has not yet encountered antigen expresses __________ on the cell surface. a. IgM and IgD b. IgM c. IgD d. IgM and IgG e. IgG f. IgE

50.All of the following processes occur in mature B cells after antigen encounter EXCEPT a. alternative splicing. b. affinity maturation. c. proliferation. d. somatic recombination.

51.Identify the correct order of gene segments in a rearranged heavy-chain gene in a naive B cell. a. V-D-J-Cμ-Cδ b. V-J-D-Cμ-Cδ c. V-D-J-Cδ-Cμ d. V-J-D-Cμ-Cα1 e. V-D-J-Cμ-Cα1

52.Which of the following determines the isotype of an immunoglobulin?

a. the composition of the hypervariable regions b. whether the immunoglobulin is membrane-bound or secreted c. its light chain d. its heavy chain e. the composition of the cytoplasmic tails of Igα and Igβ

53.Naive B cells are defined by their expression of a. no immunoglobulins on the cell surface because somatic recombination has not yet commenced. b. both membrane-bound and secreted forms of immunoglobulin. c. both IgM and IgD on the cell surface. d. V(D)J recombinase. e. uracil-DNA-glycosylase (UNG).

54.Which of the following statements regarding Igα and Igβ proteins is correct? a. They associate with IgM on the cell membrane, but not with IgD. b. They are required for the joining of the V, D, and J gene segments during somatic recombination. c. They facilitate signal transduction through their short cytoplasmic tails. d. They facilitate transport of the IgM molecule to the cell surface. e. They are generated through the process of somatic recombination.

55.The highest degree of diversity resulting from somatic recombination is concentrated __________ of the VH and VL domains, whereas the point mutations caused by somatic hypermutation are found __________. a. in CDR3; throughout the V region b. in CDR3; in CDR1 and CDR2 of VH and VL domains c. in CDR1 and CDR2; in CDR3 d. in CDR1 and CDR2; throughout the V region e. in all three CDRs; in C regions

56.As an adaptive immune response progresses, the production of variant antibodies that compete more effectively for antigen occurs, and B cells producing these

antibodies are preferentially selected based on their improved binding to antigen.

This phenomenon is referred to as a. isotype switching. b. neutralization. c. allelic exclusion. d. affinity maturation. e. somatic rearrangement.

57.All of the following are required for isotype switching EXCEPT a. switch-region recombination. b. J chain. c. activation-induced cytidine deaminase (AID). d. B-cell proliferation. e. uracil-DNA glycosylase (UNG).

58.Which of these isotypes activate complement? a. IgA, IgD, IgE, IgG1, IgM b. IgE, IgG1, IgG2, IgG3, IgM c. IgA, IgD, IgE, IgG4 d. IgG1, IgG2, IgG3, IgG4 e. IgA, IgG1, IgG2, IgG3, IgM

59.Which of the following can be found in serum in a monovalent form? a. IgG4 b. IgD c. IgA1 d. antibodies made up of four C domains e. IgG3

60.Neutralizing antibodies a. interfere with antigen degradation. b. facilitate uptake of antigen through Fc regions.

c. stimulate complement activation. d. inhibit interaction of antigen with human cell surfaces. e. sensitize mast cells and basophils.

61.Which of the following statements regarding human immunoglobulins is correct? a. Immunoglobulins make up five classes (or isotypes) called IgA, IgD, IgE, IgG, and IgM. b. Regardless of their isotype, immunoglobulins all have the same effector function. c. Antibodies consist of four identical heavy chains and four identical light chains. d. Peptide bonds hold the heavy and light chains together. e. The constant regions make up the antigen-binding site.

62.Which of the following statements about the production and use of monoclonal antibodies is NOT true? a. Production of monoclonal antibodies requires a purified form of antigen. b. A monoclonal antibody has specificity for only one epitope of an antigen. c. B cells are fused with a tumor cell called a myeloma, to immortalize the resulting hybridoma. d. Monoclonal antibodies made in mice have limited therapeutic potential. e. Humanized monoclonal antibodies reduce complications associated with using mouse monoclonal antibodies.

63.The mutational mechanism that results in the production of antibodies that bind antigen with higher affinity is called a. somatic recombination. b. isotype switching. c. somatic hypermutation. d. clonal selection. e. antigen processing.

64.The process of __________ results in change in the constant region of the heavychain of antibodies, causing a change in the effector function and transport

properties of antibodies. a. complement fixation b. neutralization c. isotype switching d. somatic hypermutation e. somatic recombination

65.The process used to produce either surface or secreted forms of the immunoglobulin heavy chain is called a. alternative RNA splicing and processing. b. isotype switching. c. somatic recombination. d. somatic hypermutation. e. opsonization.

66.The IgA immunoglobulin isotype a. can be transported across the placenta. b. can be transported across epithelium. c. cannot activate complement. d. cannot neutralize viruses. e. can sensitize mast cells.

67.The IgE isotype a. can sensitize mast cells. b. can be transported across the placenta. c. can be transported across epithelium. d. can activate complement. e. can neutralize viruses.

68.IgM and IgD are coexpressed on naive B cells by a process called a. isotype switching. b. somatic recombination.

c. somatic hypermutation. d. alternative mRNA splicing and processing. e. affinity maturation.

69.Which immunoglobulin’s main function is to mediate sensitization of mast cells? a. IgA b. IgD c. IgE d. IgG e. IgM

70.Which immunoglobulin is transported most efficiently across mucosal epithelium? a. IgA b. IgD c. IgE d. IgG e. IgM

71.__________ forms dimers, whereas __________ forms pentamers. a. IgG; IgD b. IgE; IgM c. IgD; IgM d. IgA; IgM e. IgM; IgG

72.A newborn derives passive immunity from its mother as a result of placental transfer of __________ during pregnancy. a. IgA b. IgD c. IgE d. IgG e. IgM

73.__________ is secreted into the bloodstream, whereas __________ is secreted into mucus such as gastrointestinal fluid, colostrum, saliva, tears, and sweat. a. Monomeric IgM; pentameric IgM b. Monomeric IgA; dimeric IgA c. Monomeric IgA; dimeric IgG d. Monomeric IgA; monomeric IgM e. Dimeric IgA; pentameric IgM

74.Which of the following activities are associated with activation-induced cytidine deaminase (AID)? a. diversification of the VH domain but not the VL domain b. synthesis in naive B cells prior to antigen activation c. generation of mast cell activating immunoglobulin isotypes d. synthesis of IgD in developing B cells e. conversion of cytosine to guanine

75.The process of __________ results in the amplification of particular B cells with specificity for antigen. a. germline recombination b. somatic recombination c. clonal selection d. antigen processing e. antigen presentation

76.Select the correct statement concerning the antibody molecule.

a. “A” is identical in amino acid sequence to the region labeled “B”. b. “C” forms part of the antigen-binding site. c. Both “A” and “D” contain hypervariable and framework regions. d. “E” contains both hypervariable and framework regions. e. Beta-pleated sheet structure is found only in regions “B”, “C”, and “E”.

77.Select the correct statement concerning the antibody molecule.

a. “A” and “D” contain amino acids coded for by non-templated nucleotides. b. “B” and “C” are encoded by V, D, and J gene segments. c. The region of the chromosome encoding “D” remains in the germline organization in B cells expressing the B-cell receptor. d. The region of the chromosome encoding “E” is flanked by recombination signal sequences (RSSs). e. “E” can be either the κ or λ isotype.

78.Select the correct statement concerning isotype switching.

a. To generate an antibody of the IgG1 isotype, the AID enzyme targets “D” and “E”. b. After an IgG1 antibody is generated by isotype switching, the gene regions remaining in the B cell’s DNA include “VDJ”, “B”, “C”, “D”, and “F”. c. “A” is involved in isotype switching to IgD. d. The RAG enzyme generates a double-stranded DNA break at “A” to allow isotype switching to IgG3 or IgG1. e. In an individual lacking a functional AID gene, both “B” and “C” could be expressed in a primary RNA transcript.

79.Select the INCORRECT statement concerning isotype switching.

a. “D” and “E” are referred to as switch regions. b. Isotype switching to IgG1 requires the AID enzyme to be activated. c. The antigen-binding region of the antibody molecule does not change during isotype switching from IgM to IgG3. d. The first constant region expressed by B cells is labeled “D”. e. Isotype switching from “B” to “F” only occurs in B cells that are proliferating in response to antigen.

80.What is an epitope?

81.Define the term multivalent antigen.

82.How does a linear epitope differ from a conformational epitope?

83.Do antibodies bind their antigens via noncovalent bonding or via covalent

bonding?

84.What is the basic structural difference between the immunoglobulins produced by B cells and their descendants before antigen encounter and after antigen encounter?

85.In which way(s) do the immunoglobulins produced by B cells and their descendants before antigen encounter and after antigen encounter resemble each other?

86.What is the final arrangement of gene segments in the rearranged immunoglobulin heavy-chain gene V region, and in what order do these gene segment rearrangements occur?

87.The third hypervariable region (CDR3) is the most variable site in an immunoglobulin V region. It differs in its composition between the light-chain and heavy-chain V regions. Explain what this difference is and how the diversity in CDR3 is generated.

88.What is the difference between polyclonal antibodies and monoclonal antibodies?

89.Briefly describe how monoclonal and polyclonal antibodies are produced.

90.Explain the process responsible for the co-expression of IgM and IgD by mature, naive B cells.

91.Describe the process responsible for altering the expression of membrane-bound immunoglobulin to secreted antibody.

92.Explain why it is desirable that the Igα and Igβ proteins do not vary in sequence from cell to cell in the same way that immunoglobulins do. Include the function of the Igα and Igβ proteins in your response.

93.Describe the molecular process that leads to affinity maturation and the outcome.

94.Describe the process of isotype switching, including the molecular mechanism that allows it to occur.

95.Define isotype switching and explain why it is important.

96.Monoclonal antibodies are used for a wide range of applications including serological assays and diagnostics probes in the laboratory, and as therapeutic reagents in the clinic. Discuss why “humanizing” monoclonal antibodies is necessary for use as therapeutic reagents but is not necessary when monoclonal antibodies are used as serological or diagnostic reagents.

97.How is additional diversity introduced into the variable region during the process of somatic recombination? Include the following terms in your answer: junctional diversity, P nucleotides, N nucleotides, terminal deoxynucleotidyl transferase (TdT).

98.Isotype switching and immunoglobulin gene rearrangement by somatic recombination are both recombinational processes but have very different outcomes. List four ways in which they differ from each other.

99.What would be the effect of a genetic defect that resulted in a lack of recombination between the switch regions in the immunoglobulin C-region genes?

100.

Explain which of the four types of monoclonal antibody is most desirable

for the treatment of chronic conditions in humans and provide an example.

101.

Match each antibody term with the correct description. a. Hinge region b. κ c. Fab d. α e. Fc 1. __________ is the stem that carries out effector function of antibodies through interaction with cell-bound receptors and serum proteins.

2. __________ provides flexibility to permit binding to different antigenic arrangements.

3. __________ is a heavy-chain isotype.

4. __________ are the arms of the antibody that bind antigen.

5. __________ is a light-chain isotype.

102.

Match each term with its proper description. a. Hybridoma b. Myeloma c. Monoclonal antibody d. Antiserum e. Chimeric monoclonal antibody 1. __________ is derived from blood following vaccination with an antigen.

2. __________ is a pure type of antibody synthesized by a single clone of cells.

3. __________ is an immortalized cell line generated by fusing a B cell with a tumor cell.

4. __________ is a tumor of plasma cells.

5. __________ is an engineered antibody containing mouse V regions and human C regions.

103.

Match each term with the correct description. a. Monoclonal antibody production b. Isotype switching c. Opsonization d. Somatic hypermutation

e. Somatic recombination 1. __________ is the rearrangement of V, D, and J segments to form an immunoglobulin.

2. __________ is the derivation of antibodies from a single clone of B lymphocytes that have identical antigen specificity.

3. __________ entails change of immunoglobulin class but preservation of antigen specificity.

4. __________ comprises nucleotide changes in variable regions of immunoglobulin genes affecting affinity for antigen.

5. __________ is the enhancement of receptor-mediated phagocytosis of immunoglobulin-coated antigen.

104.

Describe the structure of an antibody molecule and how this structure enables it to bind to a specific antigen. Include the following terms in your description: heavy chain (H chain), light chain (L chain), variable region, constant region, Fab, Fc, antigen-binding site, hypervariable region, and framework region.

105.

Explain how a vast number of immunoglobulins of different antigen specificities can be produced from the relatively small number of immunoglobulin genes present in the genome. Include the following terms in your explanation: somatic recombination; germline configuration; V, D, and J segments.

106.

How do recombination signal sequences ensure that gene segment rearrangement occurs in the right order?

107.

There are multiple types of monoclonal antibodies used for therapeutic purposes. Explain how mouse monoclonal antibodies are produced and describe the multiple approaches taken to generate more humanized monoclonal antibodies.

108.

There are multiple types of monoclonal antibodies used for therapeutic purposes. Explain how mouse monoclonal antibodies are produced and describe the multiple approaches taken to generate more humanized monoclonal antibodies.

Answer Key Chapter 04 1. Answer:

B

2. Answer:

A

3. Answer:

A

4. Answer:

B

5. Answer:

A

6. Answer:

B

7. Answer:

A

8. Answer:

B

9. Answer:

A

10.Answer:

B

11.Answer:

A

12.Answer:

B

13.Answer:

A

14.Answer:

B

15.Answer:

A

16.Answer:

A

17.Answer:

B

18.Answer:

B

19.Answer:

B

20.Answer:

A

21.Answer:

E

22.Answer:

D

23.Answer:

B

24.Answer:

C

25.Answer:

B

26.Answer:

C

27.Answer:

A

28.Answer:

A

29.Answer:

B

30.Answer:

E

31.Answer:

C

32.Answer:

A

33.Answer:

C

34.Answer:

B

35.Answer:

D

36.Answer:

B

37.Answer:

B

38.Answer:

C

39.Answer:

D

40.Answer:

A

41.Answer:

C

42.Answer:

D

43.Answer:

E

44.Answer:

B

45.Answer:

D

46.Answer:

C

47.Answer:

B

48.Answer:

B

49.Answer:

A

50.Answer:

D

51.Answer:

A

52.Answer:

D

53.Answer:

C

54.Answer:

D

55.Answer:

A

56.Answer:

D

57.Answer:

B

58.Answer:

E

59.Answer:

A

60.Answer:

D

61.Answer:

A

62.Answer:

A

63.Answer:

C

64.Answer:

C

65.Answer:

A

66.Answer:

B

67.Answer:

A

68.Answer:

D

69.Answer:

C

70.Answer:

A

71.Answer:

D

72.Answer:

D

73.Answer:

B

74.Answer:

C

75.Answer:

C

76.Answer:

C

77.Answer:

A

78.Answer:

E

79.Answer:

D

80.Answer:

An epitope is the specific part of the antigen that is recognized by an antibody and binds to the complementaritydetermining regions in the antibody variable domains. Epitopes are sometimes referred to as antigenic determinants.

Epitopes can be part of a protein or can be carbohydrate or lipid structures present in the glycoproteins, polysaccharides,

glycolipids, and proteoglycans of pathogens.

81.Answer:

Multivalent antigens are complex macromolecules that contain more than one epitope.

82.Answer:

Linear epitopes are epitopes in proteins that comprise a contiguous amino acid sequence.

They are also called continuous epitopes. In contrast, a conformational epitope is formed by amino acids that are brought together as a result of protein folding and are not adjacent in the protein sequence.

Conformational epitopes are also known as discontinuous epitopes.

83.Answer:

Antibodies bind antigens via noncovalent bonding such as hydrogen bonds, hydrophobic interactions, van der Waals forces, and electrostatic attraction.

84.Answer:

Before antigen encounter, antibodies are produced in a membrane-bound form. After antigen encounter, antibodies are secreted in a soluble form.

85.Answer:

The membrane-bound and soluble forms of antibody produced by a given B cell possess the same antigen specificity.

86.Answer:

A D-gene segment first joins to a J to form DJ, followed by a V becoming

joined to DJ to form VDJ, which encodes a complete variable region.

87.Answer:

CDR3 of the light chain is composed mainly of the coding joint between the V and J segments, which is formed during somatic recombination, with junctional diversity being generated by the addition of P and N nucleotides.

CDR3 of the heavy chain is composed mainly of the D gene segment plus its coding joints, with a V gene segment on one side and a J gene segment on the other. P and N nucleotides are also added to these joints during recombination. In addition, the D gene segment sequences differ between immunoglobulins.

88.Answer:

Polyclonal antibodies are a mixture of antibodies of different specificities and affinities for antigen. They are the product of numerous different B cells responding to antigen. In contrast, monoclonal antibodies have a single specificity and affinity for one antigen epitope. They derive from a single B cell.

89.Answer:

Polyclonal antibodies are produced in vivo by immunizing an animal with antigen and allowing sufficient time for an immune response to occur. Antiserum, which contains all the antibodies

found in the blood, is then prepared. Polyclonal antibodies are the product of numerous different B cells responding to antigen. To generate monoclonal antibodies, an animal is immunized with antigen. A single responding B cell is fused with a myeloma tumor cell to produce a hybrid immortalized cell line. The antibody-producing “hybridoma” is then cloned in vitro and grown to produce unlimited amounts of the desired monoclonal antibody.

90.Answer:

Naive B cells express IgM and IgD simultaneously through a mechanism involving alternative ways of processing the RNA transcript before translation. A primary transcript containing leader (L), V, D, J, Cμ, and Cδ is produced first.

This transcript contains two distinct polyadenylation signal sequences, one following the Cμ exons (pA1) and the other following the Cδ exons (pA2). Processing results in the removal of either Cμ or Cδ exons (plus introns) through alternative splicing. The resulting mRNAs, which encode either Cμ or Cδ, are polyadenylated at the pA1 or pA2 site, respectively.

91.Answer:

Whether immunoglobulin is expressed as a transmembrane-anchored protein or a secreted protein is determined by alternative processing of the heavy-chain RNA transcript. All the heavychain C genes contain MC (membrane-coding) exons, which encode the transmembrane region and cytoplasmic tail, and an SC (secretion-coding) exon, which encodes the carboxy terminus of the secreted antibody. The primary RNA transcript contains the MC and SC exons. In naive resting B cells or memory B cells, cleavage and polyadenylation of the transcript at a site (pAm) following the MC exons and deletion of the SC exon by RNA splicing produces the membranebound immunoglobulin.

On B-cell activation and differentiation into plasma cells, the SC exon is retained in the transcript, and a polyadenylation signal sequence, pAs, immediately following it is used to produce an mRNA encoding the secreted form of the heavy chain.

92.Answer:

Igα and Igβ are essential for escorting immunoglobulins from the endoplasmic reticulum membrane to the cell membrane, where they remain associated with the immunoglobulin to form the functional B-cell

antigen receptor. The long cytoplasmic tails of Igα and Igβ contain amino acid motifs that interact with intracellular signaling proteins after the receptor has been activated by the binding of antigen to the immunoglobulin. Igα and Igβ proteins have no need to be variable, because they do not interact directly with antigen. Igα and Igβ perform specific signaling functions, which require conserved amino acid sequences, and they also have evolved a sequence and structure that enable them to interact with all the different immunoglobulin isotypes. Extensive variation in Igα and/or Igβ could therefore compromise their interaction with immunoglobulins and their signal transduction capabilities.

93.Answer:

Affinity maturation is the phenomenon observed during a B-cell response in which antibodies with increasing affinity for the antigen are produced as the response proceeds.

This occurs as a result of the process known as somatic hypermutation. In somatic hypermutation, which occurs only in activated B cells, random point mutations are introduced into the rearranged V regions of H-chain and L-chain genes at a rate six orders of magnitude higher than

spontaneous mutation.

Some of these mutations give rise to immunoglobulin with higher affinity for the antigen than the original immunoglobulin. Those B cells producing higheraffinity surface immunoglobulin will be preferentially selected for activation by the antigen and will come to dominate the response, differentiating into plasma cells producing highaffinity antibodies.

94.Answer:

Isotype switching is the process by which antibodies change their heavy-chain constant regions, thus acquiring different effector functions, while preserving the variable region and antigen specificity. The light chain is unaffected by isotype switching. The molecular mechanism involves a recombination between DNA sequences called switch regions, which lie upstream (on the 5′ side) of heavy-chain C genes.

All heavy-chain C genes except Cδ have a switch region. Recombination between two switch regions results in the excision of DNA (as a circular DNA molecule) between the two and the movement of the new heavy-chain C gene next to the preserved V region.

Transcription will produce an mRNA encoding the same V-region sequence

and the new C region.

Switching can occur between the first switch region and any other switch region that lies downstream (on the 3′ side). Isotype switching is not random but is influenced by T-cell cytokines.

95.Answer:

Isotype switching is the process by which antibodies change their heavy-chain constant regions, thus acquiring different effector functions, while preserving the variable region and antigen specificity. The light chain is unaffected. Isotype switching is important because the different antibody isotypes have different effector functions, and efficient immune responses rely upon the production of the most appropriate effector function to combat a given pathogen.

96.Answer:

Mice are used routinely to generate monoclonal antibodies. The constant regions of mouse antibodies are sufficiently different from the constant regions of human antibodies in amino acid composition that, if mouse antibodies are infused into a patient, an immune response will be stimulated and directed against the mouse constant-region epitopes.

This immune response

neutralizes the monoclonal antibody and in practice limits its intended use to one effective dose. When monoclonal antibodies are used for serological or diagnostic purposes in the laboratory, the monoclonal antibodies do not need to be humanized because laboratory assays are performed in vitro.

97.Answer:

The rejoining and repair of DNA during the recombination process leads to additional variation in sequence at the junctions between the rearranged gene segments. This is called junctional diversity and contributes considerably to the final diversity of immunoglobulin specificities. Two sources of junctional diversity are introduced: P (palindromic) and N (nontemplated) nucleotides. P nucleotides are generated through endonuclease activity and repair around a hairpin loop at the ends of the gene segments to be joined. N nucleotides are nucleotides added at random at the junctions by terminal deoxynucleotidyl transferase (TdT) activity.

98.Answer:

(1) Gene rearrangements affect the variable region of immunoglobulins, whereas isotype switching affects the constant region. (2) Different

recombination-signal sequences and enzymes are used for the two processes. (3) Isotype switching occurs only after antigen stimulation, whereas gene rearrangement occurs only during B-cell maturation in the bone marrow. (4) All isotype switch recombinations are productive, but not all gene rearrangements are.

(5) Only heavy chains are involved in isotype switching, whereas both heavy-chain and lightchain genes are involved in somatic recombination.

99.Answer:

The B cells in a person carrying such a defect would be unable to switch antibody isotype and would be unable to produce any antibody other than IgM. Because IgM antibodies can implement fewer effector functions than IgG antibodies, which constitute the main class of antibody produced in an adaptive immune response, one would expect that immunity would be impaired. In addition, no IgA antibodies could be produced, leaving the person highly vulnerable to infection through mucosal surfaces. There are, in fact, rare inherited genetic deficiencies that result in an inability to switch isotype. They are called hyper IgM immunodeficiencies

because the patient is unable to produce any antibody other than IgM. The most frequent one affects the expression of a cell-surface molecule called CD40 ligand in T cells, which is required for the interaction between T cells and B cells that stimulates isotype switching, as we shall learn later in this book.

100.

Answer: Fully human monoclonal antibodies are the most desirable, because they will not stimulate an anticonstant region antibody response in the recipient and can therefore be used for repeated treatment in chronic diseases without complications and without reducing therapeutic efficacy. Adalimumab is an example of a fully human monoclonal antibody used to treat rheumatoid arthritis. It neutralizes the inflammatory cytokine TNF-α to decrease inflammation of the joints.

101.

Answer:

1. E 2. A 3. D 4. C 5. B

102.

Answer:

1. D 2. C

3. A 4. B 5. E 103.

Answer:

1. E 2. A 3. B 4. D 5. C

104.

Answer: An antibody molecule is made of four polypeptide chains—two identical heavy chains and two identical and smaller light chains, with a total molecular weight of approximately 150 kDa. Each chain is made up of a series of structurally similar domains known as immunoglobulin domains.

The amino-terminal portion of each H chain combines with one L chain, and the two carboxy-terminal portions of the H chains combine with each other, forming a Y-shaped quaternary structure. Disulfide bonds hold the H and L chains together, hold the two H chains together (interchain disulfide bonds), and stabilize the domain structure of the chains (intrachain disulfide bonds). The arms of the antibody molecule are called Fab (fragment antigen binding) and interact with antigen.

The stalk is called Fc (fragment crystallizable)

and is made up of H chains only. The aminoterminal domains of an H and an L chain together make up a site that binds directly to antigen and varies greatly between different antibodies.

These domains are referred to as the variable region, and each antibody has two identical antigenbinding sites. The remaining domains of both H and L chains are the same in all antibodies of a given class (isotype).

These domains are referred to as the constant region. The variable region of each chain includes hypervariable regions of amino acid sequences that differ the most between different antibodies. These are nested within less variable sequences known as the framework regions. The hypervariable regions make loops at one end of the domain structure and are also known as complementaritydetermining regions because they confer specificity on the antigenbinding site.

105.

Answer: In developing B cells, gene rearrangements within the genetic loci for immunoglobulin light and heavy chains can produce an almost unlimited variety of different variable regions, and thus produce the huge repertoire of antibodies with different specificities for many

types of antigen. This gene rearrangement mechanism is called somatic recombination. In the germline configuration, before gene rearrangement, the immunoglobulin loci in progenitor B cells are composed of sequences encoding the constant regions and families of gene segments encoding different portions of the variable region. Heavychain loci contain a series of gene segments called variable (V), diversity (D), and joining (J). Light-chain loci contain only V and J gene segments. In somatic recombination in developing B cells, one of each family of gene segments is randomly selected and joined together to give a complete variable-region sequence, which is subsequently expressed as an immunoglobulin heavy or light chain.

Immunoglobulin gene rearrangement is irreversible, leading to permanent alteration of the chromosome; it occurs exclusively in B cells.

106.

Answer: Gene rearrangement by somatic recombination involves recombination signal sequences (RSSs) that flank V, D, and J segments and are recognized by the enzymes involved in cutting and rejoining the gene segments. An RSS is composed of a

conserved nonamer sequence and heptamer sequence separated by a spacer region. There are two types of RSS, one with a spacer of 12 bp and one with a spacer of 23 bp. To ensure that segments are brought together in the right order, an RSS with a 12-bp spacer is always brought together with one with a 23-bp spacer. This is called the 12/23 rule. This ensures that in the heavychain locus, V rearranges to DJ and not directly to J or another V, and in the light-chain locus, V rearranges to J and not to another V. 107.

Answer: The four types of therapeutic antibody include (i) mouse monoclonal antibodies, (ii) chimeric monoclonal antibodies, (iii) humanized monoclonal antibodies, and (iv) fully human monoclonal antibodies. (i) Mouse monoclonal antibodies are produced from hybridoma cell lines obtained by immortalizing mouse B cells by fusing them with a tumor cell.

Hybridomas secreting antibody with the appropriate specificity for antigen are cloned and propagated. (ii) Chimeric monoclonal antibodies are produced by fusing the coding regions of the variable regions of mouse monoclonal antibodies, known to have specificity for one epitope of an

antigen, with the coding regions of human constant regions. (iii) Humanized monoclonal antibodies retain only the complementaritydetermining regions of mouse monoclonal antibodies, and all remaining regions are replaced with humanderived regions. (iv) Fully human monoclonal antibodies are made either by using human hybridoma cell lines or by using transgenic mice whose immunoglobulin genes have been replaced by human immunoglobulin genes.

108.

Answer: The four types of therapeutic antibody include (i) mouse monoclonal antibodies, (ii) chimeric monoclonal antibodies, (iii) humanized monoclonal antibodies, and (iv) fully human monoclonal antibodies. (i) Mouse monoclonal antibodies are produced from hybridoma cell lines obtained by immortalizing mouse B cells by fusing them with a tumor cell.

Hybridomas secreting antibody with the appropriate specificity for antigen are cloned and propagated. (ii) Chimeric monoclonal antibodies are produced by fusing the coding regions of the variable regions of mouse monoclonal antibodies, known to have specificity for one epitope of an antigen, with the coding

regions of human constant regions. (iii) Humanized monoclonal antibodies retain only the complementaritydetermining regions of mouse monoclonal antibodies, and all remaining regions are replaced with humanderived regions. (iv) Fully human monoclonal antibodies are made either by using human hybridoma cell lines or by using transgenic mice whose immunoglobulin genes have been replaced by human immunoglobulin genes.

Name: ___________________________ Class: _________________ Date: __________

Chapter 05 1. T cells and B cells recognize the same types of antigen. a. True b. False

2. T cells and B cells require MHC molecules for the recognition of peptide antigens. a. True b. False

3. T cells require an accessory cell called an antigen-presenting cell, which bears MHC molecules on its surface. a. True b. False

4. T-cell receptor and immunoglobulin genes are encoded on the MHC. a. True b. False

5. The T-cell receptor has structural similarity to an immunoglobulin Fab fragment. a. True b. False

6. T cells recognize antigen when the antigen a. forms a complex with membrane-bound MHC molecules on another hostderived cell. b. is internalized by T cells via phagocytosis and subsequently binds to T-cell receptors in the endoplasmic reticulum. c. is presented on the surface of a B cell on membrane-bound

immunoglobulins. d. forms a complex with membrane-bound MHC molecules on the T cell. e. bears epitopes derived from proteins, carbohydrates, and lipids.

7. T-cell receptors structurally resemble a. the Fc portion of immunoglobulins. b. MHC class I molecules. c. secreted antibodies. d. a single Fab of immunoglobulins. e. CD3 ε chains.

8. If viewing the three-dimensional structure of a T-cell receptor from the side, with the T-cell membrane at the bottom and the receptor pointing upwards, which of the following is inconsistent with experimental data? a. The highly variable CDR loops are located across the top surface. b. The membrane-proximal domains consist of Cα and Cβ. c. The portion that makes physical contact with the ligand comprises Vβ and Cβ, the domains farthest from the T-cell membrane. d. The transmembrane regions span the plasma membrane of the T cell. e. The cytoplasmic tails of the T-cell receptor α and β chains are very short.

9. Which of the following processes occur in both B and T cells? a. alternative splicing to produce a secreted form of the antigen receptor b. alternative splicing to produce different isoforms of the antigen receptor c. isotype switching d. somatic hypermutation e. somatic recombination

10.When comparing the T-cell receptor α-chain locus with the immunoglobulin heavy-chain locus, which of the following is correct? a. The T-cell receptor α locus differs because it is embedded within the δ locus.

b. Each locus is encoded on a different chromosome. c. The T-cell receptor α-chain locus contains D segments. d. The T-cell receptor α-chain locus contains fewer V and J regions. e. The T-cell receptor α-chain locus contains more C regions. f. Both contain exons encoding a leader peptide.

11.Unlike the C regions of immunoglobulin heavy-chain loci, the C regions of the Tcell receptor β-chain loci a. are functionally similar. b. do not contain D segments. c. are more numerous. d. are encoded on a different chromosome from the variable β-chain gene segments of the T-cell receptor. e. do not encode a transmembrane region. f. possess non-templated P and N nucleotides.

12.Which of the following statements regarding γ:δ T cells is correct? a. The δ chain is the counterpart to the α chain in α:β T-cell receptors because it contains V and J segments in the variable region. b. They share some properties with NK cells. c. They may simultaneously express both the γ:δ and the α:β T-cell receptors on the cell surface. d. Their activation is limited to recognition of a peptide:MHC molecule complex e. Expression of the T-cell receptor on the cell surface is not dependent on the CD3 complex.

13.During T-cell receptor __________-gene rearrangement, two D segments may be used in the final rearranged gene sequence, thereby increasing overall variability of this chain. a. α b. β c. γ d. δ

e. ε

14.The degradation of pathogen proteins into smaller fragments called peptides is a process commonly referred to as a. endocytosis. b. promiscuous processing. c. antigen processing. d. antigen presentation. e. peptide loading.

15.All of the following are primarily associated with CD4 T-cell function EXCEPT that it a. improves phagocytic mechanisms of tissue macrophages. b. assists B cells in the production of high-affinity antibodies. c. kills virus-infected cells. d. facilitates responses of other immune-system cells during infection. e. assists macrophages in sustaining adaptive immune responses through their secretion of cytokines and chemokines.

16.The primary reason for transplant rejections is due to differences in __________ between donor and recipient. a. CD3 b. MHC molecules c. T-cell receptor α chains d. γ:δ T cells e. β2-microblobulin

17.The vesicular system includes the a. cytosol, nucleus, and nuclear pores. b. nucleus, endoplasmic reticulum, Golgi apparatus, and lysosomes. c. endoplasmic reticulum, Golgi apparatus, lysosomes, endocytic vesicles, and exocytic vesicles. d. nucleus, endoplasmic reticulum, Golgi apparatus, lysosomes, endocytic

vesicles, and exocytic vesicles.

18.Which statement accurately describes immunoproteasomes? a. They make up about 15 percent of cellular protein. b. They are composed of the same cap and catalytic subunits as the constitutive proteasome. c. They produce a higher proportion of peptides containing acidic amino acids at the carboxy terminus compared with constitutive proteasomes. d. They lack the cap found in constitutive proteasomes. e. They are produced in response to IFN-γ produced during innate immune responses.

19.Identify which of the following statements is true regarding the transporter associated with antigen processing (TAP). a. TAP is a homodimer composed of two identical subunits. b. TAP transports proteasome-derived peptides from the cytosol directly to the lumen of the Golgi apparatus. c. TAP is an ATP-dependent, membrane-bound transporter. d. Peptides transported by TAP bind preferentially to MHC class II molecules. e. TAP deficiency causes a type of bare lymphocytes syndrome resulting in severely depleted levels of MHC class II molecules on the surface of antigen-presenting cells.

20.Which set of proteins best describes the class I peptide-loading complex? a. tapasin, calreticulin, ERp57, β2-microglobulin, TAP b. calnexin, tapasin, calreticulin, ERp57, β2-microglobulin c. calreticulin, ERp57, β2-microglobulin, TAP d. calnexin, tapasin, calreticulin, ERp57, β2-microglobulin, TAP e. invariant chain, HLA-DO, HLA-DM

21.Which of the following best describes the function of tapasin? a. Tapasin is an antagonist of HLA-DM and causes more significant increases in MHC class I than MHC class II on the cell surface.

b. Tapasin is a lectin that binds to sugar residues on MHC class I molecules, T-cell receptors, and immunoglobulins and retains them in the ER until their subunits have adopted the correct conformation. c. Tapasin is a thiol-reductase that protects the disulfide bonds of MHC class I molecules. d. Tapasin participates in peptide editing by trimming the amino terminus of peptides to ensure that the fit between peptide and MHC class II molecules is appropriate. e. Tapasin is a bridging protein that binds to both TAP and MHC class I molecules and facilitates the selection of peptides that bind tightly to MHC class I molecules.

22.Peptide editing a. involves the removal of amino acids from the amino-terminal end by endoplasmic reticulum aminopeptidase (ERAP). b. is due to cathepsin S-mediated cleavage of invariant chain. c. does not occur for MHC class II. d. relies on tapasin for both MHC class I and II molecules. e. requires the upregulation of HLA-DM by interferon-γ.

23.In contrast to immunoglobulins, α:β T-cell receptors recognize epitopes present on __________ antigens. a. carbohydrate b. lipid c. protein d. carbohydrate and lipid e. carbohydrate, lipid, and protein

24.Which of the following characteristics is common to both T-cell receptors and immunoglobulins? a. Somatic recombination of V, D, and J segments is responsible for the diversity of antigen-binding sites. b. Somatic hypermutation changes the affinity of antigen-binding sites and contributes to further diversification. c. Class switching enables a change in effector function.

d. The antigen receptor is composed of two identical heavy chains and two identical light chains. e. Carbohydrate, lipid, and protein antigens are recognized and stimulate a response.

25.The antigen-recognition site of T-cell receptors is formed by the association of which of the following domains? a. Vα and Cα b. Vβ and Cβ c. Cα and Cβ d. Vα and Cβ e. Vα and Vβ.

26.The most variable parts of the T-cell receptor are a. Vα and Cα. b. Vβ and Cβ. c. Cα and Cβ. d. Vα and Cβ. e. Vα and Vβ.

27.How many complementarity-determining regions contribute to the antigen-binding site in an intact T-cell receptor? a. 2 b. 3 c. 4 d. 6 e. 12

28.IgG possesses __________ binding sites for antigen, and the T-cell receptor possesses __________ binding sites for antigen. a. 1; 1

b. 2; 1 c. 1; 2 d. 2; 2 e. 2; 4

29.In terms of V, D, and J segment arrangement, the T-cell receptor α-chain locus resembles the immunoglobulin __________ locus, whereas the T-cell receptor βchain locus resembles the immunoglobulin __________ locus. a. λ light chain; κ light chain b. heavy chain; λ light chain c. κ light chain; heavy chain d. κ light chain; λ light chain

30.In B cells, transport of immunoglobulin to the membrane is dependent on association with two invariant proteins, Igα and Igβ. Which of the following invariant proteins provide this function for the T-cell receptor in T cells? a. CD3γ b. CD3δ c. CD3ε d. ζ e. All of these answers are correct.

31.Owing to the location of the δ-chain locus of the T-cell receptor on chromosome 14, if the __________-chain locus rearranges by somatic recombination, then the δ-chain locus is __________. a. α; also rearranged b. α; deleted c. α; transcribed d. β; deleted e. γ; also rearranged

32.Which of the following is a characteristic of antigen recognition by T helper cells? a. The recognition of peptides ranging from 8–9 amino acids in length.

b. The requirement for the degradation of antigen by antigen-presenting cells. c. The binding of MHC class I molecules. d. The recognition of the intact protein antigen. e. All of these answers are correct.

33.Which of the following statements regarding CD8 T cells is NOT correct? a. When activated, CD8 T cells will activate B cells. b. CD8 is also known as the CD8 T-cell co-receptor. c. CD8 binds to MHC molecules at a site distinct from that bound by the T-cell receptor. d. CD8 T cells kill pathogen-infected cells by inducing apoptosis. e. CD8 T cells are MHC class I-restricted.

34.Antigen processing involves the breakdown of protein antigens and the subsequent association of peptide fragments on the surface of antigen-presenting cells with a. immunoglobulins. b. T-cell receptors. c. complement proteins. d. MHC class I or class II molecules. e. CD4.

35.Which of the following statements regarding T-cell receptor recognition of antigen is correct? a. α:β T-cell receptors recognize antigen only as a peptide bound to an MHC molecule. b. αβ T-cell receptors recognize antigens in their native form. c. α:β T-cell receptors, like B-cell immunoglobulins, can recognize carbohydrate, lipid, and protein antigens. d. Antigen processing occurs in extracellular spaces. e. Like α:β T cells, γ:δ T cells are restricted to the recognition of antigens presented by MHC molecules.

36.Which of the following describes a ligand for an α:β T-cell receptor? a. carbohydrate:MHC complex b. lipid:MHC complex c. peptide:MHC complex d. All of these answers are correct. e. None of these answers are correct.

37.MHC class II molecules are made up of two chains called __________, whose function is to bind peptides and present them to __________ T cells. a. alpha (α) and beta (β); CD4 b. alpha (α) and beta2-microglobulin (β2m); CD4 c. alpha (α) and beta (β); CD8 d. alpha (α) and beta2-microglobulin (β2m); CD8 e. alpha (α) and beta (β); γ:δ T cells

38.The variable regions of the T-cell receptor contact a. the binding pockets of MHC. b. both peptide and the α helices of the MHC molecule. c. the membrane-proximal domains of the MHC molecule. d. the constant regions of antibody molecules. e. the co-receptors CD4 or CD8 .

39.The peptide-binding groove of MHC class I molecules is composed of the following extracellular domains: a. α1:β1 b. β1:β2 c. α2:β2 d. α2:α3 e. α1:α2

40.To which domain of MHC class II does CD4 bind?

a. α1 b. β1 c. α2 d. β2 e. α3

41.To which domain of MHC class I does CD8 bind? a. α1 b. β1 c. α2 d. β2 e. α3

42.MHC molecules have promiscuous binding specificity. This means that a. a particular MHC molecule has the potential to bind to different peptides. b. when MHC molecules bind to peptides, they are degraded. c. peptides bind with low affinity to MHC molecules. d. many alleles of MHC genes exist in the population. e. None of these answers describes promiscuous binding specificity.

43.T-cell receptors interact not only with peptide anchored in the peptide-binding groove of MHC molecules, but also with a. anchor residues. b. CD4. c. α helices of the MHC molecule. d. β2-microglobulin. e. invariant chain.

44.Cross-presentation occurs when a. viral antigens are presented by MHC class I molecules on the surface of a cell that is not actually infected by that particular virus.

b. cytosol-derived peptides enter the endoplasmic reticulum and bind to MHC class II molecules. c. phagolysosome-derived peptides bind to MHC class II molecules. d. viral antigens are presented by MHC class I molecules on the surface of a virally-infected cell. e. one peptide is able to bind to multiple distinct MHC isoforms on a cell.

45.In reference to the interaction between T-cell receptors and their corresponding ligands, which of the following statements is correct? a. The organization of the T-cell receptor antigen-binding site is distinct from the antigen-binding site of immunoglobulins. b. The variable region of the T-cell receptor binds to peptide, and the constant region of the T -cell receptor binds to the MHC. c. The T-cell receptor binds its ligand without the need for a co-receptor. d. All of these statements are correct. e. None of these statements are correct.

46.The diversity of MHC class I and II genes is due to a. gene rearrangements similar to those observed in T-cell receptor genes. b. the addition of non-templated nucleotides. c. somatic hypermutation. d. extensive polymorphism at many of the alleles. e. isotype switching.

47.The combination of all HLA class I and class II allotypes that an individual expresses is referred to as their a. haplotype. b. allotype. c. isotype. d. autotype. e. HLA type.

48.Which of the following is polymorphic?

a. HLA-G b. HLA-DO c. HLA-DQ d. HLA-DM e. HLA-DR α chain

49.Of the following HLA α-chain loci, which one exhibits the highest degree of polymorphism? a. HLA-A b. HLA-B c. HLA-C d. HLA-DP e. HLA-DR

50.Which of the following is not encoded on chromosome 6 in the HLA complex? a. β2-microglobulin b. HLA-G α chain c. TAP-1 d. tapasin e. HLA-DR α chain

51.The __________ refers to the complete set of HLA alleles that a person possesses on a particular chromosome 6. a. isoform b. isotype c. oligomorph d. allotype e. haplotype

52.Peptides that bind to a particular MHC isoform usually have either the same or chemically similar amino acids at two to three key positions that hold the peptide tightly in the peptide-binding groove of the MHC molecule. The amino acids in these key positions are called __________, and they bind to __________.

a. alleles; allotypes b. anchor residues; =pockets c. pockets; anchor residues d. invariant chains; haplotypes e. restriction residues; the T-cell receptor .

53.Directional selection is best described as a. all polymorphic alleles preserved in a population. b. T-cell receptor interaction with peptide:MHC complexes directed to a planar interface. c. a mechanism in T cells that is analogous to affinity maturation of immunoglobulins. d. selected alleles increase in frequency in a population. e. selection of most appropriate transplant donor directed at the identification of identical or similar combinations of HLA alleles compared with the transplant recipient.

54.The role of the CD3 proteins and ζ chain on the surface of the cell is to a. transduce signals to the interior of the T cell. b. bind to antigen associated with MHC molecules. c. bind to MHC molecules. d. bind to CD4 or CD8 molecules. e. facilitate antigen processing of antigens that bind to the surface of T cells.

55.Which of the following accurately completes this statement: “The function of __________ T cells is to make contact with __________ and __________.” a. CD4; virus-infected cells; kill virus-infected cells b. CD8; virus-infected cells; kill virus-infected cells c. CD8; B cells; stimulate B cells to differentiate into plasma cells d. CD8; macrophages; enhance microbicidal powers of macrophages e. None of these answers are accurate.

56.The immunological consequence of a genetic defect in either RAG-1 or RAG-2

genes that results in a nonfunctional RAG complex is a. lack of somatic recombination in T-cell receptor and immunoglobulin gene loci. b. lack of somatic recombination in T-cell receptor loci. c. lack of somatic recombination in immunoglobulin loci. d. lack of somatic hypermutation in T-cell receptor and immunoglobulin loci. e. lack of somatic hypermutation in T-cell receptor loci.

57.Which of the following removes CLIP from MHC class II molecules? a. HLA-DQ b. HLA-DO c. HLA-DP d. HLA-DM e. HLA-DR.

58.CD8 T-cell subpopulations are specialized to combat __________ pathogens, whereas CD4 T-cell subpopulations are specialized to combat __________ pathogens. a. bacterial; viral b. dead; live c. extracellular; intracellular d. intracellular; extracellular e. virulent; attenuated

59.MHC class I molecules present peptide antigens derived from a(n) __________ compartment, whereas MHC class II molecules present peptide antigens derived from a(n) __________ compartment. a. extracellular; intracellular b. intracellular; extracellular c. opsonization; neutralization d. neutralization; opsonization e. self-protein; non-self-protein

60.Which of the following describes the sequence of events involved in the processing of peptides that will be presented as antigen with MHC class I? a. plasma membrane > TAP1/2 > proteasome > MHC class I > endoplasmic reticulum b. TAP1/2 > proteasome > MHC class I > endoplasmic reticulum> plasma membrane c. proteasome > TAP1/2 > MHC class I > endoplasmic reticulum > plasma membrane d. proteasome > TAP1/2 > endoplasmic reticulum > MHC class I > plasma membrane e. endoplasmic reticulum > proteasome > MHC class I > TAP1/2 > plasma membrane

61.One type of bare lymphocyte syndrome is caused by a genetic defect in MHC class II transactivator (CIITA) that results in the inability to synthesize MHC class II and display it on the cell surface. The consequence of this would be that a. B cells are unable to develop. b. CD8 T cells cannot function. c. CD4 T cells cannot function. d. intracellular infections cannot be eradicated. e. peptides cannot be loaded onto MHC molecules in the lumen of the endoplasmic reticulum.

62.Which of the following describes the sequence of events involved in the processing of peptides that will be presented as antigen with MHC class II? a. protease activity > removal of CLIP from MHC class II > binding of peptide to MHC class II > endocytosis > plasma membrane b. endocytosis > protease activity > removal of CLIP from MHC class II > binding of peptide to MHC class II > plasma membrane c. removal of CLIP from MHC class II > binding of peptide to MHC class II > protease activity > endocytosis > plasma membrane d. binding of peptide to MHC class II > endocytosis > removal of CLIP from MHC class II > protease activity > plasma membrane e. endocytosis > protease activity > binding of peptide to MHC class II > removal of CLIP from MHC class II > plasma membrane

63.Which of the following cell types does not express MHC class I? a. erythrocyte b. hepatocyte c. lymphocyte d. dendritic cell e. neutrophil

64.Which of the following cell types is not considered a professional antigenpresenting cell? a. macrophage b. neutrophil c. B cell d. dendritic cell e. All of these answers are professional antigen-presenting cells.

65.Which of the following HLA-DRB genotypes is not possible in an individual? (X: X represents diploid genotype.) a. DRB1: DRB1 b. DRB1, DRB3: DRB1, DRB4 c. DRB1: DRB1, DRB5 d. DRB1, DRB4: DRB1 e. DRB3: DRB1, DRB5.

66.Which is the most likely reason that HIV-infected people with heterozygous HLA loci have a delayed progression to AIDS compared with patients who are homozygous at one or more HLA loci? a. The greater number of HLA alleles provides a wider variety of HLA molecules for presenting HIV-derived peptides to CD8 T cells even if HIV mutates during the course of infection. b. Heterozygotes have more opportunity for interallelic conversion and can therefore express larger numbers of MHC alleles. c. Directional selection mechanisms favor heterozygotes and provide selective advantage to pathogen exposure. d. As heterozygosity increases, so does the concentration of alloantibodies in

the serum, some of which cross-react with and neutralize HIV.

67.Identify the event that would immediately follow the step shown in this antigen processing pathway figure.

a. TAP must transport peptides across the endoplasmic reticulum membrane. b. The HLA-DM molecule must interact with MHC class II. c. The invariant chain must interact with MHC class II. d. CLIP must be bound to the MHC class II molecule. e. None of these answers are correct.

68.Where on the class I molecule illustrated in the figure below would you find the differences in amino acids that lead to the high polymorphism associated with MHC?

a. distributed across the α1, α2, and α3 domains b. distributed across the α3 domain and the β2-microglobulin protein c. sites of peptide binding and interaction with the T-cell receptor d. limited to the floor of the peptide-binding groove e. limited to the alpha helices

69.Match each T-cell receptor term with the correct description. a. T-cell receptor δ-chain gene b. CD3 complex c. T-cell receptor β-chain gene d. CD4 e. T-cell receptor γ-chain gene 1. __________ positioned in the T-cell receptor α-chain locus between Vα and Jα gene segments 2. __________ made up of γ, δ and ε components 3. __________ counterpart to the T-cell receptor α-chain gene 4. _________ composed of V, D and J gene segments 5. __________ transmembrane protein composed of four extracellular domains

70.Match each term related to the MHC with the correct description. a. directional selection b. cross-presentation c. heterozygote advantage d. balancing selection e. interallelic conversion f. polymorphism 1. ______¬____ mechanism enabling extracellular antigens to bind to MHC class I molecules 2. ______¬____ evolutionary maintenance of divergent MHC molecule phenotypes 3. ______¬____ mode of selection can be imposed by epidemics of infectious disease 4. ______¬____ mechanism used to increase polymorphisms of HLA class I and class II alleles involving homologous recombination between different alleles of the same gene 5. ______¬____ presentation of a wider range of peptides when MHC isotypes inherited from each parent are different 6. ______¬____ the presence of multiple alleles in the population

71.Match the function with the correct HLA isotypes. a. form ligands for receptors on NK cells b. participate in peptide loading of MHC class II molecules

c. present antigen to CD4 T cells d. present antigen to CD8 T cells 1. ______¬____ HLA-A, HLA-B, HLA-C 2. ______¬____ HLA-E, HLA-F, HLA-G 3. ______¬____ HLA-DP, HLA-DQ, HLA-DR 4. ______¬____ HLA-DM, HLA-DO

72.Explain the importance of promiscuous binding specificity exhibited by MHC class I and class II molecules.

73.Identify the three functions of the invariant chain.

74.Explain how interferon-γ produced during an infection enhances antigen processing in the MHC class I pathway.

75.Explain specifically how interferon-γ produced during an infection enhances antigen presentation in the MHC class II pathway.

76.Discuss how T-cell receptors differ from immunoglobulins in the way that they recognize antigen. Use the following terms in your answer: peptides, antigenpresenting cells, MHC molecules, and antigen-binding sites.

77.Pathogens that infect the human body replicate either inside cells (such as viruses) or extracellularly, in the blood or in the extracellular spaces in tissues.

Identify (i) the class of T cells that are stimulated by intracellular pathogens, (ii) their co-receptor, (iii) the MHC molecule used for recognition of antigen, and (iv) the T-cell effector function.

78.Provide an explanation of why it is believed that MHC class I genes are the evolutionary ancestors of MHC class II genes.

79.Explain the likely reason T-cell receptors do not undergo isotype switching.

80.Explain how professional antigen-presenting cells optimize antigen presentation to T cells despite the relatively limited capacity of any particular MHC molecule to bind different pathogen-derived peptides.

81.What is the difference between MHC variation due to multigene families and MHC variation due to allelic polymorphism?

82.What evidence supports the proposal that MHC diversity evolved by natural selection caused by infectious pathogens rather than exclusively by random DNA mutations?

83.How many HLA-DR α:β combinations can be made by an individual who is heterozygous at all HLA-DRβ loci, inherits the DRβ haplotype DRB1 from their mother, the DRβ haplotype DRB1, DRB4 from their father, and also inherits different allelic forms of DRA from each parent?

84.What is the maximum number of MHC class I and class II molecules that a heterozygous individual could theoretically express? Explain your answer. (Ignore the possibility of MHC class II molecules composed of chains from different isotypes.)

85.How does the relatively small number of MHC molecules have the potential to bind the huge number of antigenic peptides encountered in the environment, and what features of a peptide determine whether it will be bound by a given MHC molecule?

86.Explain the difference between interallelic conversion and gene conversion, and provide an example of each.

87.In the context of MHC isoforms, what is the difference between balancing selection and directional selection?

88.

Describe the steps required for the processing of antigen when the T cell shown in the figure is a T helper cell. Your response should include how antigen entered the cell.

89.

Compare the location of peptide loading for MHC class I and class II molecules (ignore cross-presentation) using the figure shown.

90.Describe five ways in which T-cell receptors are similar to immunoglobulins, and five ways in which they are different (other than the way in which they recognize antigen).

91.Compare the organization of T-cell receptor α and β genes (the TCRα and TCRβ loci) with the organization of immunoglobulin heavy-chain and light-chain genes.

92.(i) Describe the structure of an MHC class I molecule, identifying the different polypeptide chains and domains. (ii) What are the names of the MHC class I molecules produced by humans? Which part of the molecule is encoded within the MHC region of the genome? (iii) Which domains or parts of domains

participate in the following: antigen binding; binding the T-cell receptor; and binding the T-cell co-receptor? (iv) Which domains are the most polymorphic?

93.(i) Describe the structure of an MHC class II molecule, identifying the different polypeptide chains and domains. (ii) What are the names of the MHC class II molecules produced by humans? Which part of the molecule is encoded within the MHC region of the genome? (iii) Which domains or parts of domains participate in the following: antigen binding; binding the T-cell receptor; and binding the T-cell co-receptor? (iv) Which domains are the most polymorphic?

94.Describe in chronological order the steps of the antigen-processing and antigenpresentation pathways for intracellular, cytosolic pathogens.

95.(i) What would be the outcome if a mutant MHC class I α chain could not associate with β2-microglobulin, and (ii) what would happen if the TAP transporter were lacking as a result of mutation? Explain your answers.

96.Describe in chronological order the steps of the antigen-processing and antigenpresentation pathways for extracellular pathogens.

97.How does MHC variation due to multigene families and allelic polymorphism influence the antigens that a person’s T cells can recognize?

98.Describe the processes of antigen processing and antigen presentation, and explain why they are required before T cells can be activated.

99.What would be the outcome for antigen presentation (i) if invariant chain were defective or missing, or (ii) if HLA-DM were not expressed?

Answer Key Chapter 05 1. Answer: B 2. Answer: B 3. Answer: A 4. Answer: B 5. Answer: A 6. Answer: A 7. Answer: D 8. Answer: C 9. Answer: E 10.Answer: F 11.Answer: A 12.Answer: B 13.Answer: D 14.Answer: C 15.Answer: C 16.Answer: B 17.Answer: C 18.Answer: E 19.Answer: C 20.Answer: A

21.Answer: E 22.Answer: A 23.Answer: C 24.Answer: A 25.Answer: E 26.Answer: E 27.Answer: D 28.Answer: B 29.Answer: C 30.Answer: E 31.Answer: B 32.Answer: B 33.Answer: A 34.Answer: D 35.Answer: A 36.Answer: C 37.Answer: A 38.Answer: B 39.Answer: E 40.Answer: D 41.Answer: E 42.Answer: A

43.Answer: C 44.Answer: A 45.Answer: E 46.Answer: D 47.Answer: A 48.Answer: C 49.Answer: B 50.Answer: A 51.Answer: E 52.Answer: B 53.Answer: D 54.Answer: A 55.Answer: B 56.Answer: A 57.Answer: D 58.Answer: D 59.Answer: B 60.Answer: D 61.Answer: C 62.Answer: B 63.Answer: A 64.Answer: B

65.Answer: E 66.Answer: A 67.Answer: B 68.Answer: C 69.Answer:

1. A 2. B 3. E 4. C 5. D

70.Answer:

1. B 2. D 3. A 4. E 5. C 6. F

71.Answer:

1. D 2. A 3. C 4. B

72.Answer: Each MHC molecule can bind to a very large number of peptides made up of different sequences of amino acids. The consequence of this promiscuity is that humans need only encode a relatively small number of MHC molecules in their genome if they are to bind to the huge number of pathogen-derived peptides encountered during a lifetime of infections. Because MHC molecules are co-expressed on the cell surface, this also ensures that an appropriate density of MHC molecules populates the cell surface to ensure efficient T-cell engagement and subsequent activation.

73.Answer: (1) Invariant chain protects the peptide-binding groove of MHC class II molecules from binding to endoplasmic reticulum-derived peptides.

(2) Binding of invariant chain to MHC class II molecules stabilizes their

conformation so that they are eventually able to bind peptides.

(3) Invariant chain facilitates the transport of MHC class II molecules from the ER to the MIIC cellular compartment, where they can bind peptides.

74.Answer: Interferon-γ causes a shift from the production of constitutive proteasomes to that of immunoproteasomes. This is accomplished through increased expression of alternative subunits (LMP2 and LMP7) that are present in the immunoproteasome. These proteasomes exhibit modified protease activities favoring the production of peptides (antigen processing) that can bind to MHC class I molecules. Specifically, cleavage after hydrophobic residues is enhanced, and cleavage after acidic residues is decreased.

75.Answer: Interferon-γ increases the expression of HLA-DM but not HLA-DO. This causes a shift in the balance of these two molecules, resulting in an overall decrease in the antagonist activity of HLA-DO. If HLA-DM is more abundant, it has the ability to catalyze the release of CLIP from MHC class II molecules and facilitate the replacement of CLIP with other peptides for presentation to CD4 T cells (antigen presentation). Another way in which interferon-γ increases antigen presentation in the MHC class II pathway is by increasing the expression levels of MHC class II molecules on both professional and non-professional antigen-presenting cells.

76.Answer: First, T-cell receptors can bind to only one type of antigen, namely protein fragments called peptides. Immunoglobulins can bind to peptides, intact proteins, carbohydrates, and lipids. Second, unlike immunoglobulins, T-cell receptors cannot bind to a free antigen directly, but instead require accessory antigen-presenting cells that present the peptide antigens in association with cell-surface glycoproteins called MHC class I and class II molecules. Third, Tcell receptors possess a single antigen-binding site; immunoglobulins have at least two binding sites for antigen, and more in the case of secreted dimeric IgA (four sites) and secreted pentameric IgM (ten sites).

77.Answer: (i) Pathogens that are propagating within cells (for example viruses) are eradicated by the actions of cytotoxic T cells. (ii) Cytotoxic T cells express a glycoprotein called CD8, a T-cell co-receptor that interacts with (iii) MHC class I on antigen-presenting cells. (iv) Once activated, cytotoxic T cells kill cells infected with the pathogen, which are displaying pathogen peptides on MHC class I molecules, and thereby inhibit further replication of the pathogen and infection of neighboring cells.

78.Answer: MHC class I molecules not only have the role of presenting antigen to T cells, but they also possess additional functions in the body not associated with MHC class II molecules. For example, they participate in iron homeostasis, IgG uptake in the gastrointestinal tract, and the regulation of NK-cell function in innate immunity. In addition, MHC class I and class I-like genes are not confined to chromosome 6, in contrast with MHC class II genes. Finally, vertebrates exist (such as Atlantic cod) that have only MHC class I genes in their genome, and lack MHC class II genes.

79.Answer: T-cell receptors are not made in a secreted form, and their constant regions do not contribute to T-cell effector function. Other molecules secreted by T cells are used for effector functions. There is therefore no need for isotype switching in T cells, and the T-cell receptor loci do not contain numerous alternative C genes.

80.Answer: Professional antigen-presenting cells express several different types of MHC molecule on the cell surface, and each type has the potential to bind to different peptides. In addition, MHC molecules are highly polymorphic, so that most individuals are heterozygous and encode different allelic forms at each gene locus. The variety of peptides that can bind to these MHC molecules is therefore increased.

81.Answer: Multigene family refers to the presence of multiple genes for MHC class I and MHC class II molecules in the genome, encoding a set of structurally similar proteins with similar functions. MHC polymorphism is the presence of multiple alleles (in some cases several hundreds) for most of the MHC class I and class II genes in the human population.

82.Answer: MHC polymorphisms are non-randomly localized, predominantly to the region of the molecule that makes contact with peptide and T-cell receptors. Random DNA mutations, in contrast, would be scattered through the gene, giving rise to amino acid changes throughout MHC molecules and not just in those areas important for peptide binding and presentation.

83.Answer: m and p denote maternal and paternal allotypes, respectively. The answer is 6. The possible combinations are as follows: DRA-m: DRB1-m; (2) DRA-m: DRB1-p; (3) DRA-m: DRB4-p; (4) DRA-p: DRB1-m; (5) DRA-p: DRB1-p; and (6) DRA-p: DRB4-p 84.Answer: There are three MHC class I isotypes in humans (HLA-A, HLA-B, and HLA-C), and they are expressed from both chromosomes. Assuming that each gene is heterozygous, the maximum number of different MHC class I α chains that could be expressed is 6. Because β-microglobulin is invariant, this means that six different MHC class I molecules could be produced. For MHC class II molecules, assuming complete heterozygosity and the presence of two functional DRB genes (DRB1 and DRB3, 4, or 5) on both chromosomes, the maximum number of MHC class II molecules that could be expressed is 16.

Therefore, the total number of different MHC class I and MHC class II molecules that can be expressed is 22.

85.Answer: MHC molecules have promiscuous binding specificity, which means that one MHC molecule is able to bind a wide range of peptides with different sequences. For all MHC molecules, only a few of the amino acids in the antigen peptide are critical for binding to amino acids in the peptide-binding groove. The critical amino acids in the peptide are called anchor residues; they are the same or similar in all peptides that bind to a given MHC molecule.

The other amino acid residues in the peptides can be different. Hence, a very large number of discrete peptides can bind to each MHC isoform, the only constraint being the possession of the correct anchor residues at the appropriate positions in the peptide. MHC class I molecules also bind peptides that are typically nine amino acids long, whereas MHC class II molecules bind longer peptides with a range of lengths.

86.Answer: Interallelic conversion is a recombination between homologous alleles of the same gene. An example of interallelic conversion would involve recombination between HLA B*5101 and HLA B*3501. Gene conversion is a recombination between non-homologous alleles of different genes. An example of gene conversion would involve recombination between HLA B*1501 and HLA Cw*0102.

87.Answer: Balancing selection increases the proportion of heterozygotes in a population, whereas directional selection increases the frequency of a protective allele in the population in response to a new pathogen.

88.Answer: T helper cells expressing CD4 recognize MHC class II. MHC class II molecules present peptides generated from extracellular antigens.

Extracellular antigen is taken up by the antigen presenting cell through endocytosis or phagocytosis, where it enters vesicles called endosomes. The endosomes become increasingly acidic and merge with other vesicles that contain proteases. The low pH of the endosomes activates proteases, which break down proteins to produce peptides that will bind to MHC class II. 89.Answer: Both MHC class I and II molecules are synthesized in the endoplasmic reticulum. Peptide loading of MHC class I occurs in the endoplasmic reticulum as peptides generated by the proteasome are pumped by TAP across the endoplasmic membrane. Peptides bind to the open groove of the class I molecule and the peptide:MHC class I complex is transported through the Golgi to the cell membrane. For MHC class II, peptide loading occurs after the late endosomes, which contain peptides, merge with vesicles containing the MHC class II molecules bound to CLIP. At this site, the CLIP peptide bound to the groove of MHC class II is exchanged for the antigen peptide with the help of HLA-DM. The peptide:MHC class II complex is transported to the cell surface in outgoing vesicles.

90.Answer: Similarities. (1) The T-cell receptor has a similar overall structure to the membrane-bound Fab fragment of immunoglobulin, containing an antigenbinding site, two variable domains, and two constant domains. (2) T-cell receptors and immunoglobulins are both generated through somatic recombination of sets of gene segments. (3) The variable region of the T-cell

receptor contains three complementarity-determining regions (CDRs) encoded by the Vα domain and three CDRs encoded by the Vβ domain, analogous to the CDRs encoded by the VH and VL domains. (4) There is huge diversity in the T-cell receptor repertoire, and it is generated in the same way as that in the B-cell repertoire (by combination of different gene segments, junctional diversity due to P- and N-nucleotides, and the combination of two different chains). (5) T-cell receptors are not expressed at the cell surface by themselves but require association with the CD3 γ, δ, ε, and ζ chains for stabilization and signal transduction, analogous to the Igα and Igβ chains required for immunoglobulin cell-surface expression and signal transduction. ferences. (1) A T-cell receptor has one antigen-binding site; an immunoglobulin has at least two. (2) T-cell receptors are never secreted. (3) T-cell receptors are generated in the thymus, not the bone marrow. (4) The constant region of the T-cell receptor has no effector function, and it does not switch isotype. (5) T-cell receptors do not undergo somatic hypermutation.

91.Answer: The organization of the TCRα locus resembles that of an immunoglobulin light-chain locus in that both contain V and J gene segments and no D gene segments. The TCRα locus on chromosome 14 contains multiple V and J gene segments and 1 C gene. The immunoglobulin light-chain loci, λ and κ, are encoded on different chromosomes (22 and 2, respectively). The λ and κ locus contain multiple V and J segments and 1 C gene segment. The arrangement of the κ locus more closely resembles that of the TCRα locus except that there are more J segments in the T-cell receptor locus.

The organization of the TCRβ locus resembles that of the immunoglobulin heavy-chain locus; both contain V, D, and J gene segments. Both the TCRβ locus and the immunoglobulin heavy-chain locus contain multiple V, D and J gene segments. They differ in the number and function of C genes. There are fewer C genes in the TCRβ locus (n=2), and each C gene is associated with a set of D and J gene segments. In comparison, the immunoglobulin heavychain locus contains multiple C genes (n=9), each specifying a different immunoglobulin isotype. The heavy-chain C genes determine the effector function of the antibody.

92.Answer: (i) The complete MHC class I molecule is a heterodimer made up of one α chain and a smaller chain called β-microglobulin. The α chain consists of three extracellular domains α1, α2, and α3—a transmembrane region and a cytoplasmic tail. Β2-Microglobulin is a single-domain protein noncovalently associated with the extracellular portion of the α chain, providing support and stability. (ii) The polymorphic class I molecules in humans are called HLA-A, HLA-B, and HLA-C. The α chain is encoded in the MHC region by an MHC class I gene. The gene for β2-microglobulin is elsewhere in the genome. (iii) The antigen-binding site is formed by the α1 and α2 domains, the ones farthest from the membrane, which create a peptide-binding groove. The region of the MHC molecule that binds to the T-cell receptor encompasses the α helices of the α1 and α2 domains that make up the outer surfaces of the peptide-binding groove. The α3 domain binds to the T-cell co-receptor CD8. (iv) The most polymorphic parts of the α chain are the regions of the α1 and α2

domains that bind antigen and the T-cell receptor. Β2-Microglobulin is invariant; that is, it is the same in all individuals.

93.Answer: (i) MHC class II molecules are heterodimers made up of a α chain and a β chain. The α chain consists of α1 and α2 extracellular domains, a transmembrane region, and a cytoplasmic tail. The β chain contains β1 and β2 extracellular domains, a transmembrane region, and a cytoplasmic tail. (ii) In humans there are three polymorphic MHC class II molecules called HLA-DP, HLA-DQ, and HLA-DR. Both chains of an MHC class II molecule are encoded by genes in the MHC region. (iii) Antigen binds in the peptide-binding groove formed by the α1 and β1 domains. The α helices of the α1 and β1 domains interact with the T-cell receptor. The β2 domain binds to the T-cell co-receptor CD4. (iv) With the exception of HLA-DRα, which is dimorphic, both the α and β chains of MHC class II molecules are highly polymorphic. Polymorphism is concentrated around the regions that bind antigen and the T-cell receptor in the α1 and β1 domains.

94.Answer: Proteins derived from pathogens located in the cytosol are broken down into small peptide fragments in proteasomes. The peptides are transported into the lumen of the endoplasmic reticulum (ER) using the transporter associated with antigen processing (TAP), which is a heterodimer of TAP-1 and TAP-2 proteins anchored in the ER membrane. Meanwhile, MHC class I molecules are assembling and folding in the ER with the assistance of other proteins.

Initially, the MHC class I α chain binds calnexin through an asparagine-linked oligosaccharide on the α1 domain. After folding and forming its disulfide bonds, the α chain binds to β2-microglobulin, forming the MHC class I heterodimer. At this stage, calnexin is released, and the heterodimer joins the peptide-loading complex composed of tapasin, calreticulin, and ERp57, which position the heterodimer near TAP, stabilize the peptide-loading complex, and render the heterodimer in an open conformation until a high-affinity peptide binds to the heterodimer through a process known as peptide editing. The heterodimer consequently changes its conformation, is released from the peptide-loading complex, and leaves the ER as a vesicle. Arrival at the Golgi apparatus induces final glycosylation, and finally the peptide:MHC class I heterodimer complex is transported in vesicles to the plasma membrane, where it presents peptide to CD8 T cells.

95.Answer: (i) If an MHC class I α chain is unable to bind β2-microglobulin, it will be retained in the ER and will not be transported to the cell surface. It will remain bound to calnexin and will not fold into the conformation needed to bind to peptide. Thus, antigens will not be presented using that particular MHC class I molecule. (ii) If TAP-1 or TAP-2 proteins are mutated and not expressed, peptides will not be transported into the lumen of the ER. Without peptide, an MHC class I molecule cannot complete its assembly and will not leave the ER. A rare immunodeficiency disease called bare lymphocyte syndrome (MHC class I immunodeficiency) is characterized by a defective TAP protein, causing less than 1 percent of MHC class I molecules to be expressed on the

cell surface in comparison with normal. Thus, T-cell responses to all pathogen antigens that would normally be recognized on MHC class I molecules will be impaired.

96.Answer: Extracellular pathogens are taken up by endocytosis or phagocytosis and degraded by enzymes into smaller peptide fragments inside acidified intracellular vesicles called phagolysosomes. MHC class II molecules delivered into the ER and being transported to the cell surface intersect with the phagolysosomes, where these peptides are encountered and loaded into the antigen-binding groove. To prevent MHC class II molecules from binding to peptides prematurely, invariant chain (Ii) binds to the MHC class II antigenbinding site in the ER. Ii is also involved in transporting MHC class II molecules to the phagolysosomes via the Golgi as part of the interconnected vesicle system. Ii is removed from MHC class II molecules once the phagolysosome is reached. Removal is achieved in two steps: (1) proteolysis cleaves Ii into smaller fragments, leaving a small peptide called CLIP (class IIassociated invariant chain peptide) in the antigen-binding groove of the MHC class II molecule; and (2) CLIP is then released by HLA-DM catalysis. Once CLIP is removed, HLA-DM remains associated with the MHC class II molecule, enabling the now empty peptide-binding groove to sample other peptides until one binds tightly enough to cause a conformational change that releases HLA-DM. Finally, the peptide:MHC class II complex is transported to the plasma membrane.

97.Answer: T cells recognize peptide antigens in the form of peptide:MHC complexes, which they bind using their T-cell receptors. To bind specifically, the T-cell receptor must fit both the peptide and the part of the MHC molecule surrounding it in the peptide-binding groove. (i) Because each individual expresses a number of different MHC molecules from the MHC class I and class II multigene families, the T-cell receptor repertoire is not restricted to recognizing peptides that bind to just one MHC molecule. Instead, the T-cell receptor repertoire can recognize peptides that have different anchor residues during an immune response, increasing the likelihood of antigen recognition and, hence, T-cell activation. (ii) The polymorphism in MHC molecules is localized to the regions affecting T-cell receptor and peptide binding. Thus, a T-cell receptor that recognizes a given peptide bound to variant “a” of a particular MHC molecule is likely not to recognize the same peptide bound to variant “b” of the same MHC molecule. Polymorphism also means that the MHC molecules of one person will bind a different set of peptides from those in another person. Taken together, these outcomes mean that because of MHC polymorphism, each individual recognizes a somewhat different range of peptide antigens using a different repertoire of T-cell receptors.

98.Answer: Antigen processing is the intracellular breakdown of pathogen-derived proteins into peptide fragments that are of the appropriate size and specificity required to bind to MHC molecules. Antigen presentation is the assembly of peptides with MHC molecules and the display of these complexes on the surface of antigen-presenting cells. Antigen processing and presentation must occur for T cells to be activated because (1) T-cell receptors cannot bind to

intact protein, only to peptides, and (2) T-cell receptors do not bind antigen directly, but rather must recognize antigen bound to MHC molecules on the surface of antigen-presenting cells.

99.Answer: (i) Defects in the invariant chain would impair normal MHC class II function because invariant chain not only protects the peptide-binding groove from binding prematurely to peptides present in the ER but is also required for transport of MHC class II molecules to the phagolysosome. (ii) If HLA-DM were not expressed, most MHC class II molecules on the cell surface would be occupied by CLIP rather than endocytosed material. This would compromise the presentation of extracellular antigens at the threshold levels required for T-cell activation.

Name: ___________________________ Class: _________________ Date: __________

Chapter 06 1. Memory B cells are derived from germinal center B cells as immune responses subside. a. True b. False

2. Memory B cells have long life spans. a. True b. False

3. Memory B cells possess high-affinity antigen receptors as a consequence of affinity maturation. a. True b. False

4. Memory B cells have more stringent requirements for activation than naive B cells do. a. True b. False

5. Memory B cells express only IgM and retain the capacity to switch to the most beneficial isotype during secondary responses. a. True b. False

6. Which of the following cell-surface markers differentiates hematopoietic stem cells from other cell constituents in the bone marrow? a. pre-B-cell receptor

b. BAFF receptor c. CD34 d. CD4 e. membrane-bound stem-cell factor (SCF).

7. Which of the following statements is correct? a. The κ light-chain genes rearrange before the heavy-chain genes. b. The κ light-chain genes rearrange before the λ light-chain genes. c. The λ light-chain genes rearrange before the heavy-chain genes. d. The λ light-chain genes rearrange before the κ light-chain genes. e. The μ heavy-chain genes rearrange first and then the λ light-chain genes rearrange.

8. Immature B cells develop into mature B cells in the a. sub-endosteum. b. bone marrow. c. thymus. d. blood. e. secondary lymphoid organs.

9. Place the following phases of a B cell’s life history in the correct chronological order. a. negative selection, positive selection, repertoire assembly, circulate to secondary lymphoid organs, develop into plasma cells b. repertoire assembly, positive selection, negative selection, circulate to secondary lymphoid organs, develop into plasma cells c. repertoire assembly, negative selection, positive selection, develop into plasma cells, circulate to secondary lymphoid organs d. repertoire assembly, negative selection, positive selection, circulate to secondary lymphoid organs, develop into plasma cells e. circulate to secondary lymphoid organs, repertoire assembly, negative selection, positive selection, develop into plasma cells

10.Place the following stages of B-cell development in the correct chronological order. a. stem cell, early pro-B cell, small pre-B cell, large pre-B cell, immature B cell b. stem cell, small pre-B cell, large pre-B cell, early pro-B cell, immature B cell c. stem cell, early pro-B cell, large pre-B cell, small pre-B cell, immature B cell d. immature B cell, stem cell, early pro-B cell, large pre-B cell, small pre-B cell e. early pro-B cell, stem cell, large pre-B cell, small pre-B cell, immature B cell

11.Large pre-B cells are characterized by which of the following? a. They do not express CD19 at the cell surface. b. Rearrangement of light-chain genes commences. c. Nonproductive rearrangement of both heavy-chain loci has already occurred. d. Allelic exclusion of the immunoglobulin light-chain loci has already occurred. e. μ is assembled with VpreBλ5

12.Using these figures, choose the correct response concerning B cell development.

a. The immunoglobulin heavy-chain genes in cell 1 are in germline configuration. b. Cell 1 is pluripotent. c. The heavy chain is expressed on the surface of cell 2. d. Both cells 1 and 2 are located in the bone marrow. e. The light-chain genes are rearranged in cell 2.

13.Which of the following do NOT associate with one another during B-cell development? a. IL-7: IL-7 receptor of late pro-B cells b. Pax-5: CD19 gene c. surrogate light chain: δ heavy chain d. VpreB: λ5 e. SCF: Kit f. pre-B-cell receptor: Igα and Igβ

14.The surrogate light chain of the pre-B-cell receptor is composed of a. E2A and EFB. b. Igα and Igβ. c. VpreB and λ5. d. RAG-1 and RAG-2. e. Pax-5 and CD19.

15.Which of the following best describes the consequences of a genetic defect in the λ5 gene? a. B-cell immunodeficiency and chronic bacterial infections b. inability to produce functional μ chains c. production of a functional pre-B-cell receptor but lack of a functional B-cell receptor d. production of different light chains owing to defects in allelic exclusion e. normal rearrangement of the light-chain genes

16.Which of the following statements about B cell development is correct? a. N nucleotides are more abundant in rearranged light-chain genes than in rearranged heavy-chain genes. b. The second checkpoint in B-cell development requires the assembly of a functional B-cell receptor. c. Receptor editing occurs after B cells respond to antigen and are undergoing isotype switching. d. The first checkpoint in B-cell development ensures that the B-cell receptor

will not recognize self-antigens. e. RAG-1 and RAG-2 proteins are constitutively expressed at the large pre-Bcell stage.

17.The pre-B-cell receptor signals a. increased transcription of the RAG1 and RAG2 genes. b. reorganization of the chromatin structure of the heavy-chain locus to prevent gene rearrangement. c. the rearrangement of a second μ heavy chain. d. increased transcription of the Tdt gene. e. All of these answers are true.

18.An important advantage of having two gene loci (κ and λ) for the light chain is a. that the likelihood of a successful rearrangement of light-chain genes increases. b. that immunoglobulins are homogeneous and not heterogeneous in mature B cells. c. that different effector functions are conferred by the two different light-chain loci. d. that surrogate light-chain transcription cannot compete with κ and λ transcription and enables B-cell development. e. All of these answers are correct.

19.Which of the following is correctly matched? a. early pro-B cell: VDJ rearranged b. pre-B-cell receptor: κ light chain /μ heavy chain c. mature B cell: IgM plus IgD d. small pre-B cell: VJ rearranged e. immature B cell: VpreBλ5/μ heavy chain.

20.Which of the following are beneficial consequences of clonal expansion at the large pre-B cell stage? a. Autoreactive B cells are eliminated before the expenditure of energy

needed to rearrange a functional light-chain gene. b. The energy used to make a functional heavy chain is not wasted as the heavy chain can pair with multiple light chains. c. RAG gene expression is decreased, which in turn signals light-chain rearrangement. d. Fewer B cells will share the same heavy chain. e. All of these answers are correct.

21.When expression of __________ is turned off in small pre-B cells, the result is the presence of P nucleotides but an absence of N nucleotides in around 50 percent of light-chain genes. a. Kit b. CD19 c. TdT d. Pax-5 e. RAG-1 and RAG-2

22.A defect in which of the following proteins blocks B-cell development at the pre-Bcell stage, resulting in almost no circulating antibodies in individuals with this defect? a. IL-7 receptor b. terminal deoxynucleotidyltransferase (TdT) c. Pax-5 d. Bruton’s tyrosine kinase (Btk) e. CD19

23.The consequence of allelic exclusion at the immunoglobulin loci ensures that a. B-cell receptors have a low-avidity binding. b. B cells express antigen receptors of a single specificity. c. both kappa and lambda light chains are used. d. all functional copies of a gene are expressed. e. one B cell is able to produce multiple antibodies, each having a distinct antigen specificity.

24.A developing B cell unable to generate a productive rearrangement on any of the four light-chain loci will undergo a. self-renewal. b. apoptosis. c. allelic exclusion. d. malignant transformation. e. differentiation into a B-1 cell.

25.All of the following participate in signal transduction in developing B cells EXCEPT a. terminal deoxynucleotidyl transferase (TdT). b. FLT3. c. CD19. d. Igα and Igβ. e. Bruton’s tyrosine kinase (Btk). f. CD45.

26.Negative selection of developing B cells ensures that a. there is not an overabundance of circulating B cells that would compete with other important cell types in the circulation. b. only antigen-activated B cells leave the bone marrow. c. clonal expansion of B cells does not occur in the absence of infection. d. B-cell receptors that bind to normal constituents of the body do not emerge. e. B cells do not leave secondary lymphoid tissues.

27.Receptor editing occurs a. to establish self-tolerance of the B-cell repertoire. b. after encounter with foreign antigen in secondary lymphoid organs. c. in mature B cells. d. during heavy chain gene rearrangement. e. to express an excess of IgM over IgD on the surface of mature B cells.

28.The development of B cell tumors may be associated with a. the overexpression of Myc protein. b. chromosomal translocations involving a proto-oncogene and an immunoglobulin gene. c. overproduction of the Bcl-2 protein. d. the removal of cell division restraints. e. All of these answers are correct.

29.Which of the following is a characteristic of B-2 cells? a. They are sometimes referred to as CD5 B cells. b. They comprise only 5 percent of the B-cell repertoire. c. In adults, they are renewed by cell division in the peripheral circulation. d. They are located primarily in secondary lymphoid organs. e. They are not dependent on T helper cells for activation.

30.Which of the following chemokines are correctly associated with the producing cell? a. CCL19 is produced by lymph-node dendritic cells b. CXCL13 is produced by follicular dendritic cells c. CCL21 is produced by stromal cells of secondary lymphoid tissues d. All of these answers are correct. e. None of these answers are correct.

31.Plasma cells a. rapidly proliferate in secondary lymphoid follicles. b. may migrate to the bone marrow. c. differentiate into mature B cells. d. are naive B cells. e. express high levels of membrane-bound immunoglobulin.

32.Germinal centers are the site where a. isotype switching and somatic hypermutation occur.

b. centroblasts mature from centrocytes. c. naïve B cells are activated by antigen. d. naïve B cells are activated by CD4 helper T cells. e. All of these answers are correct.

33.Which of the following is true of centrocytes? a. They have not undergone somatic hypermutation. b. They develop from plasma cells. c. Isotype switching is complete. d. They produce secreted forms of immunoglobulins. e. They lack MHC class II molecules on the cell surface.

34.Immunological tolerance in the B-cell repertoire is called __________ tolerance when it develops in primary lymphoid organs, and __________ tolerance when it is induced outside the bone marrow. a. primary; secondary b. apoptotic; anergic c. stromal; follicular d. receptor-mediated; systemic e. central; peripheral

35.A plasma cell is characterized by which of the following features? a. It migrates to the medulla of lymph nodes, the lamina propria, or the bone marrow. b. It dedicates 70 percent of total protein synthesis to antibody production. c. Levels of MHC class II molecules are elevated. d. It undergoes extensive proliferation in germinal centers. e. It produces high levels of IgM and IgD.

36.When producing monoclonal antibodies, why is it important to use as a fusion partner a myeloma cell that is unable to produce its own immunoglobulin? a. to ensure that allelic exclusion of μ chain occurs normally b. to ensure that the antibodies are homogeneous and able to make strong

bivalent attachments to multivalent antigens c. to ensure that the monoclonal antibodies are not autoreactive d. to provide a greater opportunity for making a successful rearrangement at the light-chain locus e. to ensure that antibodies are secreted and not membrane-bound

37.The proto-oncogene __________ is associated with the development of Burkitt’s lymphoma. a. BCL-2 b. Myc c. CD5 d. CD19 e. Btk

38.Which of the following characterizes the B-1 cells that develop prenatally? a. They lack N nucleotides. b. They possess polyspecificity for bacterial polysaccharide antigens. c. They arise early in embryonic development preceding the development of the majority subset of B cells. d. They have little or no IgD on the cell surface. e. All of these answers are correct.

39.What is the fate of an immature B cell that encounters and has specificity for selfantigen? a. If further heavy-chain and light-chain gene rearrangements are possible, it undergoes apoptosis. b. Somatic hypermutation. c. Decrease in production of IgD. d. Continued rearrangement of heavy-chain genes. e. Continued rearrangement of light-chain genes.

40.Which of the following pertains to the fate of immature B cells that have specificity for univalent self-antigens?

a. The cells acquire a state of unresponsiveness called anergy. b. IgD is retained in the cytosol. c. IgD on the cell surface is required to activate the B cell when bound to selfantigen. d. The cells have a much longer life-span than mature B cells. e. They divide and secrete antibodies that bind to the self-antigens.

41.The circulatory route through a lymphoid tissue for both immature B cells and mature B cells that do not encounter specific antigen is: a. bloodstream →HEV of lymphoid cortex → primary lymphoid follicle → efferent lymphatic vessel b. afferent lymphatic vessel → primary lymphoid follicle →HEV of lymphoid cortex →efferent lymphatic vessel c. afferent lymphatic vessel →medullary cords → primary lymphoid follicle →efferent lymphatic vessel d. primary lymphoid follicle →HEV of lymphoid cortex →afferent lymphatic vessel →efferent lymphatic vessel e. bloodstream →afferent lymphatic vessel → HEV of lymphoid cortex →efferent lymphatic vessel

42.Select the true statement about B cell development. a. Pre-B-cell receptor signaling relies on genes regulated by Pax-5. b. RAG-1 and RAG-2 expression is dependent upon the B-cell specific transcription factor E2A. c. The Pax-5 transcription factor switches on the gene for CD19. d. A mutation in Pax-5 gene would prevent B cell development past the stage of heavy chain gene rearrangement. e. All of these answers are correct.

43.The light chain genes remain in the germline configuration in cells numbered ________________. Answer using the figure shown.

a. 1 b. 1, 2 c. 1, 2, 3 d. 1, 2, 3, 4 e. 1, 2, 3, 4, 5

44.Cells numbered __________ express the Pax5 transcription factor. Answer using the figure shown.

a. 1 b. 1, 2, 3, 4, 5 c. 2, 3 d. 2, 3, 4 e. 2, 3, 4, 5

45.Match the name of the B-cell tumor with the correct description. a. multiple myeloma b. chronic lymphocytic leukemia (CLL) c. Hodgkin’s disease d. Burkitt’s lymphoma e. follicular center cell lymphoma 1. __________ most cases caused by B-1 cells 2. __________ derived from germinal center B cells 3. __________ arises from mature naive B cells in the lymph node follicles 4. __________ derived from plasma cells in the bone marrow 5. __________ associated with chromosomal translocations involving the proto-oncogene MYC

46.Discuss the importance of the bone marrow stroma for B-cell development.

47.What would be the effect of anti-IL-7 antibodies on the development of B cells in the bone marrow, and at which stage would development be impaired? Explain your answer.

48.What are the two main checkpoints of B-cell development in the bone marrow?

49.What is the fate of developing B cells that produce (i) functional or (ii) nonfunctional heavy and light chains?

50.Explain how the two checkpoints of B-cell development correlate with the process of allelic exclusion that ensures that only one heavy-chain locus and one lightchain locus produce functional gene products.

51.What would be the consequence if terminal deoxynucleotidyl transferase (TdT) were expressed throughout the whole of small pre-B-cell development?

52.Describe the (i) impact of and (ii) treatment for a lack of functional Bruton’s tyrosine kinase on B-cell development.

53.Explain why immunological memory is important in acquired immunity.

54.Describe how immunoglobulin expressed during a primary immune response differs qualitatively and quantitatively from the immunoglobulin expressed during a secondary immune response.

55.Give three properties that distinguish B-1 cells from B-2 cells.

56.Do you think that B-1 cells should be categorized as participants in innate immune responses or in acquired immune responses? Explain your rationale.

57.Identify two properties that are shared by anergic B cells and plasma cells.

58.What key property is different between anergic B cells and plasma cells?

59.Describe the six functionally distinct phases of B-cell development.

60.Describe the outcome on B cell development if an early-pro-B cell were exposed to an inhibitor that prevents chromatin remodeling. Your response should include the key events that depend upon chromatin remodeling that occur at the early pro-B cell stage.

61.What is the role of primary lymphoid follicles in eliminating B cells that have antigen receptors specific for soluble self-antigen?

62.Explain how B cells undergo the process of negative selection and indicate at which stage of development and at which location these events occur.

63.Hinda Mundy, 26 years old, grew concerned when a lump appeared in her lower neck, and she had pain in her chest and a dry cough. She also told her physician that she had experienced fatigue, night sweats, unintentional weight loss, pruritis (dry, itchy skin), and intermittent fevers over the past few months.

Immunohistological staining of a biopsy of the enlarged lymph node revealed the presence of large multinucleated Reed–Sternberg cells. Polymerase chain reaction (PCR) tests confirmed immunoglobulin gene rearrangements; however, B-cell antigen expression was absent. Hinda entered complete remission after treatment with four cycles of chemotherapy combined with radiotherapy. These

symptoms and treatment are most consistent with which of these diagnoses?

Hodgkin’s lymphoma; multiple myeloma; acute lymphoblastic; leukemia (ALL); Waldenström’s magroglobulinemia; chronic lymphocytic leukemia (CLL) Explain your reasoning.

64.Multiple myeloma involves the unregulated proliferation of an antibody-producing plasma cell (myeloma cell) independently of antigen stimulation or T-cell help.

Myeloma cells populate multiple sites in the bone marrow, where they produce immense quantities of monoclonal immunoglobulin as well as suppressing normal marrow function. Myeloma cells also synthesize and secrete excessive amounts of free light chains (known as Bence-Jones protein), which, because of their low molecular weight (~25 kDa) are excreted as free light chains in the urine. There are two observations in a given patient: the free light chains are both monoclonal, and all are of either the κ or the λ type. Explain both of these observations.

65.Why do you think patients with multiple myeloma are more susceptible than normal to pyogenic infections, such as pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae?

Answer Key Chapter 06 1. Answer:

A

2. Answer:

A

3. Answer:

A

4. Answer:

B

5. Answer:

B

6. Answer:

C

7. Answer:

B

8. Answer:

E

9. Answer:

D

10.Answer:

C

11.Answer:

E

12.Answer:

D

13.Answer:

C

14.Answer:

C

15.Answer:

A

16.Answer:

B

17.Answer:

B

18.Answer:

A

19.Answer:

C

20.Answer:

B

21.Answer:

C

22.Answer:

D

23.Answer:

B

24.Answer:

B

25.Answer:

A

26.Answer:

D

27.Answer:

A

28.Answer:

E

29.Answer:

D

30.Answer:

D

31.Answer:

B

32.Answer:

A

33.Answer:

C

34.Answer:

E

35.Answer:

A

36.Answer:

B

37.Answer:

B

38.Answer:

E

39.Answer:

E

40.Answer:

A

41.Answer:

A

42.Answer:

E

43.Answer:

B

44.Answer:

E

45.Answer:

1. B 2. C 3. E 4. A 5. D

46.Answer:

Bone marrow stromal cells provide the necessary environment for B-cell development by expressing secreted products and membrane-bound adhesion molecules. For example, VCAM-1 adhesion molecule binds to the integrin VLA-4 on early B-cell progenitors. The cytokine SCF (stem cell factor) acts on early pro-B cells via the Kit receptor, and IL-7 plays an important role in later stages of B-cell development, serving to stimulate the growth and cell division of late pro-B and pre-B cells.

47.Answer:

If anti-IL-7 antibody were introduced into this environment, developing B cells would not be able to divide or continue development. The developing B cells would be arrested at the late pro-B-cell or pre-B-cell stage and would not progress normally to the immature B-cell stage. IL-7 plays an important role in B-cell maturation.

48.Answer:

Checkpoint 1 is marked by the formation of a complex of a μ heavy chain complexed with the surrogate light chain VpreBλ, Igα, and Igβ. This checkpoint tests if the heavy chain is able to pair with a light chain. Checkpoint 2 occurs when a complete B-cell receptor, comprising μ heavy chains, κ or λ light chains, and Igα and Igβ chains, is expressed on the Bcell surface. The expression of the functional B-cell receptor on the cell surface prevents further rearrangement of the light chain genes.

49.Answer:

At checkpoint 1, if the V(D)J rearrangement gives rise to a functional pre-B-cell receptor, the late pro-B cell will be permitted to survive and undergo clonal proliferation. If V(D)J rearrangement produces a nonfunctional heavy chain and no pre-B-cell receptor is assembled, the pro-B cell undergoes apoptosis and dies. Similarly, at checkpoint 2, production of a functional light chain results in the assembly of a functional surface immunoglobulin and the survival and maturation of

the B cell. Nonproduction of a light chain results eventually in apoptosis.

50.Answer:

Checkpoint 1 delivers an important signal to the cell, verifying that a functional heavy chain has been made. This triggers the cessation of heavy-chain gene rearrangement followed by the inactivation of surrogate light-chain synthesis. Thus, only one heavy-chain locus ends up producing a product. As surrogate light chain becomes unavailable, μ accumulates and is retained in the endoplasmic reticulum, ready to bind to functional light chain when that is synthesized after successful light-chain gene rearrangement. Checkpoint 2 signals the cessation of light-chain rearrangement. This ensures that only one light-chain locus out of the possible four produces a functional product.

51.Answer:

N nucleotides would be added at the VJ joints of all rearranged light-chain genes during gene rearrangement (instead of about half), resulting in an increase in immunoglobulin diversity. It is interesting to note that because TdT is not expressed until after birth, B-1 cells that are generated prenatally lack N nucleotides in the VD and DJ junctions of their rearranged heavy-chain genes as well as in the VJ junctions of all light-chain genes.

52.Answer:

(i) In the absence of functional Bruton’s tyrosine kinase (Btk), B-cell development is blocked at the pre-B-cell stage.

Because mature B cells cannot develop, children experience a form of immune deficiency known as X-linked agammaglobulinemia (the gene for Btk is located on the X chromosome, so affected individuals are typically males).

Affected individuals experience recurrent infections with common extracellular bacteria such as Haemophilus influenzae or Streptococcus pneumoniae. (ii) Affected individuals are treated with infusions of immunoglobulin.

53.Answer:

Memory enables faster, more efficient recall responses when antigen is encountered subsequently. This enables the body to get rid of a pathogen before it has time to cause disease.

54.Answer:

Immunoglobulin produced during a primary immune response is mainly IgM, in low concentration (titer) and of low affinity for the antigen. Immunoglobulin expressed during a secondary immune response has undergone isotype switching and is often of the IgG isotype. It also has a higher titer and, through the process of somatic hypermutation, will have a higher affinity for its corresponding antigen.

55.Answer:

Unlike conventional B-2 cells, B-1 cells express the cellsurface protein CD5, possess few N nucleotides at VDJ junctions, and have a restricted range of antigen specificities.

They produce IgM antibodies of low affinity and respond mainly to carbohydrate, rather than protein, epitopes.

Individual B-1 cells are polyspecific for antigen; that is, their immunoglobulins bind several different antigens.

56.Answer:

B-1 cells are probably best associated with innate immune responses because of their rapid response to antigen, their limited diversity, and their polyspecificity.

57.Answer:

They both express decreased levels of IgM on the cell surface and are nonresponsive to antigen.

58.Answer:

Anergic B cells do not secrete antibody. Plasma cells, in contrast, secrete very large amounts of antibody.

59.Answer:

(1) Repertoire assembly: Bone marrow expression of diverse B-cell receptors. (2) Negative selection: Modification, elimination or inactivation of autoreactive B cells. (3) Positive selection: Selection of a small subset of immature B cells to become mature B cells in secondary lymphoid organs. (4) Searching for infection: Patrolling for infectious material by recirculating continuously between lymph, blood and secondary lymphoid organ compartments. (5) Finding infection: B cells become activated by antigen in secondary lymphoid tissues and then undergo clonal expansion. (6) Attacking infection: B cells differentiate into plasma cells and memory cells in secondary lymphoid tissues.

60.Answer:

In the stem cell, the chromatin containing the immunoglobulin loci is kept in a “closed” form and is not transcribed. At the early pro-B cell stage, the transcription factor Pax-5 binds to enhancer sequences located in the heavy chain locus, which allows an opening of the chromatin around the V, D, and J gene segments. Transcription occurs from promoters upstream of the D and J segments allowing RAG enzymes to recombine D and J segments. Transcription of the promoter upstream of a V segment allows V-DJ recombination. In the absence of chromatin remodeling, these events would not occur, and the cell would not develop past the pro-B cell stage.

61.Answer:

To survive, circulating B cells must enter primary follicles where survival signals are delivered by cells in the follicles, including follicular dendritic cells (which are the stromal cells of primary lymphoid follicles). Circulating B cells that fail to enter follicles in secondary lymphoid tissues will die in the

peripheral circulation with a half-life of about 3 days. B cells with antigen receptors specific for soluble self-antigen are generally rendered anergic in the bone marrow or the circulation. Anergic B cells that enter secondary lymphoid organs are held in the T-cell areas adjacent to primary follicles and are not permitted to penetrate the follicle. As a result, they do not receive the necessary stimulatory signal for survival. Instead, anergic B cells will undergo apoptosis in the T-cell zone. This is an efficient cleansing mechanism and serves to delete potentially autoreactive B cells from the circulation.

62.Answer:

Immature B cells that express receptors specific for common multivalent self-antigens undergo apoptosis unless receptor editing can produce a receptor that does not have specificity for self-antigen. This process of clonal deletion begins in the bone marrow, and apoptotic cells are phagocytosed by macrophages. Immature B cells bearing receptors for monovalent self-antigen are instead rendered anergic. These anergic B cells are produced in the bone marrow and when exported to the periphery survive for only 1–5 days. Immature B cells reactive to self-antigen in the periphery cannot carry out receptor editing. They either undergo apoptosis or become anergic.

63.Answer:

Hodgkin’s lymphoma. Two clues are crucial to this diagnosis: the first is the presence of Reed–Sternberg cells, a hallmark of Hodgkin’s lymphoma; the second is the existence of rearranged immunoglobulin loci in these cells but their inability to express mature B-cell receptors. Multiple myeloma, Waldenström’s magroglobulinemia, and CLL, in contrast, are B-cell tumors that do make mature B-cell receptors. ALL derives from a lymphoid progenitor, and the immunoglobulin loci are unrearranged.

64.Answer:

In a normal response to infection, a diverse array of plasma cells will produce different light chains against many different antigens. In multiple myeloma, the tumor originates from a single plasma cell expressing heavy and light chains with specificity for a single antigen (clonotypic immunoglobulin).

Because B cells express only κ or λ light chains, the tumor will also express only κ or λ, but not both. Therefore, BenceJones protein for a given patient will be of one type or another, but not both.

65.Answer:

Although patients will have elevated immunoglobulin levels (usually IgG or IgA), most of the immunoglobulin will be produced by the myeloma cells and will be monospecific.

Hence, normal concentrations of polyclonal immunoglobulin

will be severely compromised. Pyogenic infections caused by encapsulated bacteria are cleared by humoral immune responses that use antibody-mediated complement activation and antibody-enhanced phagocytosis. An insufficiency of pathogen-specific polyclonal immunoglobulins puts these patients at greater risk of these infections.

Name: ___________________________ Class: _________________ Date: __________

Chapter 07 1. Immature T cells failing to successfully recombine a β-chain locus on the first attempt die by apoptosis. a. True b. False

2. Apoptotic T cells are ingested by medullary epithelial cells. a. True b. False

3. Allelic exclusion of the T-cell receptor α and β chains is effective; therefore, all T cells express only one T-cell receptor on the cell surface. a. True b. False

4. T-cell receptor rearrangements have many features in common with immunoglobulin rearrangement, including the use of the RAG-1 and RAG-2 genes. a. True b. False

5. The expression of the pre-T-cell receptor is required to halt β-, γ-, and δ-chain rearrangements. a. True b. False

6. In which of the following ways does the developmental pathway of α:β T cells differ from that of B cells?

a. Their antigen receptors are derived from gene rearrangement processes. b. When the first chain of the antigen receptor is produced it combines with a surrogate chain. c. Cells bearing self-reactive antigen receptors undergo apoptosis. d. MHC molecules are required to facilitate progression through the developmental pathway. e. They both develop in primary lymphoid tissues.

7. Which of the following cell-surface glycoproteins is characteristic of stem cells, but stops being expressed when a cell has committed to the T-cell developmental pathway? a. CD2 b. CD3 c. CD25 d. CD34 e. MHC class II

8. Which of the following processes is not dependent on an interaction involving MHC class I or class II molecules? a. positive selection of αβ T cells b. recognition of self-peptide by αβ T cells c. negative selection of αβ T cells d. peripheral activation of mature naive T cells e. positive selection of γδ T cells.

9. If a double-negative thymocyte has just completed a productive β-chain gene rearrangement, which of the following describes the immediate next step in the development of this thymocyte? a. A pre-T-cell receptor is assembled. b. Rearrangement of γ- and δ-chain genes commences. c. Expression levels of RAG-1 and RAG-2 are elevated. d. The linked δ-chain genes are eliminated. e. This cell will inevitably differentiate into a committed γ:δ T cell.

10.All of the following cell-surface glycoproteins are expressed by double-negative thymocytes undergoing maturation in the thymus except __________. a. CD2 b. CD5 c. CD127 (IL-7 receptor) d. CD34 e. CD1A

11.__________ is a T-cell-specific adhesion molecule expressed before the expression of a functional T-cell receptor while the thymocytes are still in their double-negative stage of development. a. CD4 b. CD8 c. CD25 d. CD2 e. CD3

12.Double-negative CD3- thymocytes proliferate in the __________, and negative selection occurs in the __________. a. cortico-medullary junction; cortex b. subcapsular zone; cortico-medullary junction c. medulla; cortico-medullary junction d. medulla; subcapsular zone e. subcapsular zone; bone marrow

13.Which of the following statements about Notch 1 is correct? a. Notch 1 is expressed on thymic epithelial cells. b. In the absence of Notch 1 expression, T cells can complete their differentiation. c. Notch 1 activates genes leading to both T-cell and B-cell development. d. Notch 1 contains two distinct domains, one of which is proteolytically cleaved and becomes a transcription factor in the nucleus. e. The intracellular domain of Notch 1 must interact with a ligand on thymic

epithelium to initiate cleavage and separation of the Notch 1 extracellular and intracellular domains.

14.Which of the following is the first stage of T-cell receptor gene rearrangement in α:β T cells? a. Vα > Dα b. Dα > Jα c. Vβ > Dβ d. Dβ > Jβ e. Vα > Jα

15.Which of the following is the first T-cell receptor complex containing the β chain to reach the cell surface during the development of T lymphocytes? a. γ:β:CD3 b. β:CD3 c. α:β:CD3 d. β:CD44 e. pTα:β:CD3

16.Genetic deficiencies in each of the following would impair the development of a fully functional T-cell repertoire except a. RAG-1 or RAG-2. b. Notch1. c. Pax-5. d. IL-7 receptor (CD127). e. TAP-1 or TAP-2.

17.__________ of thymocytes is necessary to produce a T-cell repertoire capable of interacting with self-MHC molecules. a. Positive selection b. Negative selection c. Apoptosis

d. Receptor editing e. Isotype switching

18.Which of the following statements are true of a T cell that expresses two α chains (and thus two different T-cell receptors)? a. Both T-cell receptors must engage with MHC molecules expressed on the thymic epithelium for positive selection to occur. b. It is not possible to have a T cell expressing two α chains. c. Because only one of the two T-cell receptors is likely to bind strongly to a self-peptide presented by a self-MHC molecule, the thymocyte will not be signaled to undergo negative selection. d. One of the T-cell receptors may be autoreactive but escape negative selection because its peptide antigen is present in tissues other than the thymus. e. Subsequent gene rearrangements may give rise to a γ:δ T-cell receptor.

19.Once a thymocyte has productively rearranged a β-chain gene, which of these event(s) can occur subsequently? a. β binds to pTα and is expressed on the cell surface with the Igα/Igβ complex. b. Rearrangement of β-chain genes continues as a result of increased expression of RAG-1 and RAG-2. c. The pre-T cell undergoes positive and negative selection. d. Expression of CD34 and CD2 gives rise to double-positive thymocytes. e. The pre-T cell proliferates and begins to express CD4 and CD8.

20.Which of the following statements regarding positive selection is correct? a. All subsets of developing T cells undergo positive selection before export to the peripheral circulation. b. T-cell receptor editing is linked to the process of positive selection. c. Positive selection results in the production of T cells bearing T-cell receptors that have the capacity to interact with all allotypes of MHC class I and class II molecules, and not just those of the individual. d. Positive selection ensures that autoreactive T cells are rendered nonresponsive.

e. If there is a genetic defect in AIRE, then T-cell development is arrested as positive selection commences.

21.Thymocytes that are not positively selected a. undergo genetic reprogramming and differentiate into a different cell type. b. are exported to the periphery, where they are phagocytosed by macrophages. c. make up about 98 percent of developing thymocytes and die by apoptosis in the thymic cortex. d. are eliminated because of their reactivity with self antigens. e. try out different β chains to acquire reactivity with self-MHC molecules.

22.If the process of positive selection did not occur, then a. a condition resembling immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) would develop. b. a condition resembling autoimmune polyendocrinopathy–candidiasis– ectodermal dystrophy (APECED) would develop. c. naive T cells would be unable to undergo differentiation in secondary lymphoid tissues. d. malignant transformation would be more likely because of the accumulation of multiple mutations. e. only a very small percentage of circulating T lymphocytes would be able to become activated.

23.Immediately after positive selection, a. the thymocyte reaches maturity and is exported to the periphery. b. RAG proteins are degraded and are no longer synthesized. c. receptor editing commences to eliminate reactivity against self antigens. d. the developing thymocyte acquires a double-negative phenotype. e. expression of pTα is repressed.

24.Allelic exclusion a. occurs for both T-cell receptor α and β genes.

b. does not occur for B-cell receptor light-chain genes. c. is not linked to positive or negative selection. d. is linked to RAG protein expression. e. All of these answers are correct.

25.Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is caused by a defect in a. cathepsin L. b. a transcription factor that regulates tissue-specific gene expression in the thymus. c. the production of regulatory CD4 T cells. d. FoxP3. e. T-cell receptor gene rearrangement.

26.Identify the statement which accurately describes how antigen processing and presentation of self antigens by thymic epithelial cells differs from that of antigenpresenting cells in peripheral tissues. a. Thymic epithelium uses the transcription factor AIRE to activate thymic expression of tissue-specific genes. b. Thymic epithelium uses cathepsin L for proteolytic degradation of self proteins. c. The thymoproteasome produces a novel set of peptides that binds tightly to MHC class I. d. All of these answers are correct. e. None of these answers are correct.

27.All of the following types of protein are processed and presented by macrophages in the thymus except a. tissue-specific proteins. b. soluble proteins from extracellular fluids. c. ubiquitous proteins. d. proteins made by macrophages. e. proteins derived from other cells that macrophage phagocytose.

28.Double-negative thymocytes initiate rearrangement at the __________ locus (loci) before all other T-cell receptor genes. a. γ and δ b. β c. α and β d. α, γ, and δ e. β, γ, and δ

29.The function of negative selection of thymocytes in the thymus is to eliminate a. single-positive thymocytes. b. double-positive thymocytes. c. alloreactive thymocytes. d. autoreactive thymocytes. e. apoptotic thymocytes.

30.Which of the following statements is correct? a. In adults the mature T-cell repertoire is self-renewing and long-lived and does not require a thymus for the provision of new T cells. b. T cells and B cells are both short-lived cells and require continual replenishment from primary lymphoid organs. c. The human thymus is not fully functional until age 30, at which time it begins to shrink and atrophy. d. In DiGeorge syndrome the bone marrow takes over the function of the thymus and produces mature peripheral T cells. e. None of these statements are correct.

31.Individuals with a defective autoimmune regulator gene (AIRE) exhibiting a. DiGeorge syndrome. b. autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED). c. severe combined immunodeficiency (SCID) lacking both B and T cells. d. MHC class I deficiency. e. MHC class II deficiency.

32.The human thymus begins to degenerate as early as one year after birth. This process is called __________ and is marked by the accumulation of __________ once occupied by thymocytes. a. thymectomy; dendritic cells b. involution; fat c. differentiation; γ:δ T cells d. negative selection; γ:δ T cells e. involution; thymic stroma

33.Which of the following statements about the successive rearrangement of αβ Tcell receptors is correct? a. Unproductive rearrangement to the Cβ1 locus can be rescued by a second rearrangement to the Cβ2 locus. b. Unproductive rearrangement to the Cβ2 locus can be rescued by a second rearrangement to the Cβ1 locus. c. A developing T cell with an unproductive β-chain rearrangement on the paternal chromosome can survive only if the δ-chain successfully rearranges. d. A developing T cell that successfully rearranges one α chain locus will not rearrange the second α chain locus e. All of these answers are correct.

34.Cell #1 in the figure is a committed T cell progenitor located in the cortex of the thymus. Select the correct statement concerning cell #1.

a. Cell #1 expresses both CD4 and CD8 on its cell surface.

b. Cell #1 is transducing a signal through Lck. c. Cell #1 has already undergone allelic exclusion. d. Cell #1 expresses Notch1 and GATA-3. e. Cell #1 is undergoing positive selection.

35.Cell #2 in the figure originated from a committed T cell progenitor (cell #1) and is at the first checkpoint stage of thymocyte development. Select the correct statement about cell #2.

a. V–D-Jβ and V–Jα rearrangement occurred between the developmental stages of cell #1 and cell #2. b. ZAP-70 is active in cell #2 and leads to proliferation of the thymocyte. c. The beta-chain locus is in the germline configuration in cell #2. d. Cell #2 is at the double positive stage. e. Cell #2 is undergoing positive selection to be restricted to self-MHC.

36.Antibodies that block the MHC class II molecule are injected into the thymus of a young mouse. Select the correct response. a. The mouse will have circulating CD4 T cells, but no CD8 T cells. b. The mouse will have circulating CD8 T cells, but no CD4 T cells. c. The mouse will lack both CD4 and CD8 T cells in the periphery. d. The thymocytes of this mouse will not be able to reach the double positive stage. e. The thymocytes will develop normally, and the mouse will have normal levels of CD4 and CD8 T cells in the periphery.

37.The T-cell receptor alpha chain __________. a. corresponds to the heavy chain of the immunoglobulin molecule. b. has limited opportunities for a successful rearrangement due to the small number of available gene segments. c. begins to rearrange at the double-positive thymocyte stage. d. can pair with a rearranged delta chain . e. rearranges prior to the T-cell receptor beta chain.

38.Match the immunodeficiency with the corresponding cause or consequence. a. IL-7 receptor deficiency b. DiGeorge syndrome c. SCID or severe combined immunodeficiency (due to lack of B and T cells) d. Bare lymphocyte syndrome e. APECED 1. __________ absence of functional AIRE 2. __________ absence of functional MHC class I or MHC class II molecules 3. __________ absence of T cells because of signaling defects by thymic stromal cells 4. __________ absence of functional RAG-1 and 2 5. __________ absence of T cells due to absence of thymus

39.In T cells, allelic exclusion of the α-chain locus is relatively ineffective, resulting in the production of some T cells with two T-cell receptors of differing antigen specificity on their cell surface. Will both these receptors have to pass positive selection for the cell to survive? Explain your answer.

40.MHC class II deficiency is inherited as an autosomal recessive trait and involves a defect in the coordination of transcription factors involved in regulating the expression of all MHC class II genes (HLA-DP, HLA-DQ, and HLA-DR). What is the effect of MHC class II deficiency on T cell development?

41.Explain why a low level of circulating antibody is associated with an inherited MHC class II deficiency that results in the lack of expression of all MHC class II genes (HLA-DP, HLA-DQ, and HLA-DR).

42.As we age, our thymus shrinks, or atrophies, by a process called involution, yet Tcell immunity is still functional in old age. Explain how T-cell numbers in the periphery remain constant in the absence of continual replenishment from the thymus.

43.How does the maintenance of the mature T-cell and B-cell repertoire differ?

44.How do regulatory CD4 T cells (Treg) function?

45.How can Treg be distinguished from other non-regulatory CD4 T cells?

46.What is the general name for the antigens against which the immune system is normally tolerant?

47.Identify the cells expressing Notch1 and the Notch1 ligand and describe the role Notch1 plays in T-cell development.

48.Explain how the expression and processing of self-antigens in thymic epithelium is advantageous for the process of negative selection.

49.The T-cell receptor β-chain locus can undergo successive gene rearrangements to rescue unproductive V(D)J rearrangements.

What aspects of gene segment rearrangement at the TCRβ locus make this possible?

50.Explain two ways in which the expression and processing of self antigens in thymic epithelium differs from the expression and processing of self antigens outside the thymus.

51.The surrogate light chain operating during pre-B-cell development is made up of VpreB:λ. Its expression with μ on the pre-B-cell surface is an important checkpoint in B-cell maturation. Name the T-cell analog of VpreB: λ5 and discuss how it is functionally similar.

52.Is there a potential problem in having T cells with dual specificity surviving the positive and negative selection process in the thymus and being exported to the periphery?

53.Mature B cells undergo somatic hypermutation after activation, which, after affinity maturation, results in the production of antibody with a higher affinity for antigen than in the primary antibody response. Suggest some reasons why T cells have not evolved the same capacity.

54.What is central tolerance?

55.Explain two different ways that autoreactive, mature T cells can be prevented from causing autoimmunity after they have exited the thymus and entered the peripheral circulation.

56.Compare the impact of a RAG-1 and an MHC class I mutation on both thymocyte development and the population of mature, circulating lymphocytes. The mutation in each case leads to a nonfunctional protein.

Answer Key Chapter 07 1. Answer: B 2. Answer: B 3. Answer: B 4. Answer: A 5. Answer: A 6. Answer: D 7. Answer: D 8. Answer: E 9. Answer: A 10.Answer: D 11.Answer: D 12.Answer: B 13.Answer: D 14.Answer: D 15.Answer: E 16.Answer: C 17.Answer: A 18.Answer: D 19.Answer: E 20.Answer: B

21.Answer: C 22.Answer: E 23.Answer: B 24.Answer: D 25.Answer: B 26.Answer: D 27.Answer: A 28.Answer: E 29.Answer: D 30.Answer: A 31.Answer: B 32.Answer: B 33.Answer: A 34.Answer: D 35.Answer: B 36.Answer: B 37.Answer: C 38.Answer:

1. E 2. D 3. A 4. C 5. B

39.Answer: Only one of the receptors will have to be positively selected for the cell to get the

survival signals necessary for it to pass on to the next stage. Even if the other receptor does not react with self MHC, this will have no effect on the cell.

40.Answer: MHC class II deficiency affects the development of CD4 T cells in the thymus. If the thymic epithelium lacks MHC class II, positive selection of CD4 T cells will not take place. CD8 T cells are not affected because MHC class I expression is unaffected by this defect. This defect will affect levels of circulating immunoglobulin.

41.Answer: To produce antibody, B cells require T-cell help in the form of cytokines produced by CD4 T helper cells. Low immunoglobulin levels (hypogammaglobulinemia) in MHC class II deficiency are attributed to the inability of B cells to proliferate and differentiate into plasma cells in the absence of cytokines produced by T helper cells.

42.Answer: After thymic atrophy or thymectomy, T cells in the periphery self-renew by cell division, and they are long lived.

43.Answer:

B cells are short lived and replenish from immature precursors derived from the bone marrow. In comparison, as we age the thymus atrophies, and longlived peripheral T cells self-renew by cell division.

44.Answer: When Treg cells recognize self-antigen presented by MHC class II, they act to suppress the activation and proliferation of naive autoreactive CD4 T cells. This is one form of peripheral tolerance.

45.Answer: Unlike non-regulatory CD4 T cells, Treg express CD25 on the cell surface and the FoxP3 transcriptional repressor protein.

46.Answer: self antigens 47.Answer: Notch1 is a membrane-bound receptor found on thymocytes that participates in the

regulation of early T-cell development. Its ligand (Notch ligand) is a membrane-bound protein on the surface of thymic epithelial cells. After binding of the extracellular domain of Notch1 to the extracellular portion of Notch ligand, the intracellular domain of Notch1 is released by proteolysis and subsequently translocates to the nucleus. In the thymocyte nucleus, this domain forms a transcription factor complex that displaces repressor proteins from genes involved in T-cell development and initiates transcription of these genes by recruiting transcription activator proteins.

48.Answer: Medullary epithelial cells in the thymus produce a transcription factor called autoimmune regulator (AIRE), which causes several hundred genes normally expressed in other tissues to be expressed in these cells.

The proteins can then be processed to form self peptides that will be presented by MHC class I molecules. Generating a more comprehensive repertoire of self-peptides in the thymus increases the types of potentially autoreactive T cell that are removed from the peripheral T-cell repertoire during negative selection.

49.Answer: Successive gene rearrangement is possible at a TCRβ locus because there are two sets of D, J, and C gene segments downstream of the cluster of V gene segments: (Vβ)n…Dβ1…(Jβ1)n…Cβ1…Dβ2…(Jβ2)n…Cβ2.

If a first rearrangement involving Dβ1 and a Jβ1 segment is unproductive, an upstream V gene segment can rearrange to the second D gene segment and an associated J segment.

If this is unproductive, no more rearrangements can be made.

50.Answer: (i) As well as expressing their own thymusspecific self antigens, medullary epithelial cells in the thymus produce a transcription factor called autoimmune regulator (AIRE), which causes several hundred genes normally expressed in other tissues to be expressed in these cells. The proteins can then be processed to form self peptides that will be

presented by MHC class I molecules. (ii) The thymic epithelium uses different proteases for self-protein degradation; cathepsin L is used for peptide production instead of cathepsin S, which is used by other cell types. (iii) The thymoproteasome is expressed in cortical epithelial cells of the thymus and produces self peptides that have unique anchor residues and bind with high affinity to MHC, but with typically lower affinity to the T-cell receptor.

51.Answer: The analog of VpreB: λ5 in developing T cells is the protein preTα (pTα), which combines with the T-cell receptor β chain, the first of the two T-cell receptor chains to be expressed, to form the pre-T-cell receptor. The β chain, like the immunoglobulin heavy chain, contains V, D, and J segments. pTα also binds CD3 and ζ components to this complex, and the assembly of the complete complex induces Tcell proliferation and the cessation of rearrangement at the TCRβ loci (leading to allelic exclusion). Formation of the analogous pre-B-cell receptor complex of VpreB: λ5 and heavy chain with Igα and Igβ in B cells similarly prevents further rearrangement of the heavy-chain loci.

52.Answer: Yes. Imagine this situation: The T cell with dual specificity could be activated appropriately during a genuine infection by a professional antigen-presenting cell plus foreign antigen 1 using T-cell receptor 1. But that same T cell, because it is now an activated effector T cell, would also be able to respond to a second peptide, which might be a self-peptide, using T-cell receptor 2, without requiring the co-stimulatory signals that only professional antigen-presenting cells deliver.

Thus it could cause a reaction against a self tissue, either directly, if it is a CD8 cytotoxic T cell, or indirectly, if it is a CD4 T cell, by activating potentially autoreactive B cells.

Furthermore, interferon-γ produced in the response against foreign antigen 1 could activate nonprofessional antigen-presenting cells nearby, inducing the expression of MHC class II with presentation of the self peptide

above. Effector T cells with T-cell receptor 2 could make an autoimmune response against it.

53.Answer: Because T cells drive almost all immune responses, once they have been activated their receptors must continue to recognize the exact complex of foreign antigen and MHC molecule (which does not change) that activated them. Because of this requirement for dual recognition (MHC restriction), somatic hypermutation would be more likely than not to change the T-cell receptor to make it unable to recognize either the peptide or the MHC molecule, or the combination of both, thus rendering it unable to give help to B cells or to attack infected cells. This would destroy both the primary immune response and the development of immunity. Even changes that simply increased the affinity of the T cell for its antigen would have no real advantage because it would not make the immune response any stronger or improve immunological memory in the same way that affinity maturation of B cells does. Also, if somatic hypermutation changed the specificity of the T-cell receptor so that it now recognized a self peptide, this could result in an autoimmune reaction. These considerations do not apply to B cells, because they require T-cell help to produce antibody and will only receive it if their B-cell receptor still recognizes the original antigen.

54.Answer: Central tolerance is the mechanism that operates to ensure that lymphocytes do not contain antigen receptors specific for host components. This is achieved through a process involving the removal of self-reactive T and B cells called negative selection during thymic development. Both T and B cells are removed by apoptosis after the engagement of T-cell receptors and immunoglobulins, respectively, if the interaction with their ligands is especially strong. The consequence is the removal of autoreactive lymphocytes that could cause damage to healthy, uninfected cells and tissues.

55.Answer: (i) Peripheral tolerance can be maintained by the action of FOXP3-expressing T regulatory cells which function to limit the activity of CD4 and CD8 T cells responding to self-antigen. (ii) A second form of peripheral tolerance occurs when naive CD4 or CD8 T cells encounter a self-antigen in the absence of infection. This type of interaction causes the T cell to receive signals leading either to anergy or activation-induced cell death.

56.Answer: A mutation in RAG1 will block thymocyte development at an early stage. Without functional RAG enzymes, the beta chain of the T-cell receptor cannot rearrange. If there is no functional beta chain produced, there will be no pre-T-cell receptor formed, and the thymocyte will undergo apoptosis at the double negative stage. Because RAG1 is also required for rearrangement of immunoglobulin genes, the individual will lack both circulating B and T cells. In an individual with a mutation in the MHC class I genes, the thymocytes will be able to rearrange their T-cell receptor genes and develop to the double positive stage. Thymocytes with a receptor that recognize MHC class I will not be positively selected, and this individual will have only mature CD4 T cells circulating in the periphery. The mutation in MHC class I should not alter B cell development.

Name: ___________________________ Class: _________________ Date: __________

Chapter 08 1. Which of the following contributes to the activation of naive T cells? a. neutrophils b. B cells c. macrophages d. dendritic cells e. basophils

2. Macrophages exhibit all of the following characteristics except a. they trap and degrade pathogens in secondary lymphoid organs. b. they deliver co-stimulatory signals to naive T cells needed for T-cell priming. c. they migrate from sites of infection to nearby secondary lymphoid organs. d. they remove and degrade apoptotic lymphocytes from secondary lymphoid tissues. e. they reside in both the cortex and medulla of lymph nodes.

3. Which of the following describes an activated dendritic cell upon arriving in a lymph node? a. located in follicles and medulla of the lymph node b. associated mainly with antigen uptake and processing c. bears highly elaborated finger-like processes called dendrites d. expresses low levels of MHC class II molecules e. carries out apoptosis of lymphocytes.

4. Dendritic cells take up, process or present antigen by each of the following routes except a. receptor-mediated endocytosis of bacteria. b. macropinocytosis of bacteria or viruses. c. delivery of viral peptides from cytosol to endoplasmic reticulum during viral

infection. d. cross-presentation from endosomes to the MHC class I pathway. e. cross-presentation from the MHC class I pathway to the MHC class II pathway.

5. Activated T cells express __________, which binds to B7 with 20 times higher affinity than CD28 and results in __________ of T-cell activity and proliferation. a. high-affinity IL-2 receptor; stimulation b. CD40L; suppression c. VLA-4; stimulation d. CTLA4; suppression

6. Which of the following is associated with immature dendritic cells in the skin before their activation? a. Toll-like receptors b. CTLA4 c. CCR7 d. DC-SIGN e. ICAM-3

7. All of the following are correctly matched EXCEPT a. TH1: T-bet. b. Treg: FoxP3. c. IL-12: dendritic cells. d. TH17: RORγT. e. TH2: Bcl6.

8. Naive lymphocytes homing to lymphoid tissue use __________ to bind to CD34 and GlyCAM-1 on high endothelial venules. a. L-selectin b. CD2 (LFA-2) c. ICAM-1

d. CCL21 e. CD28

9. The co-stimulatory molecule __________ on professional antigen-presenting cells binds __________ on the surface of naive T cells. a. DC-SIGN; ICAM-3 b. B7; CD28 c. ICAM-1; LFA-1 d. MHC class II; T-cell receptor e. MHC class II; CD4

10.An adhesion molecule called __________ is expressed exclusively on activated dendritic cells and binds to __________ on naive T cells in the T-cell areas of secondary lymphoid tissue. a. DC-SIGN; ICAM-3 b. CD2; LFA-3 c. MHC class II; T-cell receptor d. L-selectin; GlyCAM-1 e. ICAM-1; LFA-1

11.The area of contact between membranes of a T cell and an antigen-presenting cell where a clustering of protein–protein interactions occur is called a(n) a. immunoreceptor tyrosine-based activation motif (ITAM). b. polarization. c. cross-presentation center. d. granuloma. e. immunological synapse.

12.All of the following are included in the central supramolecular activation complex (c-SMAC) EXCEPT a. CD4 or CD8. b. ICAM-1. c. CD28.

d. T-cell receptor. e. PKC-θ.

13.Talin is best described as a a. protein tyrosine kinase. b. transcriptional activator. c. cytoskeletal protein. d. pro-inflammatory cytokine. e. cytokine receptor that associates with Janus kinases (JAKs).

14.The primary effect of inositol trisphosphate (IP3) during T-cell activation is to a. cause an increase in cytosolic calcium concentration. b. activate phospholipase C-γ. c. activate a MAP kinase cascade. d. activate ZAP-70. e. produce naive T cells.

15.Which of the following is NOT a transcription factor, a component of a transcription factor, or an activator of transcription? a. Fos b. AP-1 c. NFκB d. NFAT e. JAKs

16.The enzyme that generates diacylglycerol (DAG) and inositol trisphosphate (IP3) from phosphatidylinositol bisphosphate (PIP2) is a. protein kinase C-θ (PKC-θ). b. calcineurin. c. phospholipase C-γ (PLC-γ). d. protein tyrosine kinase ZAP-70. e. protein tyrosine kinase Lck.

17.All of the following statements regarding interleukin-2 (IL-2) or its receptor are true EXCEPT a. the low-affinity IL-2 receptor is a membrane-bound heterodimer composed of α and β chains. b. IL-2 production increases approximately 100-fold if a co-stimulatory signal is delivered. c. T-cell proliferation occurs upon binding of IL-2 to the high-affinity IL-2 receptor. d. the high-affinity IL-2 receptor is assembled after T-cell activation. e. Rapamycin is an immunosuppressive drug that inhibits signaling of IL-2 through the IL-2 receptor.

18.If a non-professional antigen-presenting cell that lacks co-stimulatory molecules presents peptide: MHC complexes to a T cell specific for that peptide, then a. the T cell delivers a signal to the non-professional antigen-presenting cell to activate the expression of co-stimulatory molecules. b. the T cell begins to express the α chain of the IL-2 receptor. c. the T cell differentiates into a TH1 cell. d. T-cell tolerance occurs as a result of anergy. e. the T cell is more heavily reliant on signals transmitted through CD4 or CD8 in order to become activated.

19.Which of the following statements regarding leprosy is FALSE? a. It is caused by the bacterium Mycobacterium leprae. b. Disease progression is influenced depending on whether the immune response is polarized toward either a TH1 or TH2 response. c. The tuberculoid form of leprosy is associated with localized inflammation and granuloma formation. d. In lepromatous leprosy, the patient makes a TH2 response that clears the mycobacteria from the body. e. The less severe form of leprosy presents with high levels of IL-2 and IFN-γ produced by responding T cells.

20.Which of the following statements is FALSE regarding CD8 T cells? a. CD8 T cells have only one effector function, which is cytotoxicity. b. Compared with naive CD4 T cells, naive CD8 T cells have more stringent requirements for co-stimulatory activity. c. Effector CD8 cells require co-stimulation to kill their target cells. d. The most potent antigen-presenting cell for naive CD8 T cells is the dendritic cell.

21.An important way in which effector T cells differ from naive T cells is that a. the cell-surface level of LFA-1 is lower on effector T cells. b. L-selectin is upregulated during differentiation of effector T cells. c. cellular proliferation occurs after effector T cells leave the secondary lymphoid tissues. d. the provision of co-stimulatory signals is not required to induce a response by effector T cells. e. effector T cells do not recirculate between lymph, blood, and secondary lymphoid tissues.

22.All of the following indicate correct intermolecular associations EXCEPT a. Janus kinases (JAKs): serglycin. b. L-selectin: GlyCAM-1. c. VLA-4: VCAM-1. d. JAKs: signal transducers and activators of transcription (STATs). e. CD40: CD40 ligand.

23.During cytokine signaling, __________ translocate(s) to the nucleus and direct(s) the upregulation of gene expression. a. perforin b. STATs c. CD40 ligand d. TGF-β e. CXCL2

24.Which of the following cytokines is secreted by both CD8 T cells and TH1 cells? a. IL-4 b. IL-5 c. IFN-γ d. TNF-α e. IL-13

25.Which of the following cytokines is NOT secreted by TH2 cells? a. IL-4 b. IL-5 c. IL-10 d. TGF-β e. lymphotoxin (LT)

26.In a person with lepromatous leprosy, the lesions would contain mRNA for a. lymphotoxin (LT). b. IL-2. c. IL-5. d. IFN-γ. e. granulysin.

27.The release of lytic granules from cytotoxic T cells is aimed specifically at infected target cells while preserving the integrity of neighboring, uninfected cells. This is best explained by the observation that a. only target cells bearing appropriate peptide:MHC class I complexes are susceptible to necrosis. b. redistribution of lytic granules in the T cell delivers them to confined areas on the target cell in contact with the T cell. c. regulatory T cells deliver survival signals to uninfected neighboring cells that renders them resistant to cytotoxins. d. the amount of cytotoxins in a given cytotoxic T cell is so limited that only the cell closest to the T cell will succumb to the effects of perforin and granzyme.

e. uninfected cells are highly resistant to the effects of cytotoxins.

28.All of these statements refer to regulatory T cells EXCEPT a. they produce anti-inflammatory cytokines. b. they express elevated levels of CD25. c. they express FoxP3. d. they enhance the production of new effector T cells. e. they suppress the function of existing T cells.

29.Identify the MISMATCHED pair. a. TFH cells: Bcl6 b. TH1: GATA3 c. TH1 cells: IFN-\gamma d. TH2: IL-4 e. Treg: TGF-\beta

30.Which of the following is incorrect regarding sphingosine 1-phosphate (S1P) and its receptor? a. It is a lipid that has chemotactic activity. b. S1P gradients are established in lymph nodes with lowest concentrations in T-cell areas. c. CD69 upregulates S1P receptor expression on the surface of naive T cells. d. S1P is synthesized by all cells.

31.Which of the following is produced by CD8 T cells? a. IL-10 b. TGF-β c. IFN-γ d. IL-4 e. IL-17

32.Which of the following is NOT produced by T follicular helper (TFH) cells? a. CD4 b. IL-4 c. IFN-γ d. TNF-α e. IL-21

33.Which of the following is NOT produced by TH17 cells? a. ICOS (inducible T-cell co-stimulator) b. IL-17 c. CD4 d. IL-21 e. STAT3

34.Which of the following is a feature of regulatory T cells (Treg)? a. Treg express CD8 and control effector cells by inducing apoptosis. b. Treg express high levels of CD25 (IL-2 receptor α chain) and secrete proinflammatory cytokines such as IFN-γ. c. Physical association between Treg and their target cells is not required for Treg function. d. By interacting with dendritic cells in secondary lymphoid tissue, Treg prevent the interaction and activation of naive T cells. e. Treg express the transcription factor GATA3.

35.T cells failing to encounter specific antigen leave lymph nodes via the a. germinal center. b. bloodstream. c. high endothelial venules. d. afferent lymph. e. efferent lymph.

36.Clonal expansion and differentiation of naive T cells to effector T cells depends on the activation of the transcription factor(s) __________ through a ZAP-70mediated signal transduction pathway. a. AP-1, NFkB, and NFAT b. IL-2, NFkB, and NFAT c. NFκB, Ras, and DAG d. GATA3, STAT3, and T-bet e. Foxp3

37.Fos, a component of the transcription factor AP-1, is activated during T-cell signaling by a process involving a GTP-binding protein called a. inositol trisphosphate. b. Ras. c. protein kinase C-θ. d. Lck. e. ZAP-70.

38.__________ is a second messenger in the T-cell signaling pathway leading to the activation of NFAT. a. diacylglycerol (DAG) b. NFκB c. inositol trisphosphate d. Fos e. Ras

39.Which of the following is a protein tyrosine kinase involved in T-cell activation culminating in T-cell proliferation and differentiation? a. AP-1 b. ZAP-70 c. NFκB d. NFAT e. calcineurin

40.Binding of __________ to __________ induces T-cell proliferation and differentiation of activated T cells. a. CD4; MHC class II b. CD28; B7 c. LFA-1; ICAM-1 d. IL-2; the high-affinity IL-2 receptor e. IL-2; the low-affinity IL-2 receptor.

41.Expression of IFN-γ is induced in a CD4 TH1 cell under the direction of the transcription factor a. T-bet. b. FoxP3. c. AP-1. d. GATA-3. e. NFAT.

42.IL-4 is induced in a CD4 TH2 cell under the direction of the transcription factor a. T-bet. b. FoxP3. c. AP-1. d. GATA-3. e. NFAT.

43.Tuberculoid leprosy is characterized by a __________-type response in which patients __________. a. TH2; usually survive b. TH2; eventually die c. TH1; usually survive d. TH1; eventually die e. Treg; eventually die

44.Many cytokine receptors are associated with cytoplasmic protein kinases called __________, which become activated when the cytokine receptors bind to their respective cytokines. a. ZAP-70 b. STATs c. Lck d. ITAMS e. JAKs

45.Signal transducers and activators of transcription (STATs) are __________ that are phosphorylated by __________. a. transcription factors; JAKs b. protein kinases; other STATs c. cytokine receptors; JAKs d. cytokines; cytokine receptors e. transcription factors; Lck

46.The process by which cytotoxic T cells kill their targets involves a. inducing the target cell to undergo necrosis. b. inducing apoptosis (programmed cell death) in the cytotoxic T cell. c. DNA fragmentation in lengths of multiples of 200 base pairs in the target cell. d. shedding of membrane-bound vesicles and swelling of the target cell. e. release of nucleases by the cytotoxic T cell.

47.Which of the following characteristics permits activated CD8 T cells to destroy any cell type harboring viable and replicating pathogens such as viruses? a. The pathogen is located in extracellular spaces. b. CD8 T cells enable macrophages to kill intracellular pathogens. c. Cross-presentation of intracellular viral proteins to MHC class II molecules. d. MHC class II molecules are expressed ubiquitously by most nucleated cells. e. MHC class I molecules are expressed ubiquitously by most nucleated cells.

48.Parents who were distantly related to each other brought their 11-week-old infant, Kristen, to the emergency room after she had a seizure accompanied by a persistently high fever and running nose. Her liver and spleen were enlarged.

Laboratory tests revealed abnormally high levels of lymphocytes and of the cytokines IFNγ, TNF-α, and IL-6. The physician suspected a primary or congenital immunodeficiency. A frameshift mutation in the perforin gene PRF1 was found on both chromosomes. Kristen was diagnosed with the rare, potentially life-threatening disease known as familial hemophagocytic lymphohistiocytosis (FHL). Kristen was given immunosuppressive therapy followed by a matched unrelated hematopoietic stem cell transplant. Two years later Kristen is a healthy toddler. Which of the following would NOT be likely features of FHL? a. impaired cytotoxic activity of CD8 T cells b. inhibition of transcriptional activators required for IL-2 synthesis c. inability to kill virus-infected cells d. persistent activation of CD8 T cells causing secretion of large amounts of IFN-γ e. IFN-γ activation of macrophages, which in turn drives the production of IL6, TNF-α, and other pro-inflammatory molecules

49.T cell anergy is a. the opposite of self-tolerance. b. due to T cells encountering their antigen on B7-expressing cells. c. observed in cells secreting IL-2. d. prevented by the addition of adjuvants to vaccines. e. reversible by exposing a T cell to a mature dendritic cell.

50.Select the correct statement concerning TH17 cells in the figure.

a. The cytokines that induce TH17 differentiation include IL-6 and TNF-alpha (labeled “a”). b. The transcription factor RORgammaT turns on expression of the IL-17 gene (labeled “b”). c. An activated TH17 cell secretes IL-17, IL-4, and IL-23 (labeled “c”). d. TH17 cells function to activate naive B cells (labeled “d”).

51.T cell differentiation a. is determined by the type of peptide presented by the MHC class I or class II molecules. b. that results in a TH1 response requires the secretion of IL-12 by cytotoxic T cells. c. that occurs in response to multicellular parasites leads to the production of high levels of IgG antibodies. d. is not dependent on the expression of particular transcription factors. e. due to co-stimulation by ICOS results in the activation of B cells.

52.Select the correct statements concerning adhesion molecules expressed on T cells in the figure.

a. The ligand for LFA-1 (labeled “A”) is L-selectin. b. Effector T cells express VLA-4, but they do not express LFA-1. c. Naive T cells express both VLA-4 and LFA-1. d. The ligand for VLA-4 (labeled “B”) belongs to the integrin family. e. The ligand for VLA-4 (labeled “B”) allows effector T cells to enter infected tissues.

53.The T-cell receptor on the effector CD8 T cell shown in the figure below binds to antigen presented on the virally infected target cell. Select the statement that best describes the sequence of events following TCR binding.

a. The granule membranes will fuse with the plasma membrane followed by rearrangement of the MTOC, Golgi, and cytoskeleton. b. Granzymes are released, forming pores in the target cell membrane. c. The cytoskeleton reorganizes to align the MTOC, Golgi apparatus, and lytic granules with the synapse. d. Immediately after lysis of the target cell, the effector cytotoxic T cell undergoes apoptosis. e. The CD8 molecule binds to the peptide:MHC class II complex on the infected target cell.

54.Macrophage activation at the site of infection a. requires interferon-gamma produced by effector TH2 cells. b. results in the expression of CD40 on the macrophage surface. c. leads to decreased phagosome fusion with lysosomes. d. does not involve changes in gene expression. e. results in enhanced killing of intravesicular bacteria.

55.All of the statements concerning the interaction between the B cell and TFH cell

shown in this figure are correct EXCEPT

a. the B cell and the TFH cell recognize different epitopes of the same antigen. b. the peptide presented to the TFH cell was endocytosed following antigen binding to the B cell receptor. c. peptide is presented to the TFH cell by MHC class II. d. linked recognition refers to the interaction between CD40 and CD40L. e. the naive B cell and TFH cell form a cognate pair, and the B cell is activated.

56.An infant has autoreactive T cells that have been activated in response to selfantigens present in the gut, skin, and endocrine glands. Without treatment the child will likely die by 2 years of age. This condition could be caused by a. the presence of anergic CD4 T cells. b. the lack of functional FoxP3 transcription factor. c. the lack of functional T-bet transcription factor. d. the lack of B7 expression on dendritic cells. e. All of these answers are correct.

57.Select the correct statement concerning the JAK-STAT pathway. a. The JAK-STAT pathway is activated by phosphatases.

b. The STAT proteins must dimerize to enter the nucleus and initiate gene expression. c. The JAK-STAT pathway involves phosphorylation of the amino acid serine on target proteins. d. JAKs associate with the cytoplasmic tails of the T-cell receptor. e. The STAT proteins interact with the JAK kinases in the cell prior to cytokine binding.

58.Cells are taken from four individuals infected with a multicellular parasite. A Northern blot analysis of cytokine mRNA is carried out on their antigen-specific CD4 T cells. Select the most accurate statement from the figure shown.

a. Their antigen-specific T cells would produce mRNA that most closely matches blot A. b. Their antigen-specific T cells would produce mRNA that most closely

matches blot B. c. Their antigen-specific T cells would produce mRNA in a pattern that does not match blot A or B. d. The pattern of cytokine mRNA produced by activated CD4 T cells is not determined by the nature of the pathogen.

59.Cells are taken from four individuals infected with a viral pathogen. A Northern blot analysis of cytokine mRNA is carried out on their antigen-specific CD4 T cells. Select the most accurate statement from the figure shown.

a. Their antigen-specific T cells would produce mRNA that most closely matches blot A. b. Their antigen-specific T cells would produce mRNA that most closely matches blot B. c. Their antigen-specific T cells would produce mRNA in a pattern that does not match blot A or B.

d. The pattern of cytokine mRNA produced by activated CD4 T cells is not determined by the nature of the pathogen.

60.Naive T cells a. are activated by dendritic cells in the medulla of the lymph node. b. leave the lymph node via high endothelial vessels. c. are activated by mature dendritic cells that present antigen and express costimulatory molecules. d. leave the lymph node to proliferate in the blood after their activation by dendritic cells. e. All of these answers are correct.

61.All of the following statements are accurate about T cell co-receptors EXCEPT a. they participate in one signal required for activation of naive T cells. b. they bind to the MHC molecule expressed on the dendritic cell. c. their cytoplasmic tails associate with a protein kinase. d. they are involved in the activation events leading to the synthesis of IL-2. e. they are located in the immunological synapse p-SMAC.

62.When effector CD4 T cells respond to antigen, a. they can become polarized, which means they circulate only to one type of secondary lymphoid tissue. b. a TH2 response will lead to effective immunity against bacteria hidden inside macrophages. c. the choice to differentiate to a TH1 or TH2 cell is driven by the production of cytotoxins. d. they may differentiate into TH1 cells, which corresponds to cell-mediated immunity. e. they may differentiate into TH2 cells that secrete TGF-beta.

63.ZAP70 is a protein that a. is activated after DAG activates PKC-theta. b. binds to phosphorylated ITAMs.

c. functions as a phosphatase to phosphorylate target proteins. d. is active in CD4 T cells, but not in CD8 T cells. e. leads to an increase in the intracellular calcium concentration, but that cannot activate PLC-gamma.

64.Match the cell type with its description. a. mature dendritic cells b. TH17 cells c. TH2 cells d. TH1 cells e. TFH cells 1. __________ produces cytokines that activate 2. __________ facilitate antibody production and isotype switching 3. __________ express the T-bet transcription factor 4. __________ possess elaborate finger-like processes that interact with T cells 5. __________ involved in neutrophil recruitment to infected tissues

65.Match the molecule with its ligand. a. B7 b. CD2 c. L-selectin d. ICAM-1 e. CCR7 f. ICAM-3 1. __________ sialyl-LewisX carbohydrate of CD34 and GlyCAM-1 2. __________ CCL21 and CCL19 3. __________ LFA-3 4. __________ CD28 5. __________ LFA-1 6. __________ DC-SIGN

66.Match the term with its description. a. immunoreceptor tyrosine-based activation motifs (ITAMs)

b. signal transducer and activator of transcription (STAT) c. immunological synapse d. VLA-4 e. CD40 1. __________ when phosphorylated, it translocates as a dimer to the nucleus and facilitates expression of target genes 2. __________ facilitates binding of effector T cells to activated endothelium 3. __________ on cytoplasmic tails of CD3 proteins used for transmitting activation signals 4. __________ a receptor on macrophages that facilitates killing of intravesicular bacteria 5. __________ region of contact containing adhesion molecules and other cell-surface receptor-ligand pairs between a lymphocyte and its target cell

67.At which anatomical sites do naive T cells encounter antigen?

68.In which sites specifically would a pathogen or its antigens end up, and how would they be transported to these sites if they (i) entered the body through a small wound in the skin, or (ii) got into the bloodstream?

69.How do naive T cells arrive at the lymph nodes?

70.Do all T cells leave the secondary lymphoid tissue after priming, and if so, how?

71.Identify three types of professional antigen-presenting cell.

72.Compare the location of dendritic cells and macrophages in the lymph node.

73.Which cell-surface glycoprotein distinguishes professional antigen-presenting cells from other cells and is involved in the co-stimulation of T cells?

74.Explain what happens when the T-cell receptor binds peptide:MHC in the absence of B7.

75.What cytotoxins do cytotoxic T cells produce?

76.Why are dendritic cells so important in adaptive immune responses? Explain what they do.

77.Explain what feature of B cells makes them useful as professional antigenpresenting cells in an immune response.

78.Unlike innate immune responses, which can begin within hours of the onset of an infection, adaptive immune responses involving T cells usually take several days.

What accounts for this delay between the initiation of an infection and the engagement of an adaptive immune response?

79.Which selectins, mucin-like vascular addressins, and integrins have a role in the circulation of T cells between the blood and lymph nodes?

80.Describe in chronological order how T cells migrate across lymph node high endothelial venules (HEVs) from the blood using chemokines and adhesion molecules.

81.Explain the functional differences between immature and mature dendritic cells.

82.Discuss why immature and mature dendritic cells have distinct functions.

83.Why are Toll-like receptors (TLRs) important for adaptive immune responses?

84.What receptors does B7 bind to on the T cell, and what signal does it deliver in each case?

85.Virus-infected cells attacked and killed by effector cytotoxic T cells are often surrounded by healthy tissue, which is spared from destruction. Explain the mechanism that ensures that cytotoxic T cells kill only the virus-infected cells (the target cells).

86.What are the roles of the following molecules in the signal transduction pathway leading from the T-cell receptor: (i) the CD3 complex; (ii) protein tyrosine kinase Lck; (iii) CD45; (iv) ZAP-70; (v) the ζ chain; (vi) inositol trisphosphate (IP3); (vii) calcineurin?

87.Describe two distinct mechanisms by which naive CD8 T cells can be activated.

88.The etiological agent responsible for leprosy is Mycobacterium leprae, which survives and replicates within the vesicular system of macrophages. Explain the difference between tuberculoid leprosy and lepromatous leprosy in the context of T-cell differentiation and effector function.

Answer Key Chapter 08 1. Answer:

D

2. Answer:

C

3. Answer:

C

4. Answer:

E

5. Answer:

D

6. Answer:

A

7. Answer:

E

8. Answer:

A

9. Answer:

B

10.Answer:

A

11.Answer:

E

12.Answer:

B

13.Answer:

C

14.Answer:

A

15.Answer:

E

16.Answer:

C

17.Answer:

A

18.Answer:

D

19.Answer:

D

20.Answer:

C

21.Answer:

D

22.Answer:

A

23.Answer:

B

24.Answer:

C

25.Answer:

E

26.Answer:

C

27.Answer:

B

28.Answer:

D

29.Answer:

B

30.Answer:

C

31.Answer:

C

32.Answer:

D

33.Answer:

A

34.Answer:

D

35.Answer:

E

36.Answer:

A

37.Answer:

B

38.Answer:

C

39.Answer:

B

40.Answer:

D

41.Answer:

A

42.Answer:

D

43.Answer:

C

44.Answer:

E

45.Answer:

A

46.Answer:

C

47.Answer:

E

48.Answer:

B

49.Answer:

D

50.Answer:

B

51.Answer:

B

52.Answer:

E

53.Answer:

C

54.Answer:

E

55.Answer:

D

56.Answer:

B

57.Answer:

B

58.Answer:

B

59.Answer:

A

60.Answer:

C

61.Answer:

E

62.Answer:

D

63.Answer:

B

64.Answer:

1. C

2. E 3. D 4. A 5. B 65.Answer:

1. C 2. E 3. B 4. A 5. D 6. F

66.Answer:

1. B 2. D 3. A 4. E 5. C

67.Answer:

Naive T cells encounter antigen, and start the primary immune response, in a secondary lymphoid tissue (for example lymph nodes, spleen, Peyer’s patches, tonsils).

68.Answer:

(i) Lymph nodes. The pathogen, and dendritic cells that have ingested the pathogen, are carried to the nearest lymph node in the afferent lymph. (ii) Spleen. Pathogens circulating in the blood enter the spleen directly from the blood vessels that feed it.

69.Answer:

Naive T cells are delivered to all secondary lymphoid organs from the blood. They can also pass from one lymph node to another via a lymphatic vessel.

70.Answer:

After differentiation, CD8 effector cells and CD4 TH1, TH2, TH17, and regulatory T cells exit from the lymphoid tissue (via efferent lymph, which delivers them eventually into the blood) in search of infected tissues. Antigen-activated CD4 TFH cells remain in the lymphoid tissue where they provide help to

antigen-specific B cells.

71.Answer:

The three types of professional antigen-presenting cells are dendritic cells, macrophages, and B cells.

72.Answer:

Dendritic cells are found in the outermost part of the cortex in the T-cell-rich areas; macrophages are distributed throughout the cortex and medulla.

73.Answer:

Expression of B7, a co-stimulator molecule, distinguishes professional antigen-presenting cells from other cells.

74.Answer:

If they engage antigen in the absence of B7 expression and, hence, co-stimulation, T cells will become irreversibly nonresponsive (anergic) instead of activated. This is one mechanism by which T-cell tolerance may be achieved.

75.Answer:

The cytotoxins include perforin, granzymes, serglycin, and granulysin, molecules that induce apoptosis (programmed cell death) of the target cell.

76.Answer:

Dendritic cells engulf, process and then transport antigens to a nearby secondary lymphoid tissue, such as lymph nodes, where they then encounter antigen-specific T cells, which then differentiate into effector T cells. Effector T cells are then able to leave the secondary lymphoid tissue and travel to the site of infection and perform their particular effector response to eradicate the infection.

77.Answer:

B cells are armed with cell-surface immunoglobulin that binds with a very high degree of specificity to intact pathogen moieties. Once bound, the immunoglobulin:native antigen complex is internalized by receptor-mediated endocytosis, and the pathogen is degraded within endocytic vesicles. Pathogenderived peptides from this degraded material bind to MHC class II molecules within the endocytic vesicles and are subsequently presented on the cell surface to CD4 T cells.

78.Answer:

First, antigen needs to be transported to a nearby secondary lymphoid tissue, processed, and presented by antigenpresenting cells to naive CD8 or CD4 T cells for T-cell priming.

Second, the number of T cells specific for a given pathogen will be only around 1 in 10,000 to 1 in 100,000 (10–4 to 10–6) of the circulating T-cell repertoire; thus it can take some time before the relevant T cells circulating through the secondary lymphoid tissues reach the tissue containing the antigen that will activate them. Finally, it takes several days for an activated T cell to proliferate and differentiate into a large clone of fully

functional effector T cells.

79.Answer:

T cells (and B cells) express L-selectin, which binds to sulfated carbohydrates of mucin-like vascular addressins in HEVs. Two types of mucin-like vascular addressin are involved: GlyCAM-1 and CD34 expressed on lymph-node HEVs. Activated LFA-1 is an integrin that binds to ICAM-1 on the endothelial cell.

80.Answer:

Chemokines such as CCL19 and CCL21 are secreted by dendritic cells and stromal cells and bind to the surface of high endothelial cells. Interactions between L-selectin and vascular addressins cause the naive T cell to slow down and attach.

Chemokines activate LFA-1, which binds with high affinity to an intercellular adhesion molecule, ICAM-1, expressed on the endothelium. Finally, the T cell squeezes between the endothelial cells in a process called extravasation, and hence gains entry into the lymph node.

81.Answer:

Immature dendritic cells are very effective in the process of antigen capture, uptake, and processing. They have specialized pathways of antigen processing for extracellular antigens that can present these antigens on both MHC class I and class II molecules. They do not express co-stimulatory molecules. Immature dendritic cells migrate to nearby lymphoid tissue after antigen ingestion. Upon arrival in the lymphoid tissue, they differentiate into mature dendritic cells.

These mature dendritic cells are now non-phagocytic and express the co-stimulatory molecule B7.

82.Answer:

Immature dendritic cells need to be phagocytic because they are located in sites susceptible to infection. Expression of B7 in non-lymphoid tissue is not required because this is not where T cells circulate and sample peptide:MHC complexes.

Once outside the infected tissue, mature dendritic cells no longer need to phagocytose material. They do, however, need to express B7 molecules, because without co-stimulation, T cells do not receive the necessary activation signal for differentiation into effector T cells.

83.Answer:

Stimulation of TLRs on dendritic cells by pathogen components induces the expression of chemokine receptor CCR7 on the dendritic cell. This enables dendritic cells laden with pathogen antigens to migrate from the site of infection to the nearest draining lymph node in response to chemokines produced by the lymph node. Stimulation of TLRs and other receptors on dendritic cells and macrophages also induces the expression of B7 co-stimulatory molecules, which makes these cells into professional antigen-presenting cells that are able to

activate naive T cells, and increases expression of MHC class I and II. 84.Answer:

When B7 binds to CD28, the B7 receptor expressed earliest on T cells, an activating signal is delivered, and T cells undergo clonal expansion and differentiation. This interaction requires that the T-cell receptor and co-receptor are engaged specifically with a peptide:MHC molecule complex. The second B7 receptor, CTLA4, binds B7 with about 20-fold higher affinity than does CD28. An inhibitory signal is delivered to the T cell when B7 on the professional antigen-presenting cell binds to CTLA4. This mechanism serves to regulate T-cell proliferation and to suppress T-cell activation after an immune response.

85.Answer:

Cytotoxic T cells focus their killing machinery on target cells through the formation of a synapse. The cytoskeleton and the cytoplasmic vesicles containing lytic granules are oriented toward the area on the target cell where peptide:MHC class I complexes are engaging T-cell receptors. In the T cell, the microtubule-organizing center, Golgi apparatus, and lytic granules, which contain cytotoxins, align toward the target cells. The lytic granules then fuse with the cell membrane, releasing their contents into the small gap between the T cell and the target cell, resulting in the deposition of cytotoxins on the surface of the target cell. The cytotoxic T cell is not killed in this process and will continue to make cytotoxins for release onto other target cells, thereby killing numerous target cells in a localized area in succession.

86.Answer:

(i) The CD3 subunits γ, δ, and ε associated with the antigenbinding T-cell receptor help transmit the signal from the T-cell receptor–peptide–MHC interaction at the cell surface into the interior of the cell through immunoreceptor tyrosine-based activation motifs (ITAMs) present on their cytoplasmic tails.

These are phosphorylated by associated protein tyrosine kinases, such as Lck, when the antigen receptor is activated, and in turn activate further molecules of the signaling pathway. (ii) Lck associates with the tails of the CD4 and CD8 coreceptors. When these participate in binding to peptide: MHC complexes, Lck is activated and phosphorylates ZAP-70, a cytoplasmic protein tyrosine kinase. (iii) When ZAP-70 (iv) is phosphorylated, it binds to the phosphorylated ITAMs of (v) the ζ chain, which initiates the signal transduction cascade by activating phospholipase C-γ (PLC-γ). (vi) IP3, which is produced by the action of PLC-γ on membrane inositol phospholipids, causes an increase in intracellular Ca2+ levels, which leads to the activation of the protein calcineurin. (vii) Calcineurin activates the transcription factor NFAT by

removing an inhibitory phosphate group. Activated NFAT enters the nucleus, and together with the transcription factors NFκB and AP-1, will initiate the transcription of genes that lead to T-cell proliferation and differentiation.

87.Answer:

(i) Virus-infected dendritic cells provide adequate costimulation (via B7) and can activate CD8 T cells directly without the involvement of CD4 T cells. CD8 T cells receive signal 1 (MHC:T-cell receptor) and signal 2 (B7:CD28), synthesize IL-2 and the high-affinity IL-2 receptor, and proliferate and differentiate into cytotoxic T cells. (ii) In some cases, virus-infected dendritic cells cannot on their own fully activate naive CD8 T cells, but the CD8 T cell begins to express IL-2 receptors. With the provision of help from effector CD4 T cells in the form of IL-2 secretion, these CD8 T cells are fully activated. For this to occur, simultaneous interaction with both the naive CD8 T cell and the effector CD4 T cell must occur.

88.Answer:

Effective immune responses against intravesicular pathogens living in macrophages are mediated by TH1 cells rather than TH2 cells. In tuberculoid leprosy, the predominant effector T cells produced after infection are TH1 cells. These are effective in containing the infection, although they do not clear it completely. The disease is chronic and progresses slowly, and the damage to skin and peripheral nerves is caused mainly by the inflammatory responses initiated by activated macrophages. In lepromatous leprosy, in contrast, the predominant T cells produced are TH2 cells. Humoral immunity is induced, which results in the production of antibodies that are ineffective against intracellular bacteria. As a result, M. leprae replicates unchecked, causing severe tissue destruction and eventually the death of the patient.

Many factors influence the differentiation of CD4 T cells into TH1 or TH2 cells, including the cytokines produced by the antigen-presenting cells and leukocytes involved in the innate immune responses, the antigen concentration and peptide: MHC density, T-cell receptor affinity for peptide: MHC, and the cytokines produced by TH1 and TH2 cells themselves. If TH1 cells dominate an immune response, a cell-mediated immune response is favored. If TH2 cells dominate, a humoral immune response is favored.

Name: ___________________________ Class: _________________ Date: __________

Chapter 09 1. Which of the following is NOT a function of antibodies? a. They neutralize pathogens by masking their surface. b. They act as molecular adaptors that bridge together pathogen and phagocyte surfaces. c. They exert toxic effects directly. d. They act as opsonins that mediate phagocytosis. e. They activate complement fixation.

2. To mount an effective antibody response that results in the synthesis of highaffinity antibodies, which of the following must occur? a. recognition of thymus-independent (TI) antigens b. isotype switching c. increased expression of TLR9 by B cells d. affinity maturation e. decreased expression of CD40 by B cells

3. Immunoreceptor tyrosine-based activation motifs (ITAMs) are located on a. the cytoplasmic tails of IgM. b. tyrosine kinases Blk, Fyn, and Lyn. c. the cytoplasmic tails of Igα and Igβ. d. breakdown products of C3b deposited on pathogen surfaces. e. thymus-independent antigens.

4. Identify the mismatched association. a. Syk: Igβ cytoplasmic tails b. tyrosine kinase Lyn: CD81 c. B-cell co-receptor: CD21/CD19/CD81 d. C3b fragments: C3d and iC3b

e. tyrosine kinase Lyn: CD19

5. A primary focus of clonal expansion is best described as a. the location in the B-cell zone where conjugate pairs of B and T cells undergo cellular proliferation, isotype switching, and somatic hypermutation. b. the location in the medullary cords where conjugate pairs of B cells and T cells undergo cellular proliferation and IgM is secreted. c. the dark zone of the germinal center where centroblasts divide and pack closely together. d. the initial wave of B-cell proliferation induced by T-independent antigens.

6. A primary focus forms after a circulating naive B cell forms a conjugate pair with __________ in the __________ of a lymph node. a. TH1 cell; B-cell zone b. cytotoxic T cell; T-cell zone c. follicular dendritic cell; germinal center d. TFH; medullary cords e. CD40 ligand; T-cell zone

7. Which of the following does not bind to a molecule found on the surface of an activated B cell? a. MHC class II b. T-cell receptor c. BAFF d. IL-6 e. CD40 ligand

8. B cells migrating directly from a primary focus to the medullary cords in a lymph node after activation with a T-dependent antigen differentiate into plasma cells that secrete predominantly a. IgD. b. IgE.

c. sIgA. d. IgG. e. IgM.

9. Lymphoblasts upregulate a transcription factor called __________ when they terminally differentiate into plasma cells. a. NFκB b. Bcl-xL c. B-lymphocyte induced maturation protein 1 (BLIMP-1) d. CD40 e. ICAM-1

10.The primary focus of B-cell expansion forms in the __________, whereas a secondary focus of B-cell expansion creates the __________. a. T-cell area; medullary cords b. medullary cords; T-cell area c. T-cell area; B-cell area d. medullary cords; germinal center e. light zone; dark zone

11.Proliferating centroblasts use the DNA-modifying enzyme activation-induced cytidine deaminase for a. cell proliferation. b. differentiating into plasma cells. c. apoptosis. d. upregulation of CD40. e. isotype switching.

12.What is the fate of centrocytes in which somatic hypermutation has resulted in high-affinity receptors for antigen? a. They die by apoptosis. b. They reduce expression of Bcl-xL.

c. They stop processing and presenting antigen to TFH cells. d. CD40 on the centrocyte engages with CD40 ligand on TFH cells. e. They undergo phagocytosis by tingible body macrophages.

13.The main function of Bcl-xL is to __________ in the centrocyte. a. provide death signals b. induce somatic hypermutation c. upregulate the expression of activation-induced cytidine deaminase d. prevent apoptosis e. induce isotype switching

14.Engulfment of apoptotic centrocytes is facilitated by __________ in germinal centers. a. follicular dendritic cells b. antibodies c. tingible body macrophages d. antigen-specific B cells e. antigen-specific TFH cells

15.Which of the following is an accurate description of how centroblasts differ from centrocytes? a. Centroblasts cease their expression of cell-surface immunoglobulins. b. Centroblasts divide more slowly than centrocytes. c. Centroblasts express CD40 but centrocytes do not. d. Centrocytes, but not centroblasts, initiate the process of isotype switching. e. Centroblasts participate in affinity maturation.

16.If a centrocyte does not interact with antigen and engage CD40 shortly after its formation, then a.

17.__________ is a mechanism that drives the preferential selection of immunoglobulins with the highest affinity for antigen. a. Anergy b. Isotype-switching c. Affinity maturation d. Antibody-dependent cell-mediated cytotoxicity e. Transcytosis

18.__________ in the switch regions positioned 5′ to each heavy-chain C gene is induced by __________. a. Somatic hyper mutation; TI antigens b. Chromatin remodeling; B-cell co-receptor signaling c. Recombination; survival signals received from follicular dendritic cells d. Transcription; helper T-cell cytokines e. Gene repression; apoptotic signals received from tingible body macrophages

19.Plasma cells and memory B cells differentiate most immediately from a. centrocytes. b. centroblasts. c. B-1 cells. d. IgG-secreting B cells.

20.Which of the following statements is true regarding the complement component C4B? a. Deficiency of C4B is associated with systemic lupus erythematosus (SLE). b. C4B has similar properties to those of C4A. c. The thioester bond of C4B is preferentially acted upon by amino groups of macromolecules. d. C4B is encoded in the class II region of the MHC. e. The gene for C4B is duplicated or deleted in some individuals.

21.Which of the following is able to bind to C1q?

a. planar conformation of IgM b. nonplanar conformation of IgM c. IgE d. C3 e. complement receptor CR1

22.IgM is particularly efficient at fixing complement because it a. is a much larger antibody than the other isotypes. b. has an extra CH domain. c. is made first in an immune response and therefore has first access to C1q. d. has five binding sites for C1q. e. has easy access to extravascular areas.

23.C3 convertase of the classical pathway is __________, whereas C3 convertase of the alternative pathway is __________. a. C1a; C3bBb b. C4bC2a; C3bBb c. C3bCR1; C3bBb d. C4bC2a; C3bCR1 e. C1a; C3bCR1.

24.Which of the following statements are true regarding C4? a. There are two forms of C4 encoded by separate genes residing in the class II region of the MHC. b. Evolution of the different forms of C4 probably occurred as a result of gene duplication and diversification. c. Because there are two forms of C4, C4 deficiency is the least common human immunodeficiency. d. C4A and C4B have identical properties. e. C4A deficiency is associated with a lowered resistance to infection.

25.Complexes of IgG bound to soluble multivalent antigens can activate the classical pathway of complement, resulting in the deposition of __________ on the

complex, targeting the complex for endocytic uptake by cells bearing __________. a. C4b; CR2 and Fc receptors b. C3b; CR2 and Toll-like receptors c. C5-9; CR1 and Fc receptors d. C3b; CR1 and Fc receptors e. C2a; CR2 and Toll-like receptors

26.A distinguishing feature of FcγRIIB1 compared with FcγRIIA is a. its ability to activate cells and induce endocytosis. b. the existence of ITIMs in its cytoplasmic tails. c. its inability to bind to IgG1. d. its expression on NK cells.

27.For IgG2 to be effective at stimulating uptake of IgG2-coated bacteria, a. an individual must express allotype H131 of FcγRIIA. b. an individual must express allotype R131 of FcγRIIA. c. the ITIMs of FcγRIIB2 must be non-functional. d. complement must be fixed on the surface of the bacterium.

28.Naive B cells search for specific antigen displayed by follicular dendritic cells in primary follicles. Naive T cells, however, search for specific antigen presented by a. myeloid dendritic cells. b. subcapsular sinus macrophages. c. medullary sinus macrophages. d. centrocytes. e. tingible body macrophages.

29.Which of the following does NOT occur following mast cell activation? a. The release of mediators that decrease the permeability of blood vessels. b. The release of serotonin. c. The release of histamine.

d. Degranulation of prepackaged granules. e. The expulsion of parasites due to muscular contractions. .

30.Some types of B-cell tumor have been treated with rituximab, an anti-CD20 monoclonal antibody, which exerts its effect through a mechanism known as __________ involving the participation of NK cells. a. degranulation b. neutralization c. opsonization d. antibody-dependent cell-mediated cytoxicity e. receptor-mediated endocytosis

31.Which of the following is a characteristic of follicular dendritic cells in the primary follicles of secondary lymphoid tissues? a. They are bone marrow derived hematopoietic cells. b. They provide a stable depository of intact antigens able to bind to B-cell receptors. c. They secrete high levels of type I interferons. d. They internalize immune complexes through CR2 receptor cross-linking. e. They produce cytokines that induce B cells to proliferate and become centroblasts.

32.The B-cell co-receptor is composed of a. Igα; Igβ; CD19. b. Igα; Igβ; Lyn tyrosine kinase. c. CR2 (CD21); CD19; CD81. d. CD14; CD19; CD81. e. CD40; MHC class II; CED19.

33.C3d and iC3b are breakdown products of __________, which binds to __________ of the B-cell co-receptor. a. C3a; CR2 b. C3b; CR2

c. C3c; CD81 d. C3c; CD19 e. C3b; CD19.

34.When bound to CR1, C3b is cleaved by __________, generating pathogenassociated B-cell co-receptor ligands. a. factor I b. CR2 c. C3d d. CD19 e. Lyn

35.The Igα-associated tyrosine kinase __________ phosphorylates the cytoplasmic tail of CD19, which mediates signal transduction in activated B cells. a. CD81 b. Blk c. Fyn d. Lyn e. Syk

36.A B cell’s sensitivity to antigen can be increased 1000 to 10,000-fold by a. simultaneously ligating the B-cell receptor and co-receptor. b. simultaneously ligating the B-cell receptor and Toll-like receptor. c. ligating the B-cell co-receptor and phosphorylating Ig-α ITAMs. d. increasing levels of Syk proteins in the vicinity of co-receptor ligation. e. ligating cytokine receptors on the B-cell surface.

37.The process that drives an increase in antibody affinity for antigen is known as a. apoptosis. b. affinity maturation. c. antibody-dependent cell-mediated cytotoxicity. d. opsonization.

e. clonal expansion.

38.FcRn has which of the following characteristics? a. It binds to monomeric IgA in acidified endocytic vesicles. b. It transports IgG out of the blood into tissue across the endothelium. c. It is similar in structure to an MHC class II molecule. d. It protects IgA from degradation by plasma proteases. e. It is degraded as part of the transport process.

39.The process involving receptor-mediated transport of macromolecules from one side of a cell to the other is called a. phagocytosis. b. exocytosis. c. transcytosis. d. signal transduction. e. opsonization.

40.Of the following, which group of children is the most vulnerable to infection? a. babies born at term b. babies born prematurely c. infants of 3–6 months d. infants receiving first vaccination e. babies receiving formula and not breast milk

41.__________ occurs as a result of influenza virus binding to oligosaccharide components on erythrocyte surfaces causing them to clump together. a. Passive immunization b. Opsonization c. Hemagglutination d. Neutralization e. Complement activation

42.Which of the following is NOT matched correctly? a. protein F; fibronectin b. neutralization; IgE c. breast milk; IgA d. influenza; hemagglutinin e. mucosal epithelium; IgA.

43.Bacteria use __________ to attach to the surface of cells during colonization. a. hemagglutinins b. toxins c. breakdown products d. anti-inflammatory molecules e. adhesins

44.Denatured toxin molecules called __________ are used to vaccinate individuals to stimulate the production of __________. a. toxoids; neutralizing IgG antibodies b. adhesins; neutralizing antibodies c. toxoids; passive immunity d. adhesins; complement proteins e. toxoids; C-reactive protein

45.Which of the following is NOT a characteristic of systemic lupus erythematosus? a. It is an autoimmune disease. b. It is associated with a deficiency of C4A. c. Increased levels of immune complexes are detected in the blood. d. CR1 receptor levels are decreased. e. Immune complexes are deposited on the kidney glomeruli, which can lead to kidney complications.

46.Which of the following antibodies does not activate the classical pathway of complement?

a. IgM b. IgG1 c. IgG3 d. IgE

47.The γ chain of the FcγRI receptor is closely related to the __________, which contains __________. a. FcRn; MHC class I-like structure b. ζ chain of the T-cell receptor complex; ITAM motifs c. γ chain of the FcγRIII receptor; ITIM motifs d. γ chain of the FcαRI receptor; ITIM motifs e. γ chain of the FcεRI receptor; ITIM motifs

48.Of the Fc receptors for IgG, which one is similar to FcεRI in its ability to bind antibody in the absence of antigen but does not transduce an activating signal until antigen cross-linking occurs? a. FcγRI b. FcγRIIA c. FcγRIIB2 d. FcγRIIB1 e. FcγRIII

49.Which of the following individuals would be most susceptible to fulminant meningococcal disease or septic shock when infected with Neisseria meningitidis? a. homozygous for allotype H131 of IgG2 b. heterozygous for allotype H131 of IgG2 c. homozygous for allotype R131 of IgG2 d. heterozygous for allotype R131 of IgG2

50.Antibody-dependent cell-mediated cytotoxicity (ADCC) is carried out by __________ after cross-linking of IgG1 or IgG3 antibodies on __________receptors.

a. NK cells; FcγRI b. neutrophils; FcγRI c. NK cells; FcγRIII d. macrophages; FcγRIIB2 e. mast cells; FcεRI

51.The symptoms of allergy are induced after cross-linking of IgE antibody on FcεRI receptors found on the surface of__________. a. B cells b. dendritic cells c. macrophages d. mast cells e. neutrophils

52.The FcαRI receptor binds to __________:antigen complexes and facilitates the phagocytosis of opsonized antigens. a. dimeric IgA b. IgM c. IgE d. IgG e. monomeric IgA

53.Isotype switching a. occurs in the subcapsular sinus. b. depends on the dendritic cell that activates a TFH cell. c. requires CD40 ligand expression on the activated B cell. d. relies on the affinity of the B-cell receptor for antigen. e. requires cytokines but not cognate interaction between the B cell and the TFH cell.

54.Transcription of the switch regions upstream of a heavy-chain C gene a. leads to chromatin accessibility.

b. leads to expression of activation-induced cytidine deaminase. c. occurs in the light zone of the germinal center. d. does not require an activated TFH cell. e. is involved in isotype switching to IgG but not to IgE.

55.All of the following are true about the cytokine IL-21 EXCEPT a. it is involved in the differentiation of centrocytes into plasma cells. b. it is involved in the differentiation of centrocytes into memory cells. c. it is secreted by TFH cells. d. it is required for isotype switching to IgG and IgA. e. it is required for ICOS stimulation.

56.The lack of expression of __________ leads to hyper-IgM syndrome. a. IL-4 b. CD40 c. CD40 ligand d. Complement C4 e. CD19

57.For gene expression changes to occur in a B cell that binds to antigen, which of the following must occur? a. Syk phosphorylates the cytoplasmic tail of surface IgM. b. CD3 is phosphorylated by a kinase. c. ITIMS in Igα and Igβ are phosphorylated. d. Syk binds phosphorylated ITAMs and is activated. e. Lyn is activated, allowing Igα and Igβ to associate with the B-cell receptor.

58.The process of two or more B-cell receptors binding to antigen on the microbial surface is called a. cross-linking. b. signal transduction. c. phosphorylation.

d. co-receptor activation. e. complementarity.

59.Individuals with DiGeorge syndrome a. have hyper-IgM syndrome. b. produce antibodies to thymus-independent antigens. c. produce antibodies to thymus-dependent and thymus-independent antigens. d. lack normal numbers of B cells. e. produce antibodies that have undergone isotype switching and affinity maturation.

60.CD5-expressing B-1 cells a. undergo affinity maturation following antigen activation. b. recognize repetitive carbohydrate or protein bacterial epitopes. c. do not express the B-cell co-receptor. d. present pathogen-derived peptides on MHC class II and receive help from T follicular helper cells. e. are missing in individuals with systemic lupus erythematosus (SLE).

61.Select the INCORRECT statement concerning centrocyte differentiation in the figure shown.

a. The cell labeled “1” secretes IL-21. b. The molecule labeled “2” helps induce B-cell proliferation. c. This centrocyte can differentiate into a plasma cell, but not a memory cell. d. The molecule labeled “3” is expressed on activated, but not resting, CD4 T cells. e. For the centrocyte to survive, the B-cell receptor must have high affinity for the antigen.

62.Select the INCORRECT statement concerning the prevention of bacterial toxin binding to the surface of a human cell. a. It may be due to passive or active immunity. b. It occurs naturally, but is not an approach used by current human vaccines. c. It is due to neutralizing antibodies. d. It may be carried out by high-affinity IgG or IgA depending on location. e. It requires T follicular helper cells.

63.Select the event which does NOT occur between antigen activation of a naive B cell and the release of cytokines by the T cell in the figure shown.

a. CCR7 expression is induced in the B cell. b. CD40L expression is increased on the T cell. c. NFkB is activated in the B cell. d. BLIMP-1 expression is increased in the B cell. e. The cytoskeleton of the TFH cell reorients.

64.Select the correct response concerning the transport of antibodies from the blood to the extracellular spaces of tissues in the figure below.

a. The endothelial cell shown in panel “A” is undergoing pinocytosis. b. The pH of the endocytic vesicles shown in panels “A” and “B” is the same. c. The isotype of the antibody labeled “D” is IgA. d. The molecule labeled “E” is the poly-Ig receptor. e. The antibody shown in panel “C” has been modified during its transit.

65.Select the correct statement concerning a Streptococcal pyogenes bacterial infection at a mucosal surface in the figure shown.

a. The secretory component found on the antibodies shown in the left panel was produced by cleavage of the FcRn. b. Plasma cells secreting antigen-specific antibodies entered the airway via transcytosis. c. The antibodies bound to antigen in the left panel are protective, as they will activate the classical pathway of complement. d. The antibodies shown in the left panel are protective, as they will activate antibody dependent cell-mediated cytotoxicity. e. Immediate neutralization of the protein F epitope following infection requires a memory response.

66.Select the correct statement concerning NK cells in an unvaccinated individual infected for the first time with influenza and expressing viral glycoproteins on the target cell in the figure shown.

a. NK cells express the activating FcγRIIA that recognizes antigen-bound antibody. b. This NK cell will be able to kill virus-infected target cells via antibodies by the second day of infection. c. The isotype of the antigen-bound antibody recognized by the NK cell must be IgG. d. This is the only mechanism by which NK cells can kill virus-infected cells. e. NK cells express multiple types of activating and inhibitory Fc receptors on their cell surface.

67.Females who are homozygous for mutations leading to nonfunctional activationinduced cytidine deaminase (AID) are a. quite common in the population. b. able to fight infections via ADCC. c. able to produce antibodies that cross the placenta. d. able to produce high-affinity antigen-specific antibodies in response to the influenza vaccine. e. likely to develop a type of hyper-IgM syndrome.

68.Match each lettered term to its description. a. CCP modules b. ICAM-1 c. CR2 d. BLIMP-1 e. CD40 ligand f. Bcl-xL g. germinal center reaction h. CD69 1. __________ expressed in centrocytes and prevents apoptosis 2. __________ associated with the development of swollen lymph nodes 3. __________ required to induce production of activation-induced cytidine deaminase 4. __________ expressed on B cells, follicular dendritic cells, and subcapsular sinus macrophages and binds C3d 5. __________ CR2-associated and needed for binding to C3d-tagged antigens 6. __________ controls lymphoblast differentiation by acting as a transcription factor 7. __________ binds to LFA-1 on T cells and fortifies cognate B–T interactions 8. __________ early indicator of B-cell activation and repressor of SIP receptor expression

69.Match the cell type found in the lymph node in column A with its description. a. centroblast b. tingible body macrophage c. naive B cell d. follicular dendritic cells (FDC) e. memory B cell 1. __________ not bone marrow-derived hematopoietic cells 2. __________ engulf apoptotic centrocytes 3. __________ undergo somatic hypermutation 4. __________ make up the mantle zone 5. __________ differentiate under the influence of an IL-4-secreting TFH cell

70.Describe the way in which follicular dendritic cells (FDCs) are similar to subcapsular sinus macrophages.

71.What is the main effector function of IgM antibody?

72.What are two similarities between the activation of mast cells and NK cells via FcεRI and FcγRIII, respectively? Be specific.

73.Name the isotypes of the antibodies involved in (i) placental transfer and (ii) transfer into breast milk, and explain why these antibodies are important.

74.Explain whether it is possible for a pregnant mother who has an autoimmune disease to transfer autoreactive antibodies to the developing fetus.

75.How does IgE induce the forcible ejection of parasites and toxic substances from the respiratory and gastrointestinal tracts?

76.Explain why expression of CD40 ligand by TFH cells is important in the boundary area of primary follicles in secondary lymphoid tissue as it relates to the targeted delivery of secreted cytokines to the B-cell surface.

77.Why is IgM efficient at (i) preventing blood-borne infections and (ii) fixing complement?

78.Explain why IgM is less efficient than other antibody classes in inducing phagocytosis of immune complexes.

79.Explain how the poly-Ig receptor transports dimeric IgA antibodies across cellular barriers, and specify the type of cell barrier involved.

80.Explain three differences between the activation of mast cells and NK cells via FcεRI and FcγRIII, respectively. Be specific.

81.Describe the course of events that results in the swollen lymph nodes characteristic of many infections. Use the following terms in your answer: B lymphoblasts, centroblasts, centrocytes, follicular dendritic cells, germinal center, primary focus, primary follicle, somatic hypermutation, boundary region, and tingible body macrophages.

82.Explain the molecular origin of the secretory component and its significance after the release of dimeric IgA from the apical face of the gut epithelium.

83.From an immunological viewpoint, why would it be inadvisable for a mother who has recently given birth to move with her newborn to a foreign country where there are endemic diseases not prevalent in her homeland?

Answer Key Chapter 09 1. Answer:

C

2. Answer:

D

3. Answer:

C

4. Answer:

B

5. Answer:

B

6. Answer:

D

7. Answer:

A

8. Answer:

E

9. Answer:

C

10.Answer:

D

11.Answer:

E

12.Answer:

D

13.Answer:

D

14.Answer:

C

15.Answer:

A

16.Answer:

B

17.Answer:

C

18.Answer:

D

19.Answer:

A

20.Answer:

E

21.Answer:

B

22.Answer:

D

23.Answer:

B

24.Answer:

B

25.Answer:

D

26.Answer:

B

27.Answer:

A

28.Answer:

A

29.Answer:

A

30.Answer:

D

31.Answer:

B

32.Answer:

C

33.Answer:

B

34.Answer:

A

35.Answer:

D

36.Answer:

A

37.Answer:

B

38.Answer:

B

39.Answer:

C

40.Answer:

B

41.Answer:

C

42.Answer:

B

43.Answer:

E

44.Answer:

A

45.Answer:

D

46.Answer:

D

47.Answer:

B

48.Answer:

A

49.Answer:

C

50.Answer:

C

51.Answer:

D

52.Answer:

E

53.Answer:

B

54.Answer:

A

55.Answer:

E

56.Answer:

C

57.Answer:

D

58.Answer:

A

59.Answer:

B

60.Answer:

C

61.Answer:

C

62.Answer:

B

63.Answer:

A

64.Answer:

A

65.Answer:

E

66.Answer:

C

67.Answer:

E

68.Answer:

1. F 2. G 3. E 4. C 5. A 6. D 7. B 8. H

69.Answer:

1. D 2. B 3. A 4. C 5. E

70.Answer:

FDCs and subcapsular macrophages use their CR1 and CR2 receptors not for the purpose of receptor-mediated endocytosis, but rather to bind to antigens tagged with C3d or C3b and to hold them at the cell surface for extended periods of time. Tethering the antigen in this manner facilitates screening by naive B cells as they travel through secondary lymphoid tissues.

71.Answer:

The main effector function of IgM is complement activation; it can also neutralize pathogens and toxins.

72.Answer:

Similarities: (1) Activation of both mast cells and NK cells occurs only when their Fc receptors are bound to antigen:antibody complexes. (2) When cross-linking occurs, both mast cells and NK cells release the contents of granules through exocytosis, which involves the fusion of vesicles containing preformed proteins with the cell membrane.

73.Answer:

(i) IgG antibodies transported transplacentally provide passive protection in the bloodstream and extracellular spaces of tissues until the baby can begin making its own antibodies, after which time maternal IgG levels decrease. (ii) IgA is transferred into the infant’s gastrointestinal tract in breast milk and protects the gastrointestinal epithelia from colonization and invasion by ingested microorganisms.

74.Answer:

It is possible for autoreactive antibodies to be transferred passively to a fetus via the placenta if the isotype is IgG. Any reaction will persist only for as long as the antibodies are present.

75.Answer:

When IgE binds to antigen, leading to cross-linking of FcεRI on mast cells in connective and mucosal tissues, the mast cells rapidly release chemicals that activate smooth muscle to contract. Muscle activity leads to vomiting and diarrhea in the gastrointestinal tract, and sneezing and coughing in the respiratory tract, helping to expel the offending pathogen or toxic material.

76.Answer:

CD40 ligand on TFH cells binds to CD40 on B cells, signaling B cells to activate NFκB. NFκB is a transcription factor that upregulates ICAM-1 expression on B cells, which binds to LFA-1 on the TFH cell. As a result, cognate interactions between the B cell and TFH cell are strengthened, and a synapse at the point of contact facilitates the reorientation of the T-cell cytoskeleton and secretory apparatus of the Golgi.

This ensures that T-cell cytokines are released onto a localized area of the B-cell surface.

77.Answer:

(i) IgM is the first antibody to be produced by plasma cells during a primary antibody response and is secreted as a pentamer that circulates in the blood. Because of the large size of pentameric IgM, it does not penetrate effectively into infected tissues and is most effective against pathogens in the bloodstream. (ii) In the classical pathway of complement activation, at least two Fc regions are needed to bind C1, the first complement component in the pathway. A single pentameric molecule of IgM can thus initiate complement activation. In contrast, two IgG antibodies in close proximity to each other are needed to bind C1.

78.Answer:

Phagocytic cells carry both complement receptors and Fc receptors for IgG (FcγR) and IgA (FcαR), but there are no Fc receptors for IgM. Thus, immune complexes of IgM and antigen alone cannot be taken up by macrophages through Fc receptor-mediated endocytosis. An IgM: antigen: C3b

complex can be phagocytosed by a macrophage after binding to complement receptors, but this is not as efficient as having both complement receptors and Fc receptors cooperating in inducing phagocytosis.

79.Answer:

Dimeric IgA is made in mucosa-associated lymphoid tissue (MALT) and is transported across the barrier of the mucosal epithelium. First, dimeric IgA binds to the poly-Ig receptor on the basolateral surface of an epithelial cell, followed by uptake through receptor-mediated endocytosis into an endocytic vesicle. On reaching the opposite face of the cell, the apical surface, the vesicle fuses with the membrane.

Here the poly-Ig receptor is cleaved proteolytically between the membrane-anchoring and the IgA-binding regions, thus releasing IgA into the mucous layer on the surface of the epithelium. Dimeric IgA remains attached to a small piece of the poly-Ig receptor, called the secretory component, which holds the IgA at the epithelial surface through interactions with molecules in the mucus. The rest of the poly-Ig receptor is degraded and serves no further purpose.

80.Answer:

There are at least five correct options: (1) Mast cells bind IgE, whereas NK cells bind IgG. (2) Exocytosis of granules from mast cells occurs at random around the cell membrane.

Exocytosis of granules from NK cells is highly polarized, focusing only on the target cell to minimize damage to neighboring cells. (3) IgE binds to FcεRI with high affinity in the absence of antigen; mast cells become activated when antigen becomes available and binds to the receptor-bound IgE. NK cells bind IgG with low affinity, and bind IgG effectively only when it is already bound to multivalent antigen. (4) Activated mast cells release inflammatory mediators (histamine and serotonin) that affect other cells, for example endothelium, causing increased vascular permeability and vasodilation. Activated NK cells release apoptosis-inducing compounds (perforin and granzyme/fragmentin) in a directed manner that kill target cells directly. (5) Antibody-dependent cell-mediated cytotoxicity (ADCC) carried out by NK cells could be induced in newborn infants by maternal IgG acquired transplacentally.

IgE cannot be transferred across the placenta, and so newborn babies cannot activate mast cells via maternal IgE.

81.Answer:

B lymphoblasts that have bound specific antigen and encountered their cognate T cells in the boundary regions between primary follicles and the T-cell area of a lymph node are activated and start to proliferate, forming a primary focus. The B cells move from the primary foci into primary follicles, which are primarily

B-cell areas, where they become centroblasts—large, metabolically active, dividing cells. As centroblasts accumulate and proliferate, the primary follicle enlarges and changes morphologically into a germinal center. Centroblasts undergo somatic hypermutation while dividing in the germinal center, producing centrocytes with mutated surface immunoglobulin.

Only cells with mutated surface immunoglobulin that can take up antigen efficiently through receptormediated endocytosis and present it to helper T cells (TFH) will be selected to differentiate into plasma cells or memory cells. Antigen will be encountered at the surface of follicular dendritic cells as an immune complex. If B cells do not encounter their specific antigen, they will undergo apoptosis and then be ingested and cleared by tingible body macrophages.

This process takes around 7 days after an infection begins, and the increase in cell numbers due to lymphocyte proliferation accounts for the swollen lymph nodes.

82.Answer:

During transcytosis the poly-Ig receptor is cleaved by a protease, leaving a small piece of the original receptor, called the secretory component, still bound to the J chain via disulfide bonds. Once dimeric IgA is released at the apical face, the carbohydrate moieties of the secretory component anchor the antibody to mucins of the mucus, enabling the antibodies to bind subsequently to microbes in the mucus and inhibit the ability of microbes to bind to and invade the mucosal epithelium of the gut. Instead, the microbe is expelled from the body via mucosal secretions in the feces.

83.Answer:

Newborn infants are afforded passive immunity to the pathogens in their environment through IgG and dimeric IgA. IgG is transferred transplacentally, and dimeric IgA is acquired through breast milk. If an endemic infection develops in the newborn infant, the IgG antibodies in the infant’s bloodstream may not have the appropriate specificity for the foreign antigens because the mother would not have encountered these antigens previously in their homeland, and therefore the newborn infant would not have acquired them passively during fetal development. Furthermore, without maternal IgG, infants are particularly susceptible to infection for the first 6 months of their life, when their immune systems are unable to produce significant levels of IgG. In addition, infections that breach mucosal surfaces may be more likely to develop during this time because dimeric IgA against such a pathogen will not be formed in the breast milk until about a week after the mother has been exposed to the

same pathogen.

Name: ___________________________ Class: _________________ Date: __________

Chapter 10 1. Because the mucosae __________, this tissue is predisposed to infection. a. constitute thin, permeable barriers b. secrete a continuous layer of mucus c. produce enzymes and proteoglycans d. are associated with secretory IgA production e. are not connected to the lymphatics

2. Identify which of the following is NOT a property of secreted mucins. a. contain glycosylated cysteine residues b. constitute a viscous matrix stabilized by disulfide bonds c. bind to positively charged immune effector molecules d. encoded by seven genes in humans e. expressed in different mucosal tissues

3. Unlike secreted mucins, membrane mucins a. do not trap and kill nearby microorganisms. b. are not cross-linked by disulfide bonds. c. do not possess repetitive domains. d. are not glycosylated. e. are not large, extended glycoproteins.

4. Commensal microorganisms in the gastrointestinal tract facilitate all the following EXCEPT a. competition with pathogenic variants for nutrients and space. b. conversion of toxic substances to benign derivatives. c. degradation of plant fibers to make their nutrients available. d. peristalsis, which moves digested food through the intestine. e. synthesizing of essential metabolites.

5. The large population of microbes that contribute to the gut microbiota and have an important role in food processing are called a. lamina propria. b. Peyer’s patches. c. microfold cells. d. commensal microorganisms. e. opportunists.

6. All of the following are part of Waldeyer’s ring EXCEPT a. salivary glands. b. palatine tonsils. c. lingual tonsils. d. adenoids.

7. Which of the following pairs is INCORRECTLY matched? a. appendix: large intestine b. mesenteric lymph nodes: urogenital tract c. effector compartment: lamina propria d. adenoids: base of nose e. villi: small intestine

8. At which anatomical location are Peyer’s patches? a. stomach b. small intestine c. cecum d. large intestine e. Waldeyer’s ring

9. Laboratory animals reared in gnotobiotic conditions a. are fed probiotics to disrupt the composition of their microflora.

b. lack normal gut microbiota. c. develop appendicitis. d. have larger secondary lymphoid tissues than do control animals. e. have elevated levels of SIgA in the gut lumen.

10.__________ microorganisms are microbes that colonize mucosal surfaces but under normal circumstances do not cause disease. a. Opportunistic b. Commensal c. Parasitic d. Mesenteric e. Pathogenic

11.__________ make(s) up the membranes of connective tissue that help to anchor the gastrointestinal tract and hold it in place. a. The mesentery b. Peyer’s patches c. The lamina propria d. The subepithelial dome e. Waldeyer’s ring

12.Select the INCORRECT statement concerning Waldeyer’s ring. a. It protects the respiratory tract. b. It protects the gastrointestinal tract. c. It is important for the secretory IgA response. d. It is composed of an inductive and an effector compartment. e. It does not contain B cells.

13.Which of the following describes M cells in the gut? a. They derive their name from mucus cells. b. They deliver antigens and pathogens from the lymphoid tissue to the luminal side of the gut mucosa by transcytosis.

c. They are located in the dome area of a Peyer’s patch. d. They are protected from digestive enzymes by a thick glycocalyx and a layer of mucus. e. The M cells express MHC class II and present antigen to CD4 T cells.

14.Select the INCORRECT statement concerning the mucosal tissues of a healthy intestinal tract. a. The mucosal tissues always contain a large number of activated T effector cells. b. The mucosal tissues contain plasma cells secreting dimeric IgA. c. The mucosal tissues contain intraepithelial lymphocytes that express CD8. d. The mucosal tissues contain large numbers of resident neutrophils. e. The mucosal tissues are populated with both α:β and γ:δ effector T cells.

15.Which of the following migrates from non-mucosal tissue to draining lymph nodes to facilitate the induction of adaptive immune responses? a. dendritic cells b. macrophages c. NK cells d. neutrophils e. commensal microorganisms

16.__________ assists in the differentiation of blood-derived monocytes into intestinal macrophages. a. TGF-β b. B7 c. IL-12 d. CXCL8 e. CD14

17.All of the following are expressed by intestinal epithelial cells EXCEPT a. NOD receptors. b. TLRs.

c. FcαR. d. NLRP3. e. NFκB.

18.M cells, unlike dendritic cells, a. do not secrete digestive enzymes into the lumen of the gut. b. are not associated with Peyer’s patches. c. do not facilitate the transport of microbes from the gut lumen to the GALT. d. do not process and present their antigen to naive T cells.

19.The significance of MAdCAM-1 on the endothelium of blood vessels is that it binds to a. the integrin α4β7 on effector lymphocytes homing to mucosal tissues. b. B cells destined to become intraepithelial lymphocytes. c. dendritic cells and causes the upregulation of antigen processing and presentation. d. the chemokine CCL25, which is secreted by gut epithelia. e. intestinal helminths and mediates killing of these parasites.

20.In addition to M cells, __________ can capture pathogens directly from the lumen of the gut. a. intraepithelial lymphocytes b. plasma cells c. Paneth cells d. dendritic cells e. macrophages

21.Which of the following is NOT associated with the process by which effector B cells produce secretory IgA in breast milk? a. J chain b. MAdCAM-1 c. CCR7

d. poly-Ig receptor e. transcytosis

22.Bacteria located in the cytosol of epithelial cells of the gastrointestinal tract are detected by a. poly-Ig receptors. b. defensins. c. NLRP3. d. NOD proteins. e. TLR5.

23.Secretory IgA binds to pathogens in all the following locations EXCEPT the a. lamina propria. b. lumen of the gut. c. blood. d. Peyer’s patches.

24.What is the function of the TNF-family cytokine APRIL made by epithelial cells of the colon? a. elevates rate of M-cell proliferation b. degrades IgA1 c. mediates isotype switching from IgM to IgA2 d. binds to J chain of dimeric IgA e. upregulates MAdCAM-1 production

25.All of the following soluble factors enhance isotype switching from IgM to IgA in B cells EXCEPT a. retinoic acid. b. IL-9. c. TGF-β. d. IL-10. e. B-cell activating factor (BAFF).

26.Select the INCORRECT statement concerning the transport of antibody across mucosal epithelium. a. IgE can be transported by the poly-Ig receptor resulting in low levels of IgE in respiratory and digestive tract secretions. b. Both IgA1 and IgA2 can be transported by the poly-Ig receptor in the digestive tract. c. IgG is the predominant isotype found in secretions of the nose and lower respiratory tract. d. The J chain of IgM is required for its transport from the basal to the luminal side of the gut epithelium. e. FcRn is expressed on endothelial cells of small intestine blood vessels.

27.Which of the following is NOT an activity associated with secretory IgA and secretory IgM in mucosal secretions? a. toxin neutralization b. complement fixation c. binds to mucin through disulfide bonds d. restricts commensal microorganisms to gut lumen e. limits population size of commensal microorganisms

28.IgA proteases produced by Streptococcus pneumoniae mediate all the following effects except for a. separation of Fab and Fc regions. b. interference with Fc-mediated phagocytosis. c. enhanced adherence of Fab-coated bacteria to mucosal epithelium. d. preferential cleavage of IgA2 over IgA1.

29.__________ compensates for the absence of secretory IgA in selective IgA deficiency because it can be secreted by mucosal tissues using the same receptor needed for transcytosis. a. Monomeric IgA b. IgD

c. IgE d. IgG e. IgM

30.__________ is the vascular addressin found on endothelial cells of intestinal mucosa that binds to integrins of gut-homing effector lymphocytes. a. CCL25 b. C-cadherin c. NOD1 d. MAdCAM-1 e. CCR9

31.The dominant immunoglobulin synthesized at mucosal surfaces is a. IgA. b. IgD. c. IgE. d. IgG. e. IgM.

32.Which of the these does NOT occur following B-cell activation by antigen in the mucosa of the respiratory tract? a. Lactating mothers will provide antigen-specific natural IgA in breast milk. b. Secretory IgA will be synthesized in the lamina propria of all mucosae. c. The effector B cell will not enter the bloodstream, but instead will remain in the mucosa and differentiate into a plasma cell. d. The effector B cell will recirculate through all mucosal tissues, including respiratory and gastrointestinal mucosae. e. Dimeric IgA will be secreted into the lamina propria.

33.In which of the following tissues is IgA2 produced at approximately twice the level of IgA1? a. spleen b. mammary glands

c. large intestine d. gastric mucosa e. upper small intestine

34.Secretory IgA is best described as a. a non-inflammatory immunoglobulin that restricts the passage of antigens across mucosal surfaces. b. a complement-activating immunoglobulin that causes destruction of invasive microflora through the membrane-attack complex. c. an opsonizing antibody that facilitates uptake by M cells through Fc receptors d. an inflammatory immunoglobulin that stimulates the chemotaxis of neutrophils into mucosal surfaces. e. a monomeric IgA that neutralizes antigen effectively at mucosal surfaces.

35.Secretory IgA and __________ can bind to the poly-Ig receptor and be transported into the lumen of the gut or across other mucosal surfaces. a. IgG b. IgE c. IgD d. monomeric IgM e. pentameric IgM

36.The normal development of secondary lymphoid tissue in the gut depends on a. vitamin K. b. mucus. c. secretory IgA. d. defensins. e. commensal microorganisms.

37.Mucosal tissues can be found everywhere EXCEPT a. spleen. b. kidney.

c. pancreas. d. lactating mammary glands. e. lungs.

38.Select the correct statement concerning gut mucosal surfaces. a. The smaller surface area of the gut mucosae as compared to the skin helps limit pathogen exposure. b. The loose joining of mucosal tissue epithelial cells aids gas exchange and food absorption. c. Mucins allow the easy movement of pathogens, which ensures they can be recognized by B and T cells. d. Mucus may prevent commensal microbes from entering internal tissues. e. There is a low turnover of mucosal epithelial cells, which improves the ability of mucus to be protective.

39.Plasma cells and effector T cells of the gut-associated lymphoid tissue are found in the a. inductive compartment. b. lamina propria. c. mesenteric lymph nodes. d. adenoids. e. lumen or opening of the gut.

40.Monocytes arriving in the intestines differentiate into inflammation-anergic intestinal macrophages under the influence of a. NFkB. b. IL-12. c. transforming growth factor (TGF)-β. d. IL-6. e. IL-10.

41.Intestinal macrophages that differentiate in the lamina propria under normal conditions

a. are not able to activate NFkB. b. are not phagocytic. c. are not able to kill internalized pathogens. d. express the Fc receptor CD16. e. release IL-1 when activated.

42.Homing of effector T cells to the gut requires T-cell expression of __________ and __________, which allow cells to leave the blood and to interact with the gut epithelium, respectively. a. CCR7; CCL25 b. MAdCAM-1; E-cadherin c. MAdCAM-1; integrin α4β7 d. integrin α4β7; integrin αEβ7 e. integrin αEβ7; integrin α4β7

43.Select the statement that best describes a systemic immune response that occurs in a non-mucosal tissue. a. Inflammatory cytokines are produced sporadically and lead to damaged host tissues that must be repaired. b. Effector T and B cells are present in the tissue prior to infection with a pathogen. c. Macrophages kill ingested microbes without the activation of NF-kB. d. Epithelial cells continuously secrete transforming growth factor (TGF)-β. e. The systemic immune response is best described as being proactive rather than reactive.

44.Regulatory T cells __________ to limit inflammation. a. activate NFkB b. secrete IL-10 c. secrete IL-1 d. recruit neutrophils e. increase the number of CD4 TH17 cells

45.Select the INCORRECT statement concerning the immune response in either a mucosal or a non-mucosal tissue.

a. One cytokine shown being released in panel A is IL-1. b. Neutrophils recruited from the blood play a major role in controlling the infection in panel A. c. Activated effector B and T cells were present in panel B prior to the invasion of the pathogen. d. Complement plays a major role in controlling the infection in panel B. e. Dendritic cells may migrate to a draining lymph node in both panels A and B.

46.In the gut, __________ predominate in the epithelium and __________ in the lamina propria. a. B cells; plasma cells b. mast cells; neutrophils c. CD4 T cells; CD8 T cells d. CD8 T cells; CD4 T cells e. naive T cells; effector T cells

47.Select the INCORRECT statement concerning intraepithelial lymphocytes. a. They are relatively rare cells with about one intraepithelial lymphocyte for every 100 epithelial cells. b. They contain the same granules as cytotoxic CD8 T cells.

c. They may express either αβ or γδ T-cell receptors. d. Their T-cell receptors have a restricted range of antigen specificities. e. They express CCR9.

48.Food entering the healthy gut a. is not taken up by M cells, and thus it is ignored by the immune system and results in oral tolerance. b. leads to the presentation of protein antigen by CD103 dendritic cells and the activation of TH17 cells. c. generates FoxP3 antigen-specific T cells. d. contacts dendritic cells that do not migrate to the mesenteric lymph nodes, thus resulting in oral tolerance. e. is not bound by secretory IgA.

49.If a commensal microorganism breaches the epithelial barrier of the gut, which of the following does NOT occur? a. The mucosal immune system ignores the beneficial microorganism, resulting in tolerance. b. The mucosal immune system treats the invading microbe as a pathogen. c. Dendritic cells present peptides from the commensal microbe and activate naive CD4 T cells. d. B cells are activated and differentiate into plasma cells secreting antibodies specific for the commensal microbe. e. Commensal microbe antigen-specific secretory IgA is secreted by plasma cells in the lamina propria.

50.Poliovirus exploits __________ to establish an infection. a. dendritic cells b. goblet cells c. microvilli d. regulatory T cells e. M cells

51.Select the correct statement concerning intestinal epithelial cells.

a. Signals from the molecules labeled “A” result in activation of NFkB, but do not lead to the formation of the NLRP3 inflammasome. b. The molecule labeled “C” is bound to an inhibitor that is removed following signals generated by the molecule labeled “B”. c. The secreted molecules labeled “D” are NOD1 and NOD2 proteins. d. The cells labeled “E” are present at high levels in the mucosal tissue prior to the presence of the invading bacteria.

52.Select the INCORRECT statement concerning selective IgA deficiency. a. Chronic lung disease is more common in individuals with the deficiency than in unaffected individuals. b. The incidence of the disorder is roughly equal in human populations from around the world. c. Improvements in hygiene and vaccination offset the reduction in IgA infants receive due to shortened periods of breastfeeding, thus allowing individuals to survive infancy.

d. Affected individuals are more susceptible to protozoan parasites. e. Affected individuals may have inherited alleles that contribute to a reduction in the secretion of TGF-β.

53.Select the correct statement concerning the gut-associated lymphoid tissue.

a. The mucosal immune system allows beneficial commensal microbes to be present in the locations labeled “A” and “E”. b. The region labeled “A” lacks effector cells. c. The cells labeled “B” can initiate short-lived inflammatory responses. d. The cells in the region labeled “C” are called goblet cells and secrete mucus. e. Antigen-specific CD4 helper T cells cannot be activated in the domeshaped region below label “D” and must be activated in the mesenteric lymph node.

54.Dendritic cells bias isotype switching to IgA using all the following EXCEPT a. BAFF. b. APRIL. c. iNOS. d. CCL21. e. retinoic acid.

55.Features of some or all mucosal tissues include each of the following EXCEPT a. the slow regeneration of tissues to improve food absorption and gas exchange. b. communication between the body and the environment. c. sensory activities such as smell. d. the presence of a high percentage of the body’s lymphocytes. e. fragile, permeable barriers.

56.The number of commensal bacteria is greatest in the a. stomach. b. small intestine. c. colon (large intestine). d. Peyer’s patches. e. appendix.

57.Which of the following is NOT a feature of mice raised under “germ-free” conditions? a. smaller spleens b. reduced CD8 T-cell cytotoxicity c. impaired lymphocyte homing to sites of inflammation d. anatomical changes to the gut e. reduced secretory IgA and high levels of IgG and IgE in the blood

58.Antibodies delivered to the lumen of the gut a. are held in place by forming disulfide bonds with mucin. b. are held in place through interactions with FcRs. c. interact with the high concentration of complement components in the mucosal secretions leading to the generation of the classical C3 convertase. d. bind to pathogens but not to the beneficial commensal microbes. e. induce inflammation to recruit lymphocytes.

59.An individual lacking functional APRIL protein is a. more likely to have higher concentrations of IgA2 than IgA1 in mucosal tissues. b. more likely to have higher concentrations of IgA1 than IgA2 in mucosal tissues. c. more likely to have IgA that is resistant to proteolytic cleavage by pathogens such as Streptococcus pneumoniae. d. more likely to have fewer T regulatory cells than an unaffected individual. e. more likely to have pro-inflammatory gut macrophages than an unaffected individual.

60.One unique feature of the mucosal immune system of the gut that distinguishes it from a systemic immune response in the skin is a. the generation of plasma cells that isotype switch in response to signals from TFH cells. b. the movement of antigen-presenting dendritic cells from the site of infection to draining lymph nodes. c. the development of inflammation-anergic macrophages. d. the activation of CD8 cytotoxic T cells in response to viral infections. e. the presence of epithelial cells forming a barrier between the body and the environment.

61.Match the lettered term with its function in the numbered terms. a. M cells b. brush border c. FoxP3-positive T cells d. Paneth cells e. goblet cells 1. __________ mucus secretion 2. __________ secrete antimicrobial products in crypts 3. __________ portals for antigen transport 4. __________ suppress immune responses to food antigen 5. __________ microvilli on enterocytes for nutrient absorption

62.Identify two locations where secretory IgA can bind to antigens in mucosal tissue,

and for each give the fate of the antigen upon binding to secretory IgA.

63.Why do children who have had their tonsils or adenoids removed respond less effectively to the oral polio vaccine than children who still have these tissues?

64.What property of the mucosal immune system enables breast milk to contain antibodies against microorganisms encountered in the gut or other mucosal tissues? Explain your answer.

65.Explain why individuals who have selective IgA deficiency do not succumb to repeated infection through mucosal surfaces.

66.Explain how secondary lymphoid tissues of the mucosa are both similar to and different from secondary lymphoid tissues elsewhere in the body (the systemic immune system).

67.Describe two ways in which dendritic cells capture antigen from the intestine for presentation to T lymphocytes.

68.Describe the route that a Peyer’s patch–activated T lymphocyte follows, beginning with a naive T lymphocyte in a high endothelial venule and ending with an effector T lymphocyte in the lamina propria.

69.Identify ways in which intestinal macrophages are similar to and different from macrophages in non-mucosal tissues.

Answer Key Chapter 10 1. Answer:

A

2. Answer:

A

3. Answer:

B

4. Answer:

D

5. Answer:

D

6. Answer:

A

7. Answer:

B

8. Answer:

B

9. Answer:

B

10.Answer:

B

11.Answer:

A

12.Answer:

E

13.Answer:

C

14.Answer:

D

15.Answer:

A

16.Answer:

A

17.Answer:

C

18.Answer:

D

19.Answer:

A

20.Answer:

D

21.Answer:

C

22.Answer:

D

23.Answer:

C

24.Answer:

C

25.Answer:

B

26.Answer:

A

27.Answer:

B

28.Answer:

D

29.Answer:

E

30.Answer:

D

31.Answer:

A

32.Answer:

C

33.Answer:

C

34.Answer:

A

35.Answer:

E

36.Answer:

E

37.Answer:

A

38.Answer:

D

39.Answer:

B

40.Answer:

C

41.Answer:

A

42.Answer:

D

43.Answer:

A

44.Answer:

B

45.Answer:

D

46.Answer:

D

47.Answer:

A

48.Answer:

C

49.Answer:

A

50.Answer:

E

51.Answer:

B

52.Answer:

B

53.Answer:

C

54.Answer:

D

55.Answer:

A

56.Answer:

C

57.Answer:

E

58.Answer:

A

59.Answer:

B

60.Answer:

C

61.Answer:

1. E 2. D 3. A 4. C 5. B

62.Answer:

1) lamina propria; transcytosis to intestinal lumen 2) mucus layer; neutralization of antigen at mucosal surfaces

63.Answer:

Tonsils and adenoids are located in the oral cavity and are composed of extensive secondary lymphoid tissue making up Waldeyer’s ring. They are responsible for the production of secretory IgA specific for infectious material entering the gut and airways. The oral polio vaccine elicits the most effect protective immunity through the production of secretory IgA, including the secondary lymphoid tissues of Waldeyer’s ring.

64.Answer:

In nursing mothers, B cells activated in the gut or other mucosal tissue can home to the lactating mammary gland and secrete their dimeric IgA antibodies into the breast milk. This is due to a general property of the mucosal immune system in that lymphocytes activated in a mucosal tissue carry the integrin α4:β7 that binds to the vascular addressin MAdCAM-1, which is expressed on the walls of blood vessels serving different types of mucosal tissue. Thus, lymphocytes activated in one mucosal tissue can recirculate to another one as well as to the tissue in which they were activated.

65.Answer:

Individuals with selective IgA deficiency possess compensatory mechanisms for combating infections at mucosal surfaces, most notably by making increased levels of IgM, which can be secreted as a pentamer across mucosal epithelium. As infants, they will get IgA from breast milk if their mother is not IgA deficient.

66.Answer:

Mucosal secondary lymphoid tissues have the same general microanatomy and organization as those of secondary lymphoid tissues found at other anatomical locations, with distinct compartmentalization of B-cell and T-cell zones. Both mucosal and systemic secondary lymphoid tissues function as sites where naive lymphocytes are activated by antigen and adaptive immune responses are initiated. In the systemic immune system, adaptive immune responses are activated in secondary lymphoid tissues that are quite distinct from and often distant from the site of infection. In contrast, in the mucosal immune system, the adaptive immune response is initiated at secondary lymphoid tissues at the site of infection.

67.Answer:

i. M-cell-dependent capture relies on the transcytosis of microorganisms across the gut epithelium into pockets

containing dendritic cells. The dendritic cells then process and present antigens to T lymphocytes in either the T-cell areas of the Peyer’s patch or the mesenteric lymph node. ii. M-cell-independent capture occurs in the lamina propria as a result of dendritic cells extending cytoplasmic processes between intracellular enterocyte junctions. Antigen is taken up by these processes and processed, and the dendritic cell then presents antigens to T cells in gut-associated lymphoid tissue or mesenteric lymph nodes.

68.Answer:

The chemokines CCL21 and CCL19 synthesized in Peyer’s patches bind to CCR7 on naive T cells and recruit them into the lymphoid tissue across a high endothelial venule. The T cells bearing appropriate antigen-specific receptors are stimulated by dendritic cells and undergo proliferation and differentiation within the Peyer’s patches. Activated T cells then leave the Peyer’s patch and enter the lymph, and travel through mesenteric lymph nodes before arriving via the lymph at the thoracic duct and then enter the bloodstream. From the bloodstream, activated T cells home only to mucosaassociated lymphoid tissue because during their differentiation they cease to express CCR7 and Lselectin, which are otherwise required to enter systemic lymphoid tissues. Instead, they now express α4:β7, which binds to MAdCAM-1 on gut-associated endothelia and CCR9, the chemokine receptor for CCL25, which is synthesized in the lamina propria. They cross the vascular endothelium into the lamina propria (some subsequently entering the epithelium), where they secrete cytokines and mediate killing.

69.Answer:

Intestinal macrophages recognize, phagocytose, and kill microorganisms that have breached the epithelial surface, and eliminate cells dying by apoptosis just as macrophages from non-mucosal tissues do. However, intestinal macrophages do not create or sustain a state of inflammation as do non-mucosal tissue macrophages.

They do not produce inflammatory cytokines, induce a respiratory burst, express B7 co-stimulators, or secrete cytokines needed for naive T-cell activation. Intestinal macrophages also have a shorter life span than systemic macrophages.

Name: ___________________________ Class: _________________ Date: __________

Chapter 11 1. Memory T cells can persist in the absence of antigen. a. True b. False

2. The CD45RA isoform is associated with stronger signals in response to antigen. a. True b. False

3. T-cell survival is dependent on the cytokines IL-7. a. True b. False

4. Adhesion molecules are no longer required by memory T cells. a. True b. False

5. The Bacille Calmette–Guérin (BCG) vaccine is commonly used in the United States to provide protection against tuberculosis. a. True b. False

6. BCG is a heat-killed strain of bovine Mycobacterium tuberculosis. a. True b. False

7. Lipopolysaccharide-deficient Salmonella typhi is used to vaccinate against

typhoid fever. a. True b. False

8. Capsular polysaccharide vaccines are conjugated to proteins to induce highaffinity IgG antibodies. a. True b. False

9. A state of inflammation impairs effective immune responses to microbial products. a. True b. False

10.Which of the following statements is INCORRECT regarding memory B cells? a. Memory B cells are maintained for life. b. In secondary responses, the number of pathogen-specific B cells is increased compared to a primary response. c. The sensitivity of memory B cells is improved compared with naive B cells because affinity maturation has occurred. d. Memory B cells express high levels of FcγRIIB1. e. Memory B cells differentiate into plasma cells more rapidly than do naive B cells.

11.Which of the following does not characterize immunological memory? a. The host retains the capacity to mount a secondary immune response. b. The host retains the ability to respond to pathogen many years after primary exposure. c. Memory T cells are activated more quickly when exposed to pathogen. d. Memory B cells produce higher-affinity antibody than naive B cells. e. Memory T cells undergo somatic hypermutation.

12.What would be the outcome if a naive B cell were to bind to pathogen coated with

specific antibody made by an effector B cell in a primary immune response using FcγRIIB1, and simultaneously bind to the same pathogen using its B-cell receptor? a. a positive signal leading to the production of low-affinity IgM antibodies b. a positive signal leading to isotype switching and the production of IgG, IgA, or IgE antibodies c. a positive signal leading to somatic hypermutation and the production of high-affinity IgM antibodies d. a negative signal leading to inhibition of the production of low-affinity IgM antibodies e. a negative signal leading to apoptosis

13.Which of the following explains why the first baby born to a RhD– mother and a RhD+ father does not develop hemolytic disease of the newborn? a. Fetal erythrocytes do not cross the placenta and therefore do not stimulate an antibody response. b. The antibodies made by the RhD– mother during the first pregnancy are predominantly IgM and have low affinity for the Rhesus antigen. c. Maternal macrophages in the placenta bind to anti-Rhesus antibodies and prevent their transfer to the fetus. d. Hemolytic disease of the newborn is a T-cell-mediated disease and maternal T cells do not cross the placenta during pregnancy. e. The Rhesus antigen is not immunogenic and does not stimulate an antibody response.

14.By which process are fetal erythrocytes destroyed in hemolytic anemia of the newborn? a. lysis of erythrocytes by cytotoxic T cells b. lysis of erythrocytes by complement activation c. clearance of antibody-coated erythrocytes by macrophages in the fetal spleen d. lysis of erythrocytes by NK cells via antibody-dependent cell-mediated cytotoxicity e. cytotoxicity caused by major basic protein released from eosinophils

15.When a naive B cell binds to an IgG:antigen complex on its cell surface using FcγRIIB1, while simultaneously binding to the same antigen using membranebound IgM, a. the IgG:antigen complex is endocytosed. b. the B cell is induced to undergo apoptosis. c. the B cell will switch isotype to IgG. d. the B cell undergoes affinity maturation. e. the B cell secretes large amounts of IgM before becoming a memory B cell.

16.All of the following are true for highly mutable pathogens, such as influenza virus, EXCEPT a. they gradually escape from immunological memory. b. they interfere with the generation of a primary response against new epitopes in subsequent exposures c. they typically lead to the generation of an effective and long-lasting vaccine. d. they can generate memory B cells following an initial exposure.

17.Which of the following are not a component of immunological memory? a. effector B cells b. memory T cells c. memory B cells d. long-lived plasma cells

18.Long-lived plasma cells a. are derived from short-lived plasma cells. b. have higher affinity for antigen due to hypermutation and selection. c. are resident in the secondary lymphoid tissue. d. are metabolically inactive.

19.Unlike naive T lymphocytes, a. memory T lymphocytes obtain energy from glycolysis. b. memory T lymphocyte populations may include TH1 or TH2 T cells.

c. effector T cells do not undergo mitosis when stimulated by antigen. d. effector T cells do not express mTORc1. e. effector T cells undergo high rates of autophagy.

20.Select the statement that is correct concerning long-lived plasma cells and memory B cells. a. Both cell types lack surface immunoglobulin. b. Both cell types share a similar cellular morphology. c. Both cell types have undergone somatic hypermutation. d. Only long-lived plasma cells have undergone isotype switching.

21.During a secondary immune response, high-affinity IgG antibodies are produced.

Which of the following best explains why low-affinity IgM antibodies are not made? a. Naive pathogen-specific B cells are suppressed by negative signaling through FcγRIIB1. b. Naive pathogen-specific B cells isotype switch and hypermutate much more quickly during secondary immune responses. c. Memory B cells outnumber naive B cells. d. Low-affinity IgM antibodies are made only when antigen concentration is exceedingly high.

22.Which of the following cell-surface molecules cannot distinguish naive from memory B cells? a. IgM b. CD45RA c. IgG d. isotype-switched antibody e. FcγRIIB1

23.__________ accounts for the production of different isoforms of the CD45 protein observed in naive, effector, and memory T cells. a. Isotype switching

b. Affinity maturation c. Alternative splicing d. Somatic hypermutation e. Recirculation to peripheral tissues

24.Memory B cells differ from memory T cells in which of the following ways? a. They suppress naive antigen-specific lymphocytes during secondary immune responses. b. They are more readily activated than naive cells. c. They secrete their antigen receptors throughout their life span. d. They generate long-lived clones of memory cells during the primary immune response.

25.RhoGAM is administered to pregnant RhD– women to a. stimulate only anti-RhD IgM antibody. b. cause selective removal of anti-RhD memory B cells from the maternal circulation. c. inhibit a primary immune response to RhD antigen. d. block transcytosis of IgG to fetal circulation by interfering with FcRn function. e. prevent maternal IgG from crossing the placenta into the fetal circulation.

26.Identify the mismatched pair. a. variolation: smallpox b. Salk vaccine: killed poliovirus c. vaccinia virus: cowpox d. rotavirus: segmented DNA virus e. Sabin vaccine: TVOP

27.Recombinant DNA technology has been especially useful in the production of __________ that are used in subunit vaccines. a. viral proteins b. viral nucleic acids

c. mutated viruses d. viral polysaccharides e. infectious particles

28.With reference to RotaTeq, identify the INCORRECT statement. a. It is an attenuated vaccine derived from a human rotavirus. b. It has been genetically engineered to express a variety of human VP4 and VP7 glycoproteins. c. It is a mixture of five cattle rotaviruses. d. Standard tissue culture methods are used for its production. e. It took decades of research to develop this vaccine to an adequate standard.

29.Which of the following is an example of a subunit vaccine? a. hepatitis B vaccine b. Bacille Calmette–Guérin (BCG) vaccine c. trivalent oral polio vaccine d. influenza vaccine e. tetanus vaccine

30.All of the following are examples of adjuvants EXCEPT a. alum. b. MF59. c. inactivated Bordetella pertussis. d. virosomes. e. RhoGAM.

31.A newly identified antigen protein of Neisseria meningitidis called fHbp increases virulence by a. interfering with the alternative pathway of complement activation. b. binding to host-derived heparin. c. increasing the adhesiveness of the bacterium.

d. inhibiting phagocytosis. e. inducing inflammation.

32.__________ is the approach that mines a pathogen’s genome to reveal potential antigens and derives clues about cellular location, function, and ability to stimulate protective antibodies based on nucleotide sequence. a. Conjugation b. Attenuation c. Reverse vaccinology d. Herd immunity e. Neutralization

33.The reason that vaccines against influenza must be administered annually, unlike vaccines against measles, is a. the antigens that stimulate protection against influenza virus are inside the virion and not on the surface. b. influenza is an RNA virus with a higher mutation rate. c. influenza stimulates T-independent responses that fail to generate memory cells. d. the polysaccharide antigens of influenza stimulate poor immune responses.

34.When a subpopulation of unvaccinated individuals is protected against a pathogen due to vaccination of the vast majority of individuals in the overall population, this is called a. reverse vaccinology. b. subunit vaccination. c. partial immunization. d. combined immunity. e. herd immunity.

35.After a campus outbreak of Neisseria meningitidis (meningococcal serogroup B), a devastating bacterial disease, which affected at least eight students at Princeton University, the US Food and Drug Administration approved the use of Bexsero to prevent the development of additional cases on that campus. Bexsero

is considered to provide broader protective coverage than the US-licenced vaccines conventionally used against this disease. Which of the following methodologies was used to develop Bexsero? a. conjugation of neisserial capsular polysaccharide to tetanus toxoid b. reverse vaccinology c. formalin treatment of secreted toxins d. production of a combination vaccine that includes DTP plus a meningococcal polysaccharide diphtheria toxoid conjugate e. engineering a non-pathogenic cattle strain of N. meningitidis to express antigens associated with pathogenic human strains

36.Select the correct statement about vaccines. a. Only viral vaccines can be produced using subunit components. b. Only bacterial vaccines make use of toxoids. c. Only viral vaccines require adjuvants. d. Only viral vaccines incorporate capsular polysaccharides. e. Only viral vaccines can be made with an attenuated pathogen.

37.Chronic infections a. may be caused by pathogens that alter or evade the host’s immune system. b. are caused by both the influenza and the measles virus. c. that have historically been common in the human population are now readily prevented by available vaccines. d. are caused by pathogens that are eliminated from the host within weeks following infection. e. are not the target of vaccine development because they are caused by rare pathogens that infect low numbers of people globally.

38.The Rotarix vaccine a. targets more than one viral coat protein because the rotavirus mutates frequently. b. is a subunit vaccine generated by recombinant gene technology. c. prevents paralysis in infected children.

d. does not need to generate neutralizing antibodies to prevent infection. e. was generated after sequencing the cattle rotavirus genome.

39.How do memory B cells active in a secondary immune response differ from the naive B-cell population activated in a primary immune response? a. The antibody produced is of lower affinity in a secondary immune response. b. The frequency of antigen-specific B cells is lower in a secondary immune response. c. Higher levels of IgM are produced in secondary immune responses. d. The level of somatic hypermutation is higher in a secondary immune response. e. B cells do not require T-cell help in secondary immune responses.

40.Which of the following explains why infections with influenza virus erode immunological memory over time? a. Influenza virus epitopes remain stable from one flu season to the next. b. The immune response to new epitope variants is suppressed in naive B cells. c. The antibody response is directed only toward new epitope variants, resulting in a decreased memory response. d. Cross-linking of B-cell receptor and FcγRIIB1 on memory B cells induces isotype switching. e. Naive B cells are suppressed by cytokines made by memory B cells.

41.Naive T cells do not express a. CD4 or CD8 co-receptors. b. CD45RA. c. CD127 (IL-7 receptor). d. IFN-γ.

42.The production of CD45RO results from the removal of __________ during __________ processing. a. some of the exons encoding the intracellular domain; post-translational

b. some of the exons encoding the intracellular domain; post-transcriptional c. some of the exons encoding the extracellular domain; post-translational d. some of the exons encoding the extracellular domain; post-transcriptional e. the phosphatase domain; post-translational

43.Effector memory cells enter __________, whereas central memory cells enter __________. a. B-cell follicles; T-cell zones of secondary lymphoid tissues b. T-cell zones of secondary lymphoid tissues; B-cell follicles c. secondary lymphoid tissues; primary lymphoid tissues d. T-cell zones of secondary lymphoid tissues; inflamed tissues e. inflamed tissues; T-cell zones of secondary lymphoid tissues

44.Treatment is available to prevent hemolytic disease of the newborn, which can occur in families in which the birth mother is __________ and the birth father __________. a. RhD–; RhD– b. RhD+; RhD+ c. RhD–; RhD+ d. RhD+; RhD–

45.__________ involves deliberate stimulation of the immune system and induction of protective immunity to a particular disease-causing pathogen by mimicking infection in the absence of disease. a. Variolation b. Attenuation c. Vaccination d. Conjugation e. Herd immunity

46.The treatment of viruses with radiation, heat, or formalin leads to a. inactivation.

b. attenuation. c. increased viral replication in the host cells. d. neutralization. e. the loss of adjuvant activity.

47.An example of a live-attenuated virus vaccine is a. vaccinia. b. Salk polio vaccine. c. measles vaccine. d. hepatitis A. e. HPV or human papillomavirus.

48.Select the correct statement concerning the poliovirus vaccine. a. Salk developed an inactivated poliovirus vaccine and Sabin further improved the inactivated vaccine. b. The poliovirus vaccine was developed to prevent infection of the gut mucosal surfaces by poliovirus. c. Poliovirus can infect multiple animal species, thus requiring additional poliovirus vaccines for other animals before it can be eliminated. d. Herd immunity for poliovirus is high in the US, therefore immunization with the poliovirus vaccine is no longer recommended for children. e. Despite having an effective vaccine, dozens of cases of polio occur annually in the United States.

49.An example of an inactivated virus vaccine is a. Sabin polio vaccine. b. pertussis vaccine. c. mumps vaccine. d. hepatitis B vaccine. e. rabies vaccine for humans.

50.For a viral subunit vaccine to be effective, all of the following must occur EXCEPT a. B cells must be activated.

b. cytotoxic T cells must be activated. c. neutralizing antibodies must be induced. d. CD4 TFH cells must be activated. e. it must be derived from viral surface components.

51.A conjugate vaccine is one that couples __________ to __________ to stimulate T-dependent antibody responses. a. polysaccharide; a protein carrier b. a protein carrier; irradiated DNA c. protein carrier; toxoids d. adjuvant; toxoids e. polysaccharide; B cells

52.__________ vaccines are the most effective at evoking memory responses against a virus in an immunized host. a. Conjugate b. Subunit c. Killed d. Live-attenuated e. Toxoid

53.Which of the following vaccines is least likely to pose a risk in an individual with an immunodeficiency? a. Sabin polio vaccine b. measles vaccine c. hepatitis B vaccine d. vaccinia vaccine e. yellow fever vaccine.

54.All of the following are accurate concerning a hepatitis C infection EXCEPT a. it may lead to a chronic infection of the liver. b. an infected individual is at an increased risk of developing liver cancer.

c. an infected individual may experience episodes of liver destruction and regeneration. d. it may result in an acute infection that is cleared. e. it may be prevented by a vaccine.

55.All of the following explain why the safety standards for vaccines are set higher than those for drugs EXCEPT a. some vaccines can induce a disease state. b. vaccines provoke side effects in otherwise healthy children. c. vaccines are much more costly to develop and test than most drugs. d. vaccination programs are targeted at large populations. e. vaccines are often administered to the very young.

56.An adjuvant enhances the effectiveness of vaccines by inducing the expression of __________ on __________. a. co-stimulatory molecules; dendritic cells b. CD28; macrophages c. MHC class II molecules; T cells d. T-cell receptor; T cells e. immunoreceptor tyrosine-based activation motifs; dendritic cells

57.In order to generate an IgG response in infants and children, a vaccine against a new strain of encapsulated bacteria a. induces activation of TFH cells that recognize an epitope from the polysaccharide capsule. b. includes the polysaccharide capsule synthetically linked to an immunogenic carbohydrate. c. requires the B cell to internalize a protein. d. triggers B cells through the FcγRIIB1receptor. e. leads to a T-cell independent response.

58.Jenny O’Mara was five months pregnant when she stepped on a rusty piece of scrap metal while hauling rotted wood from a dilapidated shed in her garden. The sliver of metal cut through her sneaker and pierced her heel deeply. Her

physician gave her an intramuscular injection tetanus booster vaccine. When Jenny’s baby was born she decided to breastfeed. If the baby’s antibodies were tested for specificity to tetanus 2 months after birth, what would be the expected finding? a. the presence of anti-tetanus toxoid IgA antibodies b. the presence of anti-tetanus toxoid IgM antibodies c. the presence of anti-tetanus toxoid IgG antibodies d. the presence of IgM antibody specific for Clostridium tetani cell-wall components e. the presence of IgG antibody specific for Clostridium tetani cell-wall components

59.Memory T cells a. express higher levels of CD45RO than do naive T cells. b. rely more heavily on CD28-mediated co-stimulation for their activation. c. no longer express CD4 or CD8 co-receptors. d. express the same pattern of adhesion and cytokine receptors as naive T cells. e. must always circulate to the secondary lymphoid tissues for their reactivation.

60.Long-lived plasma cells do NOT a. divide. b. provide defense against pathogens located in the gut. c. actively degrade and renew their cellular components. d. secrete antibody unless activated by CD4 T cells. e. serve as a form of immunological memory.

61.Resident memory T cells a. circulate through tissues in a similar pattern to naive T cells. b. must return to the secondary lymphoid organ to receive co-stimulatory signals for activation. c. persist in non-lymphoid tissues that have effectively cleared an infection with a pathogen.

d. are the type of memory T cell most likely to activate a B cell. e. are the rarest type of memory T cells.

62.The memory cell type present in large numbers in the gut, skin, lungs, and reproductive tract is the a. effector memory T cell. b. central memory T cell. c. CD45RA memory T cell. d. resident memory T cell.

63.Select the correct response concerning memory T-cell migration.

a. The type of memory T cells that activate B cells have a pattern of migration that is shown in panel “A”.

b. The pattern of migration of effector memory T cells is shown in panel “C”. c. Tissue resident memory T cells have a pattern of migration shown in panel “B”. d. The type of memory T cells expressing the skin-homing addressin CCR4 is shown in panel “A”.

64.After receiving a vaccine for the encapsulated bacteria known as Group B streptococcus, the participants in a clinical trial produced antigen-specific IgG due to all of the following EXCEPT a. TFH cells recognizing the bacterial polysaccharide. b. CD40L becoming activated on TFH cells. c. B cells internalizing the vaccine conjugate through receptor-mediated endocytosis. d. an adjuvant, such as alum, being added to the vaccine e. B cells presenting peptide from the conjugated toxoid protein.

65.Select the correct statement concerning smallpox.

a. Virus-specific antibody persists in individuals who were vaccinated 40 years ago due to repeated exposure to the smallpox virus.

b. Individuals who generated memory CD4 and CD8 T cells were vaccinated with the smallpox virus. c. Virus-specific antibody in the blood must be continuously replaced by longlived plasma cells. d. The vaccinia virus does not provide protective immunity against the variola virus. e. Smallpox-specific memory cells will provide protective immunity against a future influenza infection.

66.Protective immunity a. is induced by vaccines but not by natural exposure to the pathogen. b. is maintained over decades due to the presence of stable antibodies that survive in the circulation. c. is due to memory B cells, but not memory T cells. d. to the vaccinia virus vaccine may last 50 years. e. following a natural infection with measles virus is short-lived

67.Autophagy a. involves degradation of cellular components in the lysosomes. b. occurs following apoptosis. c. describes the process by which macrophages take up and break down microbes. d. is not involved in immunological memory.

68.The light gray stain shows the amount and distribution of phosphorylated S6 protein in two daughter CD8 T cells generated following activation by antigen.

The CD8 T cell on the right

a. inherited a lower concentration of mTORC1. b. will form a clone of effector CD8 T cells. c. will form a clone of memory CD8 T cells. d. will undergo apoptosis. e. is the product of symmetric cell division.

69.Resident memory T cells a. have a limited T-cell receptor repertoire. b. lack expression of the CD45RO marker. c. circulate in the blood to provide rapid protection against blood-borne pathogens. d. are found in epithelial barrier tissues.

70.Smallpox a. virus infects multiple animal species, thus making it challenging to eradicate. b. virus mutates rapidly, thus making it challenging to eradicate. c. can be prevented by a vaccine that includes a virus able to replicate in the skin. d. is one of three epidemic infectious diseases to have been globally eradicated by vaccination.

71.Which of the following approaches would NOT limit the risk of developing polio disease following immunization with a polio vaccine?

a. immunization first with the oral polio vaccine, followed by subsequent immunization with the inactivated polio vaccine b. immunization first with the inactivated polio vaccine, followed by subsequent immunization with the oral polio vaccine c. immunization with the Salk polio vaccine only d. immunization with the inactivated polio vaccine rather than the liveattenuated polio vaccine

72.Influenza hemagglutinin and neuraminidase a. are not good targets for the generation of neutralizing antibodies because they are found on the inside of the virus particle. b. sequences remain stable each year due to the proofreading mechanism of the DNA virus. c. vary in sequence, due in part to the error-prone replication of this virus. d. are used by the virus to attach to cells of the gut epithelium, leading to infection.

73.The DTP vaccine a. was falsely linked to autism, which resulted in a drop in vaccination rates and a corresponding rise in the number of cases of disease. b. protects against three common viral infections. c. made with whole killed B. pertussis did not lead to herd immunity for whooping cough. d. made with whole killed B. pertussis led to both longer-term protection and more side effects than the acellular version.

74.Individuals who are immunocompromised and cannot receive vaccinations may still be protected against measles or polio due to a. long-lived plasma cells. b. herd immunity. c. adjuvants. d. reverse vaccinology.

75.Poliovirus

a. is an unlikely candidate for global eradication. b. can be prevented by a vaccine described as being trivalent. c. causes paralysis in almost 100% of infected individuals. d. is transmitted by face-to-face contact.

76.Select the correct statement concerning hemolytic anemia of the newborn.

a. The first pregnancy of an RhD– mother shown in the left panel would produce high levels of IgG that cross the placenta. b. The first pregnancy of an RhD– mother shown in the left panel requires engagement of the FcγRIIB1receptor to produce IgG. c. The second pregnancy of an RhD– mother shown in the middle panel will likely lead to loss of erythrocytes in the newborn baby. d. The anti-RhD antibody infused in the mother as shown in the right panel could be either IgG or IgM to be effective. e. An RhD+ mother will require the anti-RhD antibody infusion prior to a second pregnancy to protect the fetus.

77.An adjuvant in development for use in human vaccines includes synthetic DNA composed of CpG nucleotides that activates a. CD45RO. b. CD40. c. TLR4. d. TLR3. e. TLR9.

78.A vaccine for SARS-CoV-2 in clinical trials generated neutralizing IgG antibodies,

antigen-specific CD8 cytotoxic T effector cells, and memory B cells. Select the correct statement about the SARS-CoV-2 vaccine and the clinical trial results. a. CD4 T cells were unlikely to have been activated by the vaccine. b. Peptides generated from the SARS-CoV-2 vaccine were presented in MHC class II molecules. c. Neutralizing antibodies provide protection by activating complement. d. Dendritic cells did not need to be activated by the vaccine to produce neutralizing antibodies or CD8 effector cells. e. The vaccine is an example of passive immunity that will generate longlasting protection.

79.A subsequent exposure to the measles pathogen leads to a __________ in the individual. a. primary immune response b. vaccination c. reinfection d. secondary immune response e. passive immunization

80.Explain why memory B cells are more efficient at responding to pathogens than are naive B cells.

81.Identify three characteristics of smallpox that aided in the global eradication of this disease through a rigorous vaccination program.

82.Explain why the DTP vaccine stimulates a much stronger protective immunity than does the DT vaccine.

83.Identify two cases in which distrust of vaccines has led to an increase in the incidence of infections.

84.What is the risk to a population that over time reduces its use of a vaccine?

85.Why is determining the genome sequences of human pathogens important in the development of new and more effective vaccines?

86.Give four reasons why secondary immune responses are faster and more effective than primary immune responses.

87.Explain why only memory B cells, and not naive B cells, participate in secondary immune responses to particular pathogens, and why this is advantageous to the host.

88.Explain how immunological memory operates in the short term in response to repeated exposures to the same pathogen within weeks or months and in the long term in response to a subsequent exposure years later.

89.Explain why the suppression of naive B cells in secondary immune responses is advantageous for fighting the measles virus but disadvantageous for fighting the influenza virus.

90.Connect the components of a conjugate vaccine to the cellular events required to produce protective IgG antibodies against bacterial polysaccharide components and the development of memory.

91.Identify the risks associated with live-attenuated virus vaccines.

92.Compare subunit and conjugate vaccines and give an example of each.

93.Compare inactivated and live-attenuated virus vaccines and give an example of each.

94.Compare variolation and vaccination for smallpox and explain which procedure carries a higher risk.

Answer Key Chapter 11 1. Answer:

A

2. Answer:

B

3. Answer:

A

4. Answer:

B

5. Answer:

B

6. Answer:

B

7. Answer:

A

8. Answer:

A

9. Answer:

B

10.Answer:

D

11.Answer:

E

12.Answer:

E

13.Answer:

B

14.Answer:

C

15.Answer:

B

16.Answer:

C

17.Answer:

A

18.Answer:

B

19.Answer:

B

20.Answer:

C

21.Answer:

A

22.Answer:

B

23.Answer:

C

24.Answer:

A

25.Answer:

C

26.Answer:

D

27.Answer:

A

28.Answer:

A

29.Answer:

A

30.Answer:

E

31.Answer:

A

32.Answer:

C

33.Answer:

B

34.Answer:

E

35.Answer:

B

36.Answer:

B

37.Answer:

A

38.Answer:

A

39.Answer:

D

40.Answer:

B

41.Answer:

D

42.Answer:

D

43.Answer:

E

44.Answer:

C

45.Answer:

C

46.Answer:

A

47.Answer:

C

48.Answer:

B

49.Answer:

E

50.Answer:

B

51.Answer:

A

52.Answer:

D

53.Answer:

C

54.Answer:

E

55.Answer:

C

56.Answer:

A

57.Answer:

C

58.Answer:

C

59.Answer:

A

60.Answer:

A

61.Answer:

C

62.Answer:

D

63.Answer:

A

64.Answer:

A

65.Answer:

C

66.Answer:

D

67.Answer:

A

68.Answer:

B

69.Answer:

D

70.Answer:

C

71.Answer:

A

72.Answer:

C

73.Answer:

D

74.Answer:

B

75.Answer:

B

76.Answer:

C

77.Answer:

E

78.Answer:

B

79.Answer:

D

80.Answer:

During germinal-center reactions, isotype switching, somatic hypermutation, and affinity maturation generate memory B cells with higher-affinity receptors than those of naive B cells. This feature enables memory B cells to bind to pathogen antigens at very early stages of infection when the pathogen population is very small. Memory B cells also differentiate into plasma cells more rapidly than do naive B cells. These two characteristics allow antibody production to occur much sooner than would be the case with naive B cells.

81.Answer:

(i) The smallpox virus evolves slowly, so the antigenic epitopes encountered in a vaccine are likely to be the same as or very similar to the actual virus if exposed to the virus later in life. (ii) The vaccine is a live virus administered through the skin, so the immune responses that are induced

will closely resemble those provoked by a natural infection and establish long-lived memory B cells and memory T cells. (iii) Smallpox, unlike other poxviruses, infects only humans. This eliminates the possibility of alternative reservoirs in other animal populations and therefore requires the interruption of only one chain of transmission (namely human-to-human) to impede dissemination.

82.Answer:

The diphtheria (D) and tetanus (T) toxoids are purified proteins that on their own do not stimulate Toll-like receptors or other receptors of the innate immune response. Hence, an inflammatory response is not initiated by the DT vaccine, which consequently results in the failure to initiate an adaptive immune response. When inactivated Bordetella pertussis is added to make the tripartite vaccine (DTP), it efficiently activates the innate immune response by acting as an adjuvant and inducing inflammation. It also provides additional pathogenic antigens to which the host responds.

83.Answer:

(i) A resurgence of whooping cough was documented in Japan between 1975 and 1980. Distrust in the vaccine followed the death of two children who had recently been vaccinated with DTP. (ii) A resurgence of measles was documented in the UK at the turn of the 21st century.

Distrust was linked to unsubstantiated claims that the MMR vaccine induced autism in children.

84.Answer:

As the number of susceptible individuals increases to a certain threshold, herd immunity is no longer effective in protecting individuals who have never been vaccinated. The outcome is the resurgence of the disease and an epidemic.

85.Answer:

Determination of genome composition enables researchers to understand the life cycle of the pathogen and to identify unanticipated genes of importance for pathogenicity. Armed with specific sequence knowledge, recombinant DNA methodology can be used to engineer attenuated strains, either through site-directed mutagenesis or the deletion of virulence genes, or to produce subunit vaccines. In the case of SARS-CoV-2, rapid sequencing of the viral genome led to vaccine trials within months.

86.Answer:

(i) Memory cells outnumber naive pathogen-specific lymphocytes because they have already gone through clonal selection and proliferation when antigen was encountered previously. (ii) Memory cells can be activated more quickly than naive lymphocytes. (iii) Memory cells are not restricted to circulation between

the bloodstream and secondary lymphoid organs, but can also enter non-lymphoid tissues and can therefore respond to infections sooner. (iv) Owing to the molecular processes of somatic hypermutation and isotype switching, immunoglobulins made by memory B cells are of a higher quality and possess constant regions that will direct secreted antibody to the appropriate anatomical locations to combat infection. They will therefore compete more efficiently for antigen than naive lymphocytes and in so doing will inhibit the activation of naive lymphocytes.

87.Answer:

Naive B cells carry the inhibitory Fc receptor FcγRIIB1.

Complexes composed of antigen and IgG produced in the primary response, or by reactivated memory cells, cross-link FcγRIIB1 and the B-cell receptor, which suppresses naive B-cell activation. In contrast, memory B cells do not carry this receptor, and so are not inhibited in this way. The suppression of naive B cells means that only reactivated memory B cells (which have already undergone isotype switching and somatic hypermutation) make antibodies.

Thus all the antibodies made are of high affinity and are primarily of the IgG, IgA, or IgE isotype. Suppression of naive B cells eliminates repetition of the events that took place in the primary immune response, which would, if not inhibited, lead to the production of low-affinity IgM antibodies rather than high-affinity, isotype-switched antibodies that are more effective at removing the pathogen.

88.Answer:

Short-term immunological memory operates after an adaptive immune response has cleared the infection in an individual and while the pathogen is still present in the community. If the individual is re-exposed and re-infected, antibodies generated in the first round of infection can bind immediately to the pathogen, blocking its action by neutralization and mediating its removal and destruction by complement fixation and phagocytosis. In addition, any remaining effector T cells or activated B cells can respond straight away to the presence of antigen. These activities ensure that the infection does not re-establish itself and also generate a fresh supply of antibodies and effector cells.

Long-term immunological memory is mediated through longlived memory lymphocytes that are generated in the primary immune response. These are cells that can be rapidly stimulated by re-exposure to the same antigen to produce a strong and effective immune response that rapidly clears the pathogen.

89.Answer:

The measles virus is a relatively invariant pathogen that has little, if any, antigenic change. Antibodies made by memory B cells will be just as effective in a recall response as those made in a primary challenge. In fact, antibodies made in secondary immune responses by memory B cells will be more effective because of isotype switching and somatic hypermutation. In contrast, the influenza virus is highly mutable; as a result, new strains emerge each year bearing new epitopes that have not previously stimulated a primary response. Memory response and the suppression of naive B cells restrict antibody production to only those epitopes shared by the infecting strain and the original strain. Over time, the influenza virus will express only a limited number of epitopes that are able to activate memory B cells, and the new epitopes will lack the capacity to stimulate naive B cells.

90.Answer:

Vaccines containing purified polysaccharide components induce weak T-cell-independent B-cell responses limited to low-affinity IgM antibodies and no memory B-cell production.

By linking the bacterial polysaccharide covalently to a potent IgG-stimulating protein such as the tetanus or diphtheria toxoid, peptide epitopes become available for the activation of CD4 TFH cells. First, dendritic cells process the toxoid epitope and activate CD4 T cells, which differentiate into TFH cells. Then naive B cells bearing IgM antibodies specific for the polysaccharide take up the conjugate by receptormediated endocytosis. The toxoid epitopes are subsequently presented with MHC class II molecules on the B-cell surface to activated toxoid-specific CD4 TFH. The resulting T cell–B cell cognate interaction provides everything needed for an efficient immune response generating high-affinity, polysaccharide-specific protective IgG antibodies and the establishment of both T-cell memory and B-cell memory.

91.Answer:

Live-attenuated virus vaccines are mutant viruses that can replicate, albeit inefficiently, in human cells, thus simulating conditions of a normal viral infection. The attenuated vaccine strains of virus have been obtained by growing the virus over many generations in non-human cells (for example monkey cells) so that it acquires multiple mutations that allow it to replicate but prevent it from spreading in the human body and causing disease. When introduced into humans as a vaccine, there is a small chance that some or all of the mutations may revert to the original nucleotide sequence, restoring the properties of the virulent strain of the virus. This occurs very rarely with the poliovirus used in the trivalent oral polio vaccine (TVOP) and, now that polio is

very rare in the United States, this vaccine is no longer recommended and an inactivated poliovirus vaccine is used instead. The more rounds of replication the vaccine virus undergoes in the human host before being contained by the immune response, the greater is the potential for genetic reversion. This is why individuals who suffer from inherited or acquired immunodeficiencies should never receive liveattenuated virus vaccines.

92.Answer:

Subunit vaccines are composed only of particular antigenic pathogen components known to induce protective immune responses. Recombinant DNA technology enables the production of antigenic proteins in the absence of other pathogen gene products. Examples are hepatitis B vaccine and Bexsero vaccine. Conjugate vaccines are made by covalently coupling antigenic polysaccharide found in bacterial capsules to a carrier protein (often a toxoid). This converts the otherwise T-independent bacterial polysaccharide antigen into a T-dependent antigen. T cells respond to an epitope on the protein carrier, whereas B cells respond to epitopes on the polysaccharide portion of the conjugate. This ensures that T-cell help is provided to B cells making anti-capsule antibodies. Examples include vaccines against Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae. Both types of vaccine would require an adjuvant.

93.Answer:

Inactivated virus vaccines are made of virus particles that are not able to replicate because they have been chemically or physically treated (for example by heat) in a way that inactivates the nucleic acid. Examples are Salk polio vaccine, rabies vaccine, and influenza vaccine. In comparison, live-attenuated virus vaccines are made of viruses that have lost their pathogenicity, yet still have a limited ability to replicate in human cells. Attenuated viruses accumulate mutations after being grown in non-human cells.

Their ability to replicate generally induces a strong immune response. Examples of attenuated viral vaccines are Sabin polio vaccine (oral), measles vaccine, mumps vaccine, yellow fever vaccine, and varicella vaccine.

94.Answer:

Variolation and vaccination are both procedures used to confer immunological protection against the smallpox virus, variola. They both use live virus and stimulate humoral and cell-mediated immune responses against the smallpox virus without the need for an additional adjuvant. Variolation, a method used for only a short period in the 18th and 19th centuries because of the risk of developing smallpox, used dried pustules derived from humans exhibiting relatively mild

symptoms of smallpox infection. Vaccination, a safer alternative causing only mild infection, used dried pustules from cows infected with cowpox, or vaccinia virus.Vaccinia and variola share some viral surface antigens, so some of the antibodies made against cowpox surface antigens during immunization are able to bind to shared surface antigens also expressed on the surface of the smallpox virus. Through neutralization, these anti-cowpox antibodies are able to bind to and prevent the entry of smallpox into host cells if the host is infected naturally with the smallpox virus. As mentioned, because variolation used the variola virus, it carried a much higher risk for the individual; some recipients developed smallpox and died.

Name: ___________________________ Class: _________________ Date: __________

Chapter 12 1. KIRs are more likely to detect changes in HLA-C expression compared with CD94:NKG2A. a. True b. False

2. KIRs are activating receptors of NK cells and stimulate the release of perforin and granzyme. a. True b. False

3. KIRs bind to monomorphic determinants on HLA-A, -B, and -C molecules. a. True b. False

4. All HLA-C allotypes are suitable ligands for KIRs. a. True b. False

5. KIRs are encoded in the leukocyte receptor complex (LRC) on chromosome 19. a. True b. False

6. MIC-A and MIC-B are suitable ligands for KIRs. a. True b. False

7. All of the following are characteristic of NK cells EXCEPT a. they express Toll-like receptors. b. they are tolerant of healthy cells. c. they circulate in a partly activated state. d. they all express the same selection of activating and inhibitory NK-cell receptors. e. they can be activated by FcγRIIIA (CD16a).

8. Which of the following statements regarding NK cells is FALSE? a. They express either inhibitory receptors or activating receptors, but not both. b. Their inhibitory receptors are necessary to prevent killing of healthy cells. c. They all express CD56. d. Because NK cells express diverse combinations of receptors, no single NK cell expresses them all. e. Some of their activating and inhibitory receptors use MHC class I ligands.

9. The only single receptor that can activate NK cells without the need for a second activating receptor is a. NKG2D. b. CD56. c. 2B4. d. CD94:NKG2A. e. CD16.

10.Identify which of the following would be sufficient to activate NK cells. a. NKG2A and CD94 b. NKG2D and 2B4 c. KIR2DL1 and KIR3DL1 d. CD56 and LFA-1

11.Identify which of the following is NOT a characteristic of CD94:NKG2A.

a. contains a C-type lectin domain b. is an inhibitory NK-cell receptor c. binds to carbohydrate ligands d. is a disulfide-linked heterodimer e. contains an immunoreceptor tyrosine-based inhibitory motif (ITIM)

12.Identify the MISMATCHED pair: a. CD94:NKG2A; ITIM b. NKG2D; MIC proteins c. SHP-1; Vav1 d. 2B4; IgG e. HLA-E; leader-sequence peptide

13.__________ has/have tyrosine phosphatase activity that interrupts the signaling pathways required for the activation of NK cells. a. SHP-1 b. MIC proteins c. KIR ligands d. Phosphoantigens e. Lipid-transfer proteins

14.All of the following describe Vav1 EXCEPT a. guanine-nucleotide exchange factor. b. regulated by SHP-1. c. active when phosphorylated. d. found on the surface of NK cells. e. mediates signaling that promotes NK cells’ release of cytotoxic granules.

15.All of the following contribute to the generation of functional NK cells in the bone marrow with diverse KIR phenotypes EXCEPT a. competing bidirectional promoters of KIR genes. b. delay of KIR expression until NK cells enter the circulation.

c. establishment of a level balance between activating and inhibitory signals. d. gene silencing by DNA methylatione. e. the number of KIR ligands brought by the HLA-A, -B, and -C tissue type.

16.Which of the following is FALSE regarding HLA-G? a. It is expressed as transmembrane or secreted forms. b. It binds to LILRB1 inside endosomes of NK cells. c. It stimulates the production of angiogenic factors by activating NK cells. d. It is expressed exclusively by extravillous trophoblast cells. e. It engages inhibitory receptors on uterine NK cells.

17.Extravillous trophoblast cells do NOT express a. HLA-A. b. HLA-C. c. HLA-E. d. HLA-F. e. HLA-G.

18.Which of the following maternal profiles is most strongly correlated with preeclampsia where the fetus has a C2 epitope inherited from the father? a. homozygous for KIR A haplotype and C1 epitope b. homozygous for KIR B haplotype and C1 epitope c. homozygous for KIR A haplotype and C2 epitope d. homozygous for KIR B haplotype and C2 epitope e. heterozygous for KIR A/B haplotypes and homozygous for C1 epitopes

19.Which of the following maternal profiles is most strongly correlated with obstructed labor where the fetus has a C2 epitope inherited from the father? a. homozygous for KIR A haplotype and C1 epitope b. homozygous for KIR B haplotype and C1 epitope c. homozygous for KIR A haplotype and C2 epitope d. homozygous for KIR B haplotype and C2 epitope

e. heterozygous for KIR A/B haplotypes and homozygous for C1 epitopes

20.Identify which of the following is NOT a characteristic of γδ T cells. a. Some express a homodimer of the CD8 α chain. b. They are detected earlier than αβ T cells during development. c. They undergo gene rearrangement. d. They make up the minority of resident T cells in tissues. e. Circulating cells express Vγ9:Vδ2

21.Which of the following is true for both γδ and αβ T cells? a. They both express CD28. b. They are both restricted to MHC. c. They both must express either CD4 or CD8 co-receptors. d. They are both dependent on the T-cell receptor for the recognition of antigen and their activation. e. They both originate from the same precursor cells.

22.At birth, the size of the repertoire of γδ T-cell receptors is __________ its size at adolescence. a. smaller than b. larger than c. about the same as

23.Which of the following is NOT a ligand for αβ T cells? a. peptide antigens b. lipid antigens c. sulfatides d. heterocyclic organic molecules

24.In contrast to CD1d, CD1a, b, and c are NOT expressed by a. professional antigen-presenting cells.

b. epithelial cells. c. developing thymocytes.

25.All of the following develop in the thymus EXCEPT a. αβ T cells. b. γδ T cells. c. NK cells. d. NKT cells. e. MAIT cells.

26.Which of the following is NOT a characteristic of MAIT cells? a. CD8+ b. respond to viral infection c. αβ T-cell receptors d. populate lungs, mucosal tissues, liver, and blood e. activated by microbiota that make riboflavin

27.Which of the following is NOT a characteristic of MR1? a. MHC class-I-like molecule b. binding site populated with large basic and aromatic amino acid residues c. associated with β2-microglobulin d. highly polymorphic in mammals e. encoded on chromosome 1

28.All of the following characterize MIC-A and MIC-B proteins EXCEPT a. they are recognized by NKG2D receptors of NK cells. b. they lead to phosphorylation of an ITAM. c. they lead to the activation of Vav. d. they are closely related to MHC class I heavy chains. e. they are expressed on healthy cells to prevent killing by NK cells.

29.Select the FALSE statement about Vγ9:Vδ2 T cells. a. They respond to phosphorylated metabolic intermediates (phosphoantigens) of isoprenoid biosynthesis pathways. b. Their T-cell receptor does not directly bind to the antigen as is the case with αβ T cells. c. They do not require RAG 1 or 2 for their development. d. They are not subject to positive and negative selection in the thymus. e. They have limited diversity of V gene rearrangement.

30.__________ binds to MIC-A and MIC-B, which are synthesized in response to infection in gut epithelium. a. MHC class I b. NKG2D c. CD94:NKG2A d. Fibroblast growth factor e. CD1

31.Each of the following express a limited range of diversity in their antigen receptors yet can still bind to large groups of pathogens expressing common chemical entities EXCEPT a. MAIT cells. b. γδ T cells. c. NK cells. d. NKT cells.

32.All NK cells express a. CD3. b. MIC. c. CD16. d. KIR2DL1. e. CD56.

33.Which of the following describe a characteristic of CD94:NKG2A?

a. It is an activating receptor of NK cells. b. It does not play a role in NK-cell education. c. It binds to specific allotypes of HLA-A, -B, and -C heavy chains. d. It binds to complexes of leader sequences of HLA-A, -B, and -C heavy chains bound to HLA-E. e. It is a member of the killer-cell immunoglobulin-like receptor (KIR) family.

34.__________ is a molecule expressed on both NK cells and NKT cells. a. CD3 b. MIC-A c. NKG2D d. Vγ9:Vδ2 e. Vα24–Jα18

35.If, during development, none of the KIRs expressed by an NK cell are able to interact with self-MHC class I molecules, then the NK cell retains expression of a. LILRBI. b. KIR2DL1. c. KIR2DL2/3. d. KIR3DL1. e. CD94:NKG2A.

36.CD1a, CD1b, and CD1c a. are highly polymorphic and bind to a variety of pathogen-specific lipids. b. are encoded within the MHC on chromosome 6. c. express antigen-binding sites that form an identical peptide-binding groove seen in classical MHC class I molecules. d. are associated with β2-microglobulin at the surface of antigen-presenting cells. e. can bind to and present riboflavin metabolites in the endoplasmic reticulum or in endocytic vesicles.

37.CD1d differs from CD1a, CD1b, and CD1c in that

a. CD1d does not present lipid antigens. b. CD1d has a limited tissue distribution. c. CD1d presents antigen to MAIT cells. d. CD1d coevolved with the germline Vδ1 segment. e. CD1d cycles between the plasma membrane and the endosomal compartment.

38.Select the statement that most accurately represents our current understanding of the evolution of the immune system in vertebrates. a. Innate immunity and adaptive immunity have both continued to independently evolve over the past 400 million years. b. The evolution of the innate immune system stopped after the origin of the adaptive immune about 400 million years ago. c. There has been a constant coevolution of innate and adaptive immunity over the past 400 million years. d. Adaptive immunity has changed very little in the past 400 million years.

39.NK cells a. are innate cells and do not participate in the adaptive immune response. b. depend upon the expression of MHC class I for their development and function. c. use cytotoxic granules to kill cells infected by viruses, but they do not secrete cytokines. d. circulate in the blood, but they do not enter infected tissues. e. and their activity suggest that MHC class II molecules evolved prior to the origin of adaptive immunity.

40.NK cells express receptors that recognize all of the following EXCEPT a. viral RNA. b. host stress proteins. c. IgG bound to antigen. d. MHC class II proteins. e. MHC class I proteins.

41.A healthy individual inherits approximately __________ different types of activating and inhibitory NK-cell receptor genes, which leads to __________ NK receptor phenotypes circulating in the blood. a. 10; 10 b. 10; hundreds of c. 30; dozens of d. 30; thousands of e. 1000; 10,000 or more

42.__________ provides evidence of the coevolution of innate and adaptive immunity. a. The expression of CD16 on NK cells b. The expression of CD56 on NK cells c. The expression of NKG2D on NK cells d. The expression of CD94:NKG2A

43.Select the INCORRECT statement concerning NK cell activation. a. Activation of NK cells during the first few days of a primary immune response requires signals from at least two activating receptors. b. CD16 binding to ligand is sufficient to activate NK cells during the first few days of a primary response. c. NKG2D and 2B4 binding to their ligands will lead to NK cell killing of a target cell during the first few days of a primary response. d. Infusion of IgG antibodies specific for host cell surface molecules leads to NK cell killing of host target cells.

44.In an individual born with a mutation that results in the lack of functional CD16 protein, a. antibody-dependent cell-mediated cytotoxicity will still function properly. b. MIC-A will no longer activate NK cells. c. two activating receptors binding their ligands will be required for NK cell activation. d. γδ T cells will not be activated to release cytokines. e. MAIT cells will not efficiently recognize microbial metabolites.

45.All of the following must occur for an NK cell to detect a decrease in the level of MHC class I on host tissues EXCEPT a. the NK cell must express either a KIR or a C-type lectin domain inhibitory receptor. b. the NK cell must interact with MHC class I in the bone marrow. c. DAP-12 must interact with Vav in the bone marrow. d. SHP-1 must be activated in the bone marrow.

46.Which of the following is NOT an outcome of NK cell education? a. a decrease in activating signals resulting in the dominance of inhibitory signals b. a change in the expression of granzyme B protein c. the phosphorylation of Vav d. Individuals lacking particular HLA allotypes may have NK cells that remain unresponsive to infected tissue cells in the periphery.

47.Select the correct statement concerning educated NK cells.

a. The educated NK cell from panel A would kill self-tissue target cells expressing the C1 epitope of HLA-C. b. The educated NK cell from panel A would kill self-tissue target cells expressing the C2 epitope of HLA-C. c. The educated NK cell from panel A would kill self-tissue target cells lacking

the C1 epitope of HLA-C. d. The educated NK cell from panel B would be inhibited when binding the C2 epitope of HLA-C on self-tissue target cells.

48.Which of the following is INCORRECT concerning the inhibitory NK cell receptors? a. KIR and CD94:NKG2A provide an example of divergent evolution. b. Both CD94 and NKG2A are encoded on the same chromosome. c. The leukocyte receptor complex is found on a different chromosome than the HLA genes. d. Parents and their genetic offspring may have different NK ligand-receptor interactions. e. The KIR receptors belong to the immunoglobulin superfamily.

49.The KIR gene family is diverse due to a. the number of genes located in the natural killer complex. b. the number of inherited HLA genes. c. expression of CD56. d. the number of LILR alleles. e. allelic polymorphism and gene-content variation.

50.The KIR A haplotype a. has fewer polymorphic genes that code for inhibitory receptors than the KIR B haplotype. b. is associated with a weaker inflammatory response than is the KIR B haplotype. c. has not been linked to human diseases. d. evolved to benefit human reproduction. e. is present in all human populations.

51.Cytomegalovirus (CMV) has been shown to generate a. a short-lived CD94:NKG2C NK-cell response to control the active infection. b. a long-term increased level of CD94:NKG2C-expressing NK cells having

high cytotoxic potential. c. a short-lived Vγ9:Vδ2 T-cell response with the production of cytokines. d. an upregulation of MHC class I to aid the cytotoxic CD8 T-cell response.

52.Select the INCORRECT statement concerning cytomegalovirus (CMV). a. CMV can be transmitted by a pregnant woman to her fetus. b. Downregulation of MHC class I by CMV leads to a large increase in CMVspecific NK cells in the blood. c. CMV infects cells that express HLA-E. d. CMV infection is short-lived because the virus is quickly cleared by combined innate and adaptive immunity. e. The change in NK-cell populations following CMV infection resembles the production of memory cells in the adaptive immune response.

53.Which of the following is NOT true of extravillous trophoblasts? a. They are the only fetal cells that directly contact maternal tissues. b. Their successful invasion of the spiral arteries is most closely linked to expression of HLA-B alleles. c. They share invasive properties with tumor cells. d. They lack MHC class II expression. e. They interact with uterine NK cells leading to secretion of cytokines and growth factors by the NK cells.

54.Endothelial protein C receptor binds a. phospholipids. b. complement component C3. c. peptides. d. riboflavin metabolites. e. KIRs.

55.Vγ4:Vδ5 T cells are able to a. regulate the number of commensals in the gut. b. kill cytomegalovirus (CMV)-infected cells.

c. recognize antigen presented by CD1d. d. recognize antigen presented by MHC class I-related protein 1.

56.Select the FALSE statement concerning γδ T cells. a. γδ T cells develop in the bone marrow and thymus. b. The germline V segment repertoire is smaller in γδ T cells than αβ T cells. c. The γδ T-cell receptor is the only way to activate γδ T cells. d. γδ T cells have CDR loops that more closely resemble immunoglobulin than the αβ T-cell receptor. e. γδ T cells respond to a first exposure to antigen faster than do αβ T cells.

57.Invading pathogens and tumor cells express high levels of the self-antigen isopentenyl pyrophosphate (IPP), which activates a. CD8 T cells. b. NKT cells. c. NK cells. d. γδ T cells. e. MAIT cells.

58.Butyrophilins a. are expressed by pathogenic bacteria. b. bind to the fatty acid butyric acid. c. are involved in the evolution of γ and δ chain germline-encoded gene segments. d. are bound by the CD1 family of proteins.

59.NKT cells in the periphery can form conjugates with all of following cells except a. macrophages. b. neutrophils. c. NK cells. d. B cells. e. CD4 T cells.

60.NKT cells contribute to all of the following EXCEPT a. an increase in inflammation. b. the recruitment of neutrophils to infected tissues. c. the secretion of cytokines. d. the activation of B cells. e. the invasion of spiral arteries during implantation.

61.Select the INCORRECT statement concerning NKT cell interaction with a dendritic cell.

a. When molecule “A” binds to its ligand, NFkB is activated. b. The production of molecule “B” increases when the dendritic cell is exposed to IFN-γ. c. The molecule labeled “C” is also expressed on double-positive thymocytes. d. The molecule labeled “C” is recognized by T cells bearing Vα2–Jα1:Vβ11 T-cell receptors.

62.Select the correct statement concerning MAIT cells (dark gray) in the mucosal tissue of the gut.

a. The MAIT cells shown in panel A express Vα7.2, but do not express CD8. b. The MAIT cells could not undergo positive selection in the thymus in an animal raised under germ-free conditions. c. The MR1 protein shown in panel A will still present antigen in an animal raised under germ-free conditions. d. MAIT cells will proliferate and differentiate into effector cells as shown in panel B in animals who lack both gut bacteria and yeast, but who are infected with viruses. e. MAIT cells will proliferate and differentiate into effector cells as shown in panel B after recognizing pterins.

63.The MR1 protein a. is highly conserved among different species. b. evolves rapidly, providing new MR1 variants with altered antigen-binding sites. c. is recognized by several Vα and Jα segments. d. is not expressed in the thymus.

64.NK cells treated with a drug that blocks Vav phosphorylation are allowed to interact with a virus-infected cell lacking MHC expression; these NK cells a. would not have phosphorylated ITAMs in the cytoplasmic tail of NKG2D. b. would recruit SHP-1 to the signal pathway. c. would not release cytotoxins, such as granzyme B. d. would not express inhibitory receptors on the cell surface.

65.Charlene Cook, a 38-year-old, is 35 weeks pregnant. This is her first pregnancy and until recently she has had an uneventful pregnancy. Two weeks ago, her obstetrician noted lower-extremity edema, trace protein in her urine (10– 20 mg/dl), and normal blood pressure (120/80 mmHg). At today’s appointment her blood pressure is elevated at 160/100 mmHg, she has marked proteinuria (3+; 300 mg/dl), worsening of ankle swelling, facial and hand swelling, and she mentions sudden onset of headache and visual disturbance. Charlene is admitted immediately to the hospital and is diagnosed with pre-eclampsia. Within hours she is induced and gives birth to a healthy baby girl. In the context of uterine NKcell function, describe the events that are the likely cause of Charlene’s preeclampsia. a. There is inadequate extravillous trophoblast invasion of the spiral arteries or the uterus. b. She has maternal homozygosity for the KIR A haplotype. c. Uterine NK cells fail to secrete adequate amounts of cytokines and growth factors needed to promote angiogenesis and remodeling of the maternal arteries. d. The baby’s father and mother are homozygous for the C1 epitope. e. Insufficient activating signals were delivered to uterine NK cells.

66.Match the lettered term with its description in the numbered terms. a. CCR7 b. CCR5 c. CD27 d. CD45RA e. CD1d 1. permits entry of γδ T cells into infected tissues 2. expressed on central memory γδ T cells but not effector memory γδ T cells 3. required for entry into secondary lymphoid tissues 4. presents lipid antigens to γδ T cells 5. expressed on terminally differentiated γδ T cells

67.Match the receptor in the lettered answers with its ligand in the numbered answers. a. Vγ9: Vδ2 b. Vγ: Vδ1

c. Vγ4: Vδ5 d. Vα7.2–Jα33: Vβ2, -13, or -22 1. phosphoantigens presented by BTN3A1 2. lipid antigens presented by CD1d 3. ringed metabolites of riboflavin presented by MR1 4. phospholipid antigens presented by endothelial protein C receptor (EPCR)

68.Match the lettered term with its complement in the numbered terms. a. saposin b. sulfatide c. scaffold lipid d. BTN3A e. lipid-transfer protein f. promyelocytic leukemia zinc finger protein (PLZF) g. second signal for NKT-cell activation h. riboflavin 1. NKT-cell development 2. fills bottom of antigen-binding site to allow antigenic lipid to be accessible at the top 3. MR1 4. phosphoantigen 5. CD1d 6. CD1e 7. IL-12 8. an example of a lipid-transfer molecule found in endosomes

69.Match the term in the numbered answers with its appropriate ligand in the lettered answers. a. Vγ4:Vδ5 T-cell receptor b. CD94:NKG2A c. NKG2D d. LILRBI e. Vγ9:Vδ2 T-cell receptor f. KIR2DL1 g. CD1 1. HLA-G and broad reactivity with HLA class I

2. EPCR 3. phosphoantigen 4. HLA-E 5. MIC-A and MIC-B 6. HLA-C 7. glycolipid antigen

70.Describe the consequence of a decrease in the target cell expression of the ligand for CD94:NKG2A.

71.Explain the path taken by CD1a, -b, or -c molecules that eventually bind to pathogen-derived lipids inside endosomes.

72.How are NK cells thought to use their activating and inhibitory receptors to recognize and eliminate virus-infected cells?

73.Explain how the ligand for CD94:NKG2A serves as an indicator of non-infectious or non-malignant states of potential target cells.

74.In the context of NK-cell inhibitory and activating receptors and maternal arterial invasion, compare the cause of pre-eclampsia with that of obstructed labor. Base your response on a pregnancy involving a fetus who has inherited a C2 epitope from the father but whose mother is homozygous for C1.

75.Natural killer cells (NK cells) carry activating and inhibitory receptors on their surface. What property of NK cells do these receptors activate or inhibit, respectively? Explain your answer.

76.Why are the actions of NK cells categorized as innate immunity, and what do we know of their specificity for MHC class I molecules?

77.Charlene Cook, a 38-year-old, is 35 weeks pregnant. This is her first pregnancy and until recently she has had an uneventful pregnancy. Two weeks ago, her obstetrician noted lower-extremity edema, trace protein in her urine (10– 20 mg/dl), and normal blood pressure (120/80 mmHg). At today’s appointment her blood pressure is elevated at 160/100 mmHg, she has marked proteinuria (3+; 300 mg/dl), worsening of ankle swelling, facial and hand swelling, and she mentions sudden onset of headache and visual disturbance. Charlene is admitted immediately to the hospital and is diagnosed with pre-eclampsia. Within hours she is induced and gives birth to a healthy baby girl. In the context of uterine NKcell function, describe the events that are the likely cause of Charlene’s preeclampsia. a. There is inadequate extravillous trophoblast invasion of the spiral arteries or the uterus. b. She has maternal homozygosity for the KIR A haplotype. c. Uterine NK cells fail to secrete adequate amounts of cytokines and growth factors needed to promote angiogenesis and remodeling of the maternal arteries. d. The baby’s father and mother are homozygous for the C1 epitope. e. Insufficient activating signals were delivered to uterine NK cells

Answer Key Chapter 12 1. Answer: A 2. Answer: B 3. Answer: B 4. Answer: A 5. Answer: A 6. Answer: B 7. Answer: D 8. Answer: A 9. Answer: E 10.Answer: B 11.Answer: C 12.Answer: D 13.Answer: A 14.Answer: D 15.Answer: B 16.Answer: B 17.Answer: A 18.Answer: A 19.Answer: B 20.Answer: D

21.Answer: E 22.Answer: B 23.Answer: C 24.Answer: B 25.Answer: C 26.Answer: B 27.Answer: D 28.Answer: E 29.Answer: C 30.Answer: B 31.Answer: C 32.Answer: E 33.Answer: D 34.Answer: C 35.Answer: E 36.Answer: D 37.Answer: D 38.Answer: C 39.Answer: B 40.Answer: D 41.Answer: D 42.Answer: A

43.Answer: B 44.Answer: C 45.Answer: C 46.Answer: A 47.Answer: C 48.Answer: A 49.Answer: E 50.Answer: E 51.Answer: B 52.Answer: D 53.Answer: B 54.Answer: A 55.Answer: B 56.Answer: C 57.Answer: D 58.Answer: C 59.Answer: E 60.Answer: E 61.Answer: D 62.Answer: E 63.Answer: A 64.Answer: C

65.Answer: D 66.Answer:

1. B 2. C 3. A 4. E 5. D

67.Answer:

1. A 2. B 3. D 4. C

68.Answer:

1. F 2. C 3. H 4. D 5. B 6. E 7. G 8. A

69.Answer:

1. D 2. A 3. E 4. B 5. C 6. F 7. G

70.Answer: If a cell is infected or malignant, the levels of HLA class I molecules are decreased. This

interrupts the supply of leader-sequence peptides, and thereby also causes a decrease in HLA-E on the cell surface. In the absence of ligand, NK cells bearing CD94:NKG2A are then unable to engage their inhibitory receptors; the signals from the activating receptors mobilize the killing mechanism, leading to the elimination of the unhealthy cell.

71.Answer: CD1 begins assembly with β2-microglobulin and self lipid in the endoplasmic reticulum of restricted cell types. It progresses through the Golgi, then to Golgi-derived vesicles, and is eventually presented on the cell surface. The complex is subsequently endocytosed via clathrin-coated pits and intersects the endosomal pathway. Lipid-transfer proteins, such as saposins or CD1e, exchange self lipids for pathogen-derived lipids before the complex is transported back to the cell surface for presentation to αβ T cells.

72.Answer: Virus-infected cells often have lower levels of MHC class I molecules on their surface. This feature is thought to be exploited by NK cells, which are continually monitoring levels of MHC class I molecules on host cells. When an NK cell finds a cell that lacks or has decreased MHC class I on its surface, the signals from the activating receptors predominate over those from the inhibitory receptors and the target cell is killed. Some viruses encode proteins that mimic MHC class I molecules and interfere with NK-cell attack by ligation of the NK cells’ inhibitory receptors.

73.Answer: The ligand for the inhibitory receptor CD94:NKG2A on NK cells is HLA-E, a conserved HLA class I molecule. In common with HLA-A, -B, and -C, HLA-E must acquire a peptide in the lumen of the endoplasmic reticulum (ER) if it is to exit from the ER and progress to the surface of the target cell. Unlike HLA-A, -B, and -C, however, HLA-E is only able to bind to peptides generated from the leader sequence of HLA-A, -B, or -C after its removal from these MHC molecules. Uninfected and noncancerous cells express adequate levels of MHC molecules and a steady supply of leader-

sequence peptides ensures that normal levels of HLA-E arrive at the cell surface. This serves as an indicator of good health.

74.Answer: If a mother is homozygous for the KIR A haplotype, she expresses KIR2DL1 (an inhibitory NK-cell receptor) that binds to the C2 epitope of HLA-C on extravillous trophoblast cells. She does not, however, express KIR2DS1 (an activating NK-cell receptor) that uses the same C2 epitope ligand as KIR2DL1. In this combination, uterine NK cells do not receive sufficient activation to secrete the cytokines and growth factors that are required to adequately promote new blood vessel formation (angiogenesis). The result is shallow trophoblast invasion of the spiral arteries during implantation, which can result in an increased risk of preeclampsia in which the baby does not receive sufficient nutrients and the mother’s blood pressure rises to dangerously high levels that could lead to hemorrhage. In comparison, if a mother is homozygous for the KIR B haplotype, she expresses KIR2DS1, which counterbalances the effect of inhibitory C2-specific receptors. In this combination, uterine NK cells are activated in a manner that favors deep placental invasion and over-nourishment during pregnancy.

Elevated birth weight can lead to an obstructed labor.

75.Answer: The killing activity of the NK cell. Like cytotoxic T cells, NK cells can kill other cells by releasing molecules that induce apoptosis. When an activating receptor on an NK cell recognizes its ligand on the surface of a target cell, this tends to activate the killing function of the NK cell. But when an inhibitory receptor also recognizes its ligand on the target cell, this tends to inhibit the killing activity of the NK cell, even if activating receptors are also engaged. Whether the NK cell kills the target cell depends on the balance between the activating and inhibiting signals.

The known ligands for the inhibitory receptors are MHC class I molecules.

76.Answer: The actions of NK cells are considered part of innate immunity because NK cells can, in principle, act against any virus-infected cell: their

killing activity is not dependent on the recognition of viral protein epitopes. In addition, NK cells are already present and ready to act immediately after they encounter an infected cell. Although there are large numbers of different inhibitory and activating receptors in the NK-cell repertoire, none of these receptors is encoded by a rearranging gene, and in most cases the receptors specifically recognize HLA allotypes and are relatively insensitive to the peptides bound.

77.Answer: The baby’s father and mother are homozygous for the C1 epitope. The conditions for adequate nourishment of the fetus are established early in pregnancy and involve converting the narrow spiral arteries of the uterus into wider conduits after extravillous trophoblast invasion. These high-conductance vessels direct sufficient blood flow to the placenta during pregnancy and regulate the blood pressure of the mother.

Uterine NK cells interact with invading extravillous trophoblast cells using both inhibitory and activating receptors; which receptors are used is dependent on maternal haplotype. The KIR A haplotype lacks the activating KIR2DS1 receptor, which engages the C2 epitope, but the KIR B haplotype expresses this receptor.

Additionally, the KIR A haplotype expresses the strong inhibitory KIR2DL1 receptor which also engages the C2 epitope. In mothers who are homozygous for KIR A, the uterine NK cells encounter C2 epitopes on extravillous trophoblast cells using these strong inhibitory receptors. This causes an imbalance between inhibitory and activating signals delivered to the NK cells; KIR2DL1 will deliver strong inhibitory signals through the C2 epitope, but in the absence of KIR2DS1 there will be no activating signals delivered through the C2 epitope. If the uterine NK cells are not activated sufficiently, they will not secrete the cytokines and growth factors needed for complete invasion of the extravillous trophoblast cells, remodeling of the maternal spiral arteries, and promotion of new blood vessels. In the context of uterine NK cells, the increased risk for pre-eclampsia arises only when there is a combination of maternal homozygosity of the KIR A haplotype, and the

fetus inherits the C2 epitope from the father.

Name: ___________________________ Class: _________________ Date: __________

Chapter 13 1. Match each term with its function. a. latency b. seroconversion c. serotype d. superantigen e. gene conversion 1. rearrangement of homologous genes to expression sites by an excisionand-replacement mechanism 2. differences between genetic strains of bacteria based on antibody assays 3. development of a quiescent state that does not cause disease 4. the cause of nonspecific activation of T cells and excessive cytokine production 5. the initial onset of antiviral antibody

2. Match each term with its function. Select the most specific response and use each pathogen and condition once. a. Staphylococcus aureus b. Trypanosoma brucei c. Epstein–Barr virus d. Mycobacterium tuberculosis e. Varicella-zoster virus f. Salmonella typhimurium g. Human immunodeficiency virus h. Neisseria gonorrhoeae 1. glandular fever 2. chickenpox 3. sleeping sickness 4. toxic shock due to superantigen 5. lung infection due to infected macrophages 6. food poisoning 7. bacterial sexually transmitted disease 8. acquired immune deficiency syndrome

3. Match each deficiency disease with its specific abnormality. a. hereditary angioneurotic edema b. X-linked hyper IgM syndrome c. severe combined immunodeficiency d. MHC class I deficiency e. X-linked agammaglobulinemia f. leukocyte adhesion deficiency g. chronic granulomatous disease 1. defective transporter associated with antigen processing (TAP) 2. defective adenosine deaminase (ADA) 3. defective C1 inhibitor 4. defective CD40 ligand 5. defective Btk tyrosine kinase 6. defective CD18 7. defective NADPH oxidase

4. Match each term with its function. a. pol b. rev c. env d. nef e. vif f. gag g. vpu h. vpr i. tat 1. core and matrix protein 2. affects particle infectivity 3. transcriptional regulator 4. gp120 and gp41 5. assists viral replication and decreases expression of MHC class I and class II molecules and CD4 6. transcript export from nucleus 7. reverse transcriptase, protease, and integrase 8. initiates CD4 degradation and release of infectious virions from the cell 9. cell-cycle arrest, DNA transport to nucleus, and influences virion production

5. Match the mechanism of evasion and subversion of the immune system with the pathogen. a. variant pilin protein expression b. latent infection of sensory neurons c. reactivation of infected ganglia after stress or immunosuppression d. alternative expression of two antigenic forms of flagellin e. recombination of RNA genomes of avian and human origins f. escape from phagosome and growth and replication in cytosol g. survival in an impenetrable membrane-bounded vesicle resistant to fusion with other cellular vesicles h. coating its surface with human proteins i. inhibiting fusion of phagosome with lysosome and survival in the host cell’s vesicular system j. immunosuppression caused by nonspecific proliferation and apoptosis of T cells 1. Staphylococcus aureus 2. Toxoplasma gondii 3. Salmonella typhimurium 4. influenza virus 5. Mycobacterium tuberculosis 6. Varicella-zoster 7. Neisseria gonorrhoeae 8. Treponema pallidum 9. Listeria monocytogenes 10.Herpes simplex virus

6. Match each HIV-related term with its description. a. combination anti-retroviral therapy b. endogenous retrovirus c. clinical latency d. seroconversion e. provirus f. opportunistic pathogens g. viremic controllers 1. healthy individuals infected with HIV and who have low viremia (2,000 copies or fewer of viral RNA per milliliter of blood) 2. asymptomatic period that follows the initial phase of infection 3. anti-HIV antibodies first appear in circulatory system

4. naturally occurring retrovirus-like sequences making up 8% of the human genome 5. prevents progression to AIDS 6. commensal microorganisms actively controlled by healthy people 7. produced after cDNA integrates into the genome of the host cell

7. __________ results when a mutated gene affecting the immune system is inherited, thereby compromising the body’s defense against infection. a. Gene conversion b. Epidemics c. Primary immunodeficiency disease d. Secondary immunodeficiency disease e. Seroconversion.

8. A primary immune response against influenza virus produces antibodies that bind to a. hemagglutinin and neuraminidase. b. variable surface glycoproteins. c. EBNA-1. d. protein toxins. e. gp41 and gp120.

9. The serotypes of Streptococcus pneumoniae differ in their a. superantigen products. b. ability to fix complement. c. rates of gene conversion. d. capsular polysaccharides. e. variable surface glycoproteins.

10.Which of the following is NOT associated with the ability of influenza virus to escape from immunity? a. age b. error-prone replication of its DNA genome

c. co-infection with avian and human influenza viruses d. recombinant strains e. lack of neutralizing antibody

11.__________ does not use gene conversion to avoid immune detection. a. Salmonella typhimurium b. Trypanosoma brucei c. Treponema pallidum d. Neisseria gonorrhoeae.

12.Genes encoding __________ rearrange in trypanosomes permitting replication and survival of the pathogen until the host produces an antibody response against the altered gene product. a. pilin b. flagellin c. variable surface glycoproteins (VSGs) d. hemagglutinin

13.__________ is a strategy used by herpesviruses where replication and the generation of virus-derived peptides are avoided in order to hide from the immune response. a. Latency b. Antigenic shift c. Antigenic drift d. Seroconversion e. Gene conversion

14.Select the correct statement concerning herpes simplex virus. a. Because sensory neurons express high levels of MHC class I molecules, they provide appropriate sites for viral latency. b. Reactivation of herpes simplex virus results in virus moving from the sensory neuron to the epithelium. c. A skin rash of red blisters spread throughout the body develops as a

consequence of CD8 T-cell killing. d. Although infection with herpes simplex virus is common, individuals are able to successfully clear the virus and will not have symptoms again in their lifetime. e. Herpes simplex virus infects B lymphocytes.

15.. __________ is NOT known to reactivate herpes viruses. a. A fluctuation in hormones b. An antibody deficiency c. A bacterial infection d. Immunosuppression e. Ultraviolet radiation exposure

16.Select the correct statement concerning the family of human herpesviruses. a. They can infect epithelial cells, but not immune cells. b. They can remain latent in neurons, but not in immune cells. c. They are spread through respiratory and sexual contact, but not by saliva or through the blood. d. They are a group of single-stranded RNA viruses. e. They may cause cancer in addition to rashes or cold sores.

17.Shingles is associated with infection by a. Epstein–Barr virus. b. Staphylococcus aureus. c. herpes zoster. d. Candida albicans. e. Listeria monocytogenes.

18.Epstein–Barr virus–infected cells are poor targets for CD8 T-cell killing because a. the virus inhibits MHC class I expression. b. the virus escapes from the phagosome into the cytosol. c. infected cells do not express any viral proteins during latency.

d. the proteasome cannot generate viral peptides for presentation by MHC class I molecules.

19.Superantigens must bind to __________ before they can activate T cells. a. CD4, CD28, and MHC class I b. the MHC class II α chain, the T-cell receptor Vβ chain, and CD4 c. CD28, the MHC class II α chain, and the T-cell receptor Vβ chain d. T-cell receptor V α chain, the MHC class II α chain, and CD4

20.Superantigens a. must be present at a high concentration for their activity. b. nonspecifically activate 2–20% of the body’s CD8 T cells. c. are processed into peptides prior to T-cell activation. d. lead to the secretion of cytokines that suppress inflammation. e. activate CD8 T cells.

21.Staphylococcal superantigen-like protein 7 (SSLP7) produced by Staphylococcus aureus binds to __________ and thereby prevents the killing of the bacterium by the host’s immune system during infection. a. NK-cell activating receptors b. the C9 complement protein c. the CD8 co-receptor d. the T-cell receptor Vβ chain e. the Fc region of IgA

22.Which of the following is NOT associated with bacterial infection due to a genetic defect in or pathogen-induced subversion of normal phagocytic processes? a. leukocyte adhesion deficiency b. chronic granulomatous disease c. chronic granulomatous disease d. Chédiak–Higashi syndrome e. Listeria monocytogenes

23.IFN-γ a. improves immunity to extracellular bacteria, but not to intracellular bacteria. b. is not bound to macrophages because they lack the IFN-γ receptor. c. activates the JAK–STAT signal transduction pathway after binding to its cognate receptor. d. is secreted by NK cells, but not by CD8 T cells. e. plays a role in the adaptive immune response, but not the innate immune response.

24.Dominant mutant forms of IFNγR1 a. bind more strongly to JAK proteins and enhance signaling. b. have a truncated cytoplasmic tail. c. are able to form a dimer with IFNγR2 and initiate signaling. d. cause a more severe form of immunodeficiency than do the homozygous recessive forms. e. are not able to be expressed on the cell surface.

25.An infection with __________ would be least impacted by an antibody deficiency. a. Streptococcus pneumoniae b. Haemophilus influenzae c. Streptococcus pyogenes d. Mycobacterium tuberculosis e. Staphylococcus aureus.

26.When deficient, which of the following proteins does NOT render the individual more susceptible to encapsulated bacteria? a. C1INH b. C3 c. Bruton’s tyrosine kinase d. factor D e. CD40 ligand.

27.The best treatment for X-linked agammaglobulinemia is a. gamma globulin injections. b. GM-CSF injections. c. IFN-γ injections. d. C1INH infusions.

28.Which of the following diseases would affect males and females equally? a. Wiskott–Aldrich syndrome caused by deficiency of WASP b. hyper IgM syndrome caused by deficiency of CD40 ligand c. Chédiak–Higashi syndrome caused by deficiency of CHS1 d. agammaglobulinemia caused by deficiency of Bruton’s tyrosine kinase e. SCID caused by deficiency of common γ chain

29.Deficiencies in complement components C5–C9 and properdin (factor P) are associated with a. immune-complex disease. b. susceptibility to Neisseria. c. secondary immunodeficiency diseases. d. hereditary angioedema. e. leukocyte adhesion deficiency.

30.Paroxysmal nocturnal hemoglobinuria is caused by a. a profound deficiency of neutrophils. b. leukocytosis. c. immune-complex deposition in tissues. d. defects in recruitment of phagocytes to infected tissues. e. complement-mediated lysis of erythrocytes.

31.In hereditary angioedema, a. there is an overactivation of the C1r and C1s enzymes. b. levels of the vasoactive enzyme bradykinin remain the same as in an unaffected individual.

c. there is a hyporesponsiveness of the classical complement pathway. d. affected individuals form immune complexes that damage blood vessels. e. affected individuals cannot prevent the formation of complement on their red blood cells.

32.Select the correct statement regarding C1 inhibitor (C1INH). a. C1INH belongs to a family of serine and cysteine protease inhibitors called the properdins. b. C1INH inhibits C1r but not C1s, so partial serine protease activation is achieved in the classical complement pathway. c. C1INH is cleaved by C1. d. When bound to C1 as a pseudosubstrate, it activates the protease activity of C1. e. C1INH reversibly inactivates C1, allowing it to inhibit multiple targets.

33.Severe combined immune deficiency (SCID) describes a condition in which neither __________ nor __________ are functional. a. classical; alternative pathways of complement b. T-cell-dependent antibody responses; cell-mediated immune responses c. innate; acquired immune responses d. MHC class I; MHC class II molecules

34.Wiskott–Aldrich syndrome involves an impairment of a. lymphocytes and platelets. b. classical complement and blood-clotting pathways. c. the expression of MHC class I and class II molecules. d. T-cell and B-cell development. e. cytokine and cytokine receptor production.

35.Mutations involving adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) a. prevent normal phagocytosis. b. would not affect the secretion of IFN-γ by T cells.

c. do not affect the amount of circulating antibodies. d. interfere with the rearrangement of the T-cell receptor genes. e. target T-cell development in the thymus.

36.A deficiency in __________ causes a condition that closely resembles X-linked severe combined immunodeficiency and is characterized by inefficient cytokine signaling. a. adenosine deaminase (ADA) b. class II transactivator (CIITA) c. TAP1 or TAP2 d. RAG1 or RAG2 e. Janus 3 kinase (Jak3)

37.Patients who lack __________ are very susceptible to infections with intracellular bacteria, including the ubiquitous nontuberculous strains of mycobacteria. a. CD40 ligand b. the IL-12 receptor c. C1 inhibitor (C1INH) d. properdin (factor P) e. CD18

38.Which of the following explains why Streptococcus pneumoniae can infect an individual recurrently? a. Previous infection with S. pneumoniae wears down the immune system over time. b. S. pneumoniae is never completely eradicated during an infection and can reactivate if the host is immunocompromised. c. Immune responses against S. pneumoniae are serotype-specific and protect only against strains that possess the same capsular polysaccharide antigens. d. Anti-capsular antibodies are cleared from the host quickly after an active infection. e. The capsular polysaccharide antigens of S. pneumoniae do not induce immunological memory.

39.Protective antibodies generated in response to influenza virus bind to __________ of the viral envelope. a. hemagglutinin and neuraminidase b. polysaccharides c. variable surface glycoproteins d. superantigens e. gp41 and gp120

40.Which of the following contribute to new epidemics and the long-term survival of the influenza virus in the human population? a. New viral strains possess epitopes not recognized by antibodies made in the previous epidemic. b. The virus loses the capacity to express hemagglutinin, thereby rendering neutralizing antibodies useless. c. The virus uses gene rearrangement to achieve antigenic variation, which creates new epitopes. d. The influenza virus can only infect humans.

41.An epidemic affects __________, whereas a pandemic affects __________. a. susceptible individuals; immune individuals b. immune individuals; susceptible individuals c. global populations; local populations d. local populations; global populations

42.The mode of evolution responsible for the production of recombinant influenza viruses composed of a genome derived from two different influenza variants is called a. gene conversion. b. antigenic shift. c. latency. d. immune evasion. e. antigenic drift.

43.__________ cause(s) mild and limited disease, whereas __________ cause(s) more severe disease and higher mortality. a. Antigenic drift; antigenic shift b. Antigenic shift; antigenic drift c. Epidemics; pandemics d. Pandemics; epidemics

44.Which of the following is NOT a virus that can cause a persistent infection in the host by establishing latency? a. influenza virus b. herpes simplex virus c. varicella-zoster d. Epstein–Barr virus e. human immunodeficiency virus

45.Trypanosomes escape from adaptive immunity by altering the type of __________ expressed on the parasite surface. a. neuraminidase b. hemagglutinin c. variable surface glycoprotein (VSG) d. superantigen e. capsular polysaccharide.

46.Epstein–Barr virus infects and establishes latency in __________, gaining entry by binding to __________. a. B cells; CR2 b. T cells; CD4 c. T cells; CD8 d. neurons; MHC class I e. B cells; EBNA-1

47.Which of the following strategies is NOT used by the human cytomegalovirus to subvert host immune responses? a. degradation of MHC class I b. the cytosol; escaping from the phagosome c. a specialized membrane-bound vesicle; infection of the cell d. extracellular spaces; coating itself with human proteins e. nucleus; fusion with the nuclear membrane

48.Listeria monocytogenes replicates in __________ of macrophages after __________. a. the phagosome; inhibition of fusion of the phagosome with the lysosome b. the cytosol; escaping from the phagosome c. a specialized membrane-bound vesicle; infection of the cell d. extracellular spaces; coating itself with human proteins e. nucleus; fusion with the nuclear membrane

49.Which of the following describes staphylococcal toxic shock syndrome toxin-1? a. It binds to MHC class I molecules and T-cell receptors. b. It prevents the proliferation of naive CD4 T cells. c. It binds to the Fc region of antibodies. d. It causes excessive synthesis and release of cytokines. e. It binds and activates one T-cell clone bearing one specific T-cell receptor.

50.Which of the following statements regarding inherited immunodeficiency diseases is correct? a. Affected individuals are less susceptible to infection. b. Mortality rates are reduced by the administration of antibiotics to affected individuals. c. Most deficiency syndromes are caused by dominant gene defects. d. Women are more likely than men to inherit X-linked immunodeficiencies. e. Extracellular bacterial infections are common in deficiency syndromes with T-cell defects.

51.Individuals with an immunodeficiency affecting B-cell function are more susceptible to infections caused by which of the following pathogens? a. Toxoplasma gondii b. respiratory syncytial virus c. Haemophilus influenzae d. Listeria monocytogenes e. Mycobacterium tuberculosis

52.Women who are heterozygous for a defective Bruton’s tyrosine kinase (Btk) gene a. are more susceptible to infections caused by extracellular pyogenic bacteria. b. have a 50% chance of having a son with X-linked hyper IgM syndrome. c. mount normal B-cell immune responses despite having lowered levels of serum IgG. d. exhibit X-linked agammaglobulinemia. e. have non-random X inactivation in their B cells.

53.Which of the following deficiency syndromes affects cytoskeletal reorganization in the T cell, thus preventing its cognate interaction with a B cell? a. X-linked agammaglobulinemia b. X-linked hyper IgM syndrome c. X-linked lymphoproliferative syndrome d. X-linked SCID e. X-linked Wiskott–Aldrich syndrome

54.A mutation in the CD18 integrin molecule a. results in Chédiak–Higashi syndrome. b. prevents the normal development of T cells. c. diminishes the respiratory burst and can lead to repeated bacterial infections. d. prevents phagocyte migration and can lead to repeated bacterial infections. e. is treated by intravenous immunoglobulin.

55.__________ participates in the T-cell cytoskeletal reorganization required for Tcell cytokine production and cell-mediated interactions. a. Adenosine deaminase (ADA) b. Purine nucleotide phosphorylase (PNP) c. Wiskott–Aldrich syndrome protein (WASP) d. Myeloperoxidase e. Bruton’s tyrosine kinase (Btk)

56.Chronic granulomatous disease (CGD), a condition resulting in chronic bacterial and fungal infections, is caused by one or more defects in __________, compromising the ability of macrophages to __________. a. CD18; produce cell adhesion molecules b. NADPH oxidase; produce superoxide radical (O2–) c. CD40 ligand; produce GM-CSF d. C5–C9; defend against Neisseria e. C3; opsonize capsulated bacteria

57.A genetic defect in __________ results in the accumulation of toxic levels of nucleotide metabolites and loss of T-cell function. a. NADPH oxidase b. glucose-6-phosphate dehydrogenase c. myeloperoxidase d. SH2D1A e. adenosine deaminase (ADA)

58.MHC class II deficiency is due to a defect in a. transcriptional regulators of HLA class II loci. b. the sequence of the conserved X box of the HLA class II promoter. c. a TAP peptide transporter. d. RAG-1 or RAG-2. e. a Jak kinase.

59.Herpes simplex virus favors neurons for latency because of the low level of __________, which reduces the likelihood of killing by CD8 T cells. a. LFA-3 b. Toll-like receptors (TLRs) c. the transporter associated with antigen processing (TAP) d. MHC class I e. MHC class II

60.Select the correct statement concerning retroviruses. a. Proviruses form immediately after the RNA genome assembles with viral proteins and infectious virions are produced. b. Proviruses consist of double-stranded RNA. c. Proviruses are flanked by repetitive sequences called long terminal repeats (LTRs). d. The retrovirus provides the translational machinery to produce protein products from proviruses. e. Proviruses are temporary structures and are not passed on to the daughter cells when the infected cell undergoes cell division.

61.The pol gene of HIV produces a. integrase, protease, and gp120 proteins. b. protease and core proteins. c. matrix and core proteins. d. reverse transcriptase, integrase, and protease proteins. e. gp120 and gp41 proteins.

62.For a cell to become infected and produce new HIV virions, the infected cell must a. lack chemokine receptor expression. b. express CD8 on the cell surface. c. express functional NFκB. d. be latent. e. not contain provirus.

63.Which HIV protein(s) must be present in the virion to allow it to bind and infect target cells? a. gp120 and gp41 b. reverse transcriptase c. vif d. gag e. tat

64.Which of the following is required for fusion of the human immunodeficiency viral envelope with the host cell membrane and subsequent internalization? a. reverse transcriptase b. gp120 c. gp41 d. integrase e. protease

65.Select the correct statement about human immunodeficiency virus (HIV). a. HIV has a DNA genome. b. HIV must synthesize reverse transcriptase immediately after infecting a cell. c. Reverse transcriptase synthesizes the copy of the viral RNA genome that gets packaged in the virus particle. d. HIV envelope proteins require either the CXCR4 or CCR5 co-receptor for fusion. e. The HIV Tat protein is involved in transporting RNA to the cytosol.

66.During infection with HIV, a person is said to undergo seroconversion when a. HIV variants convert from macrophage-tropic to lymphocyte-tropic late in infection. b. anti-HIV antibodies are detectable in their blood serum. c. cellular transcription favors the production of HIV-encoded RNA. d. HIV is transferred from an infected person to an uninfected recipient. e. the initial phase of infection is followed by clinical latency.

67.A patient is diagnosed with AIDS when CD4 T-cell counts a. rise markedly after T-cell activation. b. fall below the CD8 T-cell count. c. fall below 1000 cells/μ l. d. fall below 500 cells/μ l. e. fall below 200 cells/μ l.

68.Reverse transcriptase is a(n) __________ encoded by __________. a. DNA-dependent DNA polymerase; HIV b. DNA-dependent DNA polymerase; influenza virus c. RNA-dependent DNA polymerase; HIV d. RNA-dependent DNA polymerase; influenza virus e. RNA-dependent RNA polymerase; HIV

69.HIV anti-retroviral therapy frequently targets a. reverse transcriptase and protease. b. matrix proteins and core proteins. c. gp120 and gp41. d. CD4 and CCR5.

70.Staph aureus secretes __________ that functions to prevent both FcR-mediated phagocytosis and complement-mediated lysis. a. an IgA-binding protein b. an IgM-binding protein c. C1 inhibitor d. pilins

71.Select the correct statement concerning immunodeficiency diseases. a. Immunodeficiency diseases are caused by X-linked genes only. b. Immunodeficiency diseases are not caused by dominant alleles.

c. There are no immunodeficiency diseases that target cells types other than B or T cells. d. Whole-genome sequencing and gene “knockout” studies are used to identify mutations leading to immunodeficiency. e. Defects in innate immunity do not lead to immunodeficiency diseases because the adaptive immune system compensates and provides protection.

72.Individuals with an inherited mutation leading to nonfunctional CD40 ligand protein a. have B cells with functional B-cell receptors, but they are unable to secrete any isotype of antibody. b. have normally developing germinal centers in the secondary lymphoid tissues allowing for normal isotype switching. c. have T helper cells that cannot be activated. d. have abnormally high levels of the cytokine GM-CSF secreted by activated T cells. e. display a reduction in circulating neutrophils and a high level of circulating IgM following infection.

73.Select the correct statement concerning individuals who are born lacking a functional IL-12 receptor. a. Following infection, their immune cells secrete normal levels of IFN-γ and IL-2 when compared to an individual with a functional IL-12 receptor. b. Although they can secrete high levels of IgM, they are unable to undergo isotype switching to IgA or IgE. c. They experience recurrent infections with encapsulated, extracellularreplicating bacteria such as Streptococcus or Staphylococcus. d. The function of both their NK cells and macrophages is diminished. e. These individuals should be protected from tuberculosis by being vaccinated with the Calmette–Guérin vaccine.

74.Select the correct statement concerning HIV-1 and HIV-2. a. They both evolved from a virus that jumped from chimpanzees to humans. b. Both viruses have caused pandemics.

c. Both viruses contain gag, pol, and env genes. d. It is not possible to be co-infected with both HIV-1 and HIV-2. e. Both viruses are classified as herpesviruses.

75.Individuals who have a deletion in the gene that codes for __________ resist HIV infection following exposure and still clear infections with other pathogens. a. CCR5 b. CD4 c. HLA-B57 d. CCL3 e. gp120

76.__________ cells of the innate immune system respond to particular HLA alleles early in an HIV infection and, thus, may alter the timing of progression to AIDS. a. Natural killer b. Macrophage c. Dendritic d. Cytotoxic CD8 T

77.The progression of HIV infection following antiretroviral therapy is measured by a. the CD4 T-cell count and number of HIV virions in the blood. b. the number of integrated proviruses in CD4 T cells. c. the concentration of neutralizing antibody in the blood. d. the CD8 T-cell count in the blood. e. the number of HIV virions in the secondary lymphoid tissues.

78.HIV-infected CD4 T cells a. cannot be memory CD4 T cells. b. are not replaced by hematopoiesis during clinical latency. c. may be killed by CD8 cytotoxic T cells. d. do not express any MHC class I on the cell surface.

79.HIV-specific broadly neutralizing antibodies a. target the reverse transcriptase enzyme, thus preventing infection. b. target epitopes of the highly variable region of the gp120 protein that are not conserved, thus preventing infection with a variety of HIV strains. c. do not require CD40L expression on CD4 T cells for their generation. d. may have insertions in the DNA leading to longer than normal CDR loops. e. are produced after a few years in nearly every individual infected with HIV.

80.Select the correct statement concerning an individual infected with HIV.

a. The time point marked “A” represents the transition to the symptomatic phase of HIV infection. b. During the time period labeled “B”, HIV is latent in infected T cells and there would be no Tat or Pol proteins detected in any of their CD4 T cells.

c. During the “C” phase of the infection this individual would have a low viral load. d. Once in the “D” phase of the infection this individual may have symptoms resembling children with SCIDs. e. The y-axis label shown by “E” should read “Viral RNA molecules per ml of plasma” and indicates viral load.

81.Select the correct statement concerning a bacterial infection. The Staphylococcus aureus bacterial cells are shown as large, dark gray ovals and the macrophage as the light gray cell in the upper right corner of the figure.

a. If the antibody shown is IgA, it would trigger phagocytosis by binding to the molecule labeled “A”, which is FcγRIIB1. b. The SSLP7 molecule will enhance antibody-mediated opsonization and phagocytosis. c. Complement-mediated lysis of the bacteria will be improved in the presence of the SSLP7 molecule. d. Some individuals may inherit antibody variants unable to bind SSLP7. e. SSLP7 functions in the same manner as toxic shock syndrome toxin-1.

82.Select the correct statement concerning the immune response involving CTLs, macrophages, and TH1 cells.

a. IL-12 is the cytokine labeled “A”. b. Stimulation of CTLs with IL-12 will enhance the immune response to infection with Mycobacterium avium. c. Macrophages lacking functional IFN-γ receptors will still be activated by the CTL. d. You would still observe this cycle of mutual activation in individuals having nonfunctional Jak1 or Jak2 proteins. e. You would not observe this cycle of mutual activation in individuals with nonfunctional Bruton’s tyrosine kinase.

83.Christiana Carter had no obvious problems until she was 18 months old, after which she stopped gaining weight, her appetite became poor, and she had recurrent episodes of diarrhea. At 24 months, Christiana developed a cough with pulmonary infiltrates unresponsive to treatment with the antibiotics clarithromycin and trimethoprim/sulfamethoxazole. Within 3 months, she developed lymphadenopathy, hepatosplenomegaly, and fevers. A computed tomography scan revealed enlarged mesenteric and para-aortic lymph nodes. A biopsy of an enlarged axillary lymph node revealed acid-fast bacilli, and cultures from the lymph node and blood grew Mycobacterium fortuitum. HIV was ruled out after negative tests by ELISA and PCR. Serologic testing for tetanus antitoxoid antibody showed a normal post-vaccination level. Christiana’s peripheral blood mononuclear cells (PBMCs) were cultured with interferon-γ plus lipopolysaccharide with no significant increase in TNF-α production. A variety of broad-spectrum and anti-mycobacterial antibiotics were administered, lowering the fever, and over the course of the next 2 months Christiana began to gain weight but continued to show signs of persistent infection. Which of the following is the most likely explanation for these clinical findings?

a. leukocyte adhesion deficiency b. chronic granulomatous disease c. interferon-γ receptor deficiency d. X-linked agammaglobulinemia e. severe combined immune deficiency

84.Which components of the influenza virus are the most important in the immune response? Explain why you selected these components.

85.Name three immunodeficiency diseases caused by defects in phagocytes. What are the main clinical effects of defects in phagocyte function?

86.Which immunodeficiency disease is caused by a defect in the phagocyte NADPH oxidase system, and what is the cellular effect of this defect?

87.Explain the cellular tropism of HIV, discussing the difference between macrophage-tropic and lymphocyte-tropic HIV.

88.Some people seem to be resistant to HIV infection because a primary infection cannot be established in macrophages. What is the reason for this?

89.Explain why certain staphylococcal or streptococcal infections might produce a medical emergency.

90.Explain the difference between antigenic drift and antigenic shift in the influenza virus and explain which of the two is more likely to lead to a major worldwide pandemic.

91.Why does it benefit the African trypanosome (T. brucei) to maintain more than 1000 genes encoding surface glycoproteins, when only one of these

glycoproteins is expressed on the surface of the parasite at any given time?

92.Deficiencies in antibody production can be due to a variety of underlying genetic defects. Name two immunodeficiency diseases, other than the severe combined immunodeficiencies, in which a defect in antibody production is the cause of the disease, and for which the underlying genetic defect is known. For each disease, say (i) how antibody production is affected, and (ii) what the underlying defect is and why it has this effect.

93.Explain why women who show no disease symptoms themselves can pass on some heritable diseases to their sons, whereas their daughters seem to be unaffected. Would a disease with this pattern of inheritance be caused by a recessive or a dominant allele?

94.What type of immune deficiency would you see in a child lacking the common γ chain of the receptor for cytokines IL-2, IL-4, and IL-7, among others? Explain your answer.

95.Compare the type of immunodeficiency you would see in a child lacking the common γ chain of the receptor for cytokines IL-2, IL-4, and IL-7 with the type of immunodeficiency that would be observed in a child lacking Jak3 kinase function.

96.Christiana Carter had no obvious problems until she was 18 months old, after which she stopped gaining weight, her appetite became poor, and she had recurrent episodes of diarrhea. At 24 months, Christiana developed a cough with pulmonary infiltrates unresponsive to treatment with the antibiotics clarithromycin and trimethoprim/sulfamethoxazole. Within 3 months, she developed lymphadenopathy, hepatosplenomegaly, and fevers. A computed tomography scan revealed enlarged mesenteric and para-aortic lymph nodes. A biopsy of an enlarged axillary lymph node revealed acid-fast bacilli, and cultures from the lymph node and blood grew Mycobacterium fortuitum. HIV was ruled out after negative tests by ELISA and PCR. Serologic testing for tetanus antitoxoid antibody showed a normal post-vaccination level. Christiana’s peripheral blood mononuclear cells (PBMCs) were cultured with interferon-γ plus lipopolysaccharide with no significant increase in TNF-α production. A variety of

broad-spectrum and anti-mycobacterial antibiotics were administered, lowering the fever, and over the course of the next 2 months Christiana began to gain weight but continued to show signs of persistent infection. Evaluate the following options and select the explanation that is most likely. Defend your choice.

Possible explanations are: a. leukocyte adhesion deficiency b. chronic granulomatous disease c. interferon-γ receptor deficiency d. X-linked agammaglobulinemia e. severe combined immune deficienc

97.Explain the difference between elite controllers and elite neutralizers.

98.Explain the mechanism by which human immunodeficiency virus (HIV) enters a host cell.

99.What does the term seroconversion mean in relation to an HIV infection?

100.

Which property of HIV renders the virus difficult to eradicate by the body’s immune defenses and also limits the efficacy of drug therapies?

101.

What would you predict might happen to the course of the HIV infection in a person who developed toxic shock syndrome while in the latent phase of HIV? Explain your answer.

Answer Key Chapter 13 1. Answer:

1. E 2. C 3. A 4. D 5. B

2. Answer:

1. E 2. E 3. B 4. A 5. D 6. F 7. H 8. G

3. Answer:

1. D 2. C 3. A 4. B 5. E 6. F 7. G

4. Answer:

1. F 2. E 3. I 4. C

5. D 6. B 7. A 8. G 9. H 5. Answer:

1. J 2. G 3. D 4. E 5. I 6. C 7. A 8. H 9. F 10. B

6. Answer:

1. G 2. C 3. D 4. B 5. A 6. F 7. E

7. Answer:

C

8. Answer:

A

9. Answer:

D

10.Answer:

B

11.Answer:

C

12.Answer:

C

13.Answer:

A

14.Answer:

B

15.Answer:

B

16.Answer:

E

17.Answer:

C

18.Answer:

D

19.Answer:

C

20.Answer:

B

21.Answer:

E

22.Answer:

C

23.Answer:

C

24.Answer:

B

25.Answer:

D

26.Answer:

A

27.Answer:

A

28.Answer:

C

29.Answer:

B

30.Answer:

E

31.Answer:

A

32.Answer:

C

33.Answer:

B

34.Answer:

A

35.Answer:

E

36.Answer:

E

37.Answer:

B

38.Answer:

C

39.Answer:

A

40.Answer:

A

41.Answer:

D

42.Answer:

B

43.Answer:

A

44.Answer:

A

45.Answer:

C

46.Answer:

A

47.Answer:

E

48.Answer:

B

49.Answer:

D

50.Answer:

B

51.Answer:

C

52.Answer:

E

53.Answer:

E

54.Answer:

D

55.Answer:

C

56.Answer:

B

57.Answer:

E

58.Answer:

A

59.Answer:

D

60.Answer:

C

61.Answer:

D

62.Answer:

C

63.Answer:

A

64.Answer:

C

65.Answer:

D

66.Answer:

B

67.Answer:

E

68.Answer:

C

69.Answer:

A

70.Answer:

A

71.Answer:

D

72.Answer:

E

73.Answer:

D

74.Answer:

C

75.Answer:

A

76.Answer:

A

77.Answer:

A

78.Answer:

C

79.Answer:

D

80.Answer:

D

81.Answer:

D

82.Answer:

B

83.Answer:

C

84.Answer:

Influenza hemagglutinin (HA) and neuraminidase (NA) bear the main epitopes against which protective antibodies are made. Because these proteins are expressed on the viral envelope, neutralizing antibodies can be produced and protect from reinfection with the same strain.

85.Answer:

Chronic granulomatous disease, Chédiak–Higashi syndrome, and leukocyte adhesion deficiency are three diseases caused by defects in phagocytes; others include glucose-6-phosphate dehydrogenase deficiency and myeloperoxidase deficiency. Clinical effects of such defects include persistent infections with bacteria (especially encapsulated bacteria) and fungi.

86.Answer:

Chronic granulomatous disease is caused by defects in phagocyte NADPH oxidase. Phagocytes with this defect cannot produce superoxide radicals and are less effective at intracellular killing of ingested bacteria. Macrophages infected with bacteria that they cannot kill form the granulomas characteristic of this condition.

87.Answer:

The cell tropism of HIV depends on which co-receptor is used for entry. Macrophage-tropic HIV, associated with early infection, uses the CCR5 co-receptor. Lymphocytetropic HIV, associated with a phenotypic change in late infection in about 50% of cases, uses CXCR4.

88.Answer:

About 1% of individuals of European descent are homozygous for a mutant form of CCR5 that cannot be used by HIV as a co-receptor. The mutation involves a

32-nucleotide deletion called CCR5-δ32, which alters the reading frame and results in a nonfunctional CCR5 protein. This renders such individuals resistant to primary infection by macrophage-tropic variants of HIV but still susceptible to lymphocyte-tropic strains that use the CXCR4 co-receptor.

89.Answer:

Some staphylococci produce toxins that act as superantigens; examples include staphylococcal enterotoxins and toxic shock syndrome toxin-1 (TSST-1).

Superantigens can bind simultaneously to MHC class II molecules and to T-cell receptors that possess certain types of Vβ region, resulting in the activation of all T cells carrying such a receptor. Superantigens thus nonspecifically activate a large proportion of the CD4 Tcell repertoire, resulting in the production of large quantities of cytokines from the activated T cells and from macrophages activated by these cells. The systemic production of cytokines (for example TNF-α) causes increased vascular permeability and vasodilation throughout the body, leading to loss of fluid into the tissues, rapid collapse of the circulatory system (systemic shock), and organ failure. Toxic shock therefore requires immediate medical attention, primarily to replace the intravascular fluid.

90.Answer:

Antigenic drift is due to the frequent point mutations in the RNA genome of influenza virus. Mutants that acquire changes in the HA and NA epitopes are selected because they are not subject to the serotype-specific immunity generated against the original strain. Because point mutation causes only relatively small changes at a time, this process is known as antigenic drift.

Antigenic shift is due to recombination between a human influenza virus and an avian influenza virus, leading to replacement of the human NA and/or HA with the avian type. The genome of the influenza virus is composed of eight separate pieces of RNA. When a human influenza virus and an avian influenza virus infect the same cell (usually in domestic livestock such as pigs, ducks, or chickens), reassortment of the RNAs can lead to the generation of a new human virus encoding the avian HA and/or NA that has never before been encountered by the human population. Worldwide pandemics are caused by influenza viruses that have undergone antigenic shift, because no human population has any immunity to them.

In antigenic drift, where the changes are more gradual, a population will contain some people who are immune to some epitopes and some to others. Epidemics due to

antigenic drift are usually relatively mild and limited.

91.Answer:

This strategy has been selected by evolution to maintain the long-term survival of the parasite in its host. The surface glycoproteins, known as variable surface glycoproteins (VSGs), are involved in enabling the parasite to evade the immune response of its host. The trypanosome can change the VSG that is expressed, thus rendering antibodies made against the previously expressed VSG ineffective at controlling the parasite.

Switching occurs at random during the life cycle of the trypanosome by a process called gene conversion, in which a different VSG gene is rearranged to the single “expression site,” replacing the original gene, and is expressed instead. This process is called antigenic variation and leads to the periodic rise and fall in the number of parasites that is characteristic of trypanosome infections. Antibodies made by the host against the VSG expressed on the infecting trypanosomes will start to suppress the infection and parasite numbers will fall. But if some parasites switch VSG, these antibodies will be ineffective, and parasites bearing the new VSG will multiply. Parasite numbers will rise for a time until the new immune response begins to suppress them in turn.

By then a third VSG gene is likely to have been expressed, and parasites bearing that one will begin to predominate in the host, and so the cycle continues.

92.Answer:

1. X-linked agammaglobulinemia. (i) No antibody at all. (ii) It is caused by a defect in the tyrosine kinase Btk, which is necessary for B-cell development and is encoded on the X chromosome. No mature B cells develop. 2. X-linked hyper IgM syndrome. (i) Large amounts of IgM antibody, but no antibodies of isotypes other than IgM, are produced. Virtually no antibodies are made against T-cell dependent antigens. (ii) It is caused by a defect in the protein CD40 ligand, which is encoded on the X chromosome and is expressed on T cells. T cells lacking CD40 ligand cannot give help to B cells, which thus cannot respond to most protein antigens and cannot switch isotype.

93.Answer:

Diseases with this pattern of inheritance are caused by defective alleles carried on the X chromosome and are called X-linked diseases. Generally, women have two X chromosomes, one inherited from each parent. A man only has one X chromosome, which he always inherits from his mother. A woman with one X chromosome carrying a recessive disease allele and one X

chromosome with a normal allele will show no symptoms of the disease because the normal allele will compensate.

However, if she passes on the defective X chromosome to a son, he will show the disease because he has no compensating normal allele. Unless the father also has the defective allele, which is extremely unlikely because most of these immune defects are very rare, a daughter will also not show the disease even if she inherits a defective X chromosome from her mother. Diseases that show this pattern of inheritance are always recessive. A dominant disease allele carried on an X chromosome will show up as disease equally in women (even if they are heterozygous for the gene) and in men.

94.Answer:

Severe combined immune deficiency (SCID), characterized by an almost complete absence of T-cell and B-cell function and the inability to make any effective immune responses. Because the child cannot make functional receptors for these important cytokines, their lymphocytes cannot respond to them. The inability of naive T cells to respond to IL-2 in particular blocks the proliferation and differentiation of T cells and thus all cellmediated immune responses and T-cell dependent antibody responses. Without treatment, children with SCID die early in infancy from common bacterial or viral infections.

95.Answer:

Both mutations would lead to severe combined immune deficiency (SCID), which is characterized by an almost complete absence of T-cell and B-cell function and the inability to make any effective immune responses. The lymphocytes of children lacking the common γ chain of the receptor cannot respond to IL-2, IL-4, or IL-7. The inability of naive T cells to respond to IL-2 in particular blocks the proliferation and differentiation of T cells and thus all cell-mediated immune responses and T-cell dependent antibody responses. Without treatment, children with SCID die early in infancy from common bacterial or viral infections. Because Jak3 kinase is part of the intracellular signaling pathway that leads from activated cytokine receptors that contain the common γ chain of the receptor, a lack of Jak3 kinase also leads to SCID.

96.Answer:

Interferon-γ receptor deficiency is the answer. The key finding here is the unresponsiveness of Christiana’s PBMCs to interferon-γ (IFN-γ) plus LPS. When IFN-γ binds the IFN-γ receptors of macrophages, these cells become stimulated and very effective at killing

intravesicular bacteria such as mycobacteria. Defects in the IFN-γ a receptor are associated with persistent mycobacterial infections. Because of Christiana’s age, she is likely to be homozygous for a recessive mutation in IFNγR1 that leads to the lack of receptor. Chronic granulomatous disease and leukocyte adhesion disease result from defects in NADPH oxidase and CD18, respectively, but these defects would not hinder the ability of PBMCs from affected individuals to produce TNF-α in response to IFN-γ. Because Christiana has normal levels of tetanus antitoxoid antibody, she does not have Xlinked agammaglobulinemia or severe combined immune deficiency.

97.Answer:

Elite controllers, who make up about 1 in 300 of HIVinfected people, suppress their infection so effectively that HIV RNA cannot be detected in blood samples using the standard clinical assay. They live healthy lives for decades. Elite neutralizers, who make up about 1 in 500 of HIV-infected people, make broadly neutralizing antibodies after exposure to several HIV strains. These antibodies possess many more somatic mutations than other antibodies, indicating that B cells making the broadly neutralizing antibodies have undergone many different episodes of antigen-mediated somatic mutation.

These antibodies can neutralize many strains of HIV.

98.Answer:

Human immunodeficiency virus (HIV) infects cells bearing CD4 molecules on their surface. These include TH1 and TH2 cells, macrophages, and dendritic cells. CD4 acts as a receptor involved in binding the gp120 envelope glycoprotein of HIV. A co-receptor is also required for virus entry. Two are used by HIV: the chemokine receptors CCR5 and CXCR4. CCR5 is expressed on all CD4+ cells, whereas CXCR4 is restricted to T cells. After binding to the co-receptor, another viral envelope glycoprotein, gp41, facilitates fusion between the host cell’s plasma membrane and viral envelope with the release of viral components into the cytoplasm.

99.Answer:

Seroconversion is the point during an infection at which antibodies specific for the pathogen can first be detected in the blood serum. In an HIV infection, antibody is produced when virions are being released from infected cells and are thus accessible to B-cell antigen receptors, a period referred to as acute viremia. During clinical latency, the level of infectious virus in plasma decreases markedly but does not disappear.

100.

Answer: HIV is a retrovirus that uses the enzyme reverse transcriptase to complete its life cycle. This enzyme uses the single-stranded RNA genome of HIV as a template to make a double-stranded DNA (complementary DNA or cDNA) that integrates into the host genome as a provirus.

Reverse transcriptase is an error-prone DNA polymerase that lacks proofreading capabilities. Mutations are therefore introduced into the HIV genome each time it is replicated. Such rapid mutation leads to variant viruses with modified antigens, which thus escape detection by antibodies or cytotoxic T cells specific for the original epitopes. The high rate of mutation in HIV also causes the emergence of resistance to the antiviral drugs used to treat HIV infection, which are mainly drugs that inhibit viral reverse transcriptase and protease. Mutation produces viruses with mutant enzymes that are not blocked by the drugs. Multidrug regimes are used to try to eliminate the virus before the multiple mutations needed to resist all the drugs have accumulated.

101.

Answer: Toxic shock syndrome is caused when superantigens, such as toxic shock syndrome toxin-1 (TSST-1) produced by some strains of Staphylococcus, nonspecifically activate large numbers of CD4 T cells. When a T cell is activated, the transcription factor NFκB is activated and switches on genes involved in the normal T-cell response. However, NFκB can also bind to the promoter of the HIV provirus to initiate its transcription and subsequent viral replication. Thus, if a T cell activated during toxic shock coincidentally contains an HIV provirus, NFκB will initiate the replication of HIV and the cell will die. If a significant proportion of the person’s T cells harbor the provirus, one would predict widespread reactivation of the virus and a sharp rise in the amount of HIV in the blood (viremia) after the onset of toxic shock.

Name: ___________________________ Class: _________________ Date: __________

Chapter 14 1. Which of the following is matched correctly? a. type I hypersensitivity: IgA b. type II hypersensitivity: immune complexes c. type III hypersensitivity: IgE d. type IV hypersensitivity: IgG e. type IV hypersensitivity: delayed-type hypersensitivity

2. Which of the following is associated with recognition by an antibody of a modified cell-surface protein? a. type I hypersensitivity b. type II hypersensitivity c. type III hypersensitivity d. type IV hypersensitivity e. mast-cell activation

3. Which of the following is NOT mediated by antibodies? a. type I hypersensitivity b. type II hypersensitivity c. type III hypersensitivity d. type IV hypersensitivity

4. Which of the following is associated with type III hypersensitivity? a. nickel b. synthetic human insulin c. plant oil d. mouse-derived monoclonal antibody e. helminth infection

5. __________ hypersensitivity reactions interact with soluble epitopes and NOT cell-surface associated epitopes. a. Type I and II b. Type I and III c. Type I and IV d. Type II and III e. Type II and IV

6. Adaptive immune responses targeted at infections by helminth worms and other parasitic multicellular animals does not involve a. eosinophils. b. mast cells. c. CD4 TH2 cells. d. basophils. e. neutrophils.

7. During a primary immune response IgM sometimes switches to IgE. Which of the following best describes the consequence of this early switch? a. The B cell would switch back to IgG3. b. The B cell would remain in the germinal center but would not differentiate into a plasma cell. c. The B cell would die by apoptosis. d. The IgE produced would have low affinity for antigen.

8. Select the correct statement concerning FcεRI. a. It is expressed on the surface of mast cells, but not basophils. b. It is a low-affinity receptor involved in type I hypersensitivity reactions. c. It binds to antigen-bound IgE via the Cε3 domain. d. It is a membrane-bound dimer. e. It contains ITAMs in the γ chains.

9. The sheddase __________ cleaves FcεRII on the cell surface, resulting in the production of monomeric and trimeric forms of FcεRII.

a. cathepsin G b. CR2 c. eotaxin d. major basic protein e. ADAM10

10.A mediator that is NOT released immediately by mast cells after FcεRI crosslinking is a. heparin. b. eicosanoids. c. neutral proteases. d. histamine. e. TNF-α.

11.Lipid mediators produced by activated mast cells include which of the following? a. cathepsin G b. chymase c. leukotrienes d. carboxypeptidase e. chemokines

12.All of the following are biological effects mediated by the products of mast cells EXCEPT a. chemotaxis of neutrophils, eosinophils, and effector T cells. b. growth factor secretion. c. smooth muscle contraction. d. connective tissue remodeling. e. the release of neurotoxins to kill parasites.

13.Select the correct pair. a. TNF-α: released by T helper cells but not mast cells b. connective tissue mast cell production: T-cell immunodeficiencies

c. chymotryptase: connective tissue mast cells and tissue remodeling d. heparin: lipid mediator that attracts leukocytes e. leukotrienes: reduce vascular permeability and relax smooth muscles

14.Prostaglandin D2 (PGD2) secretion does NOT lead to a. increased antibody production. b. chemotaxis of neutrophils. c. increased vascular permeability. d. vasodilation.

15.Which of the following inhibits the activity of prostaglandin synthase? a. ADAM10 b. experimental anti-IgE c. aspirin (acetyl salicylate) d. chymotryptase e. ADAM33

16.__________ released by TH2 cells promotes an elevated level of eosinophils in the circulation. a. IL-4 b. IL-13 c. TNF-α d. FcγRII e. IL-5

17.A direct result of the degranulation of mast cells located in the heart and vascular system is a. a decrease in blood pressure. b. constriction of the airway. c. wheezing. d. vomiting. e. decreased capillary permeability.

18.A direct result of the degranulation of mast cells located in the respiratory tract is a. an increase in blood pressure. b. constriction of the airway. c. an irregular heartbeat. d. vomiting. e. decreased capillary permeability.

19.Select the correct statement concerning the effects of histamine binding to the H1 receptor. a. It decreases permeability of the endothelial cells of blood vessels. b. It causes smooth muscles to relax. c. It causes mucosal epithelia to increase their production of mucus. d. It leads to an increased production of TNF-α.

20.The antigens that provoke hypersensitivity reactions are referred to as a. T-independent antigens. b. superantigens. c. subunit vaccines. d. attenuated vaccines. e. allergens.

21.Which of the following allergens is NOT likely to be encountered through inhalation? a. plant pollen b. metals c. animal dander d. mold spores e. house dust mite feces

22.Basophils

a. express FcεRII. b. lack granules in their cytosol. c. initiate the TH2 response. d. are armed by IgG. e. are involved in type IV hypersensitivity responses.

23.Aspirin (acetyl salicylate) inhibits prostaglandin synthesis by binding irreversibly to prostaglandin synthase, the first enzyme in the __________ pathway. a. cyclooxygenase b. carboxypeptidase c. metalloprotease d. lipoxygenase e. peroxidase

24.Which of the following is associated with eosinophilia? a. IL-5-induced proliferation and tissue damage b. lack of allergic response c. lack of major basic protein d. B-cell lymphoma e. decreased bone marrow function

25.Which of the following genetic polymorphisms would be LEAST likely to be associated with a predisposition to asthma? a. promoter variants of IL-4 b. structural variants of the IgG Fc receptor c. HLA class II allotypes d. β2-adrenergic receptor variant e. promoter variants of 5-lipoxygenase

26.The wheal-and-flare inflammatory reaction is an example of a. an immediate type I allergic response. b. a late-phase type I allergic response.

c. a late-phase type IV allergic response. d. an immediate type III allergic response. e. a late-phase type III allergic response.

27.Which of the following tests is used to determine whether a particular allergen is responsible for asthma? a. measure wheal-and-flare diameter after intradermal injection of allergen b. measure the late-phase reaction diameter after intradermal injection of allergen c. inject a controlled amount of allergen intradermally and observe urticaria d. measure peak expiratory flow rate (PEFR) following inhalation of allergen e. measure eosinophils in nasal secretions following inhalation of allergen

28.Anaphylaxis leads to a. smooth muscle contraction and lowered blood pressure. b. immune complex deposition on blood vessels. c. the relaxation of airway smooth muscle, which prevents air flow. d. the formation of tight junctions in the vascular endothelium. e. complement activation.

29.During a successful desensitization process, the patient’s antibodies will change from an __________ isotype to an __________ isotype. a. IgG4; IgE b. IgE; IgM c. IgA; IgM d. IgG1; IgG4 e. IgE; IgG4

30.Which of the following is NOT an appropriate treatment for a type I allergic reaction? a. Use antihistamines to block histamine binding to H1 histamine receptors. b. Use immunosuppressive steroids to suppress inflammation. c. Gradually increase the dose of injected allergen to generate antibodies that

do not trigger mast cell degranulation. d. Administer IL-4 and IL-5 to promote TH1 responses. e. Block high-affinity IgE receptors to prevent mast-cell degranulation.

31.Anita Garcia, 17 years old, and her roommate, Rosa Rosario, were celebrating a friend’s birthday at a dessert buffet at a local restaurant when Anita developed difficulty breathing and angioedema. She complained of an itchy rash, and then had difficulty swallowing. Rosa drove Anita to the emergency room two blocks away rather than wait for an ambulance. As they approached the hospital, Anita lost consciousness. Anita would benefit from an intravenous injection of __________ before any subsequent treatment. a. epinephrine b. corticosteroids c. antihistamine d. antibiotics e. a nonsteroidal anti-inflammatory drug

32.Multicellular parasites a. are primarily cleared by the activity of phagocytic cells. b. provoke strong immune responses due to the high antigenicity of parasite antigens. c. are cleared by responses occurring in mucosal tissues that are dependent upon IgA secretion. d. are most effectively cleared by type 2 immunity. e. are most effectively cleared by type 1 immunity.

33.Intestinal epithelial cells respond to multicellular worms by a. increasing the production of enterocytes. b. secreting IL-13. c. decreasing the production of mucus, which makes it more likely the worms will be expelled. d. preventing NF-kappaB activation to minimize inflammation. e. increasing their absorption of nutrients.

34.During a worm infection, __________ secrete the cytokine __________, which promotes the differentiation of CD4 TH2 cells and isotype switching to IgE. a. mast cells; IL-13 b. epithelial cells; IL-33 c. basophils; IL-10 d. CD4 TH1 cells; IFN-gamma

35.Select the correct statement concerning allergies and hygiene. a. In countries where there is a high rate of helminth infection there is also a high rate of allergy due to the production of IL-5. b. Sanitization of food and water has eliminated helminth infections from human populations. c. The rate of allergic disease has decreased due to the increased use of antibiotics. d. The hygiene hypothesis argues that the immune systems of children in industrialized countries are no longer adequately regulated by helminths.

36.Select the correct statement concerning IgE. a. During a primary immune response the majority of B cells isotype switch from IgM to IgE. b. Basophils secrete IL-4, which promotes isotype switching to IgE. c. The B-cell receptors that isotype switch to IgE do not acquire somatic mutations and remain of low affinity throughout the immune response. d. At any given time, mast cells and basophils are armed with antibody molecules restricted to only one antigen specificity.

37.The monoclonal antibody omalizumab a. is humanized, allowing it to be used as a long-term treatment. b. binds both to soluble IgE and to IgE bound to Fc receptors. c. leads to immune suppression in recipients, thus preventing its long-term use. d. does not benefit individuals with allergy-induced asthma.

38.Multicellular parasites of the gut a. trigger coughing and sneezing by activating airway mast cells. b. induce a very different local response from that of food-borne allergens. c. induce the production of leukotrienes that lead to intestinal smooth muscle contractions. d. cannot be expelled from the body, but instead are controlled by the local immune response.

39.The condition in which allergic reactions cause chronic shortness of breath, coughing, and wheezing is known as a. allergic rhinitis. b. allergic conjunctivitis. c. allergic asthma. d. anaphylaxis. e. eczema.

40.During the chronic stage of asthma, you would NOT expect to find a. continual allergen exposure. b. an increased number of eosinophils present in the airway tissue. c. a narrowing of the airways with increased mucus production. d. TH2 cytokines. e. a contraction of the bronchial smooth muscles.

41.Hives a. can be induced by injecting heparin into the skin. b. occur during the late stages of a wheal-and-flare reaction. c. are caused by an increase in the activity of tight junctions and a decrease in the permeability of local blood endothelial cells. d. are the result of allergens delivered to the skin.

42.The disease characterized by a chronic skin rash and associated with itching and fluid discharge from skin eruptions is

a. allergic rhinitis. b. allergic conjunctivitis. c. allergic asthma. d. anaphylaxis. e. eczema.

43.A loss-of-function mutation in filaggrin a. is associated with allergic asthma. b. prevents skin hydration and reduces the barrier function of skin. c. leads to angioedema in tissues. d. is associated with food allergies.

44.Select the correct statement concerning a child who has eaten shellfish for the first time and developed hives. a. The hives are likely the result of a type I hypersensitivity to the shellfish. b. The hives are likely the result of a type III hypersensitivity to the shellfish. c. It is unlikely that the child’s mast cells were triggered to degranulate by IgE bound to shellfish antigens. d. Food allergens cannot be transported out of the gut and should not cause skin reactions.

45.An inhaled agonist of the beta-adrenergic receptor that dilates bronchioles in an individual with asthma is a. epinephrine. b. omalizumab. c. antihistamine. d. albuterol. e. an immunosuppressive steroid.

46.Which of the following has likely been the most important factor in leading to the epidemic of allergy? a. the use of antibiotics to treat bacterial infections b. the absence of infection with helminth parasitic worms

c. the use of soap and other disinfectants d. the use of antihistamines e. better diagnosis of allergy and asthma

47.Select the correct statement concerning the immune response to an inhaled allergen.

a. The allergen shown in the airway in panel A is likely a carbohydrate from a plant or animal. b. The T cell activated in panel B will likely stimulate a TH2 response. c. The cytokine released by the activated T cell (dark gray) in panel C is IFNγ. d. The antibodies secreted in panel D bind to FcεRII, which induces degranulation.

48.Select the correct statement concerning an individual who receives a skin test for allergies.

a. The negative control (an injection of saline) for the skin test is labeled “A”. b. The intradermal injection shown in “C” has not resulted in the release of histamine. c. If the individual is allergic to ragweed, the injected ragweed pollen antigen will bind to armed mast cells. d. If this individual has never been previously exposed to ragweed pollen antigen, the results shown in “A” would be observed when ragweed pollen antigen was injected. e. The type of mast cells degranulating during a skin test for allergens are mucosal mast cells.

49.Select the correct statement concerning eosinophils.

a. The eosinophil shown here could be responding to a chemokine gradient that includes CCL11. b. The granules shown in the eosinophil contain preformed toxins such as major basic protein, a protein composed of multiple acidic amino acids. c. Both activated and resting eosinophils express FcεRI. d. IL-5 acts on the bone marrow to reduce the production of eosinophils, thus preventing eosinophilia. e. Activated eosinophils do not express the cyclooxygenase or lipoxygenase enzymes.

50.Identify the blood cell type highlighted by the black arrows. These cells contain granules stained pink.

a. basophils b. neutrophils c. eosinophils d. monocytes e. TH2 cells

51.Match each term with its description. a. delayed-type hypersensitivity b. hygiene hypothesis c. allergy d. immediate hypersensitivity e. allergen 1. __________ innocuous environmental antigen 2. __________ type IV hypersensitivity 3. __________ a state of hypersensitivity 4. __________ type I hypersensitivity 5. __________ epidemic of allergy

52.Match each term with its description.

a. IL-4 b. CCL3 c. TNF-α d. histamine e. tryptase 1. __________ activates endothelium 2. __________ amplifies TH2-cell response 3. __________ increases vascular permeability 4. __________ connective tissue matrix remodeling 5. __________ chemotaxis

53.Identify four different ways in which an individual may come into contact with an allergen and provide two examples of allergens for each type of contact.

54.Why does simultaneous binding of IgE to FcεRI and FcεRII NOT occur?

55.Provide a specific example of a major allergen that has protease activity.

56.Briefly explain how penicillin initiates a type I hypersensitivity response.

57.How do mast cells and B cells differ in their response when antigen binds to their surface immunoglobulins?

58.How do mast cells and B cells differ in their response when antigen binds to their surface immunoglobulins?

59.List three ways to minimize the risk of an allergic reaction in a susceptible person.

60.How do mast cells contribute to innate immunity?

61.Describe in detail the mechanism responsible for mast-cell activation during a type I hypersensitivity reaction.

62.What are the products of mast-cell activation?

63.Why are antihistamines used to treat allergic rhinitis and allergic asthma and which symptoms of each disease, respectively, do they alleviate?

64.Describe two ways in which the immunoglobulins acting as antigen receptors on the surface of a mast cell differ from the immunoglobulins acting as the antigen receptors on the surface of a B cell.

65.Some allergies can be treated by a procedure called desensitization. Explain how desensitization works, and the main risk associated with this therapy.

Answer Key Chapter 14 1. Answer:

E

2. Answer:

B

3. Answer:

D

4. Answer:

D

5. Answer:

B

6. Answer:

E

7. Answer:

D

8. Answer:

E

9. Answer:

E

10.Answer:

B

11.Answer:

C

12.Answer:

E

13.Answer:

C

14.Answer:

A

15.Answer:

C

16.Answer:

E

17.Answer:

A

18.Answer:

B

19.Answer:

C

20.Answer:

E

21.Answer:

B

22.Answer:

C

23.Answer:

A

24.Answer:

A

25.Answer:

B

26.Answer:

A

27.Answer:

D

28.Answer:

A

29.Answer:

E

30.Answer:

D

31.Answer:

A

32.Answer:

D

33.Answer:

A

34.Answer:

B

35.Answer:

D

36.Answer:

B

37.Answer:

A

38.Answer:

C

39.Answer:

C

40.Answer:

A

41.Answer:

D

42.Answer:

E

43.Answer:

B

44.Answer:

C

45.Answer:

D

46.Answer:

B

47.Answer:

B

48.Answer:

C

49.Answer:

A

50.Answer:

C

51.Answer:

1. E 2. A 3. C 4. D 5. B

52.Answer:

1. C 2. A 3. D 4. E 5. B

53.Answer:

(i) Inhalation: house dust mite feces, animal dander. (ii) Injection: drugs administered intravenously, insect venom. (iii) Ingestion: peanuts, drugs administered orally. (iv) Contact with skin: poison ivy, nickel in jewelry.

54.Answer:

This does not occur because IgE has two distinct binding sites for FcεRI and FcεRII, and when one or the other of these binding sites is occupied, the conformation of IgE is altered so that it is unable to bind to the other receptor.

55.Answer:

Present in the feces of the house dust mite Dermatophagoides pteronyssimus is a cysteine protease that

is an allergen responsible for 20% of human allergies in North America.

56.Answer:

The reactive bond in the β-lactam ring of penicillin reacts with proteins on the surface of human cells, with erythrocytes most commonly being involved. This modification generates a foreign epitope to which TH2 cells and B cells respond.

57.Answer:

After binding to antigen, mast cells become operational as effector cells without the need to undergo proliferation or differentiation. In contrast, after antigen binds to a surface immunoglobulin on a B cell, the cell must proliferate and differentiate to produce effector cells (antibody-secreting plasma cells).

58.Answer:

After binding to antigen, mast cells become operational as effector cells without the need to undergo proliferation or differentiation. In contrast, after antigen binds to a surface immunoglobulin on a B cell, the cell must proliferate and differentiate to produce effector cells (antibody-secreting plasma cells).

59.Answer:

(i) Avoid contact with allergens as much as possible by modifying their behavior and their home environment. (ii) Use pharmacological agents that inhibit allergic responses. (iii) Undergo desensitization therapy to divert immune responses from IgE to IgG4 isotype.

60.Answer:

Mast cells express Toll-like receptors, which can bind to pathogen-associated molecules and stimulate the production of cytokines and chemokines that participate in innate immune responses.

61.Answer:

If an individual becomes sensitized to antigen by making antibodies of the IgE isotype during first exposure, then a type I hypersensitivity reaction may result if antigen is encountered again. The IgE made initially binds stably via its Fc region to very high-affinity FcεRI receptors on mast-cell surfaces. When antigen binds to this IgE, cross-linking of FcεRI occurs, delivering an intracellular signal that activates the mast cell.

62.Answer:

The preformed granules of mast cells contain a wide range of inflammatory mediators that are triggered to be released extracellularly through an exocytic mechanism called degranulation. The inflammatory mediators contained in the granules and released immediately include histamine, heparin, TNF-α, and proteases involved in the remodeling of

the connective tissue matrix. The proteases include tryptase and chymotryptase (expressed by mucosal and connective mast cells, respectively), cathepsin G, and carboxypeptidase.

Additional inflammatory mediators are generated after mastcell activation, including IL-3, IL-4, IL-5, IL-13, GM-CSF, CCL3, leukotrienes C4 and D4, and platelet-activating factor.

63.Answer:

Mast cells activated by inhaled allergens in the type I hypersensitivity reaction (the cause of allergic rhinitis or asthma) release histamine. Histamine binding to its receptors on smooth muscle causes the bronchial constriction typical of asthma and difficulty in breathing. Histamine binding to receptors on vascular endothelium causes increased permeability of the epithelium and inflammation of nearby tissue, causing the runny nose and swollen eyes typical of allergic rhinitis, and an accumulation of mucus and fluid in the bronchi typical of allergic asthma. By blocking histamine action, antihistamines help alleviate these symptoms.

64.Answer:

(i) The immunoglobulin on a mast cell is an IgE antibody that has become bound to the mast cell’s FcεRI receptor, whereas the immunoglobulin on a B cell is a transmembrane form made by the cell itself. (ii) A B cell might have any class of immunoglobulin on its surface, whereas mast cells have only IgE. (iii) IgE molecules of many different antigen specificities can be bound to the surface of an individual mast cell, whereas an individual B cell carries immunoglobulin molecules of only one specificity.

65.Answer:

One approach to desensitization is the subcutaneous injection of the allergen itself into sensitized individuals with the aim of skewing the immune response from an IgE to an IgG4 isotype. This is achieved by gradually increasing the subcutaneous allergen concentration over time, which favors IgG over IgE production. When antigen is encountered subsequently, IgG will compete with IgE for binding and inhibit IgE cross-linking on mast-cell surfaces. A risk of this approach is the possibility of activating a systemic anaphylactic response after mast-cell activation. Because the patient was previously sensitized, IgE antibodies against allergen are present and, if bound to mast cells, will induce mast-cell degranulation. In the event of an anaphylactic response to an allergy shot, the patient will have epinephrine administered immediately by the attending physician or nurse practitioner.

Name: ___________________________ Class: _________________ Date: __________

Chapter 15 1. ABO or Rhesus antigen mismatches stimulate cytotoxic T-cell responses. a. True b. False

2. There are polymorphic antigens other than ABO and Rhesus antigens that can cause type II hypersensitivity reactions. a. True b. False

3. Cross-matching has now been replaced with routine use of DNA-based methods. a. True b. False

4. Lymphocytes and erythrocytes express HLA class I and II molecules. a. True b. False

5. Platelet transfusions are used to replace fluid and prevent bleeding. a. True b. False

6. Dosage of immunosuppressive drugs is often decreased in transplant patients to minimize toxic side effects, but there is a risk of rejection. a. True b. False

7. Antithymocyte globulin (ATG) is a monoclonal antibody specific for T-cell surface antigens. a. True b. False

8. Immunosuppressive antibodies produced in a different species can be used repeatedly for multiple episodes of transplant rejection without complication. a. True b. False

9. Daclizumab, an anti-CD3 humanized antibody, is used to treat and prevent acute rejection. a. True b. False

10.A possible side effect of using rabbit antithyocyte globulin (ATG) is serum sickness. a. True b. False

11.Select the INCORRECT statement concerning the characteristics of blood donations and transfusions that enable their extensive use for transplantation purposes. a. Individuals can donate on a regular basis without any deleterious effects. b. Erythrocytes do not express MHC class I or class II molecules. c. The blood components only need to function for a few weeks. d. Only the ABO antigens need to be compatible between donor and recipient. e. Blood transfusion is a straightforward and inexpensive process.

12.In routine blood transfusions, which of the following does NOT need to be matched for a successful transfusion? a. A antigens

b. B antigens c. O antigens d. Rhesus D antigen

13.Erythrocytes do NOT express a. glycolipids. b. MHC class I and II. c. Rhesus D blood group antigens. d. ABO antigens.

14.The underlying molecular basis for distinguishing blood group antigens A, B, and O is __________ at the erythrocyte surface. a. the presence or absence of fucose in glycolipids b. differences in the oligosaccharide attached to the lipid ceramide c. structural polymorphisms in the Rhesus D antigen d. the levels of MHC class I and class II molecules.

15.__________ results from alloreactions mediated by donor T cells in the graft subsequent to hematopoietic stem-cell transplantation. a. Acute rejection b. Chronic rejection c. Graft-versus-host disease (GVHD) d. Serum sickness e. Hyperacute rejection

16.Blood transfusions mismatched for ABO and/or Rhesus antigens are associated with a. type III hypersensitivity reactions. b. syngeneic immune responses. c. CD8 cytotoxic T-cell killing of erythrocytes. d. the antibodies present in the blood donor’s serum. e. activation of host complement and destruction of donor cells.

17.Alloantibodies to blood-vessel endothelium on solid organ grafts a. are specific for HLA class I and class II antigens. b. cause hyperacute rejection. c. cause acute rejection. d. target endothelium for attack by NK cells. e. are IgA and do not fix complement.

18.Which of the following is a permissible match between a blood donor and a recipient (donor: recipient)? a. O–: AB+ b. O+: AB– c. AB+: O– d. A–: O– e. AB–: O+

19.All of the following are commonly used sources of hematopoietic stem cells EXCEPT a. skin cells. b. bone marrow. c. umbilical cord blood. d. peripheral blood.

20.The direct pathway of allorecognition involves interaction of __________, whereas the indirect pathway of alloreaction involves interaction of __________. a. donor T cells with allogeneic HLA molecules on recipient dendritic cells; recipient T cells with allogeneic HLA molecules on donor dendritic cells b. recipient T cells with allogeneic HLA molecules on donor dendritic cells; donor T cells with allogeneic HLA molecules on recipient dendritic cells c. recipient T cells with allogeneic HLA molecules on donor dendritic cells; recipient T cells with peptides of allogeneic HLA molecules on recipient dendritic cells d. recipient T cells with peptides of allogeneic HLA molecules on recipient

dendritic cells; donor T cells with peptides of allogeneic HLA molecules on donor dendritic cells

21.__________ is a monoclonal antibody administered to transplant patients before and after transplantation in order to induce lymphopenia. a. Rabbit antithymocyte globulin (rATG) b. Tacrolimus c. Alemtuzumab d. Belatacept e. Basiliximab

22.Which of the following pairs is mismatched? a. methotrexate: dihydrofolate reductase b. prednisolone: NFκB c. cyclosporin: calcineurin d. basiliximab: IL-2 receptor e. OKT3: CD52

23.Which of the following drugs is active when taken by the patient and does NOT need to be converted in vivo to an active form? a. azathioprine b. cyclophosphamide c. cyclosporin d. prednisone e. mycophenolate mofetil

24.Which of the following causes the T-cell receptors to be internalized and unavailable for antigen recognition? a. alemtuzumab b. OKT3 c. rabbit antithymocyte globulin (rATG) d. cyclosporin

25.In the context of allogeneic transplantation, identify the mismatched pair. a. inhibition of inflammation: prednisone b. inhibition of co-stimulation: daclizumab c. inhibition of cytokine signaling: basiliximab d. inhibition of calcineurin: tacrolimus (FK506) e. inhibition of T-cell proliferation: azathioprine

26.__________ is NOT a drug that targets replication and proliferation of alloantigenactivated T cells. a. Rapamycin b. Methotrexate c. Mycophenolate mofetil d. Azathioprine e. Cyclophosphamide

27.Which of the following exerts its effect by inhibiting the activation of calcineurin by calcium and thereby interferes with nuclear translocation of NFAT? a. prednisone b. mycophenolic acid c. cyclophosphamide d. belatacept e. cyclosporin A

28.Hematopoietic stem-cell transplantation is appropriate for all of the following conditions EXCEPT a. thalassemia major. b. Wiskott–Aldrich syndrome. c. cirrhosis of the liver. d. sickle-cell anemia. e. non-Hodgkin’s lymphoma.

29.__________ describes the process by which transplanted pluripotent stem cells find their way to the bone marrow spaces in the bones of the body and begin to

produce new blood cells. a. Myeloablation b. Engraftment c. Relapse d. Graft-versus-leukemia e. Chemotherapy

30.Myeloablative therapy a. prevents graft-versus-host disease. b. does not destroy the recipient’s hematopoietic stem cells. c. suppresses autoreactive T cells in the graft. d. would not be used to treat genetic diseases that affect hematopoietic cells. e. provides space for colonization of transplanted stem cells in bone marrow stroma.

31.For a bone marrow recipient’s new immune system to function effectively, some HLA allotypes must be shared because a. professional antigen-presenting cells are host-derived. b. newly generated T cells are host-derived. c. otherwise an autoimmune disease would develop. d. newly generated T cells are positively selected on the recipient’s thymic epithelium. e. if all HLA molecules were mismatched, acute rejection of the grafted cells would occur.

32.The risk of __________ is the primary complication in bone marrow transplants. a. acute host-versus-graft disease b. hyperacute rejection c. chronic rejection d. acute graft-versus-host disease e. cancer

33.__________ from a bone marrow transplant facilitate alloreactive responses,

causing the condition defined as acute graft-versus-host disease. a. Natural killer cells b. Mature T cells c. Dendritic cells d. Thymocytes e. Mature B cells

34.A patient experiencing jaundice, bilirubin levels above 15 mg/dl, severe abdominal pain, and skin blistering along with loss of skin tissue would be diagnosed with __________ graft-versus-host disease. a. Grade I b. Grade II c. Grade III d. Grade IV

35.Autologous bone marrow transplantation used to treat cancer patients involves reinfusing a(n) __________-depleted stem-cell population into the patient after their cancer treatment has been completed. a. mature T-cell b. antibody c. tumor cell d. dendritic cell e. NK cell

36.Leukapheresis is used in hematopoietic stem-cell transplantation where stem cells from a suitable donor are fractionated on the basis of their expression of a. CD3. b. the same major histocompatibility antigens as the recipient. c. the same minor histocompatibility antigens as the recipient. d. the same inhibitory KIR receptors as the recipient. e. CD34.

37.Donors treated with __________ can donate bone marrow-derived stem cells

from a less invasive peripheral blood draw instead of the more invasive bone marrow aspiration. a. anti-CD3 b. cyclophosphamide c. anti-CD34 d. granulocyte colony-stimulating factor (G-CSF) e. anti-H-Y

38.Despite a slower engraftment, cord blood as a source of transplanted hematopoietic stem cells is better than bone marrow or stem cells derived from peripheral blood in that a. the recipient does not need to undergo myeloablative therapy. b. there is a higher volume of cord blood obtained than there is with bone marrow or blood-derived stem cells. c. there is a lower incidence of graft-versus-host disease. d. cord blood can be infused directly into the bone marrow of recipients. e. a greater number of stem cells express CD34.

39.Males engrafted with HLA-identical bone marrow from their sisters develop graftversus-host disease because a. T cells develop in the male thymus that are not tolerant to minor histocompatibility antigens expressed by the sister. b. mature T cells in the graft have specificity for male-specific minor histocompatibility antigens. c. there are differences between the sexes in how self proteins are modified post-translationally. d. NK-cell alloreactions occur. e. residual female hormones in the graft cause upregulation of HLA class I on male dendritic cells presenting minor histocompatibility antigens.

40.Residual leukemia cells persisting in a patient after they have received chemotherapy, irradiation, and a bone marrow transplant are sometimes eliminated by a(n) __________ effect which involves the action of __________. a. graft-versus-leukemia; alloreactive T cells and NK cells

b. haploidentical; regulatory T cells c. acute minor histocompatibility; recipient NK cells d. myeloablation; mature T cells

41.Family members who donate their bone marrow to a transplant patient and who share one of the two HLA haplotypes are providing a(n) __________ transplant. a. autologous b. HLA-matched c. haploidentical d. chimeric e. cross-matched

42.What is the term used to describe the condition of an individual who possesses two sets of hematopoietic cells, one derived from the individual’s own bone marrow and one derived from a different source—for example, an organ transplant or blood transfusion that has not been rejected? a. haploidentical b. chimeric c. cross-protected d. dimorphic e. mixed lymphocyte reaction

43.George Cunningham was diagnosed with Crohn’s disease when he was 23 years old. He was experiencing acute abdominal pain, diarrhea, rectal bleeding, anemia, and weight loss. He did not respond to conventional immunosuppressive therapies and was given a course of infliximab, an anti-TNF-α monoclonal antibody that suppresses inflammation by blocking TNF-α activity. On day 12 after receiving his first infusion, he developed a mild fever, generalized vasculitis, swollen lymph glands, swollen joints, and joint pain. Traces of blood and protein were detected in his urine. Which of the following is the most likely cause of these recent symptoms? a. Type I hypersensitivity involving anaphylaxis b. Type II hypersensitivity leading to hemolytic anemia c. Type III hypersensitivity caused by immune complex deposition in blood vessels

d. Type IV hypersensitivity involving CD8 T-cell cytotoxicity e. Type II hypersensitivity leading to thrombocytopenia

44.The term __________ describes polymorphic antigens that vary between individuals of the same species. a. xenoantigens b. immunoantigens c. alloantigens d. histoantigens e. autoantigens

45.Cyclosporin A a. activates the phosphatase calcineurin. b. prevents NF-kB activation. c. prevents T-cell proliferation by decreasing IL-2 production. d. leads to the dephosphorylation of NFAT. e. is a monoclonal antibody targeting the co-stimulatory molecules needed for T-cell activation.

46.Graft-versus-host disease (GVHD) is a consequence of a. mature T lymphocytes from the donor mounting an immune response against tissue of the recipient. b. mature T lymphocytes from the recipient mounting an immune response against tissue of the donor. c. mismatching A, B, and O antigens between donor and recipient. d. mismatching Rhesus antigen between donor and recipient. e. antibodies of the donor stimulating NK cell antibody-dependent cellmediated cytotoxicity (ADCC) of tissues of the recipient.

47.Which of the following best explains why a bone marrow donor needs to be HLAmatched to the recipient? a. The bone marrow transplant contains enough mature T cells to reconstitute the recipient and the recipient provides the antigen-presenting cells.

b. The recipient’s MHC molecules mediate positive selection of thymocytes in the thymus that interact with donor-derived MHC molecules in the periphery. c. Reconstituted T cells are restricted by donor, not recipient, HLA allotypes. d. Without an HLA match, the donor-derived thymocytes undergo negative selection. e. If the donor is not HLA matched, the reconstituted T cells will be autoreactive.

48.Select the correct statement concerning a liver transplant. a. Acute rejection is common following a liver transplant. b. The liver expresses high levels of HLA class I and II molecules. c. ABO cross-matching is not required for liver transplants. d. HLA-typing is not routinely done before a liver transplant. e. The liver is the transplanted tissue most sensitive to HLA differences.

49.Richard French, 53 years old, was diagnosed with chronic myelogenous leukemia. His elder brother, Don, is HLA-haploidentical and will donate bone marrow. Richard’s oncologist has recommended him to a medical center that favors using bone marrow depleted of mature T cells prior to infusion. The most likely rationale for employing the practice of T-cell depletion is that a. T-cell depletion will remove alloreactive T cells from the donor and prevent the potential for graft-versus-host disease (GVHD). b. mature T-cell chimerism is required to establish long-term tolerance. c. because Don is HLA-haploidentical and male, there is no risk of alloreactivity toward major or minor histocompatibility antigens. d. because of Don’s age, the expected bone marrow harvest is already marginal for successful engraftment, and depletion measures would compromise the yield of stem cells. e. the benefit of using a cocktail of immunosuppressive drugs outweighs the risk of contaminating the bone marrow during T-cell depletion.

50.Forty-four-year-old Danielle Bouvier is on the waiting list for a kidney transplant and is receiving weekly dialysis. Her HLA type is: HLA-A: 0101/0301; HLA-B: 0702/0801; HLA-DRB1: 0301/0701. Today, Danielle’s physician informed her that several potential kidney donors are available. Which of the following would be the

most suitable? a. A: 0301/0201; B: 4402/0801; DRB1: 0301/0403 b. A: 0301/2902; B: 1801/0801; DRB1: 0301/0701 c. A: 2902/0201; B: 0702/0801; DRB1: 0301/13011 d. A: 0101/0101; B: 5701/0801; DRB1: 0701/0701 e. A: 0101/0301; B: 0702/5701; DRBA: 0403/0301

51.What type of hypersensitivity reaction would result from a mismatched blood transfusion? a. Type I b. Type II c. Type III d. Type IV

52.What is the name of the clinical test used to determine the compatibility between a donor and recipient requiring a blood transfusion? a. desensitization b. cross-match test c. Arthus reaction d. HLA typing e. delayed-type hypersensitivity reaction

53.__________ is associated with a type III hypersensitivity reaction. a. Allergen binding to cell-surface components and creating foreign epitopes. b. Cross-linking of IgE on mast cells c. Formation of small immune complexes that are deposited in blood vessel walls d. Cytotoxic CD8 T-cell activation e. Graft-versus-host disease

54.When an individual receives a kidney transplant, the main concern will be to control the development of

a. graft-versus-host disease. b. transplant rejection. c. xenorecognition. d. allergic reactions. e. lymphoproliferative disorders.

55.Which of the following pairs is correctly matched? a. allograft: same person b. autograft: to treat damage caused by autoimmune processes c. isograft: syngeneic d. antithymocyte globulin: allogeneic e. same species: isograft

56.In general, the higher the patient’s panel reactive antibody (PRA), a. the greater the number of suitable transplant donors. b. the less likely it is that a hyperacute reaction will occur. c. the higher the risk of developing hemolytic disease of the newborn. d. the more limited the number of suitable transplant donors. e. the higher the risk of developing autoimmunity.

57.If __________ occurs in an organ to be transplanted, endothelial activation, leukocyte infiltration, inflammatory cytokine production, and complement activation may occur. a. a mixed lymphocyte reaction b. the transfusion effect c. kidney dialysis d. ischemia e. myeloablative therapy

58.Which of the following pairs is correctly matched? a. hyperacute rejection: indirect pathway of allorecognition b. acute rejection: anti-HLA antibodies

c. chronic rejection: alloreactive T-cell clones specific for HLA allotypes of donor d. acute rejection: direct pathway of allorecognition e. transfusion effect: direct pathway of allorecognition.

59.Acute rejection of a kidney graft involves the activation of recipient T cells by __________ of __________ origin. a. dendritic cells; recipient b. B cells; recipient c. dendritic cells; donor d. macrophages; recipient e. B cells; donor

60.Effector mechanisms of __________ rejection resemble those responsible for type IV hypersensitivity reactions. a. complement activation b. acute c. chronic d. hyperacute e. blood transfusion

61.When donor MHC: donor self-peptide complexes activate recipient T cells, a. acute rejection of transplanted organs occurs. b. suppression occurs and transplanted organs are tolerated. c. hyperacute rejection of transplanted organs occurs. d. complement pathways are activated. e. an indirect pathway of allorecognition occurs.

62.The extent to which an individual’s T cells respond to allogeneic HLA expressed on irradiated donor cells can be measured in vitro using a. a cross-match test. b. a superantigen recognition test. c. the mixed lymphocyte reaction.

d. the transfusion effect assay. e. the panel reactive antibody test.

63.In a mixed lymphocyte reaction the donor cells are irradiated to ensure that they do not a. stimulate recipient cells. b. become anergic. c. alter their level of expression of HLA molecules. d. proliferate. e. undergo apoptosis.

64.In chronic rejection, effector T cells respond to __________ complexes on __________-derived dendritic cells. a. donor MHC class I: donor self peptide; donor b. donor MHC class II: donor self peptide; donor c. recipient MHC class I: donor MHC peptide; recipient d. recipient MHC class II: donor MHC peptide; recipient e. recipient MHC class II: donor MHC peptide; donor

65.Alloantibody production after organ transplantation involves a. a mixed lymphocyte reaction. b. the indirect pathway of allorecognition by CD4 T cells. c. activation of regulatory CD4 T cells. d. the transfusion effect. e. a switch from a chronic to an acute state of organ rejection.

66.As time progresses following an organ transplant, the alloreactive T-cell response shifts from a(n) __________ pathway to a(n) __________ pathway of allorecognition. a. exogenous; endogenous b. inflammatory; cytotoxic c. hyperacute; suppressive d. autologous; heterologous

e. direct; indirect

67.Patients who have previously received a blood transfusion that has HLA-DR allotypes in common with their kidney transplant are a. less likely to reject the graft owing to the presence of regulatory CD4 T cells. b. more likely to reject the graft owing to the presence of HLA alloantibodies. c. less likely to reject the graft owing to negative selection of alloreactive Tcell clones. d. at risk of developing a hyperacute rejection. e. at risk of developing graft-versus-host disease.

68.The outcome of organ transplantation improves when a. the patient has been transfused with blood that shares HLA allotypes with the transplanted organ. b. HLA-C, HLA-DP, and HLA-DQ are matched. c. a thymectomy is performed at the time of transplantation. d. plasmapheresis is carried out before transplantation. e. therapy with immunosuppressive drugs are started one week following the transplant.

69.Which of the following pairs is correctly matched? a. prednisolone: pro-drug b. rapamycin: calcineurin c. azathioprine: cytotoxicity in dividing cells d. methotrexate: NF B e. cyclophosphamide: microbial products

70.__________ is a nitrogen mustard compound converted to a DNA-alkylating agent in the body that is used to inhibit cell proliferation after transplantation. a. Methotrexate b. Rapamycin c. FK506

d. Cyclophosphamide e. Mycophenolate mofetil

71.Prednisone is a steroid used in transplantation that a. binds to a cell-surface receptor and inhibits the function of NF B. b. cannot be combined with other cytotoxic drugs due to its toxicity. c. decreases the synthesis of I B d. causes an increase in production of prostaglandins. e. can lead to bone demineralization as an unwanted side effect.

72.Which of the following immunosuppressive drugs does NOT inhibit DNA synthesis? a. cyclophosphamide b. prednisone c. azathioprine d. methotrexate e. mycophenolate mofetil

73.__________ decreases the activity of the transcription factor NFAT by inhibiting calcineurin. a. Alemtuzumab (anti-CD52) b. Azathioprine c. Mycophenolic acid d. Cyclosporin A e. Rapamycin

74.Steroid receptors are complexed with a. Hsp90 in the cytoplasm. b. Hsp90 on the cell surface. c. calcineurin in the cytoplasm. d. calcineurin in the nucleus. e. NFκB in the cytoplasm.

75.Corticosteroids interfere with chemotaxis of leukocytes by a. decreasing the production of GM-CSF and IL-1. b. inducing apoptosis. c. inhibiting the expression of adhesion molecules on endothelial vessels. d. suppressing the activity of phospholipase A2. e. reducing nitrogen oxide synthase (NOS) activity.

76.Tacrolimus causes which of the following effects? a. reduced T-cell proliferation b. decreased production of nitric oxide c. decreased expression of MHC class I and MHC class II d. decreased activity of cyclo-oxygenase type 2 e. serum sickness

77.Which of the following is an effect of both tacrolimus and corticosteroids? a. reduced T-cell proliferation b. decreased production of nitric oxide c. decreased production of IL-3, IL-4, GM-CSF, and TNFd. decreased activity of cyclooxygenase type 2 e. serum sickness

78.A characteristic of the human eye that enables the cornea to be transplanted with a 90% success rate is that a. antigen-presenting cells in the eye do not express the co-stimulatory molecule B7. b. the cornea has a well-developed blood vessel network. c. the cornea lacks expression of HLA class I and II molecules. d. only regulatory T cells express the adhesion molecules necessary to enter the cornea. e. the aqueous humor of the anterior chamber contains TGF- , which downregulates CD40 and inhibits IL-12 secretion.

79.Which of the following is transplanted with a relatively high success rate despite major differences in HLA class I and II between donor and recipient? a. bone marrow b. heart c. cornea d. kidney

80.Liver transplantation requires that __________ be matched between donor and recipient. a. HLA class I b. HLA class II c. HLA class I and class II d. ABO antigens and Rhesus antigen e. HLA class I, HLA class II, ABO and Rhesus antigens

81.What is the probability that a sibling will be able to provide an HLA-haploidentical kidney for transplantation? a. 100% b. 75% c. 50% d. 25% e. 0%

82.The biggest challenge facing kidney transplantation is a. the requirement for a living donor. b. matching HLA alleles. c. matching ABO and Rhesus antigens. d. access to immunosuppressive drugs. e. having a sufficient number of kidney donors.

83.The only drug that does NOT directly target either signal 1 or signal 2 during T-

cell activation is

a. methotrexate. b. cyclosporin. c. tacrolimus. d. belatacept. e. anti-CD3 mAb.

84.Select the correct statement concerning the action of immunosuppressive drugs and T-cell activation.

a. Signal 1 is represented by “A” and can be blocked by cyclosporin. b. The signal shown by “B” is blocked by a monoclonal antibody that binds the beta-chain of the TCR. c. Immunosuppressive drugs targeting “C” do not affect naive resting T cells. d. In the presence of immunosuppressive drug “D”, the T cell decreases the expression of IκBα. e. The immunosuppressive drug represented by “E” is rapamycin.

85.Anti-CD52 antibodies

a. are unable to fix complement. b. permanently reduce the number of T cells in an individual. c. would not be given to a patient prior to receiving a transplant. d. may result in phagocytosis of lymphocytes.

86.Select the correct statement concerning the indirect pathway of allorecognition.

a. The donor dendritic cell is presenting peptides (yellow circles) generated from the donor’s HLA. b. The donor dendritic cell is presenting peptides (yellow circles) generated from the recipient’s HLA. c. The recipient dendritic cell is presenting peptides (yellow circles) generated from the donor’s HLA. d. The recipient dendritic cell is presenting peptides (yellow circles) generated from the recipient’s HLA.

87.Select the correct statement concerning the T-cell receptor repertoire and the recognition of allogeneic MHC.

a. Positive selection determines the number of high-affinity T-cell receptors we have for allogeneic MHC. b. The high-affinity receptors for allogeneic MHC will stimulate a mixed lymphocyte reaction in HLA-mismatched individuals. c. Negative selection will remove T cells bearing high-affinity T-cell receptors for allogeneic MHC. d. Our T-cell receptors bind to self MHC molecules with much higher affinity than they bind to allogeneic MHC. e. Fewer than 1% of the T cells from an individual who has not had a previous transplant or blood transfusion will recognize allogeneic MHC.

88.Select the correct statement concerning kidney transplants. a. The first transplants were done with cadaver donors among unrelated individuals. b. Kidney transplants are not successful among identical twins.

c. More than 100,000 kidney transplants have been performed. d. Fewer than 10% of transplanted kidneys last 10 years when there is one HLA mismatch. e. HLA DNA typing and serological cross-matching are not required for kidney transplants due to the distinctive immunological environment of the kidney.

89.Select the correct statement concerning a mixed lymphocyte reaction between a kidney donor (HLA-A: 0101/0301; HLA-B: 0702/0801; HLA-DRB1: 0301/0701) and the transplant recipient (A: 0301/2902; B: 1801/0801; DRB1: 0301/0701). a. The donor cells could be treated with cyclosporin instead of lethal irradiation and the lab could still determine histocompatibility. b. The recipient’s cells could be treated with cyclosporin instead of lethal irradiation and the lab could still determine histocompatibility. c. The donor and recipient share multiple HLA antigens and it would be unlikely to see high levels of CD8 T-cell killing of donor cells. d. You would expect to see a higher level of proliferation between the recipient and this donor than with a second donor whose HLA type is A: 0301/0201; B: 4402/0801; DRB1: 0301/0403. e. The antibodies measured in the mixed lymphocyte reaction would be directed at ABO and RhD antigens.

90.Match each term with its function. a. chronic rejection b. myeloablative therapy c. ischemia d. mixed lymphocyte reaction e. transfusion effect 1. __________ assessment of degree to which recipient’s T cells would respond to a transplanted organ 2. __________ annihilation of the immune system 3. __________ a form of type III hypersensitivity 4. __________ improved outcome of organ transplantation if previous blood transfusions containing shared HLA-DR allotypes with organ was given to recipient 5. __________ blood deprivation often accompanying organ collection

91.Match each term with its description. a. minor histocompatibility antigens b. haploidentical transplant c. autologous hematopoietic cell transplantation d. graft-versus-tumor effect e. CD34 1. __________ allotypic differences that arise from polymorphisms in human proteins 2. __________ on the surface of hematopoietic stem cells 3. __________ only one HLA haplotype is shared but not both 4. __________ removal of harmful cells from one’s own bone marrow before reinfusion 5. __________ residual leukemic cells eliminated by alloreactive T cells or NK cells in a graft

92.What explains the increased incidence of bone marrow graft failure and cancer relapse when mature T cells are depleted from donor bone marrow before engraftment?

93.How do the clinical objectives of transplantation differ from those of vaccination?

94.Which pre-surgical laboratory test should be performed to prevent the rejection of an organ transplant made between a donor of blood group AB and a recipient of blood group O?

95.Identify three general classes of drug that are used to suppress acute transplant rejection. For each class, provide i) an example and ii) explain the side effects that are associated with its use.

96.In the context of organ transplantation, what is the increased risk associated with an individual’s having received previous blood transfusions on multiple occasions?

97.What explains the observation that mixed lymphocyte reactions carried out between some dizygotic twins have a negligible stimulation index?

98.Explain why, in principle, an organ transplanted from any donor other than an identical twin is almost certain to be rejected in the absence of any other treatment.

99.Contrast acute rejection and chronic rejection.

100.

Explain why an organ transplant made between a donor of blood group AB and a recipient of blood group O will always be rejected, even if it is perfectly HLA-matched and the recipient has been given immunosuppressant drugs. What is this type of rejection called?

101.

What feature of mouse antibodies compromises their effectiveness in vivo and limits their use in suppressing acute graft rejection?

102.

Explain why a boy with leukemia who receives a bone marrow transplant from his sister that is perfectly matched for MHC class I and class II is still likely to get graft-versus-host disease. In your response, identify the effector cells involved in this reaction.

103.

From a clinical perspective, explain how the logistics of organ transplantation differ from those for a bone marrow transplant.

104.

Explain why it is necessary to match at least some of the HLA allotypes between donor and recipient in a bone marrow transplant given to remedy SCID.

105.

Alloantibodies specific for HLA class I molecules can mediate hyperacute rejection of kidney transplants. Explain under what conditions an individual would possess preexisting antibodies against HLA class I polymorphisms.

Answer Key Chapter 15 1. Answer:

B

2. Answer:

A

3. Answer:

B

4. Answer:

B

5. Answer:

B

6. Answer:

A

7. Answer:

B

8. Answer:

B

9. Answer:

B

10.Answer:

A

11.Answer:

D

12.Answer:

C

13.Answer:

B

14.Answer:

B

15.Answer:

C

16.Answer:

E

17.Answer:

B

18.Answer:

A

19.Answer:

A

20.Answer:

C

21.Answer:

C

22.Answer:

E

23.Answer:

C

24.Answer:

B

25.Answer:

B

26.Answer:

A

27.Answer:

E

28.Answer:

D

29.Answer:

B

30.Answer:

E

31.Answer:

D

32.Answer:

D

33.Answer:

B

34.Answer:

D

35.Answer:

C

36.Answer:

E

37.Answer:

D

38.Answer:

C

39.Answer:

B

40.Answer:

A

41.Answer:

C

42.Answer:

B

43.Answer:

C

44.Answer:

C

45.Answer:

C

46.Answer:

A

47.Answer:

B

48.Answer:

D

49.Answer:

A

50.Answer:

D

51.Answer:

B

52.Answer:

B

53.Answer:

C

54.Answer:

B

55.Answer:

C

56.Answer:

D

57.Answer:

D

58.Answer:

D

59.Answer:

C

60.Answer:

B

61.Answer:

A

62.Answer:

C

63.Answer:

D

64.Answer:

D

65.Answer:

B

66.Answer:

E

67.Answer:

A

68.Answer:

A

69.Answer:

C

70.Answer:

D

71.Answer:

E

72.Answer:

B

73.Answer:

D

74.Answer:

A

75.Answer:

C

76.Answer:

A

77.Answer:

C

78.Answer:

E

79.Answer:

C

80.Answer:

D

81.Answer:

C

82.Answer:

E

83.Answer:

A

84.Answer:

C

85.Answer:

D

86.Answer:

C

87.Answer:

B

88.Answer:

C

89.Answer:

A

90.Answer:

1. D 2. B 3. A 4. E 5. C

91.Answer:

1. A 2. E 3. B 4. C 5. D

92.Answer:

Mature T-cell depletion of bone marrow reduces GVHD, but graft failure and disease recurrence in cancer patients is an associated risk with this procedure. Apparently, alloreactive T-cell responses benefit engraftment by suppressing remnants of the recipient’s immune system and removing residual cancer cells through a graft-versus-leukemia (GVL) effect.

93.Answer:

Vaccination is used to stimulate a very specific, long-lasting immune response against a pathogen that provides protection in the event of subsequent encounter. The objective of transplantation, however, is to suppress the immune response to eliminate the rejection of a graft that bears foreign epitopes.

94.Answer:

Hyperacute rejection can be prevented by typing and cross-matching donor and recipient for the A, B, and O blood groups and HLA antigens. The recipient’s serum antibodies are assayed in vitro for their ability to bind to donor white blood cells.

95.Answer:

Class 1: corticosteroids. Examples: hydrocortisone and prednisone. Side effects/toxic effects: fluid retention, weight gain, diabetes, bone demineralization, and thinning of the skin.

Class 2: cytotoxic drugs. Examples: azathioprine, cyclophosphamide, and methotrexate. Side effects/toxic effects: nonspecifically prevent DNA replication in all mitotic cells causing, for example, diarrhea or hair loss. More specific effects are liver damage caused by azathioprine, and bladder damage caused by cyclophosphamide.

Class 3: T-cell activation inhibitors. Examples: cyclosporin A, tacrolimus (FK506), and rapamycin.

Side effects/toxic effects: nephrotoxicity and suppression of B-cell and granulocyte activation.

96.Answer:

There is a possibility of incompatibility between erythrocytes and leukocytes involving ABO, Rhesus antigens, HLA class I and class II molecules, and other polymorphic alloantigens. Each transfusion will stimulate alloantibody production to these polymorphic determinants, which, if present in the blood of a subsequent transfusion, will stimulate a type II hypersensitivity reaction in the recipient.

Each blood transfusion increases the alloantibody pool, making it more difficult to find donors who will not cause a hypersensitivity reaction.

97.Answer:

In about 8% of dizygotic twins, the blood circulation is joined and the twins are born chimeric with hematopoietic cells of both twins present in both circulatory systems. A state of tolerance is induced to disparate major and minor histocompatibility antigens, explaining the absence of stimulation in a mixed lymphocyte reaction. These twins would also be expected to be able to donate organs or bone marrow to each other without the development of GVHD or the need for immunosuppressive drugs.

98.Answer:

Acute rejection is due chiefly to immune responses made by the recipient’s T cells against HLA class I and II molecules of the graft that are different from those of the recipient and that the recipient’s immune system perceives as “foreign.” The differences can be due to the HLA molecules, the self peptides they bind, or both. Transplantation between identical twins and transplantation of autografts are the only situations in which the graft and the recipient are genetically identical and in

which there are no differences in either the HLA molecules or the bound peptides. In these situations, graft rejection does not occur.

Transplantation between donors and recipients who have identical HLA class I and II molecules, usually HLA-identical siblings, almost always involves differences in the peptides that are bound by the HLA molecules. These differences trigger peptidespecific alloreactive T cells to cause graft rejection through the direct pathway of allorecognition.

Although it is possible to match donor and recipient for many HLA class I and II allotypes, in practice most clinical transplants involve one or more mismatched HLA loci. For these differences in HLA type, alloreactive T-cell clones activated by either the direct or indirect pathway of allorecognition cause graft rejection. Destruction of the grafted organ is effected through a type IV delayed-type hypersensitivity response.

99.Answer:

100.

Acute rejection occurs within a few days of transplantation and is mediated by an alloreactive CD4 and CD8 T-cell-mediated adaptive immune response by the recipient against the “foreign” HLA molecules on the graft and involves the direct pathway of recognition. In contrast, chronic rejection occurs months to years after transplantation; it is mediated by anti–HLA class I and anti–HLA class II alloantibodies and involves the indirect pathway of recognition. CD4 T cells are first activated by recipient dendritic cells presenting donor-derived HLA class II allotypes of the recipient. These activated CD4 T cells in turn activate B cells, which are also presenting donor-derived allogeneic HLA peptides. This cognate interaction results in the production of anti–HLA class I (and also anti–HLA class II) antibodies.

Answer: The organ would be rejected immediately by the process of hyperacute rejection as a result of the presence in the recipient’s blood of preformed antibodies against the A and B blood group antigens present on the tissues of the graft. Such antibodies are made early in life as a result of exposure to common bacteria that carry surface carbohydrates similar to those on human cells. A person of blood group O would have made antibodies against bacterial A and B antigens, because the person does not have these antigens on their own cells and

is thus not tolerant to them. These preexisting anti-A and anti-B antibodies in the recipient’s blood will immediately attack the endothelium of blood vessels throughout the transplant, which expresses the A and B blood group antigens. Both complement and the clotting cascades are activated. Blood vessels become occluded through thrombus (blood clot) formation. The graft is deprived of oxygen and becomes engorged with blood hemorrhaging from leaky blood vessels. Hyperacute rejection occurs almost immediately after transplantation and cannot be treated once it has started.

101.

Answer: Mouse monoclonal antibodies (mAb) are antigenic in species other than mice and stimulate anti- mAb responses. Repeated doses will exacerbate this situation and lead to the formation and clearance of mAb: anti-mAb immune complexes before the antibody can bind to the T cells, thus rendering the mouse antibody ineffective. A type III hypersensitivity reaction resembling serum sickness can also result when small immune complexes are formed; that is, when mAb levels exceed anti-mAb levels. Hence, repeated doses are discouraged, and physicians must restrict this form of immunosuppressive therapy to one episode of rejection.

102.

Answer: Graft-versus-host disease is caused by T cells in the transplanted bone marrow making an immune response against antigens on the recipient’s tissues.

This can happen even though donor and recipient are HLA matched, because there are proteins other than HLA antigens that can differ between people and provoke an immune response. Such antigens are known as minor histocompatibility antigens. In a bone marrow transplant from a female to a male, the minor histocompatibility antigens most likely to cause a problem are male-specific proteins (which are encoded on the Y chromosome) that a female’s T cells will not be tolerant to and will see as “foreign” or non-self. The effector cells are CD8 cytotoxic T cells. The proteins that act as minor histocompatibility antigens are mainly intracellular proteins. Intracellular proteins of the recipient’s cells are processed into peptides by proteasomes as part of normal protein degradation and turnover. These peptides are transported into the endoplasmic reticulum and thus are eventually presented on the

surface of the recipient’s cells by HLA class I molecules. Any peptides that are different from those in the donor may be recognized as non-self by the donor’s cytotoxic T cells, which recognize peptides bound to HLA class I molecules. The naive CD8 T cells in the bone marrow can be activated to effector status by the presentation of minor histocompatibility peptides by dendritic cells in secondary lymphoid organs. Because the brother and sister share HLA class I type, the sister’s T cells will be able to recognize non-self peptides presented by her brother’s HLA molecules.

103.

Answer: First, the medical specialists involved in carrying out the transplant and overseeing the post-transplant regimen are different for organ transplantation and for bone marrow transplantation. Patients receiving organ transplants will have transplant surgeons and physicians, whereas bone marrow recipients will consult with hematologists, oncologists, and radiologists. Second, the requirement for HLA matching and immunosuppressive therapy in organ transplantation depends on which organ is being transplanted. The success of a bone marrow transplant is much more sensitive to HLA mismatches, and the recipient’s immune system is not simply immunosuppressed; rather, it is destroyed by myeloablative therapy involving chemotherapy and irradiation. Third, the pool of potential bone marrow donors is larger than the demand, unlike organ donations, for which thousands of patients are on waiting lists. Finally, the bone marrow donor is alive and healthy, whereas organ donors are on life support or have experienced a fatal accident.

104.

Answer: After the bone marrow transplant, the patient’s entire immune system, including T cells and dendritic cells, will become reconstituted from hematopoietic stem cells in the donor bone marrow.

Donor-derived T cells developing in the recipient’s thymus will, however, be positively selected on the recipient’s HLA molecules, and will only recognize antigen in that context. If the donor and recipient do not share any HLA molecules, these T cells will not be able to recognize antigen presented by the donor-derived dendritic cells or macrophages and will not be activated in response to pathogens.

Because T-cell activation is central to all adaptive

immune responses, the recipient will remain severely immunodeficient and unable to make adaptive immune responses to pathogens. In addition, HLA matching reduces the severity of graft-versus-host disease (GVHD), in which mature T cells in the donor graft respond to the allogeneic MHC class I and II molecules of the recipient and attack host tissue.

105.

Answer: If the individual has received a previous solid organ graft or blood transfusion that was not matched for HLA class I, a primary alloantibody response would have been mounted. Priming can also occur naturally during pregnancy when fetal cells bearing paternal HLA molecules enter the maternal circulatory system at birth. If the paternal HLA isoforms are different from the maternal isoforms, the mother will mount an anti-HLA alloantibody response. If a woman has multiple pregnancies with the same partner, her anti-HLA titer and memory Bcell population will increase. If a woman has multiple pregnancies with different partners who have disparate HLA allotypes, the diversity of anti-HLA antibody will also increase. Both scenarios restrict the number of possible donors for transplantation; unsuitable donors are eliminated from the list after cross-matching.

Name: ___________________________ Class: _________________ Date: __________

Chapter 16 1. During pregnancy, IgG antibodies and activated lymphocytes can cross the placenta and enter the circulatory system of the fetus. a. True b. False

2. Blood plasma exchange (plasmapheresis) can be used to remove maternal IgG from the newborn. a. True b. False

3. All autoimmune diseases involve a breach of T-cell tolerance. a. True b. False

4. Newborns of mothers with T-cell-mediated autoimmune diseases exhibit the same symptoms as their mothers. a. True b. False

5. Autoimmune diseases can be induced after an infection. a. True b. False

6. Autoimmune diseases are rarely resolved or cured. a. True b. False

7. Autoimmune responses are the result of innate immune responses directed toward self antigens. a. True b. False

8. Some forms of autoimmune disease involve IgE autoantibodies. a. True b. False

9. During pregnancy the fetus is exposed to maternal leukocytes. a. True b. False

10.Ectopic lymphoid tissue resembling secondary lymphoid tissue may develop under the influence of lymphotoxin (LT). a. True b. False

11.Autoimmune diseases, which are classified on the basis of the effector mechanism that causes the symptoms, include all of the following types of hypersensitivity reaction EXCEPT a. type I. b. type II. c. type III. d. type IV.

12.Which type of autoimmune disease is correctly matched with its cause? a. type I: IgE-mediated b. type II: effector T cells c. type III: immune complex deposition in tissues d. type IV: extracellular matrix-associated autoantigens

e. type V: cell-surface components.

13.Which of the following is an example of a type II autoimmune response? a. bacterial endocarditis b. rheumatoid arthritis c. multiple sclerosis d. systemic lupus erythematosus e. myasthenia gravis

14.Which of the following is an example of a type III autoimmune response? a. hemolytic anemia b. acute thrombocytopenia purpura c. systemic lupus erythematosus d. rheumatoid arthritis e. type 1 diabetes.

15.Which of the following is an example of a type IV autoimmune response? a. pemphigus vulgaris b. autoimmune thrombocytopenia purpura c. bacterial endocarditis d. type 1 diabetes e. mixed cryoglobulinemia

16.If autoantibodies of the IgG or IgM isotype were produced with specificity for components found on the surface of erythrocytes, which of the following would occur? a. formation of membrane-attack complex b. immune-complex deposition in renal glomeruli c. loss of HLA on cells d. hypothyroidism e. epitope spreading

17.Which of the following is the cause of red blood cell deficiency in autoimmune hemolytic anemia? a. inability of red blood cells to develop normally in the bone marrow b. loss of red blood cells due to widespread pinpoint hemorrhages c. hemolysis by assembly of membrane-attack complexes d. mismatched blood transfusion e. rapid turnover of red blood cells due to CD8 T-cell killing

18.__________ is a highly variable type III autoimmune disease in which immune complexes form and may cause glomerulonephritis of the kidney, arthritis of the joints, and vasculitis of the face. a. Pemphigus vulgaris b. Systemic lupus erythematosus c. Rheumatoid arthritis d. Multiple sclerosis e. Goodpasture’s syndrome

19.Individuals who have two defective alleles of the AIRE gene a. exhibit symptoms of autoimmunity at a young age. b. are unable to activate regulatory T cells. c. exhibit decreased predisposition to autoimmune disease. d. are very effective at inducing anergy of circulating autoreactive B and T cells. e. are more likely to be women of African or Asian origin.

20.All of the following autoimmune diseases are correctly matched with their HLA disease associations EXCEPT a. HLA-B27: ankylosing spondylitis. b. HLA-DQ2: type 1 diabetes in Africans and Asians. c. HLA-B35: birdshot chorioretinopathy. d. HLA-DR4: rheumatoid arthritis. e. HLA-DQ6: narcolepsy.

21.The haplotype A1–B8–DR3–DQ2 is associated with several common autoimmune diseases including all of the following EXCEPT a. ankylosing spondylitis. b. systemic lupus erythematosus. c. autoimmune hepatitis. d. myasthenia gravis. e. type 1 diabetes. f. primary biliary cirrhosis.

22.All the following autoimmune diseases are more prevalent in women than in men EXCEPT a. rheumatoid arthritis. b. multiple sclerosis. c. ankylosing spondylitis. d. Sjögren’s syndrome. e. Graves’ disease.

23.Which of the following is NOT a characteristic of Graves’ disease? a. weight loss b. enlarged thyroid gland c. elevated thyroid-stimulating hormone d. heat intolerance e. overproduction of T3 and T4

24.All of the following are true regarding thyroglobulin EXCEPT a. its tyrosine residues are iodinated and cross-linked. b. it is broken down to produce thyroid hormones. c. it is stored in follicles of the thyroid. d. it signals the pituitary gland to stop releasing thyroid-stimulating hormone. e. it is synthesized initially as a glycoprotein by thyroid epithelial cells.

25.Which of the following describes myasthenia gravis?

a. Ectopic lymphoid tissue forms and impairs endocrine function. b. disruption of adhesion molecules of cellular junctions c. autoimmune response to proteins of anterior chamber of the eye d. chronic inflammation of the gut mucosa e. The neuromuscular junction is impaired.

26.Which of the following is associated with antagonistic autoantibodies against cellsurface receptors or adhesion molecules? a. myasthenia gravis b. rheumatoid arthritis c. type 1 diabetes d. Graves’ disease e. multiple sclerosis

27.The reason why babies born to mothers with Graves’ disease suffer passively from the disease for only a short while after birth is that a. very little IgM is transported across the placenta. b. only antibodies, and not the B cells making the autoantibodies, cross the placenta. c. the newborn’s regulatory T cells suppress autoantibody production. d. the newborn’s thyroid gland develops resistance to the effects of maternal autoantibodies. e. thyroglobulin synthesis does not commence until months after birth.

28.The formation of ectopic lymphoid tissues occurs in all of the following conditions EXCEPT a. pemphigus foliaceus. b. chronic hepatitis C infection. c. Hashimoto’s disease. d. rheumatoid arthritis. e. Graves’ disease.

29.A(n) __________ binds to the antigen-binding site of another antibody.

a. cryptic epitope b. anti-idiotypic antibody c. molecular mimic d. receptor antagonist e. autoantibody

30.All of the following are linked to the development of rheumatoid arthritis EXCEPT a. anti-immunoglobulin autoantibodies. b. leukocyte infiltration in synovial tissue. c. increased susceptibility if the person possesses the HLA-DRB1*04:01 or 04:04 allotypes. d. peptidyl arginine deiminases. e. rheumatic fever.

31.Which of the following is associated with the treatment of rheumatoid arthritis? a. anti-immunoglobulin autoantibodies b. adalimumab c. insulin therapy d. removal of the thyroid e. pyridostigmine

32.It is believed that the allotype DRB1* __________ may confer protection against rheumatoid arthritis because it contains __________ amino acid residues at positions 70 and 71 that bind to different subsets of peptides compared with the allotypes that confer susceptibility to this disease. a. 04:01; acidic b. 04:02; acidic c. 04:04; basic d. 04:05; basic e. 04:08; acidic

33.Which of the following symptoms would NOT be observed in celiac disease? a. villous atrophy

b. anemia c. diarrhea d. ulceration of the basal membrane of the gut e. malabsorption

34.Which of the following is a characteristic of tissue transglutaminase? a. It generates positively charged peptides that bind well to the pockets of the DQ2 and DQ8 HLA allotypes. b. It converts glutamate to glutamine by deamination. c. It is downregulated during inflammation, resulting in the lack of proper digestion of gluten in the small intestine. d. It can be the target of IgG or IgA autoantibodies in celiac disease. e. There is a polymorphic variant that predisposes individuals to celiac disease.

35.Which of the following describes a process by which self-reactive lymphocytes are rendered incapable of mounting an autoimmune response? a. induction of anergy in peripheral compartments b. positive selection of autoimmune T lymphocytes in secondary lymphoid tissues c. negative selection of B and T lymphocytes in the bone marrow d. activation by regulatory T cells e. expression of AIRE in the bone marrow

36.A recent therapy developed for the treatment of rheumatoid arthritis includes the use of __________ monoclonal antibodies that suppress the autoimmune response. a. anti-TNF-α b. anti-C-reactive protein c. anti-PAD (peptidyl arginine deiminases) d. anti-rheumatoid factor e. anti-CD3

37.Chronic diseases in which the immune response targets healthy self-tissues and cells are known as a. hypersensitivity reactions. b. innate immune reactions. c. allergic reactions. d. autoimmune diseases. e. anergic reactions.

38.Thyroid-stimulating hormone is made in the __________ and induces the release of thyroid hormones after proteolytic processing of __________. a. pituitary gland; thyroglobulin b. hypothalamus; thyroxine c. pancreas; thyroglobulin d. pituitary gland; thyroid-stimulating hormone receptor e. thyroid gland; thyroid peroxidase

39.Graves’ disease causes __________, whereas Hashimoto’s disease causes __________. a. hypothyroidism; hyperthyroidism b. hyperthyroidism; hypothyroidism c. hypoglycemia; hyperglycemia d. hyperglycemia; hypoglycemia e. glomerulonephtitis; systemic vasculitis

40.Which of the following pairs is correctly matched? a. exocrine tissue: islets of Langerhans b. type 2 diabetes: insulin-dependent diabetes mellitus c. β cells of pancreas: glucagon production d. α cells of pancreas: somatostatin production e. insulitis: lymphocyte infiltration in islets of Langerhans

41.Which of the following is NOT an autoimmune rheumatic disease?

a. rheumatoid arthritis b. acute rheumatic fever c. scleroderma d. Sjögren’s syndrome e. systemic lupus erythematosus.

42.Another name for anti-immunoglobulin autoantibodies is a. C-reactive protein. b. rheumatoid factor. c. rituximab. d. thyroglobulin. e. ectopic antibodies.

43.Rituximab, used in the treatment of rheumatoid arthritis, depletes __________ through a process involving the cross-linking of __________ on the surface of NK cells and the induction of antibody-dependent cell-mediated cytotoxicity. a. NK cells; NKG2D b. T cells; NKG2D c. inflammatory cytokines; TNF-alpha d. C-reactive protein; FcγRIII e. B cells; FcγRIII

44.Which of the following autoimmune diseases affect the nervous system? a. myasthenia gravis b. mixed essential cryoglobulinemia c. Graves’ disease d. pemphigus vulgaris e. ankylosing spondylitis

45.__________ autoantibodies enhance receptor function. a. Neutralizing b. Opsonizing

c. Agonist d. Complement-fixing e. Antagonist

46.Antagonistic autoantibodies made against the insulin receptor cause a. type 1 diabetes. b. hypoglycemia. c. progressive muscle weakness. d. insulin-resistant diabetes. e. light-headedness.

47.Deficiency in the production of AIRE results in a. normal expression of tissue-specific proteins in the bone marrow and thymus. b. the development of autoimmune B-cell and T-cell responses against endocrine glands and other tissues. c. death in infancy. d. the development of IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked disease).

48.Ankylosing spondylitis has a strong association with polymorphisms found in a. HLA-B27. b. AIRE. c. HLA-DQ6. d. FoxP3. e. TNF-α.

49.Autoantibody specificities are affected by HLA class II polymorphisms. In the case of systemic lupus erythematosus, indicate which of the following associations between HLA class II and autoantigens have been observed in these patients. a. HLA-DR3; nuclear ribonucleoprotein complex b. HLA-DR5; small cytoplasmic ribonucleoprotein complex c. HLA-DR2; double-stranded DNA

d. HLA-DR4; single-stranded RNA e. HLA-DQ8; double-stranded RNA

50.__________ is an example in which physical trauma allows lymphocytes access to an otherwise immunologically privileged site. a. Systemic lupus erythematosus b. Multiple sclerosis c. Type 1 diabetes d. Myasthenia gravis e. Sympathetic ophthalmia

51.Which of the following autoimmune diseases have NOT been associated with a bacterial or viral infection? a. Reiter’s syndrome b. type 1 diabetes c. reactive arthritis d. rheumatic fever e. myasthenia gravis

52.The upregulation of __________ by IFN-γ can contribute to antigen-specific T-cell activation on thyroid epithelium. a. CD4 b. CD8 c. HLA class I d. HLA class II e. CD28

53.__________ is the term used to describe how pathogen antigens resemble host antigens and can sometimes trigger autoimmune disease. a. Intramolecular epitope spreading b. Molecular mimicry c. Intermolecular epitope spreading d. Sympathetic senescence

e. Linkage equilibrium

54.A(n) __________ is an epitope that is typically not accessible to the immune system but is revealed under inflammatory or infectious states. a. cryptic epitope b. molecular mimic c. regulatory peptide d. carrier e. adjuvant

55.The process by which the human thymus gradually decays is known as a. apoptosis. b. senescence. c. involution. d. the hygiene hypothesis. e. self-tolerance.

56.The autoreactive CD4 T cells of elderly people with rheumatoid arthritis __________. a. express high levels of CD28 b. are predominantly anergic c. express NK-cell receptors d. are highly susceptible to apoptosis in inflamed joints e. have highly diverse T-cell receptors

57.Amanda Chenoweth, 21 years of age, returned from a summer job as a pianist on a cruise ship where she was exposed daily to excessive sun; she developed a rash on her cheeks. She complained that her finger joints were stiff and painful, which made it difficult to play the piano, and that her hips became painful after sitting at the piano for long periods. Her blood sample tested positive for antinuclear antibodies and had decreased serum C3 levels. A urine albumin test showed elevated protein levels. A course of prednisone (an anti-inflammatory steroid) in combination with naprosyn (a nonsteroidal anti-inflammatory agent) was begun and her condition improved rapidly. What is the most likely cause and

clinical name of her condition? a. deterioration of the central nervous system; multiple sclerosis b. cartilage destruction by bone-cell enzymes; rheumatoid arthritis c. immune complexes fixing complement in kidney, joints, and blood vessels; systemic lupus erythematosus d. autoantibodies against acetylcholine receptor at the neuromuscular junction; myasthenia gravis e. consumption of seafood to which she was allergic; acute systemic anaphylaxis

58.At 42 years old, Stephanie Goldstein developed occasional blurred and double vision, numbness and “pins and needles” in her arms and legs (paresthesia), and bladder incontinence. After a month of these symptoms she went to her doctor, who sent her to a neurologist. An MRI scan revealed areas of demyelination in the central nervous system (CNS), and Stephanie was diagnosed with the autoimmune disease multiple sclerosis (MS). Which of the following best explains why some people are susceptible to the development of MS? a. Negative selection of autoreactive T cells occurs during T-cell development. b. Apoptosis of autoreactive B cells occurs in the bone marrow during B-cell development. c. An inability to produce immunological tolerance toward CNS-derived constituents results in the generation of self-reactive lymphocytes. d. An immunodeficiency inhibiting somatic recombination of immunoglobulins and T-cell receptors results in impaired lymphocyte development. e. Regulatory T cells fail to activate autoreactive T cells in secondary lymphoid organs.

59.Anders Anderson was seen by his pediatrician at 24 months old after a recent bout of diarrhea and vomiting. He had lost his appetite and complained that his stomach hurt. Anders was in the fifth percentile for weight, had slender limbs, wasted buttocks, and a protuberant abdomen. Jejunal biopsy revealed abnormal surface epithelium, and villous atrophy with hyperplasia of the crypts. Which of the following would be a likely clinical finding in this patient? a. glomerulonephritis b. urticarial rash c. anti-gliadin IgA antibodies

d. chronic wheezing e. low blood pressure

60.Seventeen-year-old Lisa Montague practiced piano for 3–4 hours each day while preparing for music college auditions. Some of her pieces required sustained arm-muscle activity and she began to find them hard to play, even though she had previously played them easily. When she also started to have difficulty swallowing and chewing, she told her mother, who took her to the emergency room, where the physician noticed drooping eyelids and limitation of ocular motility. An electromyogram detected impaired nerve-to-muscle transmission.

Administration of pyridostigmine rapidly improved Lisa’s symptoms. Which of the following blood-test results would be most consistent with her condition? a. elevated rheumatoid factor b. elevated anti-myelin basic protein antibodies c. elevated anti-acetylcholine receptor antibodies d. elevated anti-nuclear antibodies e. elevated anti-Rh antibodies

61.__________ cells are the most inflammatory subset of T cells and are associated with the majority of autoimmune responses and diseases. a. TH1 b. TH2 c. TH17 d. Tregs e. CD8 Tc

62.Which of the following accurately explains the difference in incidence of autoimmune disease in females and males? a. Testosterone enhances the production of antibodies. b. Estrogen enhances the production of inflammatory cytokines. c. Testosterone reduces the production of TH2 cytokines. d. Testosterone explains the stronger adaptive immune response seen in men following vaccination.

63.The mechanism of immunological privilege observed in the human eye a. prevents the entry of all immune cells and molecules into the eye. b. shows that the two eyes are physiologically separate, so that damage to one eye will not impact the second eye. c. means that immunosuppressive drugs are not needed to protect the eye, even following damage. d. can be disrupted by the activation of T cells in the lymph nodes following damage to the eye.

64.Which of the following statements is accurate concerning type 1 diabetes? a. Although antigen-specific CD8 T cells are observed, there are no autoantibodies produced. b. Patients make autoantibodies against glutamic acid decarboxylase and these autoantibodies are known to cause the disease. c. The onset of disease is linked to an infection with a rotavirus. d. Insulitis, or the infiltration of lymphocytes, is observed in the pancreas of people with type 1 diabetes.

65.The DQ6 allotype a. confers strong susceptibility to type 1 diabetes when the individual is heterozygous. b. confers strong resistance to type 1 diabetes only when the individual is homozygous. c. confers strong resistance to type 1 diabetes even when the individual is heterozygous. d. is commonly observed in individuals living with type 1 diabetes. e. promotes susceptibility to both type 1 diabetes and celiac disease.

66.Select the correct statement concerning the mechanism of celiac disease.

a. The enzyme labeled “A” binds strongly to a proline-rich fragment of glutenin. b. The molecule labeled “B” is modified by the addition of positive charges, thus allowing it to bind to negatively charged binding pockets in the HLA. c. The allotypes of “C” that lead to celiac disease include HLA-DR3 and HLADR4. d. The cell labeled “D” that is activated by a dendritic cell (DC) in a patient with celiac disease is more likely to secrete TNF-alpha than TGF-beta.

67.Select the correct statement concerning the pregnancy of a woman with an autoimmune disorder.

a. The FcRn is required for Graves’ disease to be passed to the fetus in panel B. b. If the woman has myasthenia gravis, her newborn will not develop the disease because the symptoms are caused by CD4 T cells and not antibodies. c. The baby in panel C will continue to have the same autoimmune disease that was transmitted from the mother throughout his or her life. d. Negative selection of the T-cell repertoire will be disrupted in the infant due to the presence of maternal antibodies.

68.Which of the following statements is NOT accurate concerning the CD4 T cell shown in the figure?

a. The peptides presented by the H1-specific B cell and the DNA-specific B cell are identical. b. The B cell receptors on the H1-specific and the DNA-specific B cells are identical. c. Activation of the H-1 and DNA-specific B cells lead to a broadening of the T-cell response. d. The loss of tolerance of the H1-peptide-specific CD4 T cell leads to immune-complex formation and inflammation. e. This response is an example of intermolecular epitope spreading.

69.Match the hypersensitivity type in the lettered answers with its description in the numbered answers. a. type I b. type II c. type III d. type IV 1. __________ antibodies directed against extracellular matrix or the cell surface 2. __________ T cell-mediated

3. __________ deposition of soluble immune complexes in tissues 4. __________ IgE-mediated

70.Match the autoimmune disease with its corresponding antigen. a. rheumatoid arthritis b. subacute bacterial endocarditis c. autoimmune hemolytic anemia d. mixed essential cryoglobulinemia e. multiple sclerosis f. systemic lupus erythematosus g. type 1 diabetes h. Graves’ disease i. Pemphigus vulgaris 1. __________ myelin basic protein, proteolipid protein 2. __________ DNA, histones, ribosomes, snRNP, scRNP 3. __________ thyroid-stimulating hormone receptor 4. __________ bacterial antigen 5. __________ rheumatoid factor IgG complexes 6. __________ epidermal cadherin 7. __________ synovial joint antigen 8. __________ Rh blood group antigens 9. __________ pancreatic β-cell antigen

71.Match the autoimmune disease with its consequence. a. rheumatoid arthritis b. subacute bacterial endocarditis c. autoimmune hemolytic anemia d. mixed essential cryoglobulinemia e. multiple sclerosis f. systemic lupus erythematosus g. type 1 diabetes h. Graves’ disease i. pemphigus vulgaris 1. __________ destruction of red blood cells by complement and phagocytosis, anemia 2. __________ joint inflammation and destruction 3. __________ pancreatic β-cell destruction

4. __________ glomerulonephritis 5. __________ hyperthyroidism 6. __________ blistering of skin 7. __________ glomerulonephritis, vasculitis, arthritis 8. __________ systemic vasculitis 9. __________ brain degeneration, paralysis

72.Match the autoimmune disease with its consequence. a. type 2 diabetes b. rheumatoid arthritis c. mixed essential cryoglobulinemia d. acute rheumatic fever e. pemphigus vulgaris 1. __________ skin blistering 2. __________ joint deterioration 3. __________ ketoacidosis 4. __________ heart valve scarring 5. __________ systemic vasculitis

73.Match the autoimmune disease with its antigen. a. mixed essential cryoglobulinemia b. myasthenia gravis c. Graves’ disease d. acute rheumatic fever e. multiple sclerosis 1. __________ thyroid-stimulating hormone receptor 2. __________ cell-wall components of Streptococcus 3. __________ myelin basic protein 4. __________ acetylcholine receptor 5. __________ rheumatoid factor IgG

74.Characterize two properties of endocrine glands that render them susceptible to autoimmune attack.

75.What mechanism of self-tolerance is broken in the autoimmune syndrome

APECED?

76.You have isolated a subset of CD25+ CD4+ T cells from the blood that have T-cell receptors specific for a self-antigen but do not proliferate when challenged with the antigen in vitro. What is the name given to these T cells, and what role are they thought to have in preventing autoimmunity?

77.People who are heterozygous for HLA-DQ2 and HLA-DQ8 allotypes are at greater risk of developing type 1 diabetes than those who are homozygous for HLA-DQ2 or HLA-DQ8. Explain the reason for this increased susceptibility.

78.Describe three types of unwanted and potentially harmful immune response.

79.Hashimoto’s and Graves’ diseases both impair normal functioning of the thyroid gland but do so using different immunopathological mechanisms. Compare and contrast these mechanisms.

80.What is the underlying genetic defect in the autoimmune syndrome APECED? Explain why it leads to a reduction in self-tolerance.

81.Explain the relationship between HLA-DRB1*04, smoking, the expression of peptidyl arginine deaminase, and rheumatoid arthritis.

82.Define molecular mimicry in the context of autoimmunity and describe an example.

83.Define ectopic lymphoid tissue and list four examples where this tissue forms in autoimmune disease.

84.How do the treatments for Hashimoto’s and Graves’ diseases differ, and why?

85.Explain the mechanism that gives rise to a broadening B-cell response during the course of systemic lupus erythematosus.

86.Define “epitope spreading” and describe how it is involved in an autoimmune disease affecting the skin.

Answer Key Chapter 16 1. Answer:

B

2. Answer:

A

3. Answer:

A

4. Answer:

B

5. Answer:

A

6. Answer:

A

7. Answer:

B

8. Answer:

B

9. Answer:

B

10.Answer:

A

11.Answer:

A

12.Answer:

C

13.Answer:

E

14.Answer:

C

15.Answer:

D

16.Answer:

A

17.Answer:

C

18.Answer:

B

19.Answer:

A

20.Answer:

C

21.Answer:

A

22.Answer:

C

23.Answer:

C

24.Answer:

D

25.Answer:

E

26.Answer:

A

27.Answer:

B

28.Answer:

A

29.Answer:

B

30.Answer:

E

31.Answer:

B

32.Answer:

B

33.Answer:

D

34.Answer:

D

35.Answer:

A

36.Answer:

A

37.Answer:

D

38.Answer:

A

39.Answer:

B

40.Answer:

E

41.Answer:

B

42.Answer:

B

43.Answer:

E

44.Answer:

A

45.Answer:

C

46.Answer:

D

47.Answer:

B

48.Answer:

A

49.Answer:

C

50.Answer:

E

51.Answer:

E

52.Answer:

D

53.Answer:

B

54.Answer:

A

55.Answer:

C

56.Answer:

C

57.Answer:

C

58.Answer:

C

59.Answer:

C

60.Answer:

C

61.Answer:

C

62.Answer:

B

63.Answer:

D

64.Answer:

D

65.Answer:

C

66.Answer:

D

67.Answer:

A

68.Answer:

B

69.Answer:

1. B 2. D 3. C 4. A

70.Answer:

1. E 2. F 3. H 4. B 5. D 6. I 7. A 8. C 9. G

71.Answer:

1. C 2. A 3. G 4. B 5. H 6. I 7. F 8. D

9. E 72.Answer:

1. E 2. B 3. A 4. D 5. C

73.Answer:

1. C 2. D 3. E 4. B 5. A

74.Answer:

First, endocrine glands synthesize tissue-specific proteins unique to that gland. These proteins are not normally found in primary lymphoid organs where lymphocyte maturation occurs. Hence, the population of T and B lymphocytes is not tolerant to some endocrine gland-specific proteins, and these self-proteins are thus recognized as foreign antigens. Second, endocrine glands are highly vascularized because their products need to gain access to the circulation. This feature gives leukocytes relatively easy access to endocrine tissue.

75.Answer:

The negative selection of developing autoreactive T cells in the thymus.

76.Answer:

These cells are called regulatory T cells (Treg). When activated by encounter with their corresponding self antigen, they become able to suppress the activation of naive autoreactive T cells. This active suppression of autoreactive T cells in the periphery is now thought to be an important method of preventing autoimmune reactions.

77.Answer:

Increased risk of developing type 1 diabetes is associated with the formation of a heterozygote-specific heterodimer composed of the HLA-DQ8α chain DQA1*03 and the HLADQ2β chain DQB1*02:01.

78.Answer:

Allergy. IgE antibodies made against normally innocuous environmental antigens trigger widespread mast-cell activation. This can lead to allergic diseases such as asthma

or to a potentially fatal anaphylactic reaction.

Autoimmune disease. Chronic immune responses by B cells or T cells to self antigens can cause tissue damage and chronic illnesses such as diabetes, multiple sclerosis, and myasthenia gravis. Autoimmunity is sometimes provoked as a consequence of an immune response to pathogen-derived antigen that cross-reacts on healthy host cells or tissue.

Transplant rejection. A person’s immune system will make an immune response against the foreign MHC molecules on transplanted tissue that is MHC-incompatible.

79.Answer:

Both Hashimoto’s and Graves’ diseases disrupt the normal production of the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4), which are derived from thyroglobulin in thyroid follicles. The formation of T3 and T4 requires engagement of the thyroid-stimulating hormone receptor (TSHR) with thyroidstimulating hormone (TSH) secreted from the pituitary gland, a key step in the regulation of thyroid hormone production.

This step malfunctions for these two diseases.

In Hashimoto’s disease, anti-thyroid antigen antibodies and TH1 effector cells are involved. Large numbers of lymphocytes take up residence in the gland tissue, establishing germinal centers that resemble those in lymph nodes. Eventually the thyroid tissue is destroyed, and thyroid follicles are no longer able to respond to TSH and make T3 or T4, a condition called hypothyroidism.

Graves’ disease, in contrast, results in hyperthyroidism. AntiTSHR antibodies act agonistically, mimicking TSH even in its absence. The thyroid follicle is chronically overstimulated by these antibodies and overproduces T3 and T4. The effector T cells are of the TH2 type, and the absence of lymphocyte infiltration retains the thyroid gland in operable condition.

Therefore, T3 and T4, no longer regulated by TSH, are secreted continuously in excess of concentrations required by the body.

80.Answer:

The underlying genetic defect is in a gene encoding a protein called AIRE (autoimmune regulator). This is a transcription factor that, when working normally, causes several hundred proteins otherwise expressed only in particular peripheral tissues to be expressed by medullary epithelial cells in the thymus. This induces the negative selection of T cells specific to these proteins and their deletion from the T-cell repertoire.

The T cells emerging from the thymus are therefore tolerant to a large number of antigens found primarily on organs and tissues elsewhere in the body. When AIRE is defective and these proteins are not expressed in the thymus, the population of naive T cells that develops will contain T cells

reactive against these antigens of peripheral tissues.

81.Answer:

Peptidyl arginine deaminase (PAD) is an enzyme induced in the respiratory tract after smoke-induced damage. PAD converts arginine residues in self proteins to citrulline residues, thus creating epitopes to which the T-cell repertoire is not tolerant. Citrullinated proteins are subject to proteolysis, and the resulting peptides bind to HLA-DRB1*04 and stimulate autoreactive CD4 T cells and antibodies against citrullinated self-proteins. If a joint becomes infected or is wounded, inflammation of joint tissue activates PAD, which generates the same citrullinated epitopes. HLA-DRB1*04restricted effector and memory T cells are recruited and activated, and an immune response follows, initiating the development of rheumatoid arthritis.

82.Answer:

Molecular mimicry refers to the phenomenon in which a pathogen expresses an antigen that bears a chemical similarity to a host-cell antigen. Once pathogen-specific antibodies or effector T cells are generated, they have the potential to cross-react with self-antigen. An autoimmune disease involving molecular mimicry is rheumatic fever.

Infection with Streptococcus pyogenes (such as “strep throat”) results in the production of antibodies specific to the bacterial cell-wall proteins. These antibodies cross-react with chemically similar self-antigen expressed on heart tissue. This is followed by complement activation and the production of inflammatory mediators, which cause damage to heart tissue and valves and the formation of scar tissue, which can lead to cardiovascular complications later in life. This type of immunological aftermath can be avoided if antibiotics are administered early during infection.

83.Answer:

Ectopic lymphoid tissue, also known as tertiary lymphoid tissue, is found as a result of infiltration of immune-system cells, such as lymphocytes, dendritic cells, macrophages, and follicular dendritic cells, into endocrine tissue. The cells then organize through a process known as lymphoid neogenesis to form structures that functionally resemble secondary lymphoid tissues, except that ectopic lymphoid tissue lacks a capsule and does not associate with the lymphatics. Ectopic lymphoid tissue is characteristic of Hashimoto’s thyroiditis and has also been associated with rheumatoid arthritis, Graves’ disease, and multiple sclerosis.

84.Answer:

Hashimoto’s and Graves’ diseases are treated differently because, although they both affect the thyroid gland, they exert opposing effects on the production of thyroid hormones—inhibition and overproduction, respectively.

Hashimoto’s disease is treated by administering synthetic thyroid hormones orally to replace the deficiencies in T3 and T4. Graves’ disease is treated either by suppressing thyroid function with inhibitory drugs or by thyroidectomy combined with thyroid hormone replacement therapy.

85.Answer:

In SLE, the protein epitopes recognized by autoreactive T cells are part of large macromolecular complexes composed of aggregates of histone proteins and DNA, or aggregates of ribosomal proteins and RNA. Accessible epitopes on the external surface of the complex can bind easily to antigen receptors on the surface of neighboring B cells that possess different epitope specificities (such as histone-specific antigen receptors and DNA-specific antigen receptors). If these B cells are presenting peptides to which the original autoreactive CD4 T cells are specific, then help is provided to both types of B cell and antibodies are generated to both accessible epitopes. Alternatively, if the B cell internalizes and degrades the complex and presents peptides derived from inaccessible interior proteins to CD4 T cells, then T cells with specificities to all protein components of the complex, both accessible and inaccessible, become activated and the immune response broadens.

86.Answer:

Epitope spreading is the phenomenon in which the immune response, having initially targeted a particular epitope on an antigen molecule, progressively involves other cross-reactive epitopes on the same molecule. Epitope spreading is involved in pemphigus foliaceus. Autoantibody production against the protein desmoglein, a component of desmosomes, initially involves epitopes that do not result in any tissue damage or symptoms. Only when additional desmoglein epitopes become involved, as a result of epitope spreading, does the autoimmune response cause damage to desmosomes and give rise to lesions in the skin (the disease pemphigus).

Name: ___________________________ Class: _________________ Date: __________

Chapter 17 1. A mutation in only one copy of a tumor suppressor gene can cause malignant transformation. a. True b. False

2. A neoplasm is characterized by abnormal cell division, which can cause disruption to organ function. a. True b. False

3. Malignant tumors are often encapsulated and are limited in size. a. True b. False

4. Most cancers develop in tissues that are actively undergoing division. a. True b. False

5. Cancers of immune system cells that form solid tumors are known as sarcomas. a. True b. False

6. Individuals with Li–Fraumeni syndrome who have been treated successfully for cancer are likely to develop another primary malignancy at a later time. a. True b. False

7. Which of the following pairs is NOT matched correctly? a. oncology: diagnosis and treatment of tumors b. carcinoma: characteristic cell types found in benign tumors c. mutation: changes in DNA involving substitutions, deletions, insertions, recombination, and translocations d. leukemia: cancer of the immune system affecting circulating cells e. malignant transformation: gain of ability to form a cancer

8. Which of the following pairs is NOT matched correctly? a. tumor suppressor genes: mutated in over 50% of human cancer cases b. proto-oncogene: contribute to normal cell division c. p53: induces apoptosis in cells with damaged DNA d. malignant transformation: requires five or more independent mutations e. Ras: tumor suppressor gene

9. Mutagens that increase one’s risk of developing cancer are called a. carcinogens. b. tumor antigens. c. neoplastic mutagens. d. oncogenes. e. proto-oncogenes.

10.Human papillomaviruses express proteins that bind to __________ and block its/their function. a. MIC glycoproteins b. HLA class II c. CT antigens d. TLR4 e. Rb

11.__________ is/are commonly associated with the fusion between the BCR gene and the ABL proto-oncogene.

a. Non-small cell lung carcinoma b. Bladder tumors c. Melanoma d. Head and neck squamous cell carcinoma e. Chronic myelogenous leukemia

12.Which of the following cell types in a tumor biopsy would NOT be associated with a promising prognosis? a. B cells b. memory T cells c. TFH cells d. regulatory T cells e. cytotoxic T cells

13.GM-CSF is used in cancer immunotherapy to a. reduce the blood supply to cancer cells. b. inhibit tumor-cell proliferation. c. induce tumor-cell apoptosis. d. reduce PD-1 expression. e. activate effective antigen-presenting dendritic cells.

14.Adoptive transfer of sipuleucel-T-primed dendritic cells is a form of immunotherapy used for the treatment of a. late-stage metastatic prostate cancer. b. multiple myeloma. c. chronic myelogenous leukemia. d. melanoma. e. cervical cancer.

15.Which of the following monoclonal antibodies is NOT directed at a cell-surface component? a. rituximab

b. cetuximab c. ibritumomab d. bevacizumab e. ipilimumab

16.When the immune system is involved in __________, the monitoring for cancer cells is occurring. a. malignant transformation b. apoptosis c. antineoplasia d. immunosurveillance e. immunosuppression

17.A benign tumor of glandular tissue is known as a(n) a. sarcoma. b. myeloma. c. adenoma. d. adenocarcinoma. e. lymphoma.

18.A malignant tumor is uniquely characterized by which of the following features? a. encapsulation b. localized c. restricted in size d. metastasizes to distant sites e. expression of proto-oncogenes

19.Which of the following pairs is NOT matched correctly? a. myeloma: bone marrow b. benign tumor: encapsulation c. lymphoma: circulating immune system cells d. carcinoma: epithelial cells

e. neoplasm: new growth

20.Which of the following is NOT a tumor suppressor gene? a. APC b. p53 c. ABL d. DCC

21.__________ describes the condition in which a cell becomes able to cause cancer. a. Malignant mutation b. Malignant recombination c. Malignant neoplasm d. Malignant transformation e. Malignant suppression

22.A protein expressed in response to damage to DNA that results in death to the cell is a. Ras. b. p53. c. Rb. d. Abl. e. MAGEA1.

23.Human herpesvirus 8 (HHV8) is associated with the development of __________ in immunocompromised patients. a. Burkitt’s lymphoma b. chronic myeloid leukemia c. melanoma d. myeloma e. Kaposi’s sarcoma

24.Li–Fraumeni syndrome is linked to a greater risk of cancer as a result of the inheritance of a germline mutation in one copy of a. TLR-9. b. p53. c. CTLA4. d. heat-shock protein. e. Rb.

25.Chemical and physical agents that increase mutation rates by damaging DNA and increase the likelihood of developing cancer are known as a. oncogenes. b. malignant transformers. c. antitumor suppressor agents. d. carcinogens. e. tumor-associated agents.

26.__________ agents usually cause single nucleotide substitutions in DNA, whereas __________ agents produce more significant damage to DNA. a. Mutagenic; carcinogenic b. Chemical; physical c. Benign; malignant d. Tumor-associated; tumor-specific e. Benign; oncogenic

27.Which of the following is an example of a chemical agent that increases an individual’s predisposition to developing cancer? a. cigarette smoke b. X-rays c. ultraviolet radiation d. Epstein–Barr virus e. exposure to radioactive sources

28.Burkitt’s lymphoma is a tumor associated with __________ infection, which

causes __________ to divide uncontrollably. a. Epstein–Barr virus; B cells b. hepatitis B virus; epithelial c. human T-cell leukemia; hepatocytes d. human herpesvirus; T cells e. papillomavirus; uterine cells

29.An RNA virus associated with cancer development is a. human papillomavirus (HPV). b. human immunodeficiency virus (HIV-1). c. human herpesvirus 8 (HHV8). d. Epstein–Barr virus (EBV). e. hepatitis B virus.

30.Cancers develop their own blood supply and become vascularized through a. apoptosis. b. neoplasia. c. angiogenesis. d. metastasis. e. malignant transformation.

31.Systemic distribution of cancer cells to other sites of the body through the bloodstream or lymph is a process known as a. apoptosis. b. neoplasia. c. angiogenesis. d. metastasis. e. malignant transformation.

32.The efficacy of treating bladder cancer is increased by introducing the BCG vaccine. The vaccine component attributing this antitumor effect is __________, which induces a state of chronic inflammation.

a. mycolic acid b. unmethylated CpG-containing DNA c. lipopolysaccharide d. teichoic acid e. peptidoglycan

33.Which of the following is NOT an accurate statement about cancer stem cells? a. They are self-renewing. b. They are highly susceptible to radiation. c. They are resistant to toxins used in chemotherapy. d. They may be present in low numbers without causing relapse. e. They may cause cancer if donated in organ transplants

34.Proteins not expressed on normal cells but found on tumor cells are called a. cancer stem cell antigens. b. oncogenic antigens. c. tumor-associated antigens. d. tumor-specific antigens. e. proto-oncogene products.

35.Tumor-specific antigens are derived from all of the following EXCEPT a. peptide antigens encoded by fused portions of recombined genes. b. peptide antigens containing point mutations. c. proteins modified by abnormal post-translational processes. d. reactivated embryonic genes. e. non-contiguous peptides spliced together by peptide bonds in the proteasome.

36.Which of the following statements is accurate concerning tumor-associated antigens? a. They are derived from self proteins to which the immune system is tolerant. b. They are derived from proteins encoded by mRNAs that have undergone

abnormal post-transcriptional splicing. c. They are proteins normally expressed in immunologically privileged sites. d. They are proteins expressed at unusually low levels in tumor cells. e. They are derived from viral proteins to which the immune system is not tolerant.

37.A tumor-associated antigen normally expressed only in the testis is called a(n) __________ antigen. a. MIC b. CT c. male-specific d. sex chromosome–encoded e. privileged

38.A mechanism by which cancer cells can evade an immune response involves an alteration in the amount of MIC on the cell surface by a. decreasing the level of MIC transcription. b. cleavage of MIC at the cell surface by a protease. c. switching from a transmembrane form of MIC to a secreted form. d. cytosolic degradation of MIC in proteasomes. e. alternative mRNA splicing resulting in a truncated form of MIC that is no longer able to bind to NKG2D.

39.Which of the following is a mechanism by which tumors can evade immune detection? a. increase expression levels of HLA class I b. recruit regulatory T cells c. enhance inflammatory responses d. increase expression levels of MIC on the cell surface e. increase expression levels of tumor-specific antigens

40.Which cytokine is associated with tumor-induced suppression of the immune response?

a. IL-12 b. IL-2 c. TGF-β d. IL-4 e. interferon-gamma

41.One of the side effects of treating tumor patients with anti-CTLA4 monoclonal antibodies is a. the development of autoimmune disease. b. lymphoproliferative disorder. c. increased levels of mutation in tumor cells. d. upregulation of CT antigens. e. reactivation of embryonic genes.

42.Life-threatening cancers may differ by __________, but all cancer cells __________. a. the adequacy of their blood supply; avoid apoptosis b. whether they can generate their own growth signals; constantly replicate c. the tissue they originate in; evade the immune response d. the tissue they originate in; are in the same state of differentiation

43.The immune response to the human papillomavirus vaccine targets __________ and prevents __________. a. viral E6 protein; Kaposi’s sarcoma b. viral E7 protein; Kaposi’s sarcoma c. viral E6 and E7 proteins; cervical cancer d. L1 capsid protein; cervical cancer e. L1 capsid protein; liver cancer

44.Human papillomavirus a. causes a rare sexually transmitted infectious disease. b. produces proteins that allow the infected cell to divide in the presence of damaged DNA, thus leading to increased mutations.

c. has one major genotype that leads to cervical cancer. d. does not yet have an approved vaccine. e. causes cancer in females, but not males.

45.Hodgkin’s lymphoma tumor cells are stained for expression of Pax-5 protein (left) or CD30 protein (right). A dark gray color indicates protein expression, and unstained cellular components remain light gray. Select the correct statement concerning these tumor cells.

a. Of the two proteins, CD30 would be a better target for a conjugate monoclonal antibody therapy. b. The tumor cell is expressing high levels of Pax-5 protein. c. CD30 is a transcription factor involved in B-cell receptor signaling. d. Pax-5 is a cell-surface protein expressed by all normal B cells.

46.Which of the following is NOT an outcome of a cytotoxic CD8 T cell interacting with tumor cells expressing PD-L1? a. induction of CD8 T-cell exhaustion b. increased expression of inhibitory receptors on the CD8 T cells c. decreased CD8 T-cell effector function d. a metabolic change from oxidative phosphorylation to glycolysis in CD8 T cells e. a change in the gene expression pattern in the CD8 T cell

47.Checkpoint inhibitors target proteins that are members of the __________ family. a. CD28/B7 b. CD4/CD8 c. NKG2D

d. CT antigen

48.Which of the following is NOT a step in adoptive T-cell transfer anti-tumor therapy? a. activation of T cells in vitro with IL-2 b. pre-conditioning of the patient with immunosuppressive drugs c. excision of the tumor d. reinfusion of patient’s activated T cells e. use of monoclonal antibodies linked to toxins

49.Select the correct statement concerning chimeric antigen receptor (CAR) T cells. a. CAR T cells develop their chimeric receptors in the thymus and can be found in all healthy individuals. b. The CAR contains signaling domains derived from the B-cell receptor. c. If the target cancer cell expresses CD19, the CAR CD8 T cells recognize a peptide derived from CD19 presented by an MHC class I molecule. d. CARs combine the antigen-binding site of an antibody with the signaling domains found in T cells.

50.The current CAR T cells generated against B-cell acute lymphoblastic leukemia and approved by the FDA a. cause no side effects. b. target a tumor-specific antigen. c. contain the signaling domain from the zeta chain of the T-cell receptor along with additional signaling domains. d. are generated from T cells isolated from a healthy donor and then infused into the patient. e. lack expression of a functional T cell-receptor.

51.Monocytes taken from a patient are treated with a fusion protein that is composed of an antigen specific to their tumor (small circles) linked to GM-CSF (triangle) and then reinfused back into the patient. Select the correct statement.

a. This is an example of CAR T-cell therapy. b. The monocytes will differentiate into macrophage-like cells. c. GM-CSF acts as a checkpoint inhibitor to prevent PD-1 expression. d. The tumor antigens will be processed and presented in MHC molecules to activate T cells. e. This therapy involves first treating the patients with immunosuppressive drugs to cause a massive depletion of immune cells.

52.In an immune response to a tumor, CD8 T cells may recognize __________ not coded for in the patient’s germline DNA. a. tumor-associated antigens b. mutagens c. neoplasms d. adjuvants e. neoantigens

53.Which of the following is NOT a characteristic of tumor-associated antigens? a. They are originally expressed in tissues lacking polymorphic HLA class I and class II. b. They are frequently expressed in normal mature lymphocytes. c. They are often found on the X chromosome. d. They often have functions associated with fetal development or reproduction. e. They are expressed by multiple cell types and not just tumor cells.

54.Cancer stem cells are similar to hematopoietic stem cells in that both cell types a. are resistant to radiation.

b. are found primarily in the bone marrow. c. downregulate MHC class I molecules. d. are self-renewing.

55.A patient has an aggressive melanoma and her physician would like to try a therapy that activates and expands dendritic cells. Select the best approach to activate the patient’s dendritic cells. a. chimeric T cells b. checkpoint inhibitors c. monoclonal antibody to cell surface antigens d. in vitro expansion of patient blood cells with IL-2 e. in vitro expansion of patient blood cells with GM-CSF linked to tumor antigen

56.Tumors that have evaded the immune response often a. lack β2-microglobulin. b. have increased expression of membrane-bound MIC. c. no longer secrete TGF-β. d. have increased expression of MHC class I. e. have increased p53 expression.

57.You have sequenced a peptide that binds to HLA-A1 from a normal healthy individual (A) and compared the sequence to a peptide that binds HLA-A1 from a melanoma tumor cell (B). This is an example of A) FLGGNEVGKTY B) FLEGNEVGKTY a. a fusion gene formed by chromosomal rearrangement. b. abnormal post-translational protein modification.s c. noncontiguous peptide splicing by the proteasome. d. a tumor-associated antigen. e. a tumor-specific antigen.

58.Select the correct statement concerning the activation of tumor-specific T cells.

a. The second signal required for T-cell activation is the TCR binding to MHC plus peptide. b. The molecule labeled “B” on the antigen presenting cell is CD28. c. The molecule labeled “C” is normally involved in the activation of CD8 T cells. d. T-cell exhaustion will likely occur in the absence of the antibody labeled “D”. e. The interaction of molecules “C” and “D” reduces the effector functions of the CD8 T cell.

59.A 45-year-old male patient is diagnosed with a B-cell chronic lymphocytic leukemia and treated with Rituximab. This therapy proves to be ineffective, and the patient has returned to his doctor. He is found to have a previously unrecognized NK-cell deficiency. Select the correct statement concerning this patient. a. Rituximab was likely ineffective due to the lack of functional ADAM33 metalloproteinase in the patient. b. The NK-cell deficiency is not likely linked to the ineffectiveness of the Rituximab therapy. c. An alternative therapy approach could be the use of anti-CD19 CAR T cells. d. An alternative therapy approach could be the use of GM-CSF linked to prostatic acid phosphatase.

60.Select the statement that does NOT support a role for the immune system in detecting and eliminating transformed cells. a. The number of tumor-specific T cells correlates to the survival rate of cancer patients.

b. Individuals who are immunosuppressed following organ transplants have a higher incidence of cancer. c. Tumor-specific T cells can become exhausted due to repeated antigen stimulation. d. Individuals born with a primary immunodeficiency have a higher incidence of cancer. e. Tumor cells generate their own growth signals, allowing them to proliferate.

61.Epithelial cells that have recently become transformed express more __________ on their cell surface, which activates __________. a. MHC class I; ADAM33 enzyme b. MHC class II; CD4 T helper cells c. MIC; NK cells d. CTLA4; Treg cells

62.Match the infectious agent with its associated cancer. a. human papillomavirus b. Epstein–Barr virus c. hepatitis B or C viruses d. Helicobacter pylori e. human immunodeficiency virus (HIV-1) 1. __________ liver cancer 2. __________ stomach cancers arising from ulcers 3. __________ genital cancer 4. __________ Burkitt’s lymphoma 5. __________ Kaposi’s sarcoma

63.Match the autoimmune disease with its corresponding antigen. a. ipilimumab b. nivolumab c. bevacizumab d. brentuximab e. ibritumomab 1. __________ programmed death 1 (PD-1)

2. __________ CD20 3. __________ CD30 4. __________ VEGF 5. __________ CTLA-4

64.Describe how the anti-CD20 monoclonal antibody can be modified to either i) detect or ii) eradicate a tumor.

65.Describe tumor-specific antigens and list two ways they can develop.

66.Describe tumor-associated antigens and explain their usual location in the body.

67.Describe and provide an example of the two main gene classes that can lead to malignant transformation when the proteins are not expressed correctly.

68.Explain why the incidence of cancer is higher in the elderly than in young people.

69.Describe Li–Fraumeni syndrome and its underlying cause.

70.Explain how the immune mechanisms for the detection of cancer cells are both similar to and different from those that detect virus-infected cells.

71.Explain what may occur when tumor cells are transferred from an organ donor to the transplant recipient.

72.Epithelial tumors express MIC proteins on their cell surfaces. Why does this make the tumor cells susceptible to attack by NK cells, γ:δ T cells, and cytotoxic CD8 T cells?

73.Explain how decreased levels of HLA class I on variant cancer cells can enhance or reduce tumor growth.

74.Other than a point mutation, explain how it is possible for a tumor-specific antigen to be composed of a unique sequence of amino acids not encoded in the genome of the tumor cell. Give one specific example.

75.Explain how transformed epithelial cells initially stimulate an immune response, but then after time are able to evade this same response.

Answer Key Chapter 17 1. Answer: B 2. Answer: A 3. Answer: B 4. Answer: A 5. Answer: B 6. Answer: A 7. Answer: B 8. Answer: E 9. Answer: A 10.Answer: E 11.Answer: E 12.Answer: D 13.Answer: E 14.Answer: A 15.Answer: D 16.Answer: D 17.Answer: C 18.Answer: D 19.Answer: C 20.Answer: C

21.Answer: D 22.Answer: B 23.Answer: E 24.Answer: B 25.Answer: D 26.Answer: B 27.Answer: A 28.Answer: A 29.Answer: B 30.Answer: C 31.Answer: D 32.Answer: B 33.Answer: B 34.Answer: D 35.Answer: D 36.Answer: C 37.Answer: B 38.Answer: B 39.Answer: B 40.Answer: C 41.Answer: A 42.Answer: C

43.Answer: D 44.Answer: B 45.Answer: A 46.Answer: D 47.Answer: A 48.Answer: E 49.Answer: D 50.Answer: C 51.Answer: D 52.Answer: E 53.Answer: B 54.Answer: D 55.Answer: E 56.Answer: A 57.Answer: E 58.Answer: D 59.Answer: C 60.Answer: E 61.Answer: C 62.Answer:

1. C 2. D 3. A 4. B

5. E 63.Answer:

1. B 2. E 3. D 4. C 5. A

64.Answer: i) Ibritumomab, an anti-CD20 antibody, is used in cases of non-Hodgkin’s lymphoma. When conjugated to indium-111, it aids in the identification of the location and size of primary tumors and the degree of metastasis. ii) When conjugated to yttrium-90, it precisely targets and kills tumor cells with its βradiation.

65.Answer: Tumor-specific antigens are antigens found exclusively on tumor cells and are not expressed by normal cells. They can originate from the following: (1) as the result of mutations in normal genes in the tumor cell that cause changes in amino acid sequence that generate new epitopes; (2) by the generation of hybrid genes through genetic recombination, with the consequent production of a new protein unique to the tumor cell; or (3) from viral proteins expressed as a result of viral infection or integration into the host-cell genome.

66.Answer: Tumor-associated antigens come from normal human proteins. They are usually present in very small amounts in immunologically privileged sites, such as the eyes or testes, and do not activate T cells. They are

expressed at a higher level by tumor cells and can generate a T-cell response.

67.Answer: Proto-oncogenes and tumor suppressor genes. Protooncogenes encode proteins that participate in cell division, such as growth factors, growth factor receptors, signal transduction proteins, and activators of gene expression. RAS is one example. Tumor suppressor genes encode proteins that inhibit the division of mutant cells; examples are p53, APC, and DCC. 68.Answer: For a cell to become cancerous and undergo malignant transformation, at least five or six mutations (depending on the cell type) must accumulate independently. Because of the low frequency of mutation, significant time is needed for a single cell to accrue this number of mutations. As a person ages, the prevalence of cells bearing the required mutations increases.

69.Answer: Li–Fraumeni syndrome is a condition in which there is a strong predisposition to developing multiple types of cancer, even at a young age.

Progression to cancer is related to the inheritance of a mutation in one of the copies of p53, a tumor suppressor gene, which facilitates the apoptosis of cells with DNA damage. Individuals with Li–Fraumeni syndrome need accrue only one new mutation in the functional copy of the p53 gene to develop a cell with loss of p53 activity, in contrast with other people, who

must acquire mutations on both copies.

70.Answer: NK cells and cytotoxic T cells detect cancer cells and virusinfected cells through the alteration of MHC class I expression or the recognition of peptides bound to the MHC. Unlike virus detection, which involves inflammatory responses that stimulate immediate innate immune responses, cancer cells can often grow for long periods before they induce an inflammatory state and a consequent immune response.

Tumors can generate an immunosuppressive tumor environment and prevent dendritic cells from activating tumor-specific T cells.

71.Answer: A donor undergoes treatment for a cancer (such as metastatic melanoma) and controls the tumor. However, when her kidneys or other organs are transplanted into an immunosuppressed recipient, the recipient develops a cancer, such as metastatic melanoma.

Cancer stem cells that are more resistant to the therapies used to treat cancers were likely transferred to the recipient. The recipient is immunosuppressed due to the transplant procedure, and, thus, is unable to mount an antitumor immune response.

72.Answer: MIC proteins are ligands for the activating receptor NKG2D, which is expressed by NK cells, γ:δ T cells, and cytotoxic CD8 T cells, and activates these cells to kill the tumor cells.

73.Answer: Enhancement of tumor growth occurs when cancer cells stop expressing HLA class I because these cells are no longer presenting tumor antigens to cytotoxic T cells. Variant cells are consequently able to escape immune detection. However, tumor cells that lack HLA class I are more susceptible to attack

by NK cells. The inhibitory receptor on NK cells fails to engage normally, and this causes tumor cell killing after the activation and release of cytotoxic molecules by the NK cell.

74.Answer: The proteasome not only degrades proteins into peptide fragments, but it also has the potential to splice peptides together to form a novel peptide.

The new peptide is derived from short sequences from different parts of the polypeptide that is undergoing proteolysis. An example of proteasome splicing has been demonstrated for a glycoprotein (gp100) expressed in melanocytes. A unique fused peptide sequence made up of amino acids 40–42 and 47–52 of gp100 was shown to be formed and to be presented by HLAA32, stimulating cytotoxic T-cell responses. An alternative response could be a chromosomal translocation.

75.Answer: Initially the stress protein MIC is upregulated on the transformed cells stimulating NK and γδ T cells. However, following proliferation and mutations, some of the tumor cells evade being killed by expressing a protease that cleaves MIC from the cell surface. When this

soluble MIC product binds to the NKG2D receptors on NK cells, γδ T cells, and cytotoxic T cells, it induces receptor-mediated endocytosis, thus reducing the level of NKG2D on the surface of these cells. Together with the removal of MIC from tumor-cell surfaces, this helps the tumor cells evade cell-mediated killing.