Kuby Immunology Covid-19 Digital Update, 8th Edition By Jenni Punt, Sharon Stranford, Patricia Jones

(Kuby Immunology Covid-19 Digital Update, 8e Jenni Punt, Sharon Stranford, Patricia Jones, Judy Owen) (Test Bank Latest Edition 2023-24, Grade A+, 100% Verified) Chapter 01 1. Two of the main, early theories proposed to explain how antigen-specific antibodies develop were the instructional theory and the selective theory. How did the two differ? Which was ultimately shown to be CORRECT? ANSWER: The selective theory says that, when an antigen receptor binds with an antigen, the cell becomes activated (or the cell is selected to proliferate and secrete more copies of the receptor). The instructional theory says that the antigen receptor molds itself to the antigen. The selective theory was shown to be correct.

2. Often, serendipity plays a role in significant scientific discoveries. In your own words, explain how serendipity led Pasteur to discover a cholera vaccine.

ANSWER: Pasteur developed the vaccine in chickens, which were in short supply. He challenged groups of chickens with cholera bacteria—some of which were previously exposed to an attenuated version of cholera bacteria. Only the previously exposed animals were protected from a new challenge, which led to the use of weakened pathogens as vaccines.

3. Despite its having been eradicated on a global scale, smallpox is presently considered a potential bioterrorism threat. Why? Use evidence to support your answer.

ANSWER: After eradication was achieved, smallpox vaccination programs largely ended. As populations continued to grow over time, an ever-increasing percentage of the human population remains unvaccinated and thus, is still susceptible to the disease.

4. Prior to 1999, it was claimed that a thimerosal additive in vaccines was contributing to the rising incidence of autism. If the claims were true, what resultant trend might you expect to observe in the rate of autism once thimerosal was removed from vaccines?

ANSWER: One would reasonably expect a decrease in the rate of autism. However, cases of autism continued to rise after thimerosal was removed from vaccines in 2001.

5. Given the discovery and development of effective antibiotics, make an argument for the continued use of vaccines against bacterial pathogens. Use evidence to support your answer.

ANSWER: Antibiotics are used for treatment of disease, not typically for prevention. Antibiotic treatment is not foolproof (considering the rising incidence of antibiotic resistance). Vaccines are a preventative measure, and prevention is the gold standard for infectious disease control measures.

6. You have a friend unfamiliar with immunology, and he asks you the following question: "Why do I need the flu shot every year, but don't need an annual chickenpox vaccine?" As a student of immunology, how would you explain this discrepancy to your friend? Use evidence to support your answer.

ANSWER: The virus that causes the flu changes every year - as a result, a new flu vaccine must be prepared each year based on a predication of the most common forms of the virus likely to be encountered.

Vaccines are specific in the type of pathogen against which they protect, and protection against one type does not guarantee protection against pathogens that are closely-related.

7. Provide one benefit and one drawback of generating random recognition receptors during the development of B cells.

ANSWER: A benefit is having the capacity to recognize and respond to diverse pathogens as they evolve. A drawback is that some recognition receptors could potentially recognize and target host antigens.

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Chapter 01 8. A portion of our immune systems' white blood cells is constantly circulating throughout the body via circulation and lymphatics. What is the benefit of such circulation?

ANSWER: The circulation of the white blood cells allows for a more comprehensive surveillance of the body for the presence of potential pathogens. A significant portion of the human body is constantly exposed to potential microbial pathogens.

9. Complete the following table by comparing and contrasting innate and adaptive immune responses.

Innate Immunity

Adaptive Immunity

Is mediated by what cells?

What do they recognize?

How are the receptors encoded?

Why can't they control all infections alone?

What do they do in response to antigen?

ANSWER: Is mediated by what cells?

Innate Immunity

Adaptive Immunity

Macrophages, NK cells, neutrophils, mast cells eosinophils

T cells and B cells

What do they Pathogen patterns recognize?

How are the receptors Germ line encoded?

Why can't they Pathogens evolve control all escape mechanisms infections alone?

What do they do Engulf and destroy, in response to induce inflammation antigen?

Specific epitopes Rearranged gene segments Takes too long to develop Produce antibodies, kill infected cells

10. What are the hallmarks of inflammation? Describe the physical characteristics of someone experiencing an inflammatory response.

ANSWER: Redness, swelling, heat, pain. Someone experiencing inflammation might have localized swelling and redness or itching or may be experiencing faintness due to a lowering of blood pressure if more severe.

11. Upon receiving immune serum as a treatment for a venomous snake bite, would the recipient be immune Copyright Macmillan Learning. Powered by Cognero.

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Chapter 01 from future bites of the same species?

ANSWER: In the short-term, probably, as the serum contains protective antibodies against the venom. In the long-term, no, as serum treatment is a form of passive immunity. Passive immunity does not generate long-lived memory cells.

12. Provide one common feature of and two differences between B-cell receptors and PRRs. ANSWER: A common feature is that they both are used to recognize foreign antigens. A B-cell receptor is more selective than a PRR. The DNA that encodes for a PRR in an individual is inherited. The DNA that encodes for a mature B-cell receptor from an individual is not passed on to offspring.

13. Given that an important function of the immune system is to both recognize and dispose of cancerous cells, postulate why tumors can be established in a human host.

ANSWER: There are two primary reasons. First, cancerous cells are self-originating, thus self-tolerance mechanisms can inhibit the development of an effective immune response. Second, as is common with some pathogens, genetic variability within a population of cancer cells gives them an advantage in terms of evading the immune response.

14. The hygiene hypothesis posits that there is a connection between environmental conditions and certain inappropriate immune responses. If you were a supporter of the hygiene hypothesis, what recommendations would you make to keep people healthier?

ANSWER: Expose children to more common antigens found in dirt and in the outdoors. Reduce use of antimicrobials.

15. Which is the BEST definition of "immunity"? a. The state of having been exposed to a pathogen repeatedly b. The state of being resistant to reinfection with a pathogen c. When an individual has never been exposed to a pathogen d. When the immune system is activated e. When physical barriers are not enough to prevent infection ANSWER: b 16. What happens to a pathogen as it becomes attenuated? a. It becomes more dangerous to the host. b. It gets smaller. c. It has weakened virulence. d. It becomes older. e. All of the answers are correct.

ANSWER: c 17. Which of the following advances can be credited to progress made in our understanding of immunology? a. Smallpox eradication b. Treatment of asthma c. Ability to transplant human organs Copyright Macmillan Learning. Powered by Cognero.

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Chapter 01 d. Cancer treatment e. All of the answers are correct.

ANSWER: e 18. Which of the following is the BEST example of herd immunity? a. A child infected with measles travels from Germany to the United States. Several babies contract the disease, but the outbreak is largely contained due to vaccinations. b. Certain populations of cattle are less susceptible to infection with encephalitis because of their genetic makeup. c. Once a certain threshold of individuals has been infected with a novel human pathogen, it is unlikely that any more will be. d. Geese and chickens are infected with different strains of influenza because they express different receptors on their cell surface. e. When infection spreads through a population, certain individuals generate stronger immune responses than others.

ANSWER: a 19. Which of the following diseases does NOT currently have an effective vaccine? a. Chicken pox b. Polio c. HIV d. Smallpox e. Diptheria ANSWER: c 20. Which cells are MOST likely responsible for the intense response to Antigen A following a second exposure?

a. B cells b. T cells c. Memory T cells d. Memory B cells e. Both memory T cells and memory B cells are responsible.

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Chapter 01 ANSWER: e 21. Effectors of the humoral immune system are known as a. antibodies. b. immunoglobulin. c. complement. d. B cells. e. All of the answers are correct.

ANSWER: e 22. Which of the following cell types are lymphocytes? a. Macrophages b. Mast cells c. Neutrophils d. Erythrocytes e. T cells ANSWER: e 23. Which of the following is TRUE about antigens? a. They are always derived from pathogens. b. They are always proteins. c. They are recognized by T cells or B cells. d. They must be microbial in origin. e. They usually cause cellular damage.

ANSWER: c 24. Which of the following is a fungal pathogen? a. Vibrio cholera b. Leishmania major c. Poliovirus d. Candida albicans e. Bordetella pertussis ANSWER: d 25. True or False? Overall, the human immune system views microbes as pathogens. a. True b. False ANSWER: b 26. Which of the following factors has been shown as potentially impacting immune homeostasis in favor of inflammation?

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Chapter 01 a. Diet b. Stress c. Microbiome composition d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 27. Many of the ideas raised by Ehrlich's conception of selective theory were true. Which of the following ideas (if any) were later shown to be FALSE? a. Interaction between a cell-bound receptor and pathogen could induce the cell to proliferate. b. The specificity of receptors was determined in the host prior to exposure to a foreign antigen. c. The antigen selected the appropriate receptor in a specific manner. d. The binding of a receptor to an infectious agent was like the fit between a lock and a key. e. All the ideas listed were shown to be true.

ANSWER: e 28. Which of the following cell types is MOST commonly associated with recognizing antigens found inside of cells? a. Macrophages b. B cells c. TH cells d. CTLs e. Antibodies ANSWER: d 29. Which of the following classes of cell surface receptors are directly encoded in the germ line? a. TCR b. BCR c. PRR d. Antibodies e. All of the answers are correct.

ANSWER: c 30. What is the central mechanism for establishing self-tolerance? a. Self-reactive T cells and B cells are killed during development. b. Individuals that have immune systems that respond to self-antigens do not survive to reproduce. c. Immune cells that react to self-antigens are turned off when they recognize self-tissues. d. Certain immune suppressive cytokines are maintained in tissues to dampen auto reactive immune responses. e. Peripheral tissues have mechanisms to kill T or B cells that respond to them.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 01 31. Which of the following BEST describes chemokines? a. Membrane receptors that detect the presence of soluble messengers in the environment b. Soluble proteins that recruit specific cells to an area c. Chemical messengers that induce cell differentiation d. Transcription factors that induce the expression of genes involved in cell adhesion e. Adhesion molecules that bind to the inside of blood vessels ANSWER: b 32. Which of the following statements BEST differentiates innate and adaptive immune responses? a. Innate responses are stronger during the primary and less important during the secondary response, whereas adaptive responses are less robust during primary responses and stronger during secondary responses. b. Innate responses are weaker during the primary and more robust during the secondary response, whereas adaptive responses are stronger during the primary and weaker during secondary responses. c. Innate responses are slower and weaker than adaptive responses. d. Adaptive responses are slower and weaker than innate responses. e. Adaptive responses are required for effective immune responses, whereas innate responses are not required.

ANSWER: a 33. True or False? The innate and adaptive immune responses work largely independently of one another. a. True b. False ANSWER: b 34. How do memory cells develop? a. Upon reinfection, memory centers in the brain send signals to the bone marrow to induce T-cell and B-cell differentiation. b. T cells and B cells from the primary response persist and become reactivated. c. Innate cells are trained to activate new T cells and B cells more quickly with secondary infection. d. T cells and B cells from the primary infection slowly mutate their receptors over time, priming themselves for the secondary response. e. Innate cells modify their cell surface receptors to prepare for reinfection.

ANSWER: b 35. Which of the following is the BEST example of a hypersensitivity reaction? a. T cells responding vigorously to the flu virus b. B cells failing to respond to HIV, allowing it to replicate out of control c. Inflammation of the airways in response to pollen d. Anemia as a result of iron deficiency e. T cells attacking the myelin sheath of nerves resulting in paralysis Copyright Macmillan Learning. Powered by Cognero.

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Chapter 01 ANSWER: c 36. HIV disease is a(an) a. autoimmune disease. b. hypersensitivity disease. c. immunodeficiency. d. genetic disorder. e. allergic reaction.

ANSWER: c 37. Predict the outcome of being immunosuppressed as it relates to the development of cancer. a. Immunosuppressed individuals are at lower risk of cancer because cytokines produced by the immune system induce cancer. b. Immunosuppressed individuals are at lower risk of cancer because they are more likely to contract infectious diseases. c. Immunosuppressed individuals are at higher risk of cancer because the immune system recognizes and destroys cancerous cells. d. Immunosuppressed individuals are at higher risk of cancer because they bear a higher load of microbes that damage host tissues. e. None of the answers are correct.

ANSWER: c 38. What occurs when someone receives a tissue transplant from an unrelated individual? a. The host's lymphocytes enter the tissues and become suppressed. b. The host's lymphocytes enter the tissues and become activated. c. The host's lymphocytes that react to the tissue graft are deleted in the thymus. d. The donor's lymphocytes suppress the host's lymphocytes, allowing for graft survival. e. The donor's lymphocytes destroy the host's immune system.

ANSWER: b 39. Which of the following is TRUE? a. Vaccines cause autism. b. Vaccines cause obesity. c. Vaccines cause cancer. d. Vaccines cause diabetes. e. None of the answers are correct.

ANSWER: e 40. Conditions in which the immune system attacks self-antigens are known as a. autoimmunity. b. immune deficiency.

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Chapter 01 c. hypersensitivities. d. neuroplasias. e. None of the answers are correct.

ANSWER: a

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Chapter 02 1. Imagine that you are a thymocyte that has just entered the thymus. Assuming you will survive positive and negative selection, what changes will you experience before developing in a naïve CD4+ T cell?

ANSWER: The thymocyte would change from a DN cell, to a DP cell, to an SP cell. In this case the SP cell would contain CD4 on the surface but not CD8.

2. Name three parts of the human body where you would expect to find secondary lymphoid tissues.

ANSWER: More than three answers are possible. Correct answers would include areas of the body most directly exposed to potential, outside pathogens, including the skin, the lungs, the upper respiratory tract, the small intestine, and the large intestine.

3. In your own words, explain how an NKT cell displays properties of both innate and adaptive immunity.

ANSWER: NKT cells have TCRs, yet also express surface markers associated with innate immunity. NKT cells do not require antigen presentation for activity. NKT TCRs are not diverse.

4. Plasma cells can secrete thousands of antibodies per second. Based on this observation, name two organelles that you might expect to find in abundance within an active plasma cell.

ANSWER: An abundance of Golgi and endoplasmic reticulum would be anticipated, allowing for efficient production of secreted antibodies.

5. What important role do antibodies play in the isolation of HSCs from the bone marrow?

ANSWER: Antibodies can be used to eliminate bone marrow cells that express surface molecules not expressed

by HSCs. Antibodies can also be used to select for bone marrow cells that express HSCs-associated molecular markers.

6. A graduate student observes a strain of mice that are impaired in their ability to combat parasitic worms.

Given this observation, which arm of hematopoiesis is MOST likely deficient in this strain?

ANSWER: The myeloid arm of hematopoiesis. The myeloid branch gives rise to innate cells specialized in the defense against parasitic worms including eosinophils and basophils.

7. In addition to the bone marrow, HSCs have been observed to occur within the blood. How has this observation improved the procedures used to transplant HSCs from donors to recipients that are bone marrow deficient?

ANSWER: In some cases, it is now possible to obtain HSCs directly from blood draws from donors; as opposed to bone marrow aspirations, which are painful and require anesthesia.

8. Can you think of two cellular activities occurring within a swelling lymph node that has been exposed to antigen from a pathogen?

ANSWER: Immune cells are actively migrating into the lymph node, and T and B cells within the node are proliferating via clonal selection and expansion. Collectively, these activities are contributing to swelling.

9. Beyond structural differences, name functional differences between a lymph node and the spleen.

ANSWER: Two major functional differences exist when comparing the spleen to a lymph node. First, the spleen primarily reacts to antigens present in the blood, whereas lymph nodes react to lymph-borne antigens. Second, the spleen has well-defined functions not directly related to mounting an immune Copyright Macmillan Learning. Powered by Cognero.

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Chapter 02 response including being a site where old and defective red blood cells are eliminated.

10. You have discovered a potentially new leukocyte that appears to share a common progenitor with CD8+ T cells, lack antigen-specific receptors, do not participate in antigen presentation, and have a capacity for ADCC. Using knowledge of hematopoiesis, which cell type MOST closely resembles the potentially new leukocyte?

ANSWER: Innate lymphoid cells, which arise from lymphoid progenitors. ILCs lack antigen-specific receptors, but can participate in ADCC via the expression of Fc receptors.

11. All blood cells in an adult human can trace their ancestry to which compartment within the body? a. Thymus b. Bone marrow c. Lymph node d. Peyer's patch e. None of the answers are correct.

ANSWER: b 12. If a human were unable to produce lymphoid progenitor cells, predict which part of the immune system would be MOST greatly impacted? a. Innate immunity b. Adaptive immunity c. Both innate and adaptive would be equally impacted d. Neither innate nor adaptive immunity would be impacted e. None of the answers would be impacted.

ANSWER: b 13. A pluripotent stem cell can do which of the following? a. Differentiate into a finite number of different cell types b. Differentiate into any type of cell found in the adult c. Divide an infinite number of times d. All of the answers are correct. e. None of the answers are correct.

ANSWER: a 14. Which of the following is the pluripotent stem cell that gives rise to all blood cells? a. CLP b. CMP c. CEP d. HSC e. None of the answers are correct.

ANSWER: d 15. From which of the following stem cells are NK cells derived?

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Chapter 02 a. CLP b. CMP c. CEP d. Both CLP and CMP are correct. e. None of the answers are correct.

ANSWER: a 16. Which cell can differentiate into the GREATEST variety of cells during hematopoiesis? a. B-cell progenitor b. Basophil progenitor c. T-cell progenitor d. Eosinophil progenitor e. Myeloid progenitor ANSWER: e 17. Using a light microscope, you observe a human blood smear. Among the abundance of erythrocytes, you note a leukocyte that appears to contain a multilobed nucleus. What is the MOST likely identity of the observed leukocyte? a. T lymphocyte b. B lymphocyte c. Neutrophil d. Eosinophil e. Both Neutrophil and eosinophil are equally likely.

ANSWER: e 18. From which of the following stem cells are DCs derived? a. CLP b. CMP c. CEP d. Both CLP and CMP. e. None of the answers are correct.

ANSWER: d 19. From which of the following stem cells are platelets derived? a. CLP b. CMP c. CEP d. Both CLP and CMP. e. None of the answers are correct.

ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Chapter 02 20. From which of the following stem cells are eosinophils derived? a. CLP b. CMP c. CEP d. Both CLP and CMP. e. None of the answers are correct.

ANSWER: b 21. From which of the following stem cells are helper T cells (TH) derived? a. CLP b. CMP c. CEP d. Both CLP and CMP. e. None of the answers are correct.

ANSWER: a 22. From which of the following stem cells are monocytes derived? a. CLP b. CMP c. CEP d. Both CLP and CMP. e. None of the answers are correct.

ANSWER: b 23. From which of the following stem cells are RBCs derived? a. CLP b. CMP c. CEP d. Both CLP and CMP. e. None of the answers are correct.

ANSWER: c 24. What level of gene expression is regulated by such factors as Notch1 and GATA-2? a. Replication b. Transcription c. RNA processing d. Translation e. None of the answers are correct.

ANSWER: b 25. Which lineage of immune cells constitutes the first line of defense against an infection?

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Chapter 02 a. Lymphoid b. Erythroid c. Myeloid d. All of the answers are correct. e. None of the answers are correct.

ANSWER: c 26. You have consumed a salad contaminated with Salmonella enterica, which typically causes a self-limiting, gastrointestinal disease in humans. Based on this information, which immune organ is MOST likely to first recognize and mount a response against the pathogen? a. Spleen b. SALT c. Thymus d. GALT e. Lymph node ANSWER: d 27. Which properties listed below are shared by both naïve B cells and mature T cells? a. Are derived from lymphoid progenitor cells b. Are considered lymphocytes c. Contain membrane-bound antigen receptors d. All of the answers are correct. e. None of the answers are correct.

ANSWER: e 28. Which of the following is NOT descended from the common lymphoid progenitor? a. T cells b. NK cells c. B cells d. Eosinophils e. All of the answers are descended from the common lymphoid progenitor.

ANSWER: d 29. Which of the following granulocytes contains histamine within its granules? a. Neutrophils b. Eosinophils c. Basophils d. Both Eosinophils and Basophils e. All of the answers are correct.

ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Chapter 02 30. Which of the following is NOT true about monocytes? a. They comprise between 5%-10% of circulating leukocytes. b. They have the ability to differentiate into macrophages or dendritic cells. c. They can be subdivided into inflammatory monocytes and patrolling monocytes. d. They can give rise to platelets. e. All of the answers are true.

ANSWER: d 31. Which of the following cell types is responsible for the secretion of immunoglobulins? a. TH1 b. TH2 c. TH17 d. TFH e. Plasma cell ANSWER: e 32. Which of the following cell types is responsible for regulating responses against intracellular pathogens? a. TH1 b. TH2 c. TH17 d. TFH e. Plasma cell ANSWER: a 33. Which of the following cell types is responsible for activating B cells in germinal centers? a. TH1 b. TH2 c. TH17 d. TFH e. Plasma cell ANSWER: d 34. Which of the following cell types is responsible for regulating responses against predominantly extracellular pathogens? a. TH1 b. TH2 c. TH17 Copyright Macmillan Learning. Powered by Cognero.

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Chapter 02 d. TFH e. Plasma cell ANSWER: b 35. Which of the following cell types secretes IL-17 and may play a role in antifungal responses? a. TH1 b. TH2 c. TH17 d. TFH e. Plasma cell ANSWER: c 36. Which of the following effector T lymphocyte populations is produced via the activation of a naïve T cell through antigen presented in MHC Class I? a. CTL b. TH1 c. TH2 d. TH17 e. None of the answers are correct.

ANSWER: a 37. Which of the following types of effector T lymphocytes is capable of inhibiting an immune response to an antigen recognized with its T-cell receptor (TCR)? a. TH1 b. TREG c. TH2 d. TH17 e. None of the answers are correct.

ANSWER: b 38. Which of the following descendants of the CLP act in the innate immune response? a. T cells b. NK cells c. B cells d. Plasma cells e. All of the answers are correct.

ANSWER: b 39. Which of the following is NOT considered primary lymphoid tissue?

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Chapter 02 a. Draining lymph node b. Thymus c. Peyer's patch d. Neither draining lymph node nor Peyer's patch are primary lymphoid tissue. e. None of the answers are primary lymphoid tissue.

ANSWER: d 40. In mammals, T-cell development occurs in the _____, whereas B-cell development occurs predominantly in the _____. a. thymus; bursa of Fabricius b. bone marrow; mesenteric lymph nodes c. bone marrow; thymus d. thymus; bone marrow e. None of the answers are correct.

ANSWER: d 41. As thymocytes develop, they are classified on the basis of the state of their T-cell receptors and which of the following? a. Which class of MHC they express on their surface b. The state of the immunoglobulin heavy and light chains on their surface c. The presence of coreceptor proteins CD4 and CD8 on their surface d. The expression of the transcription factor, FoxP3 e. None of the answers are correct.

ANSWER: c 42. Upon entering the thymus, thymocytes are classified as double _____ with regard to coreceptors; before exiting as single-positive, naïve T cells, they pass through a period in which they are double _____. a. positive; negative b. negative; positive c. Both "positive; negative" and "negative; positive" are correct. d. Neither "positive; negative" nor "negative; positive" are correct. e. Coreceptor expression state does not change in the thymus.

ANSWER: b 43. Contraction of which of the following types of muscles is responsible for propulsion of lymph through the lymphatic system? a. Cardiac b. Skeletal c. Smooth d. Both skeletal and smooth are correct. e. None of the answers are correct.

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Chapter 02 ANSWER: d 44. Naïve lymphocytes enter secondary lymphoid tissues via which of the following structures? a. Afferent lymphatics b. Efferent lymphatics c. HEVs d. Marginal sinus e. None of the answers are correct.

ANSWER: c 45. Which of the following does NOT appear to utilize the FRCC system as its primary means for trafficking through the lymph node? a. B cells b. T cells c. Free antigen that entered via an afferent lymphatic d. Cytokines and chemokines e. None of the answers utilizes the FRCC system.

ANSWER: a

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Chapter 03 1. Which of the following types of bonds would be LEAST likely in a receptor-ligand interaction? a. Ionic bond b. Covalent bond c. Hydrogen bond d. Hydrophobic interaction e. All of the answers are equally likely.

ANSWER: b 2. The end results of signal transduction are varied but can include a. Induction of cell division. b. Cellular differentiation. c. Altered metabolism. d. Altered protein secretion patterns. e. All of the answers are correct.

ANSWER: e 3. Ka, the association constant, is a measure of which of the following? a. The concentration of unbound ligand b. The concentration of unbound receptor c. The affinity of receptor for ligand d. The size of the receptor relative to the ligand e. The number of ligands for each receptor ANSWER: c 4. Which of the provided disassociation constants is MOST likely to be observed from an antibody binding an antigen during an immune response involving memory B cells? a. 10-3 M b. 10-5 M c. 10-2 M d. 10-10 M e. Antibody-antigen interactions cannot be measured.

ANSWER: d 5. Receptors that are multivalent tend to bind to their ligands more strongly than receptors with a single binding site. What is the term used to describe this phenomenon? a. Avidity b. Valency c. Affinity d. Magnetism e. None of the answers are correct.

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Chapter 03 ANSWER: a 6. Which of the following BEST describes how cytokines are released from activated T cells? a. Cytokines are released near where T-cell receptors are clustered. b. T cells release cytokines on the side of the cell opposite the MTOC to more efficiently distribute the response around the cell. c. T cells release cytokines evenly around the cell. d. Cytokines are released in short bursts from preformed vesicles full of cytokines. e. Cytokines are released in whatever direction the MTOC happens to be facing upon TCR ligation.

ANSWER: a 7. Receptors that dimerize upon ligand binding often contain _____ in their cytoplasmic domains. a. tyrosine kinases b. hydrophobic regions c. proteases d. metal-binding regions e. large immunoglobulin folds ANSWER: a 8. Portions of the cytoplasmic domains of many immune receptors are targets for phosphorylation. These domains are known as a. Grb domains. b. ITAMs. c. leucine zipper motifs. d. SOS domains. e. None of the answers are correct.

ANSWER: b 9. You note a population of T cells that contain primarily high-affinity IL-2R on their cell surfaces. Based on that observation, what can you predict about the activation state of the cells? a. They have not been exposed to antigen. b. T cells do not express IL-2R, so we cannot determine their activation state using these data. c. This cell population has been exposed to IL-2 and is active. d. They have been exposed to antigen but not IL-2. e. None of the answers are correct.

ANSWER: c 10. Lipid rafts are highly ordered regions of the cell membrane that are enriched in a. unsaturated fats. b. cholesterol. c. metabolic proteins.

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Chapter 03 d. clathrin. e. tubulin.

ANSWER: b 11. Which of the following are well-established ways that tyrosine phosphorylation directly affects signaling pathways? a. Inducing kinase activity b. Recruiting enzymes through SH2 domains c. Opening calcium channels d. Both inducing kinase activity and recruiting enzymes through SH2 domains e. Both recruiting enzymes through SH2 domains and opening calcium channels ANSWER: d 12. Which of the following is the CORRECT relationship? a. PIP2 = PIP3 – DAG b. PIP2 = IP3 + DAG c. PLC = PIP2 + PIP3 d. DAG = PIP2 + PIP3 e. PIP3 = IP3 + PIP2 ANSWER: b 13. Which transcription factor becomes translocated to the nucleus downstream of calmodulin activation? a. NF-κB b. NFAT c. STAT1 d. STAT2 e. STAT3 ANSWER: b 14. G proteins a. bind GTP. b. dephosphrylate ITAMs. c. are transcription factors. d. downmodulate immune responses. e. are adhesion molecules.

ANSWER: a 15. Which of the following is responsible for IL-2 expression in T cells? a. NF-κB b. NFAT Copyright Macmillan Learning. Powered by Cognero.

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Chapter 03 c. AP-1 d. Both NF-κB and NFAT are responsible. e. All of the answers are responsible.

ANSWER: e 16. Immunoglobulin domains consist of a. a series of α helices bound together by hydrophobic interactions in their side chains. b. α helices alternating with parallel β-pleated sheets. c. antiparallel β-pleated sheets folded and stabilized by hydrophobic interactions. d. compact, parallel β sheets forming a barrel structure. e. α helices held together by leucine repeats.

ANSWER: c 17. On the gel below, which bands would you expect to bind antigen?

a. B and A b. B and B c. B and C d. B and D e. B and A, B, and C ANSWER: e 18. Antibodies consist of a. two identical heavy chains and two identical light chains. b. an α chain, a β chain, a λ chain, and a κ chain. c. two α chains, an β chain, and a κ chain. d. two β chains, an α chain, and a κ chain. e. either an α chain or a β chain, a κ chain, and a λ chain.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 03 19. Which of the following isotypes of antibodies is the largest? a. IgM b. IgG c. IgA d. IgE e. IgD ANSWER: a 20. An antibody's idiotype refers to a. the kind of Fc region it contains. b. the sequence of its CDR. c. its allelic form. d. whether it is membrane bound or secreted. e. which accessory molecules associate with it.

ANSWER: b 21. Carbohydrate chains attached to the CH2 domains of IgA, IgD, and IgG are believed to a. allow for closer contact between partner chains. b. confer stability to the molecule resulting in a higher desaturation temperature. c. prevent protease degradation. d. provide space for complement protein binding. e. increase binding affinity for antigen.

ANSWER: d 22. Whether an immunoglobulin is secreted or membrane bound is directly determined by a. the sequence of the DNA in the Ig locus. b. mRNA splicing. c. the kind of B cell that is producing it. d. DNA rearrangement. e. GPI anchors.

ANSWER: b 23. Receptors that bind the constant regions of antibodies are known as a. B-cell receptors. b. T-cell receptors. c. idiotype receptors. d. toll-like receptors. e. Fc receptors.

ANSWER: e 24. Large amounts of monoclonal antibodies in the serum of an individual might be an indicator of Copyright Macmillan Learning. Powered by Cognero.

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Chapter 03 a. infection. b. T-cell deficiency. c. autoimmune disease. d. myeloma. e. stress.

ANSWER: d 25. Which of the following would be BEST for depleting an entire class of antibodies? a. Anti-idiotype antibody b. Anti-isotype antibodies c. Anti-CD19 d. Anti-CD4 e. Anti-CD8 ANSWER: b 26. Which of the following BEST describes why it is challenging for surface immunoglobulin to transduce a signal into the cell upon antigen binding? a. It takes twice as much antigen to stimulate the cells because each antibody has two antigen binding sites. b. The cytoplasmic domain of surface Ig only has three amino acids. c. Ig is rapidly dephosphorylated. d. Ig is an inflexible molecule. e. All of the answers are correct.

ANSWER: b 27. Regions of TCRs and BCRs that are particularly variable in their amino acid sequences are known for a. binding to antigen. b. sticking to denatured proteins. c. spanning the plasma membrane. d. binding to adaptor proteins. e. becoming phosphorylated.

ANSWER: a 28. Which of the following contains the MOST ITAMs? a. CD3 γ b. CD3 δ c. CD3 ζ d. TCR α e. TCR β ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Chapter 03 29. CD4 binds to a. TCR α. b. TCR β. c. MHC class I. d. MHC class II. e. CD8.

ANSWER: d 30. The antigen specific component of the B-cell receptor is a. ITAM. b. CD19. c. Ig α / β. d. CD21. e. Lyn. ANSWER: c 31. In the research laboratory, you observe that B cells, cytotoxic T cells and mast cells begin to proliferate when exposed to IL-4. In this case, this effect of IL-4 may be described as a. synergy. b. antagonism. c. redundancy. d. pleiotrophy. e. both redundancy and pleiotrophy.

ANSWER: d 32. The biological outcomes of immune system recognition can include a. migration of leukocytes into infected tissues. b. clearance of a pathogen by an activated macrophage. c. promotion of optimal antigen presentation. d. induction of long-lived B and T cells. e. All of the answers are correct.

ANSWER: e 33. Name the two key elements to a meaningful receptor-ligand interaction as a means of cell-to-cell communication.

ANSWER: The two most important elements allowing for cell-to-cell communication by receptor-ligand interactions are sufficient binding energy and time.

34. Explain the observation that receptor-ligand interactions are noncovalent despite the weak nature of such bonds versus covalent bonds.

ANSWER: Receptor-ligand interactions are based on multiple noncovalent bonds, which collectively form strong and specific bonds between ligand and receptor.

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Chapter 03 35. In your own words, explain an advantage of a bivalent versus univalent approach to receptor-ligand binding.

ANSWER: Bivalent binding assures that when one receptor binding site momentarily releases ligand, the interaction is not lost, as it is with univalent binding.

36. Structural studies of a potentially new cell surface protein reveal a hydrophobic C-terminal region, several regions consisting of β sheets, predicted disulfide bonds, and a variable N-terminal area dominated by loops.

Based on this information, what family of proteins might this protein belong to? What is a potential function of the hydrophobic C-terminal region?

ANSWER: The arrangement described suggests the protein may belong to the immunoglobulin superfamily. If so, the protein may be membrane bound, using the C-terminal region as a membrane anchor.

37. Imagine you are observing, at the molecular scale, interactions that occur when a dendritic cell activates a naïve CD4+ T cell. If the dendritic cell were exposed to an agent that disrupts the microtubule portion of the cytoskeleton prior to interaction, what would be the impact on T-cell activation?

ANSWER: The activation would likely be significantly impaired. Dendritic cells, during T-cell activation, utilize microtubule-organizing centers to redistribute cytokine-containing secretory organelles to enhance intracellular communications.

38. Compare the locations of the antigen receptors of innate versus adaptive immunity. Which has the GREATEST variety?

ANSWER: Innate. Although both innate and adaptive immunity have examples of antigen receptors that are membrane bound or secreted, innate immunity includes antigen receptors that exist solely in a soluble form. For example, mannose-binding lectin. In addition, some innate antigen receptors, such as select TLRs, are free in the cytosol and not associated with any membranes.

39. The B-cell receptor has structural and functional elements. How would you describe the B-cell receptor from both a structural and functional perspective?

ANSWER: The B-cell receptor can be divided into two parts, an antigen-recognition component (made of the membrane-bound BCR and CD21 associated with C3d) and a signal transduction component (consisting of Igα, Igβ, CD19, and CD81).

40. Three different class 1 cytokine receptor α chains bind the same β chain to form functional cellular receptors. Are there advantages to this type of "mixing and matching" of protein chains?

ANSWER: Absolutely. Combining one receptor protein chain with different partners allows increased receptor diversity and ligand affinity, while minimizing the need to generate diversity via new genetic information.

41. Can you think of a functional property of chemokines that allows them to induce the directed movement of leukocytes to a site of inflammation from the circulation?

ANSWER: At least a few chemokines display an innate affinity for carbohydrates located on endothelial cells that line blood vessels. The binding of chemokines to the inner surfaces of blood vessels helps create a chemoattractant gradient, directing circulating leukocytes (e.g., monocytes or neutrophils) to a site of inflammation.

42. Consider the following statement: Activated macrophages cannot clear pathogens without activating Copyright Macmillan Learning. Powered by Cognero.

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Chapter 03 adaptive immunity. Is the statement true or false? Justify your answer.

ANSWER: False. In some cases, activated macrophages can clear pathogens without invoking adaptive immunity through activities including phagocytosis and by promoting the movement of neutrophils and monocytes into a site of infection.

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Chapter 04 1. Which of the following is NOT entirely a response of the innate immune system? a. Phagocytosis by macrophages b. Protection from infection by the skin c. Low pH in the stomach d. Antibody-mediated complement activation e. Microbial cell lysis by defensin ANSWER: d 2. A bacterial pathogen has breached the skin barrier of a human. This is the first time this human host has been exposed to this particular pathogen. Which statement is NOT true regarding this situation? a. Innate immunity will respond to the pathogen more quickly than adaptive immunity. b. Innate immune cells will utilize PRRs to recognize PAMPs on the pathogen. c. Normal, intact skin is a good, but not perfect, barrier to pathogen entry. d. Memory T cells will aid in pathogen recognition and response. e. Phagocytes within the skin will aid in pathogen recognition and response.

ANSWER: d 3. Which of these characteristics are adaptive? a. Response takes several days to develop b. Responds more quickly upon secondary exposure to pathogens c. Pathogen receptors are extremely varied d. All of the answers are adaptive characteristics. e. None of the answers are adaptive characteristics.

ANSWER: e 4. Which of these characteristics are innate? a. Found in all multicellular plants and animals b. Receptors are encoded in the germ line c. Recognizes broad classes of pathogens d. All of the answers are innate characteristics. e. None of the answers are innate characteristics.

ANSWER: e 5. A mixture of S. aureus and the enteric bacteria E. coli was placed onto the skin of the fingertips of a volunteer. The volunteer immediately touched one of their inoculated fingertips to nutrient agar plate #1 and then waited 30 minutes and touched a different inoculated finger to nutrient agar plate #2. After incubating the plates overnight, what pattern of growth would you expect to see on the plates? a. Both E. coli and S. aureus grew on both plates. b. Plate #1 grew both, whereas plate #2 grew only S. aureus. c. Plate #1 grew both, whereas plate #2 grew only E. coli. d. Plate #1 grew only S. aureus, whereas plate #2 grew both.

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Chapter 04 e. Plate #1 grew only E. coli, whereas plate #2 grew both.

ANSWER: b 6. You have discovered a new species of bacteria that lacks peptidoglycan within its cell wall. Based on the table, which antimicrobial protein or peptide is the species likely to show resistance to?

Protein/Peptide Defensins (α and β) Dermicidin Lactoferrin

Antimicrobial Activity Disrupt membranes of bacteria, fungi, protozoan parasites, and viruses; additional toxic effe intracellularly; kill cells and disable viruses.

Antibacterial and antifungal; produces channels in membranes that disrupt ion gradients.

Binds and sequesters iron, limiting growth of bacteria and fungi; disrupts microbial membra limits infectivity of some viruses.

Cleaves glycosidic bonds of peptidoglycans in cell walls of bacteria, leading to lysis.

Lysozyme Surfactant proteins SP-A, Block bacterial surface components; promote phagocytosis.

SP-D a. Defensin b. Lactoferrin c. Dermcidin d. Surfactant protein e. Lysozyme ANSWER: e 7. Where would you be LEAST likely to find significant levels of defensins? a. The lung b. The intestine c. The liver d. The skin e. The bladder ANSWER: c

8. Which of the following is the CORRECT relationship? _____ on _____ recognize _____ on _____. a. PRRs; macrophages; PAMPs; pathogens b. PRRs; pathogens; PAMPs; macrophages c. PAMPs; macrophages; PRRs; pathogens d. PAMPs; neutrophils; PRRs; pathogens e. PRRs; macrophages; PAMPs; neutrophils ANSWER: a 9. Why are many opsonins multimeric? a. Because they are all derived from the same proto-opsonin b. Because they bind repeating structures on pathogen surfaces Copyright Macmillan Learning. Powered by Cognero.

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Chapter 04 c. So that they can be regulated allosterically d. Because they have to crosslink receptors on phagocytes for phagocytosis to occur e. Because one subunit binds pathogens, and the other has enzymatic activity ANSWER: b 10. Which of the following are associated with damaged or dead cells? a. Lysophosphatidic acid b. Altered carbohydrates c. Low CD47 d. Cell-surface annexin I e. All of the answers are associated.

ANSWER: e 11. Which of the following would you predict to result from a mutation in TLR4 that prevents binding to LPS? a. Increased susceptibility to infection with gram-positive bacteria b. Decreased susceptibility to septic shock c. Failure to develop from an embryo d. Tighter binding between bacteria and macrophages e. Increased phagocytosis ANSWER: b 12. Match the following toll-like receptors with their ligands.

TLR Ligands TLR3 Flagellin TLR4 Zymosan TLR5 dsRNA TLR6 CpG unmethylated dinucleotides TLR9 LPS a. TLR3/LPS; TLR4/CpG unmethylated dinucleotides; TLR5/dsRNA; TLR6/Zymosan; TLR9/Flagellin b. TLR3/dsRNA; TLR4/LPS; TLR5/Flagellin; TLR6/Zymosan; TLR9/CpG unmethylated dinucleotides c. TLR3/dsRNA; TLR4/LPS; TLR5/CpG unmethylated dinucleotides; TLR6/Flagellin; TLR9/Zymosan d. TLR3/CpG unmethylated dinucleotides; TLR4/Zymosan; TLR5/Flagellin; TLR6/LPS; TLR9/dsRNA e. TLR3/Zymosan; TLR4/LPS; TLR5/Flagellin; TLR6/dsRNA; TLR9/CpG unmethylated dinucleotides ANSWER: b 13. A number of strains of the bacteria Salmonella enterica contain flagella and can invade human cells. Based on the figure, which TLRs are most likely to be used to recognize such strains?

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Chapter 04

a. TLR4 and TLR 3 b. TLR 4 and TLR 7 c. TLR 5 and TLR 9 d. Only TLR 5 e. Only TLR 7 ANSWER: c 14. Which of the following is NOT usually induced in response to TLR signaling? a. TNF-α b. IL-1 c. iNOS d. IL-6 e. IL-4 ANSWER: e 15. Where would you MOST likely find a TLR that recognizes RNA? a. On the cell surface b. In the endosome/lysosome c. In the nucleus d. In the mitochondria e. In the endoplasmic reticulum ANSWER: b Copyright Macmillan Learning. Powered by Cognero.

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Chapter 04 16. Which of the following adaptor proteins activate the NF- κB pathway? a. MyD88 b. IKKα c. Calmodulin d. IL-2 receptor e. SOS ANSWER: a 17. Which cytokine is known for its antiviral properties? a. IL-2 b. IL-4 c. IFN-α d. TNF-α e. IL-1 ANSWER: c 18. What is the Latin word for "pain"? a. Rubor b. Calor c. Dolor d. Tumor e. Accio ANSWER: c 19. C-reactive protein is a(n) a. chemokine. b. cytokine. c. acute phase response protein. d. surfactant. e. cell-adhesion molecule.

ANSWER: c 20. How do natural killer cells kill their targets? a. By lysing them b. By inducing inflammation c. By inducing apoptosis d. By causing them to leave the bloodstream and be trapped by the liver e. By coating them with opsonins ANSWER: c 21. What types of cells are good targets for natural killer cells and why?

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Chapter 04 a. Bacterial cells because they contain LPS b. Gram-positive cells because they contain LTA c. Antigen presenting cells because they have high levels of costimulatory molecules d. Endothelial cells in inflamed tissues because they have high levels of adhesion molecules e. Virally infected cells because they have low levels of class I MHC ANSWER: e 22. Human cells lining the upper respiratory tract are expressing abnormal levels of surface MHC proteins due to a developing viral infection. Which cell type listed below is MOST likely to recognize the cells as infected based on altered MHC levels? a. NK cells b. Macrophages c. Dendritic cells d. Helper T cells e. B cells ANSWER: a 23. Predict the clinical outcome of a genetic defect in IRAK4, a protein required for the MyD88 pathway. a. Increased rates of cancer b. Increased rates of autoimmune disease c. Decreased muscle tone d. Increased rates of bacterial infection e. Increased TLR signaling ANSWER: d 24. Activation of dendritic cells with TLR4 or TLR5 results in the production of _____ that induces differentiation of CD4 T cells into _____. a. IL-12; TH1 b. IL-12; TH2 c. IL-10; TH1 d. IL-10; TH2 e. IL-4; TH1 ANSWER: a 25. Dendritic cells present _____ antigens on class I MHC through a process known as cross presentation. a. endogenous b. exogenous c. bacterial d. viral e. complex Copyright Macmillan Learning. Powered by Cognero.

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Chapter 04 ANSWER: b 26. Mouse B cells are observed to bind LPS in the laboratory. Based on this observation, which type of innate system-associated molecules are the B cells likely to be expressing that recognize LPS? a. MHCs b. Antibodies c. Chemokines d. TCRs e. PRRs ANSWER: e 27. Activation of B cells with TLR rather than with T-cell help would result in the overall antibody response being a. more specific. b. longer lasting. c. more polyclonal. d. reduced. e. more protective.

ANSWER: c 28. Which type of vaccine would MOST likely require an adjuvant? a. Killed bacteria b. Attenuated virus c. Inactivated virus d. Purified protein e. All of the answers are equally likely.

ANSWER: d 29. Which of the following defenses is MOST likely to protect a plant from a microbial pathogen? a. Antibodies b. CTL c. Phagocytes d. Reactive-oxygen species e. CD4 ANSWER: d 30. Would a potential vaccine that only activates the innate immune response be likely to be effective? Why or why not?

ANSWER: Probably not, as vaccines that generate a robust memory response are most desirable. Persistent memory is more associated with adaptive immunity.

31. Name three human organs or areas of the body where you would expect to find significant levels of Copyright Macmillan Learning. Powered by Cognero.

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Chapter 04 antimicrobial proteins.

ANSWER: More than three possibilities. Possible answers would include organs regularly exposed to the outside world, and hence exposed to potential pathogens. Examples include the skin, lungs, oral cavity, and intestines.

32. Using mutagenesis, you have removed a gene essential for production of pili by Escherichia coli known to cause urinary tract infections. Would you expect the mutated bacteria to retain the capacity to cause urinary tract infections?

ANSWER: Probably not, as many bacterial pathogens that cause disease within the urinary tract use pili to avoid being physically removed via urine flow.

33. Name a barrier to microbial infection in humans that contains both physical and chemical components. In the example, describe the physical component and chemical component.

ANSWER: More than one answer is possible. Examples include both the skin and mouth. Skin is a physical barrier to infection but also contains antimicrobial peptides. The mouth contains antimicrobial peptides, but the directional flow of saliva toward the stomach is a physical barrier.

34. Why does lysozyme not damage human cells?

ANSWER: Lysozyme targets peptidoglycan in the cells walls of bacteria, leading to lysis. Human cells lack peptidoglycan.

35. An innate immune cell has become activated by a PRR-activated signaling pathway. Name the distinct classes of molecules that will be upregulated in response to this type of activation and 1) will put surrounding cells into an "antiviral state" or 2) will attract additional immune cells to the site of activation.

ANSWER: 1) Interferons, and 2) Chemokines.

36. A macrophage, using TLR4, has recognized a bacterial pathogen containing LPS. Is this recognition event alone able to trigger phagocytosis? If not, can you name a PRR that can induce phagocytosis after recognition of LPS? ANSWER: No. TLRs are a class of PRRs that, alone, do not induce phagocytosis by phagocytes. SR-A is a PRR that can induce phagocytosis by phagocytes after binding LPS. 37. How can the regulated cell death of an innate immune cell be beneficial, following activation by PAMPs? ANSWER: Two answers are possible, discussing either NETosis or pyroptosis. NETosis, to produce NETs, can physically localize an infection by trapping surrounding pathogens and thus limiting their spread.

NETs also contain antimicrobial molecules, whereas the human DNA part of NETs can also serve as DAMPs. For pyroptosis, the death of the infected immune cell can prevent further spread of the intracellular pathogen, and pyroptosis can promote the release of interleukins.

38. How can receptors of the innate immune system, such as PRRs, be considered both specific and general?

ANSWER: PRRs recognize molecules shared by groups of pathogens, not those unique to a species or strain.

For example, many bacterial pathogens contain flagella, which would all be recognized by TLR5.

However, bacterial pathogens lacking flagella will not be recognized by TLR5.

39. In no more than five steps, list how an innate immune system could become activated by binding to a Grampositive bacterial pathogen using TLR2.

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Chapter 04 ANSWER: Step 1, A PAMP recognized by TLR2, such as peptidoglycan, binds to TLR2 on the surface of the immune cell, causing TLR2 dimerization.

Step 2, Dimerization of TLR2 allows binding of MyD88 adaptor protein.

Step 3, Binding of MyD88 to TLR2 leads to the activation of MAP kinase pathways within the immune cell, characterized by a series of intracellular protein phosphorylation events.

Step 4, Transcription factors NF-κB and AP-1 activate.

Step 5, NF-κB and AP-1 upregulate the expression of pro-inflammatory molecules.

40. At what point in evolution did adaptive immunity develop?

ANSWER: Around the same point that fish developed jaws.

41. Imagine you are walking barefoot across a pasture when your foot becomes punctured with a dirty splinter.

Describe the physiological and molecular changes that occur in your foot over the next few hours.

ANSWER: Answers may vary. Phagocytes in the area would respond to PAMPs and damaged cells by secreting cytokines such as IL-1, IL-6, and TNF-α. This would result in swelling and redness in the area as chemokines get released and other leukocytes leave the bloodstream and enter the tissue.

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Chapter 05 1. Which of the following complement fixation pathways can be initiated by a soluble C3 convertase? a. Alternative b. Classical c. Lectin d. All of the answers are correct. e. None of the answers are correct.

ANSWER: a 2. On a holistic scale, the complement system plays a role in a. specific pathogen defenses. b. nonspecific pathogen defenses. c. both specific and nonspecific pathogen defenses. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: c 3. Complement components can be classified into seven functional categories, including a. Enzymatic mediators. b. Inflammatory mediators. c. Membrane attack proteins. d. Regulatory complement components. e. All the answers are correct.

ANSWER: e 4. Of the molecules listed, which can be considered the key molecule in complement pathways? a. C1 b. IgM c. MBL d. C5 convertase e. None of the answers are correct.

ANSWER: d 5. In considering the following list of molecules, which can act as a bridge to connect complement labeled pathogens to effector immune cells? a. IgM b. C1 c. C1R d. C3aR e. Both C1R and C3aR are correct.

ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 05 6. Which of the following provides serine protease activity in the classical complement activation pathway? a. MASP-2 b. C1r c. C1s d. Both C1r and C1s act in the classical pathway. e. None of the answers acts in the classical pathway.

ANSWER: d 7. Which of the following is the MOST potent anaphylatoxin produced during the complement cascade? a. C3a b. C3b c. C5a d. C5b e. Ba ANSWER: c 8. To which of the following is MBL MOST structurally similar? a. C3b b. C1q c. Bb d. C5b e. None of the answers are correct.

ANSWER: b 9. Which of the following is TRUE about the C5 convertase? a. C5 convertase can consist of the membrane-bound components C3b2Bb. b. C5 convertase cleaves C5 into C5a and C5b, with the b chain attached to the pathogen surface and the chain dissociating away to serve as a potent proinflammatory chemotactic factor. c. C5 convertase is an important player in the production of the MAC. d. All of the answers are true. e. None of the answers are true.

ANSWER: d 10. Which of the following BEST explains the timing of the classical pathway of complement fixation, relative to the other pathways of complement fixation, against a pathogen in an individual who has never been exposed to said pathogen? a. No target for C1qrs exists on the surface of the pathogen in the earliest stages of the response to it. b. The chemical environment of the pathogen's surface favors the spontaneous activation of soluble C3 immediately upon exposure to the pathogen. c. C1qrs immediately recognizes carbohydrate antigens on the surface of the pathogen, allowing for rapid formation of the C4b2a C3 convertase.

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Chapter 05 d. The pathogen expresses one or more factors on its surface that act as negative regulators of C3 convertase formation. e. None of the answers are correct.

ANSWER: a 11. Which of the following binds to surface-bound C3b during formation of the alternative C3 convertase? a. Factor Bb b. Factor B c. C2a d. C4b e. Factor D ANSWER: b 12. Which of the following can be directly activated as a soluble protein in the microenvironment surrounding a pathogenic cell? a. C2 b. C3 c. Factor B d. Factor D e. C4 ANSWER: b 13. Which of the following acts as a protease that is required to generate the alternative pathway C3 convertase? a. C2 b. C3 c. Factor B d. Factor D e. C4 ANSWER: d 14. Which of the following is the first complement factor to be activated, resulting in insertion of one of its subunits into the pathogen surface in two of the three complement fixation pathways? a. C2 b. C3 c. Factor B d. Factor D e. C4 ANSWER: e 15. Which of the following, when activated itself, acts as a protease that converts soluble C3 into C3a and C3b in the alternative pathway?

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Chapter 05 a. C2 b. C3 c. Factor B d. Factor D e. C4 ANSWER: c 16. Which of the following, when activated, utilizes its "a" component instead of the "b" component in the formation of the C3 convertase? a. C2 b. C3 c. Factor B d. Factor D e. C4 ANSWER: a 17. Which of the following immunoglobulin isotypes is the MOST efficient at initiating a complement fixation cascade? a. IgG b. IgE c. IgM d. IgD e. None of the answers are correct.

ANSWER: c 18. Addition of which of the following components to any C3 convertase leads to the formation of the C5 convertase? a. C3b b. C2a c. C4b d. C5b e. C3a ANSWER: a 19. Which form of IgM is MOST readily recognized by C1q? a. Monomeric IgM b. Planar pentameric IgM c. "Staple-form" pentameric IgM d. All of the answers are recognized equally by C1q. e. None of the answers are recognized by C1q.

ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Chapter 05 20. Which of the following acts as a positive regulator of complement fixation via stabilization of C3bBb? a. DAF (CD55) b. Properdin c. Factor H d. Factor I e. MCP (CD46) ANSWER: b 21. Which of the following acts as a serine protease that, with cofactors, cleaves C3b and C4b? a. DAF (CD55) b. Properdin c. Factor H d. Factor I e. MCP (CD46) ANSWER: d 22. Which of the following facilitates dissociation of both the C4b2a and C3bBb C3 convertases? a. DAF (CD55) b. Properdin c. Factor H d. Factor I e. MCP (CD46) ANSWER: a 23. Which of the following is capable of initiating the alternative pathway of complement fixation by directly binding to the surfaces of certain cell types? a. DAF (CD55) b. Properdin c. Factor H d. Factor I e. MCP (CD46) ANSWER: b 24. The MAC consists of a multimeric complex of which of the following proteins that, by their association, forms a pore in the surface of the attacked cell? a. C3b b. C5b c. C6 d. C9 e. C4b Copyright Macmillan Learning. Powered by Cognero.

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Chapter 05 ANSWER: d 25. How does binding of complement-opsonized microbes to CR1 facilitate clearing of the microbe from the host? a. Promotion of phagocytosis of opsonized microbes by leukocytes b. Secretion of proinflammatory cytokines c. Mediating phagocytosis of C3b-opsonized pathogen by B cells d. All of the answers occur as a result of CR1 binding of complement-opsonized microbes. e. None of the answers occur.

ANSWER: d 26. Which of the following is TRUE about the binding of C5b to the pathogen surface? a. C5b binds to the pathogen surface the same way C4b and C3b do. b. C5b requires C6 binding to stabilize it before it dissociates away. c. C5b, when complexed to C6 and C7, is capable of forming the MAC on any cell membrane, pathogen, or host. d. C5b both requires C6 binding to stabilize it before it dissociates away and, when complexed to C6 and C7, is capable of forming the MAC on any cell membrane, pathogen, or host. e. All of the answers are true.

ANSWER: d 27. Which of the following is NOT an effect of C3a and C5a binding their receptors on leukocytes? a. Increased vascular permeability via induction of TNF-α and IL-6 secretion b. Induction of degranulation by granulocytes c. Increased smooth muscle contraction to aid in delivering immune cells and molecules to the site of infection d. All of the answers are effects of C3a and C5a binding their receptors. e. None of the answers are effects of C3a and C5a binding their receptors.

ANSWER: d 28. Which of the following regulates complement function by directly inhibiting formation of the MAC? a. Protectin (CD59) b. Factor I c. DAF (CD55) d. C1INH e. Factor H ANSWER: a 29. Based on your knowledge of complement activation pathways, predict which group of pathogens would be MOST susceptible to lysis by MACs. a. Gram-negative pathogens b. Eukaryotic pathogens Copyright Macmillan Learning. Powered by Cognero.

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Chapter 05 c. Enveloped viruses d. Gram-positive pathogens e. Gram-negative pathogens and enveloped viruses are equally susceptible.

ANSWER: e 30. A common denominator among the three complement pathways is antigen recognition. Can you name three molecules that act as antigen recognition molecules for the classical, lectin, and alternative pathways?

ANSWER: Antibodies for classical, lectins for the lectin pathway, and C3b for the alternative pathway. For the alternative pathway, properdin can also act as an antigen recognition molecule.

31. You suspect that you have identified a mouse line that lacks a functional complement system. A friend suggests collecting serum and looking for hemolytic activity as a first screen in determining complement activity in the line. Do you agree or disagree with your friend, and why?

ANSWER: Agree. Although the hemolytic screen will not specifically identify which components of complement are missing in the line; the screen is a good functional test as intact complement pathways typically lead to hemolysis.

32. In your own words, and using no more than two sentences, explain how DAF regulates complement to inhibit MAC-mediated lysis.

ANSWER: DAF is a membrane-bound regulator of complement. DAF accelerates the destabilization of C3 convertases.

33. Name two complement proteins whose primary functions are promoting anaphylatoxin activity. What common structural feature of the two named proteins allows for their inactivation by way of serum carboxypeptidases?

ANSWER: C3a and C5a. Both act as anaphylatoxins when formed during complement activation. C3a and C5a contain C-terminal arginine residues that are targets of carboxypeptidases. Removal of such residues leads to C5a and C3a inactivation.

34. Can you imagine how a blood-borne bacterial pathogen might activate all three arms of the complement system? How can this occur?

ANSWER: Yes. The classical pathway can be activated by antibodies produced in response to the bacterial pathogen, or by previously synthesized circulating antibodies. The lectin pathway can be activated via recognition of lectins by MBL. The alternative pathway can be activated via circulating properdin acting as a PRR. 35. Complement activation is implicated in the pathogenesis of SLE. However, the incidence of SLE is highly correlated to C4 deficiency. Can you explain this paradox?

ANSWER: Deficiencies in C4 contribute to a reduction of C3b levels, that is, less C3b is now available to bind to immune complexes and contribute to immune response contraction. The inhibition of C3bmediated opsonization allows for activation of the later stages of the complement system.

36. Some strains of staphylococcal bacteria express staphylokinase. Staphylokinase can degrade IgG. Based on this information, how will staphylokinase disrupt complement? Which pathway is most impacted?

ANSWER: Staphylokinase will inhibit antibody-complement interactions. Antibody-complement interactions Copyright Macmillan Learning. Powered by Cognero.

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Chapter 05 are critical for activation of the classical pathway.

37. During an immune response, host damage from complement is generally limited to the area in which complement is activated. Explain one property of complement proteins that contribute to this observation.

ANSWER: Activated complement proteins generally have short half-lives, which favors a rapid inactivation state.

38. Complement is subject to rigorous regulatory mechanisms. C1INH can inhibit both the classical and lectin pathways. What function feature of C1INH allows for inhibition of both pathways?

ANSWER: C1INH is a serine protease inhibitor that inhibits serine proteases of the classical pathway and the MASP-2 protease of the alternative pathway. The ability of C1INH to target more than one serine protease allows for suppression of both pathways.

39. Initially the complement system was characterized by its capacity to covert antibody binding into pathogen lysis. Does the discovery of MAC-mediated lysis align with the evolutionary history of the complement system?

ANSWER: No, it does not. Studies of complement evolution, viewed as a timeline, indicate that the proteins making up the MAC appear as relative late additions to the animal genome. The opsonization activities of complement appear to predate the appearance of the MAC components. A functional MAC only appeared around the same time as the emergence of the adaptive immune response.

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Chapter 06 1. Which of the following BEST encapsulates the findings of the Hozumi and Tonegawa experiments? a. Every possible light chain that could be formed, in terms of receptor specificity, is encoded by a separate gene within the human genome. b. Light chains are produced by means of somatic rearrangement of germ-line DNA in B cells. c. The different light-chain variable regions are produced by means of alternative splicing of premRNA that has been transcribed from a fixed, unchanging DNA sequence. d. Different light chains, each with unique specificity, are produced via the activity of alternative transcription factors that regulate antibody production at the level of transcription initiation. e. None of the answers are correct.

ANSWER: b 2. Which of the following gene segments is NOT found in the mouse IgL loci? a. V b. J c. D d. C e. All of the answers are found in the mouse IgL loci.

ANSWER: c 3. At which point in the variable segments does the RAG1/2 complex introduce a single-strand break into the DNA during somatic rearrangement? a. Between the coding region and the conserved heptamer b. Between the conserved heptamer and the 12-bp spacer c. Between the 23-bp spacer and the conserved nonamer d. Between the nonamer and 12-bp spacer e. None of the answers are correct.

ANSWER: a 4. What introduces a transient hairpin that links the two strands in the V(D)J coding regions? a. TdT b. Artemis c. RAG1/2 d. XRCC4 with DNA ligase IV e. Ku70/80 ANSWER: c 5. Several proteins must work in a coordinating fashion to achieve V(D)J recombination. Which is responsible for adding nontemplated nucleotides to the V-D and D-J joints of Ig heavy chains? a. Artemis b. RAG1 c. RAG2 Copyright Macmillan Learning. Powered by Cognero.

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Chapter 06 d. TdT e. Ku70/80 ANSWER: d 6. Which is part of the mature BCR complex but is NOT part of the pre-BCR complex? a. CD81 b. CD19 c. CD21 d. Igα e. None of the answers are correct.

ANSWER: c 7. Recognition spacer sequences are separated by how many base pairs? a. 12 b. 23 c. 7 d. 7 or 12 e. 12 or 23 ANSWER: e 8. What binds cut DNA and retains it in protein-DNA complex? a. TdT b. Artemis c. RAG1/2 d. XRCC4 with DNA ligase IV e. Ku70/80 ANSWER: e 9. What cleaves interstrand hairpin in V(D)J coding regions? a. TdT b. Artemis c. RAG1/2 d. XRCC4 with DNA ligase IV e. Ku70/80 ANSWER: b 10. What introduces single-strand break between V(D)J coding sequence and heptamer RSS? a. TdT b. Artemis c. RAG1/2 d. XRCC4 with DNA ligase IV Copyright Macmillan Learning. Powered by Cognero.

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Chapter 06 e. Ku70/80 ANSWER: c 11. What introduces nucleotides in a template-independent manner to free 3' OH created upon cleavage of the interstrand hairpin? a. TdT b. Artemis c. RAG1/2 d. XRCC4 with DNA ligase IV e. Ku70/80 ANSWER: a 12. Which protein-encoding genes, although present in genomic DNA, are uniquely expressed by lymphocytes? a. RAG1 b. RAG2 c. DNA ligase IV d. TdT e. RAG1, RAG2, and TdT ANSWER: e 13. Which protein(s) listed below is MOST directly responsible for joining gene segments during V(D)J recombination? a. RAG1 b. RAG2 c. TdT d. DNA ligase IV e. Both RAG1 and RAG2 ANSWER: d 14. What closes the final nicks in the sugar-phosphate backbone to generate coding and signal joints? a. TdT b. Artemis c. RAG1/2 d. XRCC4 with DNA ligase IV e. Ku70/80 ANSWER: d 15. What recognizes nonamer RSS to begin lymphocyte receptor rearrangement? a. TdT b. Artemis c. RAG1/2 Copyright Macmillan Learning. Powered by Cognero.

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Chapter 06 d. XRCC4 with DNA ligase IV e. Ku70/80 ANSWER: c 16. Which of the following is NOT a means of generating diversity in the variable regions of the T-cell receptor genes? a. Cleavage at the coding-heptamer RSS junction by RAG1/2 b. Somatic hypermutation following activation c. Hairpin cleavage by Artemis to generate P nucleotides d. Addition of N nucleotides by TdT e. All of the answers generate diversity in the variable regions of the T-cell receptor genes.

ANSWER: b 17. The indicated items are found in an IgL gene. Which of the labeled elements serves as a spacer?

a. VL b. 7 bp c. 12 bp d. 9 bp e. None of the answers are correct.

ANSWER: c 18. Where does RAG1/2 cut the dsDNA depicted in the figure?

a. Between the VL and the 7bp regions b. Between the 7 bp and the 12 bp regions. c. Between the 12 bp and the 9 bp regions d. Within the 12 bp region e. RAG1/2 does not cut dsDNA. ANSWER: a 19. In which cells are the IgL loci rearranged by RAG1/2? a. Developing T cells b. Developing B cells c. Developing neutrophils d. Developing monocytes Copyright Macmillan Learning. Powered by Cognero.

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Chapter 06 e. None of the answers are correct.

ANSWER: b 20. What length must the RSS spacer be to link a V element to its appropriate D element? a. 7 bp b. 23 bp c. 9 bp d. 12 bp e. None of the answers are correct.

ANSWER: e 21. To which fundamental process is rearrangement of the locus below tightly linked? a. Replication b. Transcription c. Translation d. Pre-mRNA processing e. None of the answers are correct; rearrangement is independent of other genetic processes.

ANSWER: b 22. How many Dβ -Jβ rearrangements are possible in a normal human thymocyte? a. 2 b. 6 c. 4 d. 40 e. None of the answers are correct.

ANSWER: c 23. Which of the following is capable of undergoing successive rearrangements to prevent the formation of autoreactive lymphocyte receptors? a. IgL κ b. TCR α c. IgH μ d. Both IgL κ and TCR α e. All of the answers are correct.

ANSWER: d 24. Which of the following IgH chains is NOT produced as a result of CSR? a. δ b. α1 c. λ Copyright Macmillan Learning. Powered by Cognero.

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Chapter 06 d. γ2 e. None of the answers are produced as a result of CSR. ANSWER: a 25. Which of the following TCR gene variable regions possesses a "D" segment? a. β b. γ c. δ d. Both β and δ e. All of the answers are correct.

ANSWER: d 26. Which of the following accounts for allelic exclusion in rearrangement within the IgH locus? a. Rearrangement only occurs on one homolog at a time, and once one homolog has successfully rearranged, the other is methylated to produce heterochromatin. b. Rearrangement is regulated by VpreB and λ5, which are themselves only expressed at specific times during IgH rearrangement. c. Both homologs rearrange simultaneously, undergoing multiple V-J rearrangements until a productive one occurs. d. All of the answers promote allelic exclusion in IgH. e. None of the answers are correct; allelic exclusion does not occur in IgH. ANSWER: a 27. Which of the following is used to generate diversity in the antibody repertoire? a. Presence of multiple variable gene segments that can be assembled in multiple different combinations b. Addition of N nucleotides that are not encoded in the germ line c. Exonuclease trimming of excess nucleotides at variable segment junctions d. Ability to pair a single heavy chain with different light chains, so as to avoid generation of autoreactive antibodies e. All of the answers are correct.

ANSWER: e 28. Which of the following components that are essential for rearrangement of the IgH and IgL loci are NOT utilized in rearrangement of the TCR loci? a. RAG1/2 b. Artemis c. TdT d. RSS sequences with spacers of 12 bp and 23 bp e. All of the answers are essential for rearrangement of the TCR loci ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 06 29. Which of the following accounts for the transition from membrane-bound IgM to secreted IgM upon activation of a B cell? a. CSR b. Affinity maturation c. Alternative splicing of pre-mRNA d. Additional modification of nuclear DNA via RAG1/2 e. None of the answers are correct.

ANSWER: c 30. Deficiency in RAG1 and/or RAG2 can affect the proper development of which of the following cell types, resulting in decreased numbers of circulating cells of those types? a. B cells b. T cells c. NK cells d. Both B and T cells e. All of the answers are correct.

ANSWER: d 31. Consider the following statement from the text, "Immunologists had to face the fact that there simply was not enough DNA to encode all the relevant B-cell receptors, using the one-gene, one-polypeptide chain rule." In one sentence, could you explain, in your own words, what this statement means to a fellow student in your immunology course?

ANSWER: Several answers are possible. All answers should point out that it would take more DNA to encode for all the possible B-cell receptors that can be expressed than the amount of DNA present in the human genome.

32. Sequencing studies have demonstrated the existence of antibodies in which the same heavy chain variable region is associated with more than one heavy chain constant region. In your own words, in one sentence, describe the implication of this finding.

ANSWER: The finding implies that for each antibody heavy chain, expression of the variable and constant regions is independently regulated.

33. Dreyer and Bennett proposed that antibody heavy and light chains are encoded in two separate segments in the germ-line genome. At the time, what specifically was so revolutionary about this proposal?

ANSWER: The idea that DNA in somatic cells (like B cells) could engage in recombination had not been observed; only cells in meiosis had been shown to undergo recombination.

34. Can antibody diversity in humans be explained solely by V(D)J recombination? Why or why not?

ANSWER: It cannot – the math does not add up. V(D)J recombination alone accounts for up to 2.3 × 106 possible number of heavy- and light-chain combinations in humans. Current data says that a single human can generate up to 1013 to 1014 different antibodies. Thus, other mechanisms that contribute to antibody diversity must exist, such as somatic hypermutation.

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Chapter 06 35. Do you think, after reading this chapter, the statement that all human cells in an individual contain the same genome is true or false?

ANSWER: False. Upon completing V(D)J recombination, individual B-cells ready to respond to antigen contain unique regions within their genomes that, in turn, encode for unique antibodies.

36. V(D)J recombination involves a significant number of proteins, working together in a coordinated fashion.

Can you think of two potential reasons why so many proteins are involved?

ANSWER: The use of many proteins allows for tight regulation over the process. Errors made during the cutting of genomic DNA at both strands can be catastrophic for a cell. A second reason is that having many proteins involved helps limit or restrict the process to the appropriate sites within the genome, and to ensure that the process occurs only during defined periods of cell development.

37. Taking into consideration the length of bases between recombination sequences, can you describe the functional significance of the lengths?

ANSWER: The spacer lengths are either 12 or 23 base pairs. Twelve bases is about the length of 1 turn of DNA as a double helix, and 23 bases is about the length of 2 turns. So, these lengths ensure that the ends of the recombination signal sequences would be on the same side of the DNA and thus accessible to the same recombination enzymes.

38. Expression of RAG1 and RAG2 is tightly regulated. In addition to limiting the expression of RAG1 and RAG2 to select lymphocytes, can you describe a mechanism used to regulate the activity of RAG1 and RAG2 at the protein level?

ANSWER: RAG1 and RAG2 are inactivated prior to the cell's entry into the S-phase of the cell cycle, to protect the cell from RAG1 and/or RAG2 interfering with chromatin distribution into daughter cells; by potentially causing double-stranded breaks in DNA. Kinases, which are part of the cell cycle, phosphorylate RAG1 and RAG2; targeting them for ubiquitin-dependent protein degradation.

39. If a given B cell is found to be potentially reactive to self-antigens, can the cell make an effort to correct that flaw, or is it destined for eventual removal by apoptosis?

ANSWER: The B cell can react in an effort to correct the situation, via receptor editing. Because the binding site of the B-cell receptor contains parts of both the heavy and light chains, changing just one of these is sometimes sufficient to alter receptor specificity. In addition, the DNA recombination machinery within the B cell can be switched back on (i.e., re-induce RAG1 and RAG2 expression).

40. Imagine a lymphocyte is actively undergoing V(D)J recombination. V(D)J recombination has reached a stage where alleles are being excluded from expression. Within the nucleus, where would you expect to find the excluded alleles, and why?

ANSWER: Expression inactive chromatin is more likely found in regions associated with the nuclear lamina.

Therefore, alleles destined for exclusion from expression will re-associate with the lamina.

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Chapter 07 1. MHC molecules a. are secreted by T cells and bind and neutralize antigen in the serum. b. are membrane-bound molecules found exclusively on T cells. c. bind repeating patterns found on pathogens. d. are recognized by T cells. e. are conserved between individuals.

ANSWER: d 2. A mutation in which part of a viral protein might allow the virus to evade the adaptive immune response because of its MHC binding? a. A TCR contact residue b. A residue in the transmembrane domain of an envelope protein c. A residue in the DNA-binding domain d. An anchor residue e. An amino acid on the surface of the virus ANSWER: d 3. MHC polymorphisms tend to cluster a. in the peptide-binding groove. b. in the transmembrane domain. c. in the coreceptor contact residues. d. in the framework region. e. All of the answers are correct.

ANSWER: a 4. Based on your knowledge of MHC I and II, predict which cell type would be MOST likely not to express detectable MHC I. a. Dendritic cells b. Macrophages c. Erythrocytes d. Intestinal epithelial cells e. Basophils ANSWER: c 5. Of the classical MHC genes, which, could you argue, are LEAST related to antigen presentation? a. MHC I genes b. MHC II genes c. MHC III genes d. Both MHC I and II genes e. None of the answers are correct.

ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Chapter 07 6. Which of the following are functions related to the expression of MHC molecules? a. To display self-peptides to demonstrate cell health b. To display foreign peptides c. To display self-peptides to test developing T cells for autoreactivity d. To display self-peptides to maintain self-tolerances e. All of the answers are correct.

ANSWER: e 7. Of the cells listed below, predict which is LEAST likely to be presenting antigens by MHC II during an immune response to an extracellular pathogen. a. Dendritic cells b. Macrophages c. B cells d. Intestinal epithelial cells e. None of the answers are correct.

ANSWER: d 8. MHC expression is constitutive; however, levels of MHC I and II can vary depending on conditions. Which of the following is NOT known to influence MHC expression levels? a. CITA and CIIITA b. Hepatitis B infection c. IL-4 levels d. Corticosteroids e. All of the answers are factors that can influence MHC levels.

ANSWER: e 9. How many different MHC classical class I proteins does each nucleated cell in a human heterozygous at the MHC locus express? a. None. Only APC express class I. b. One c. Two d. Three e. Six ANSWER: e 10. Which of the following would be the MOST likely source of a peptide bound to an MHC class I molecule? a. The Golgi apparatus b. Outside the cell c. The endosome/lysosome d. The cytoplasm Copyright Macmillan Learning. Powered by Cognero.

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Chapter 07 e. The chloroplast ANSWER: d 11. One way a developing fetus is protected from attack by the maternal immune system is a. expression of paternal MHC class I molecules. b. expression of paternal MHC class II molecules. c. expression of nonclassical class I molecules. d. expression of nonclassical class II molecules. e. expression of class III MHC molecules.

ANSWER: c 12. Which of the following is NOT a mouse MHC gene? a. IA b. IE c. DP d. D e. K ANSWER: c 13. Peptide-binding diversity is increased by a. multiple MHC alleles in the population, only. b. multiple homologous MHC genes in the genome, only. c. both multiple MHC alleles in the population and multiple homologous MHC genes in the genome. d. None of the answers are correct.

ANSWER: c 14. Your chances of having the same MHC haplotype as your sibling are a. 1:1. b. 1:2. c. 1:4. d. 1:8. e. 1:16.

ANSWER: c 15. The human MHC locus is one of the most polymorphic regions of the genome. What does this mean? a. It has the most different genes. b. There are many different alleles of these genes. c. Sequence variability is low in this region. d. There are many introns in this region. e. This region is regulated by many different mechanisms.

ANSWER: b Copyright Macmillan Learning. Powered by Cognero.

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Chapter 07 16. MHC diversity ultimately affects the a. variety of peptides that bind to MHC. b. variety of BCRs that are expressed on mature B cells. c. rate of somatic hypermutation. d. number of antigen-presenting cells. e. transmembrane domain.

ANSWER: a 17. Which of the following BEST represents the relationship of polypeptide units in MHC class II? a. α and β chains from any gene can pair with each other. b. Only α and β chains from the same gene can pair with each other. c. Only α and β chains of the same allele can pair with each other. d. α chains can pair with other β chains, but β chains can only pair with α chains. e. α and β chains pair until the complex is exported to the cell surface and can bind β2-microglobulin.

ANSWER: b 18. Tasmanian devils are a largely inbred population with little diversity in the MHC. Which of the following would be a likely outcome of this? a. They would compensate for low diversity in the MHC with high diversity in the TCR. b. They would compensate for low diversity in the MHC with high diversity in the BCR. c. They would rely only on innate immune responses. d. They would be at higher risk of infection. e. All of the answers are correct.

ANSWER: d 19. Which of the following cell types would be LEAST likely to express MHC class II? a. B cells b. T cells c. Dendritic cells d. Thymic epithelial cells e. Vascular endothelial cells ANSWER: b 20. Which of the following cell types would be MOST likely to express MHC class I? a. B cells b. T cells c. Dendritic cells d. Lung epithelial cells e. All of the answers are correct.

ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 07 21. Which of the following is the BEST example of self-MHC restriction of T cells? a. A T-cell clone is deleted when it binds too tightly to self-MHC. b. A T-cell clone responds more vigorously to a self-peptide than a foreign peptide. c. A T-cell clone recognizes foreign MHC. d. A T-cell clone only recognizes foreign peptides when presented by self-MHC. e. All of the answers are correct.

ANSWER: d 22. Under which of the following conditions would T-cell activation be LEAST likely to occur? a. Macrophages are incubated with antigen, then fixed with paraformaldehyde, then incubated with antigen-specific T cells. b. Macrophages are fixed with paraformaldehyde, then incubated with antigen, then incubated with antigen-specific T cells. c. Macrophages are fixed with paraformaldehyde, then incubated with digested antigen, then incubated with antigen-specific T cells. d. Macrophages are incubated with digested antigen, then fixed with paraformaldehyde, then incubated with antigen-specific T cells. e. Macrophages are incubated with antigen and then incubated with antigen-specific T cells.

ANSWER: b 23. Place the class I processing pathway in the correct order: a. Peptides exported from the ER by TAP > peptides are digested by the proteasome > peptides are loaded onto class I > class I is exported to the cell surface b. Proteins are digested by the proteasome > peptides are imported into the ER by TAP > peptides are loaded onto MHC class I > class I is exported to the cell surface c. MHC class I moves from the cell surface to the lysosome by endocytosis > class I bound peptides are replaced with antigenic peptides in the lysosome > class I returns to the cell surface d. Proteins are degraded by TAP > peptides are imported into the lysosome by the proteasome > peptide-MHC class I complexes are exported to the cell surface e. MHC class I is transported to the ER by TAP > proteins in the ER are degraded into peptides by the proteasome > peptides bind MHC class I in the ER, and the complex is exported to the cell surface ANSWER: b 24. In people infected with human cytomegalovirus, class I MHC and β2-microglobulin are produced, but very little mature class I MHC is found at the cell surface. Inhibition of which of the following molecules by human cytomegalovirus may account for this phenomenon? a. TCR b. RAG c. CLIP d. TAP e. Ii Copyright Macmillan Learning. Powered by Cognero.

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Chapter 07 ANSWER: d 25. T-cell activation can be inhibited by treating antigen-presenting cells with chloroquine. What is chloroquine's mechanism of action? a. It blocks protein synthesis. b. It disrupts the Golgi apparatus. c. It increases the pH of the lysosome. d. It blocks TLR signaling. e. All of the answers are correct.

ANSWER: c 26. What is the role of the invariant chain (Ii)? a. To prevent peptide binding to class II in the ER b. To assist in folding class II α and β chains c. To direct class II to the endocytic compartment d. To serve as a substrate for proteases in the lysosome e. All of the answers are correct.

ANSWER: e 27. A mutation that renders the MHC class II molecule DM nonfunctional would likely lead to a. cells with no class II MHC. b. cells with no DO. c. cells with class II MHC only bound with CLIP. d. cells with class II MHC bound with a variety of self-antigens. e. a deficiency in CD8+ T cells.

ANSWER: c 28. Which of the following is an example of cross presentation? a. An endogenous peptide being presented on MHC class I b. An exogenous peptide being presented on MHC class I c. An endogenous peptide being presented on MHC class II d. An exogenous peptide being presented on MHC class II e. A B-cell antigen being presented to a T cell ANSWER: b 29. Of the antigen receptors listed here—T-cell receptor, B-cell receptor, MHC I, and MHC II—which would you describe as "promiscuous" in their ligand-binding activity?

ANSWER: MHC I and MHC II. Any given MHC can bind numerous different peptide antigens, and some peptides can bind to several different MHC molecules. Thus, MHC I and II demonstrate broader ligand specificity versus T-cell and B-cell receptors.

30. Examine the figure. Can you summarize, in two sentences maximum, what this figure demonstrates about Copyright Macmillan Learning. Powered by Cognero.

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Chapter 07 MHC I-peptide antigen interactions?

ANSWER: The ability of MHC I to bind to a diverse set of antigens is partially due to the presence of the same or similar amino acids within the peptides being bound. In the figure, the same MHC I can bind to four different peptides that all contain conserved G, P, and L/I residues.

31. You might have noticed that two people may respond to the same bacterial pathogen differently. Although "Person A" might only suffer a minor disease, "Person B" may take longer to clear the same pathogen. Argue how this discrepancy can be explained, at least in part, by the determinant selection model.

ANSWER: Person A and B have different MHC II molecules. Those molecules differ in their ability to bind particular, processed bacterial antigens. Person A's MHC may have a greater capacity to present antigens that are most critical to eliminating the pathogen. Thus, person A can respond more effectively.

32. B-cell receptor and T-cell receptor diversity is generated through genomic rearrangement and gene editing mechanisms. Compare those mechanisms with mechanisms used to generate MHC diversity in an individual.

How are the mechanisms the same, and how are they different?

ANSWER: The ultimate goal of the mechanisms is the same; to increase the range of antigens that each set of receptors can bind to, and with relatively strong affinity. Although that purpose is achieved through genomic rearrangement and gene editing for B-cell and T-cell receptors, it is achieved for MHC receptors by using a combination of peptide-binding promiscuity and the expression of different MHC variants on every cell.

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Chapter 07 33. Name the primary factor contributing to the observation that human genes found within the MHC locus are inherited as a set, which is described by geneticists as a linkage disequilibrium pattern of inheritance.

ANSWER: The individual genes that make up the MHC locus (MHC I, II, and III) lie so close together, physically, that their inheritance is linked. Recombination between genes is more likely when genes are far apart.

34. You have two brothers and a sister, and your parents have different haplotypes. Are you more likely to be histocompatible with a sibling within your family or your parents?

ANSWER: You are more likely to be histocompatible with a sibling. MHC alleles are inherited as haplotypes and only rarely do parental haplotypes recombine.

35. Compare and contrast the holes-in-the–repertoire model and the determinant-selection model of immune responsiveness.

ANSWER: In the determinant-selection model, differences in responsiveness are explained by the ability or inability of MHC to bind peptide. In the holes-in-the repertoire model, differences in responsiveness are explained by the presence or absence of specific T cells. T cells that respond to certain peptides may be deleted during selection on certain MHC backgrounds.

36. Name an advantage of presenting viral antigens by both the endogenous and exogenous pathways.

ANSWER: During an active viral infection, typically, viruses will exist in both an intracellular and extracellular state. By presenting viral pathogens by both pathways, the immune system can eliminate viruses from both locations.

37. Suppose an individual is deficient in TAP (transporter associated with antigen processing). Is the deficiency MORE likely to produce symptoms of immune deficiency or autoimmunity in the person?

ANSWER: Both are possible. TAP is important in providing peptide antigens to MHC I, both self-antigens and pathogen-derived antigens.

38. In your own words, explain how the immune system can activate CD8+ T-cells to eliminate intracellular pathogens (i.e., viruses) unless a dendritic cell happens to become infected.

ANSWER: Cross presentation. The process of cross presentation allows for DCs to present exogenously derived antigens loaded on both MHC II (as expected) but also on MHC I. Activation of naïve CD8+ T cells requires presentation through MHC I. 39. Nonprotein antigens are not recognized by T cells. Is this statement true or false? Justify your answer.

ANSWER: Nonprotein antigens are recognized by T cells but not via MHC I or MHC II. For example, mycolic acid, derived from some bacterial pathogens (e.g., M. tuberculosis), are presented to T cells using nonclassical MHC molecules including CD1.

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Chapter 08 1. Committed lymphocyte progenitors originate in the a. thymus. b. bone marrow. c. spleen. d. lymph node. e. brain.

ANSWER: b 2. Name that cell. I am a small, nonproliferating cell found within the thymic cortex and contain CD4 and CD8 on my cell surface. a. DN thymocyte b. DP thymocyte c. Thymocyte d. DN1 cell e. DN4 cell ANSWER: b 3. What term BEST describes a selection process against those cells whose T-cell receptors bind too strongly to self-peptide/MHC combinations? a. Positive selection b. Negative selection c. Lineage commitment d. Hematopoietic commitment to the T-cell lineage e. None of the above is correct.

ANSWER: b 4. Which stage of DN selection is characterized by rapid proliferation of thymocytes in the subcapsular cortex of the thymus and suppression of TCR rearrangement? a. DN1 b. DN2 c. DN3 d. DN4 e. None of the answers are correct.

ANSWER: c 5. Hematopoietic stem cells cultured in the presence of which receptor differentiate into T cells rather than B cells? a. CD4 b. CD8 c. Notch ligand d. B7-1 Copyright Macmillan Learning. Powered by Cognero.

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Chapter 08 e. CD3 ANSWER: c 6. Which of the following molecules would double-negative T cells fail to express? a. CD3 b. CD4 c. MHC class I d. TAP e. All of the answers are correct.

ANSWER: b 7. Signaling through the pre-TCR occurs as a result of a. binding to MHC class I. b. binding to MHC class II. c. binding to either MHC class I or MHC class II. d. successful assembly of the pre-TCR. e. expression of CD4.

ANSWER: d 8. At what stage of T-cell development is the pre-TCR expressed? a. DN b. DP c. SP d. Pro-T cell e. None of the answers are correct.

ANSWER: a 9. Signaling through the pre-TCR results in a. maturation to the DN4 stage. b. suppression of TCR β-chain rearrangement. c. cessation of proliferation. d. TCR α-chain rearrangement. e. All of the answers are correct.

ANSWER: e 10. Which of the following represents the EARLIEST stage in T-cell development? a. DP b. DN c. SP-CD4 d. SP-CD8 e. Mature T cell Copyright Macmillan Learning. Powered by Cognero.

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Chapter 08 ANSWER: b 11. T cells selected on a b haplotype thymus would be able to respond to antigen presenting on which of the following haplotype antigen presenting cells? a. a b. b c. a x b d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 12. Injecting a TCR transgenic mouse with the peptide that it recognizes would result in an increase in which process? a. Positive selection b. Negative selection c. Complement fixation d. Phagocytosis e. All of the answers are correct.

ANSWER: b 13. MHCa mice that are irradiated and reconstituted with MHCa x b bone marrow would accept grafts from which of the following donors? a. MHCa b. MHCb c. MHCa x b d. All of the answers are correct. e. None of the answers are correct.

ANSWER: e 14. In negative selection, cells that receive _____ signal through their antigen receptors die. a. a weak b. a strong c. an intermediate d. no e. intermittent ANSWER: b 15. What happens to autoreactive cells that escape the thymus? a. They attack self-tissues. b. They can be rendered anergic.

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Chapter 08 c. They negatively regulate other autoreactive cells. d. They require TCR ligation and costimulation to be activated. e. All of the answers are correct.

ANSWER: e 16. How do self-antigens that are specific to tissues away from the thymus (like insulin or keratin for example) get in the thymus so that developing T cells that react to them can be deleted? a. Dendritic cells pick them up in the periphery and carry them to the thymus. b. Specialized macrophages in the thymus filter the bloodstream and present antigens found there to developing T cells. c. A transcription factor, AIRE, is expressed in thymic medullary epithelial cells, which allows these cells to express proteins normally found in other tissues. d. They do not get to the thymus, all tissue-specific T cells are deleted in the periphery. e. There are special chaperone proteins that bind to peripheral proteins and carry them to the thymus.

ANSWER: c 17. Superantigens differ from regular peptide antigens because they a. bind outside the peptide-binding groove. b. activate a larger proportion of T cells. c. interact with the V β domain of the TCR. d. can result in toxic shock. e. All of the answers are correct.

ANSWER: e 18. What is currently the BEST explanation for what determines whether a T cell develops into a CD8+ T cell or a CD4+ T cell? a. CD4/TCR coengagement suppresses CD8 expression, and CD8/TCR coengagement suppresses CD4 expression. b. T cells randomly downregulate CD4 or CD8, and only cells that still bind the appropriate MHC will get a strong enough signal to survive. c. CD4 or CD8 expression is determined by the strength and duration of the TCR/MHC interaction. d. CD4 or CD8 expression is predestined in the bone marrow. e. Only γδ T cells express CD8.

ANSWER: c 19. Which of the following BEST describes the relationship between natural TREGs and induced TREGs? a. Natural TREGs differentiate into induced TREGs in response to stimulation through the TCR. b. Natural TREGs are derived from memory T cells, and induced TREGs differentiate directly from developing thymocytes. c. Natural TREGs develop in the thymus, and induced TREGs develop in the periphery.

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Chapter 08 d. Natural TREGs have less diverse TCRs than induced TREGs. e. None of the answers are correct.

ANSWER: c 20. Thymocytes whose TCR preferentially interacts with MHC II generates a continuous signal that initiates which cell type to be generated? a. CD8+ T cells b. CD4+ T cells c. SP thymocytes d. DP thymocytes e. Both CD8+ T cells and CD4+ T cells.

ANSWER: b 21. Which transcription factor is characteristic of TREG cells? a. AP-1 b. NFAT c. NF-κB d. OCT-1 e. FoxP3 ANSWER: e 22. TREGs have been shown to be protective against which of the following conditions? a. Inflammatory bowel disease b. HIV disease c. Influenza infection d. MRSA e. Malaria ANSWER: a 23. Which item listed below is NOT likely an application of regulatory T-cells that suppresses immune responses? a. Inhibition of such cells before immunization may enhance responses to vaccines. b. Elimination of such cells that suppress responses to tumor antigens may enhance antitumor immunity. c. Increasing the activity of such cells could be useful in autoimmune treatments. d. Increasing the activity of such cells could be useful in suppressing organ rejections. e. All the answers are potential applications.

ANSWER: e 24. As a thymus-settling progenitor enters the thymus, which molecule appears to heavily influence the Copyright Macmillan Learning. Powered by Cognero.

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Chapter 08 progenitor to commit to T-cell development?

ANSWER: The level of expression of Notch receptor on the surface of the stem cell. Overexpression of Notch (Notch1) leads to commitment to the T-cell lineage. When Notch1 activity is removed from the same cells, B cells, rather than T cells, develop in the thymus.

25. Explain why T cells are more likely to develop into αβ T cells than γδ T cells.

ANSWER: Because, once a cell successfully produces a β chain, the pre-TCR is expressed. For a cell to become γδ it must successfully rearrange γ and δ before β, and the chances of that are much smaller.

26. In what way do the four double-negative stages of T-cell development demonstrate the organization of Tcell development according to spatial parameters?

ANSWER: The four double-negative stages occur within distinct areas of the thymus. Incoming T-cell precursors take a path within the thymus from the thymic epithelium, to the outer thymic cortex, to the thymic medulla, and then to the cortico-medullary junction.

27. What are the two major goals of lymphocyte development?

ANSWER: The two goals are (1) to ensure that all T cells have functional TCR and that (2) autoreactive cells are deleted (self-tolerance in ensured).

28. T cells are three times more likely to become TCR-αβ cells versus TCR-γδ cells. Why is this the case considering T-cell development mechanisms within the thymus?

ANSWER: Commitment to becoming a TCRcell requires a single in-frame V(D)J rearrangement event during development. Commitment to becoming a TCR-

cell requires two such events. Probability

favors the single event as more likely to occur, and, therefore, more frequently.

29. Compare and contrast the affinity hypothesis and altered peptide hypothesis to explain the thymic selection paradox (why we don't negatively select all cells that we positively select).

ANSWER: The affinity hypothesis states that the strength of the TCR/MHC/peptide interaction determines whether a T cell is positively or negatively selected. The altered peptide hypothesis states that thymic epithelial cells express a special set of peptides that mediate positive selection. There is support for both hypotheses, and both may contribute to the paradox of thymic selection.

30. In your own words, explain why thymic selection is needed?

ANSWER: Due to the randomness of TCR gene rearrangement, it is likely that T cells will be generated that contain TCRs that recognize self-antigens. Such self-reactive T cells need to be identified and eliminated via thymic selection to minimize the generation of immune responses against selfantigens.

31. At first glance, the logic of positive selection appears to be lacking. Predict what might happen in the absence of positive thymic selection.

ANSWER: Without positive selection, the body would likely contain an abundance of T cells that don't recognize any antigens, reducing the probability that a T cell will respond to foreign antigens when needed during the mounting of an immune response.

32. A classmate in your immunology course fails to see the importance of discovering AIRE. Can you convince Copyright Macmillan Learning. Powered by Cognero.

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Chapter 08 him of the importance of AIRE in understanding T-cell tolerance?

ANSWER: The discovery of AIRE helped us better understand how, in the thymus, developing T cells reactive to tissue-specific self-antigens are eliminated during selection. AIRE allows mTECs to express, process, and present proteins that are ordinarily found only in specific organs outside the thymus.

Thus, T cells showing strong reactivity to such antigens can be eliminated as part of negative selection.

33. Does thymic negative selection always need to involve death of the self-reactive T cell?

ANSWER: No. Other mechanisms have been proposed including clonal arrest, clonal anergy, and clonal editing, all of which have some experimental support.

34. The affinity model can help explain the thymic selection paradox. What is the paradox, and is the affinity model the only way the paradox can be explained?

ANSWER: The paradox is if positive selection allows only for thymocytes reactive with self-antigen to live, and negative selection eliminates thymocytes that react to self-antigens; then how do any T-cells escape elimination? In addition to the affinity model, the altered peptide model can help explain the paradox.

35. In a brief statement, can you explain how transcription factors play a role in T-cell lineage commitment?

ANSWER: Th-POK and Runx3 play important roles in CD4+ and CD8+ T-cell commitment, respectively.

Interestingly, they appear to work in part by reciprocally regulating each other. For instance, Runx3 activates expression of CD8 and inhibits expression of genes encoding CD4 and Th-POK. 36. Please list two mechanisms, independent of central tolerance, which can help maintain self-tolerance. Why are such additional mechanisms needed?

ANSWER: The activities of regulatory T cells. T-cell costimulation stringency. Unfortunately, mechanisms of central tolerance do not remove all T cells that have potential to react to self-antigens.

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Chapter 09 1. B lymphocytes are made in the a. blood stream. b. bone marrow. c. liver. d. thymus. e. totipotent cell.

ANSWER: b 2. How long does B-cell maturation from an HSC to a mature B cell take? a. 1 to 2 hours b. 1 to 2 days c. 1 to 2 weeks d. 1 to 2 months e. 1 to 2 years ANSWER: c 3. Which cell type is found in both B- and T-cell lineages? a. Common lymphoid progenitors b. Common pro-B-T cells c. Immature B cell d. Naïve lymphoid progenitor e. Pro-B-T cell ANSWER: a 4. This type of cell will leave the bone marrow and complete maturation in the spleen. a. Common lymphoid progenitor cell b. Hematopoietic stem cell c. Immature B cell d. Pro-B cell e. Pro-T cell ANSWER: c 5. All of the following are true regarding B-cell development EXCEPT a. B cells complete maturation in the spleen. b. B cells are mostly developed when they leave the bone marrow. c. B cells, like T cells, are MHC class restricted. d. Self-reactive B cells may be eliminated though apoptosis. e. Self-reactive B cells may be rendered unreactive (anergic).

ANSWER: c 6. Hematopoiesis produces Copyright Macmillan Learning. Powered by Cognero.

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Chapter 09 a. B cells only. b. Red blood cells only. c. myeloid lineage cells only. d. lymphoid and myeloid lineage cells. e. erythroid, lymphoid, and myeloid lineage cells.

ANSWER: e 7. Hematopoiesis begins at around day 7 after fertilization in mice. What is the site of precursor cells at this stage of fetal development? a. Bone marrow b. Fetal liver c. Placenta d. Primitive organ e. Yolk sac ANSWER: e 8. At what site(s) can mature HSCs be found by day 11 in the mouse model? a. AGM b. Fetal liver c. Placenta d. Yolk e. All of the answers are correct.

ANSWER: e 9. What type of cell will predominately be produced by hematopoiesis in the fetal liver of mice? a. Erythroid lineage cells b. Lymphoid lineage cells c. Myeloid lineage cells only d. Lymphoid and myeloid lineage cells e. Erythroid, lymphoid, and myeloid lineage cells ANSWER: a 10. V-DJ recombination occurs during which phase of a B cell's development? a. Activated B cell b. Mature B cell c. Naïve B cell d. Pro-B cell e. Immature B cell ANSWER: d 11. What are two functions of bone marrow stromal cells with respect to B-cell development?

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Chapter 09 a. Cytokine expression traps developing B cells in a specific location b. Recruits macrophages to phagocytize self-recognizing B cells and decreases HSC when no active infection is present c. Secretes release factors that direct the B cell to the spleen and expresses necessary cytokines d. Traps developing B cells in a specific location and recruits red blood cells to bring oxygen to developing B cells e. Triggers HSCs to produce more pro-B cells and secretes cytokines to stimulate osteoblast development ANSWER: a 12. Which of the following influence the development of B cells in the bone marrow? a. Changes in cell surface markers b. Changes in gene expression c. BCR gene rearrangements d. DNA modification by methylation e. All the answers influence B-cell development.

ANSWER: e 13. Which molecule is required for a pre-pro-B cell to begin entering the pro-B cell stage? a. IL-7 b. CXCL12 c. CD117 d. SCF e. None of the answers are correct.

ANSWER: b 14. Immature B cells in the bone marrow that are found to bear self-antigen reactive BCRs undergo which of the following? a. Clonal deletion b. Light chain receptor editing c. Development of anergy d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 15. Which molecule listed below appears to play a critical role in trafficking B cells from the bone marrow to the spleen to complete cellular maturation? a. SCF b. S1P c. IL-7 d. BIM Copyright Macmillan Learning. Powered by Cognero.

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Chapter 09 e. Both SCF and S1P are correct.

ANSWER: b 16. Individuals of retirement age or older show lower antibody mediate immune responses due to all the following reasons EXCEPT a. increased likelihood of autoimmune disorders. b. limited HSC production of pro-B cells. c. poor antibody response to vaccination. d. reduced-memory B-cell generation. e. smaller thymus.

ANSWER: e 17. What type of immunoglobulin gene rearrangement occurs during B-cell progenitor development? a. DH-JH rearrangement b. DL-JL rearrangement c. Both heavy- and light-chain rearrangement d. VH-DJH rearrangement e. VL-DJL rearrangement ANSWER: c 18. The common lymphoid progenitor cell gives rise to all the following cell lines EXCEPT a. dendritic cells. b. megakaryocytes. c. natural killer cells. d. pre-pro B cells. e. T-cell progenitor.

ANSWER: b 19. Which of the following statements regarding HSCs is/are TRUE? I. HSCs are not self-renewing.

II. HSCs can make copies of themselves.

III. HSCs give rise to one cell lineage.

IV. HSCs are multipotent.

V. HSCs express both RAG1 and RAG2 surface markers. a. Statement I only b. Statements I and III only c. Statements II and III only d. Statements II and IV only e. Statements III and V only ANSWER: d Copyright Macmillan Learning. Powered by Cognero.

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Chapter 09 20. Where can early lymphoid progenitor cells (ELPs) be found in humans? a. Blood stream b. Bone marrow c. Lymphatic tissue d. Thymus e. Both bone marrow and lymphatic tissue are correct.

ANSWER: b 21. At what stage of development does a B cell begin to express a pre-B-cell receptor? a. Pre-pro B cell b. Early pro-B cell c. Late pro-B cell d. Late pre-B cell e. Immature B cell ANSWER: d 22. At what stage of development does a B cell undergo D-JH rearrangement? a. Pre-pro B cell b. Early pro-B cell c. Late pro-B cell d. Late pre-B cell e. Immature B cell ANSWER: b 23. At what stage of development does a B cell begin to display an IgM receptor? a. Pre-pro B cell b. Early pro-B cell c. Late pro-B cell d. Late pre-B cell e. Immature B cell ANSWER: e 24. B-cell development has one checkpoint to determine if V-DJ rearrangement has produced a successful VHDJH combination that does not recognize self. If no successful combination is produced, then the B cell will undergo apoptosis. At what point of B-cell development does this checkpoint occur? a. Pre-pro-B cell b. Early pro-B cell c. Late pro-B cell d. Late pre-B cell Copyright Macmillan Learning. Powered by Cognero.

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Chapter 09 e. Immature B cell ANSWER: c 25. How does allelic exclusion prevent multiple heavy-chain rearrangements from occurring in pre-B cells? a. RAG1 and RAG2 are downregulated, and TdT activity is lost so that no additional heavy-chain rearrangements may take place. b. RAG1 is upregulated whereas RAG2 and TdT are downregulated to prevent heavy-chain recombination on the second set of chromosomes. c. RAG1 and RAG2 induce silencing of the second alleles for VH-DJH rearrangement. d. TdT initiates light-chain rearrangement. e. TdT releases a cytokine to trigger apoptosis in the pre-B cell.

ANSWER: a 26. Of the cells listed below, which one represents the MOST developed B cell? a. Pre-pro-B cell b. Pro-B cell c. Pre-B cell d. T1 B cells e. T2 B cells ANSWER: e 27. Mature naïve B cells express high levels of _____ on their cell surfaces. a. IgA b. IgD c. IgE d. IgG e. IgM ANSWER: b 28. Mature B-2 or follicular B cells are most commonly found in the a. bone marrow. b. lymph node. c. marginal zones of the spleen. d. peritoneal. e. secondary lymphoid organs.

ANSWER: e 29. Mature B-1 cells show _____ diversity in their V-region. a. high b. moderate (somewhat restricted) c. low (restricted) Copyright Macmillan Learning. Powered by Cognero.

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Chapter 09 d. high or low depending on active infection e. high or low depending on CD21 expression ANSWER: c 30. Marginal-zone B cells express a. IgD. b. IgG. c. IgM. d. IgE. e. Both IgG and IgM are correct.

ANSWER: e 31. Which type of mature B cell is MOST likely to respond to a protein antigen? a. B-1 B cells b. B-2 B cells c. MZ B cells d. B-2 B cells and MZ B cells e. B-1 B cells, B-2 B cells, and MZ B cells ANSWER: d 32. What is the initial location of B-cell and T-cell development? a. Blood for B cell and thymus for T cell b. Bone marrow for both B cell and T cell c. Bone marrow for B cell and thymus for T cell d. Secondary lymphoid organs for B cell and thymus for T cell e. Thymus for both B cell and T cell ANSWER: b 33. Which cell type undergoes negative selection of ectopic expressing self-antigen cells in primary lymphoid organs? a. B cells b. MZ B cells c. T cells d. Both B cells and T cells. e. Neither B cells nor T cells.

ANSWER: c 34. V-J rearrangement occurs in a. all B cells. b. all T cells. c. only B-1 B cells.

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Chapter 09 d. only B-2 B cells. e. both B cells and T cells.

ANSWER: e 35. In a succinct manner, can you explain how it was shown that mature, human B cells develop from HSCs in one to two weeks?

ANSWER: This finding is based primarily on cell transfer experiments. Genetically marked donor HSCs are injected into unmarked recipients. Genetically marked mature B cells then appear in the recipients one to two weeks later.

36. Mature B cells, unlike T cells, are not subject to selection processes during their development as they do not contain receptors that can recognize an array of antigens. Is this statement true?

ANSWER: No, it is false. In common with T cells, developing B cells must solve the problem of creating a diverse array of receptors capable of recognizing diverse antigens, including potential self-antigens.

Also in common with T cells, this problem is approached, in part, by selection against self-reactive B cells.

37. As B cells develop in the bone marrow, what three primary factors help immunologists define and discriminate between distinct stages of B-cell development?

ANSWER: The three primary factors, thus far identified by immunologists, are changes in cell surface markers, changes in gene expression, and immunoglobulin gene rearrangements.

38. In examining and characterizing B-cell development, investigators can use knockout genetic approaches to determine the developmental effects of eliminating the expression of targeted transcriptional factors on developmental progress. What is a limitation of the knockout approach?

ANSWER: A limitation of the knockout approach in such developmental studies is that they typically only define the first stage in differentiation at which the gene is required. Conditional knockouts and knock-in approaches can be used to work around this limitation.

39. Transgenic animals that fail to express a BCR during the immature B-cell stages lose the capacity to produce any B cells at all. What does this observation indicate?

ANSWER: The observation indicates that some low level of antigen-independent signaling through the BCR is required for the continued generation and survival of immature B cells during development.

40. BAFF is produced by macrophages and dendritic cells in response to select cytokines, and, therefore, BAFF levels may increase during infections. What is a potential advantage and disadvantage of increasing BAFF levels transiently during infections?

ANSWER: A potential advantage is to sustain the number of B cells and diverse BCRs that could, theoretically, respond to infections. However, a disadvantage is to allow B cells that would typically be removed by selection, due to a potential to respond to self-antigen, to survive in higher levels of BAFF. 41. Recent experiments have focused on identifying differences between signal transduction events leading to B-cell activation versus B-cell anergy. As a new tutor for immunology, how would you summarize these recent experiments to a student client?

ANSWER: Anergic B cells show less antigen-induced phosphorylation of signaling molecules, antigenCopyright Macmillan Learning. Powered by Cognero.

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Chapter 09 stimulated calcium release into the cytoplasm is reduced, and higher levels of BIM. Higher than normal levels of BIM make anergic B cells more prone to apoptosis.

42. Is it true to state that mature B cells, in the form of B-2 cells, are the only mature B cells? Please justify your answer.

ANSWER: Although the majority of mature B cells are B-2 cells, recent evidence had identified additional subpopulations of mature B cells. B-1 and marginal zone (MZ) B-cells also exist, arise from other developmental programs, occupy distinct anatomical locations, and have distinct functions.

43. Compare and contrast the major differences between a B-1a cell and a B-2 cell.

ANSWER: B-1a cells differ from B-2 cells in their surface markers, have a less diverse repertoire of antibody specificities, spontaneously generate natural antibodies, and can generate antibody responses without the T-cell assistance.

44. What are the significant, common trends or features when comparing the overall development of T cells and B cells?

ANSWER: The major common denominators include the commitment to a cell lineage, sequential rearrangement of antigen receptor genes, developmental checkpoints that test for productive rearrangements, and selection for cells with appropriate antigen-binding specificities.

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Chapter 10 1. What event initiates an adaptive immune response? a. The interaction of a B cell with a TH cell b. The expression of cytokines CD4 or CD8 c. The production of MHC class I or II molecules d. The interaction of a naïve T cell with an antigen-presenting cell e. The phagocytosis of a pathogen by a macrophage ANSWER: d 2. Which of the following molecules provide costimulatory signals to naïve T cells? a. CD28 b. ICOS c. CTLA-4 d. PD-1 e. Both CD28 and ICOS are correct.

ANSWER: e 3. For pathogen peptides to be seen as foreign, they must be displayed on a T cell in the context of a(an) a. B-cell marker. b. CD molecule. c. IgM molecule. d. MHC peptide. e. Pattern-recognition receptor molecule.

ANSWER: d 4. CD4+ T cells recognize a. CD8+ markers. b. IgM. c. MHC class I peptides. d. MHC class II peptides. e. both MHC class I and class II peptides.

ANSWER: d 5. CD8+ T cells exposed to MHC class I peptides are a. cytotoxic T cells. b. helper T cells. c. natural killer cells. d. dendritic T cells. e. both cytotoxic T cells and helper T cells.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 10 6. CD4+ T cells become helper T cells in response to a. exposure to antigen. b. exposure to MHC class II peptide. c. exposure to any MHC peptide. d. exposure to MZ B cells. e. exposure to TNF-β ANSWER: b 7. Naïve CD4+ and CD8+ T-cells leave the _____ and enter circulation. a. bone marrow b. liver c. lymph node d. spleen e. thymus ANSWER: e 8. A naïve T-cell refers to a T cell that a. does not express CD4+ or CD8+. b. has not left the bone marrow. c. has not yet encountered an antigen. d. is not mature. e. resides in the thymus.

ANSWER: c 9. Bonds formed between the T cell and a dendritic cell are relatively weak. Which of the following help to strengthen this association so that a T cell can see which antigen is being presented by a dendritic cell? a. CD28/LFA-5 b. CD 28 c. ICAM-1/LFA-1 d. IL-2R e. Pattern-recognition molecules ANSWER: c 10. Which of the following is required for T-cell activation? a. Antigen-specific TCR binding to MHC peptide b. Expression of CD4+ or CD8+ c. Interaction with CD80, CD86, or ICOS-L d. Both antigen-specific TCR binding to MHC peptide and expression of CD4+ or CD8+ are correct. e. Both antigen-specific TCR binding to MHC peptide and Interaction with CD80, CD86, or ICOS-L are correct.

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Chapter 10 ANSWER: e 11. Coreceptor molecules are required by TC and TH cells so that the TCR can stably bind to the MHC peptide presenting the antigen. All of the following are coreceptor molecules common to both TC and TH cells and their respective antigen-presenting cells EXCEPT a. CD2/LFA-3. b. CD28/B7. c. CD45R/CD22. d. LFA-1/ICAM-1. e. All of the answers are correct.

ANSWER: b 12. CTLA-4 is a costimulatory receptor on T cells that belongs to the same family as the CD28 costimulatory receptor. However, CTLA-4 is antagonistic to CD28. Which of the following could be a functional advantage of CTLA-4 expression within the immune response? a. CTLA-4 competes with CD28 for ligand binding so that, if CD28 binds to its ligand, the response will be magnified. b. CTLA-4 is often given to immunosuppressed individuals to trigger an immune response. c. CTLA-4 limits the immune response of TC and TH cells after an infection has been cleared. d. CTLA-4 limits TC activity in healthy individuals during a viral infection. e. CTLA-4 reduces the lag time between antigen presentation to a TH cell and B-cell activation.

ANSWER: c 13. PD-1 is a negative costimulatory signal expressed by tumor cells. What advantage would the expression of PD-1 have in a tumor cell avoiding the immune response? a. Tumor cells can avoid being killed by activated TC cells. b. Tumor cells can avoid apoptosis triggered by TH cells. c. Tumor cells avoid phagocytosis by dendritic cells. d. Tumor cells are stimulated to reproduce faster than tumor cells that do not express PD-1. e. None. Tumor cells are recognized as self and, therefore, do not pose a health threat.

ANSWER: a 14. T cells are frequently at fault for causing damage in autoimmune disorders and in transplant rejection. As an immunologist, your dream is to discover a method for decreasing T-cell response to self-antigens. Which of the following would be the BEST target for your research? a. Activated B cells because they make T-cell receptor molecules b. Antibody mediated apoptosis of dendritic cells c. CTLA-4 antagonists that block the action of CTLA-4 d. Ligands that block the binding of one costimulatory molecule e. Radiation therapy directed at all T cells Copyright Macmillan Learning. Powered by Cognero.

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Chapter 10 ANSWER: d 15. T-cell activation requires antigen being displayed in the context of an APC and interaction between costimulatory molecules on the APC and the T cell. In addition to these two signals, T-cell activity is often influenced by cytokines. Which of the following is an example of how cytokines can influence T-cell activity in the presence of MHC presentation and costimulatory ligand interaction? a. CD28 causes memory NK cells to be produced. b. CD8 triggers apoptosis in T cells that recognize self-antigens. c. IL-2 triggers T-cell proliferation. d. Opsonins recruit eosinophils to present carbohydrate antibodies to naïve TC cells. e. TNF-α increases the production of IgM by activated T cells.

ANSWER: c 16. Which type of professional antigen-presenting cells is a naïve T cell MOST likely to encounter? a. B cell b. Dendritic cell c. Macrophage d. Either B cell or dendritic cell e. Either dendritic cell or macrophage ANSWER: d 17. TSST-1 is a protein produced by some species of bacteria that acts as a superantigen. What ligand does TSST-1 bind? a. T-cell receptor b. MHC class I c. MHC class II d. Both T-cell receptor and MHC class I e. Both T-cell receptor and MHC class II ANSWER: e 18. With respect to T-cell activation, effector molecules trigger all of the following functions EXCEPT a. cell-cycle entry. b. cell division to produce additional T cells. c. cell differentiation into various types of T cells. d. cell stimulation of B cells. e. cell survival.

ANSWER: d 19. Which helper T-cell subset is MOST likely to be preferentially generated in response to a virus? a. TH17 b. TH1 Copyright Macmillan Learning. Powered by Cognero.

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Chapter 10 c. TREG d. TH22 e. None of the answers are correct.

ANSWER: d 20. Which type of T cell directs and regulates B-cell activity and differentiation? a. Memory T b. NK c. TC d. TH1 e. TH2 ANSWER: e 21. Which type of T helper cell regulates allergic reactions and protects against extracellular pathogens? a. TH1 b. TH2 c. TH17 d. TREG e. TFH ANSWER: b 22. Which type of T helper cell inhibits inflammation? a. TH1 b. TH2 c. TH17 d. TREG e. TFH ANSWER: d 23. Which of the following are characteristics of naïve CD4+ and CD8+ T cells as they leave the thymus and enter the circulation (prior to antigen stimulation)? a. Condensed chromatin b. Exhibit little transcriptional activity c. High mobility d. Very little cytoplasm relative to nucleus e. All of the answers are correct.

ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 10 24. Costimulatory signals are required to achieve optimal T-cell activation (via exposure to antigen) and are considered part of which of the three steps essential to this process? a. Signal 1 b. Signal 2 c. Signal 3 d. Both signal 1 and signal 2 e. Both signal 2 and signal 3 ANSWER: b 25. Which cells are capable of providing both signal 1 and signal 2 to a naïve T cell? a. Dendritic cell b. Macrophage c. B cells d. All of the answers are correct. e. None of the answers are correct.

ANSWER: e 26. Cross-regulation of various members of a subset of T cells is frequently observed with a. all TC cells. b. all TH cells. c. only TC1 subset. d. only T1 subset. e. only TREG subset.

ANSWER: b 27. All of the following are functions of TH1 cells EXCEPT: a. contributes to autoimmunity. b. enhances APC activity. c. enhances TC activity. d. involved with delayed type hypersensitivity reactions. e. protects against intracellular pathogens.

ANSWER: a 28. TH17 cells are involved with all of the following EXCEPT a. autoimmunity. b. delayed-type hypersensitivity. c. inflammatory response. d. protection against fungal infections. e. protection against bacterial infections.

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Chapter 10 ANSWER: b 29. Follicular helper T cells are a recent discovery in the helper T-cell lineage. What is the primary role of TFH cells? a. To help B-cell development in germinal centers b. To regulate TREG cell activity c. To stimulate dendritic cell production d. To suppress B-cell activation after pathogen has been cleared e. To suppress TC cells after an infection has been cleared ANSWER: a 30. Mycobacterium leprae, the causative agent of leprosy in humans, is an intracellular pathogen that resides in the phagosome of macrophages. Leprosy presents in two main clinical manifestations. Tuberculoid leprosy results in the formation of granulomas and a cell-mediated immune response, whereas lepromatous leprosy results in the production of high levels of IgG (hypergammaglobulinemia). If TH2 is produced in high levels during an M. leprae infection, which type of leprosy would result? a. Lepromatous leprosy b. Tuberculoid leprosy c. Either lepromatous leprosy or tuberculoid leprosy d. Neither; leprosy depends on the expression of TREG cells e. Cannot determine; insufficient clinical evidence to support either outcome ANSWER: a 31. Which of the following is MOST likely to stimulate a memory T cell? a. B cell b. Dendritic cell c. Memory cell d. All of the answers are equally likely to stimulate a memory T cell. e. None of the answers will stimulate a memory T cell.

ANSWER: d 32. What is the function of a memory T cell? a. To activate TC and TH cells during an active primary infection b. To avoid autoimmune disorders by producing memory for self-antigens during T-cell development c. To maintain an active T-cell response (TC or TH) after an infection is cleared d. To provide an almost immediate response upon subsequent exposure to a specific pathogen e. To suppress TC activity after a pathogen is cleared ANSWER: d 33. Which cell type can activate a memory T cell?

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Chapter 10 a. B cell b. Dendritic cell c. Macrophage d. All of the answers are correct. e. None of the answers is correct.

ANSWER: d 34. Memory T cells, effector T cells, and naïve T cells share several characteristics. Which of the following descriptions could ONLY be said of memory T cells? a. Memory T cells are activated by any APC. b. Memory T cells are only found in one location and do not circulate. c. Memory T cells express CD44, CD62L, and CCR7. d. Memory T cells recognize MHC class I or class II peptides displaying antigen molecules. e. Memory T cells depend upon costimulatory signals from CD2/ LFA-3, CD45R/ CD22, and LFA-1/ ICAM-2.

ANSWER: a 35. Naïve T cells are highly mobile and continuously circulate our blood, lymph, and secondary organs while scanning for stimulating antigens. Speculate the rationale for the large-scale mobility phenotype.

ANSWER: Because only approx. 1 in 105 naïve T cells is likely to be specific for a given antigen, large-scale mobility and the associated circulation patterns increases the chances that a particular T cell will find its complementary antigen.

36. You have just been infected with an intracellular bacterial pathogen (such as Listeria monocytogenes). In mounting an immune response against the pathogen, which subset of CD4+ T cells will be produced preferentially? What polarizing cytokine will favor the production of this subset? What effector cytokine will be produced by this subset?

ANSWER: In this scenario, TFH cells will be part of a response against intracellular bacterial pathogens.

Increased production of TGF

will favor the production of this CD4+ T-cell subset. IL-21 is an

effector cytokine produced by this type of CD4+ T cell.

37. True or False? The sole purpose of CD4 and CD8 molecules is to provide immunologists a means of differentiating between T-cell populations. Explain.

ANSWER: False, they have defined biological functions. First, during T-cell activation, they help stabilize the interaction between TCRs and antigen-loaded MHC. Second, the cytoplasmic tails of CD4 and CD8 help trigger the signal transduction events needed to fully activate the T cell.

38. Compare costimulatory and co-inhibitory molecules. What are the two major roles of co-inhibitory molecules?

ANSWER: The two major roles are helping to maintain peripheral T-cell tolerance and reducing inflammation both after an infection and during ongoing chronic infection.

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Chapter 10 39. CTLA-4 is not constantly expressed on naïve T cells. Is this logical? Explain.

ANSWER: If you consider the inhibitory function of CTLA-4, this observation makes sense. If expressed constantly, this might lead to a scenario of not being able to effectively activate T cells via antigen presentation. CTLA-4 expression is induced after T-cell activation, in part it is believed, to dampen the proliferative effects of TCR and CD28 engagement.

40. Based on your knowledge of CTLA-4 and PD-1, could blocking the activity of these molecules have any potential uses in clinical scenarios? Explain.

ANSWER: Yes. Inhibition of their inhibitory effects on T cells has promise as an immunotherapy for certain cancers. In these cases, molecules that block the interactions between CTLA-4, PD-1, and their ligands have been shown to enhance T-cell activity to select tumors in part, by keeping those cells active.

41. Endogenous and exogenous superantigens can directly activate the host T-cell response. Why might a pathogen purposely invite a host T-cell response?

ANSWER: Although not definitive, there is some evidence that superantigen-based T-cell activation hampers the ability of the host to mount a coordinated antigen-specific response. In addition, it is thought that large-scale, nonspecific proliferation harms the microenvironments required to start a normal immune response. Others argue that superantigens may induce T-cell tolerance to the pathogen.

42. A family member has been infected by a protozoan pathogen. Using correct terminology, summarize the subset of T cells that is likely to be activated by this type of pathogen?

ANSWER: Overall, what is called a type 2 response will occur. Type 2 responses and CD4+ T-cell subset differentiation is geared toward the clearance of protozoans, worms, and allergens. The activated T cells will include TH2 and TH9 helper subsets, which will work with other populations of immune cells (e.g., ILC2s) to generate IgE and eosinophilic responses.

43. How can advances in understanding how helper T-cell differentiation is regulated be applied to the use of vaccine adjuvants? Explain.

ANSWER: Investigators in this field anticipate that one day it will be possible to shape the effector response to vaccine antigens by varying the adjuvant(s) included in the vaccine preparation delivered to patients.

Part of shaping the effector response will include considering factors that influence which helper Tcell subsets are produced in response to the vaccine.

44. Consider memory T-cell subsets. How do the subsets thus far identified differ from one another?

ANSWER: In general, memory T-cell subsets differ in their location, circulation patterns, and functionality.

Central memory cells and memory stem cells are found in secondary immune organs and have not been committed to any specific effector lineage. In contrast, effector and tissue resident memory cells circulate among peripheral tissues (e.g., skin, liver, and lungs) and are committed to their original effector lineage upon reactivation. Both subsets respond to antigens more quickly as compared to nonmemory T cells.

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Chapter 11 1. With regard to the type of B-cell response generated, protein antigens typically provoke which of the following responses? a. TI-1 b. TI-2 c. TD d. All of the answers are correct. e. None of the answers are correct.

ANSWER: c 2. After encountering antigen, B cells express all of the following EXCEPT a. CCR7. b. CCL19. c. CXCR5. d. EBI2. e. All of the options are expressed.

ANSWER: b 3. The B-cell coreceptor CD21 associates with which host molecule? a. C3d b. CD19 c. The BCR d. Fc receptors e. None of the answers are correct.

ANSWER: a 4. Activated TH cells signal to B cells to initiate their activation program via which of the following? a. CD40L on the T cell to CD40 on the B cell b. CD40 on the T cell to CD40L on the B cell c. FasL on the T cell to Fas on the B cell d. Fas on the T cell to FasL on the B cell e. Notch ligand on the B cell to Notch1 on the T cell ANSWER: a 5. B cells follow which of the following chemotactic signals to migrate to the cortical regions of secondary lymphoid tissue? a. CCL19 b. CXCL13 c. CCL21 d. All of the answers are correct. e. None of the answers are correct.

ANSWER: b Copyright Macmillan Learning. Powered by Cognero.

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Chapter 11 6. Which of the following constitutes the critical survival cytokine for B cells in the secondary lymphoid tissue cortex? a. BAFF b. IL-7 c. IL-2 d. IL-6 e. None of the answers are correct.

ANSWER: a 7. The first immunoglobulin isotype produced during the course of a primary immune response contains which of the following heavy chains? a. γ b. κ c. δ d. μ e. None of the answers are correct.

ANSWER: d 8. Which of the following do you expect would be actively functioning in a B cell that had migrated to a germinal center? a. RAG1 b. Artemis c. AID d. Ku70 e. None of the answers are correct.

ANSWER: c 9. AID converts cytosine into which of the following bases? a. Adenine b. Thymine c. Deoxyuridine d. Guanine e. None of the answers are correct.

ANSWER: c 10. Which of the following mechanisms of mutagenesis via AID activity is possible? a. The lesion is not repaired prior to replication, resulting in a CG TA transition. b. Base excision repair, followed by error-prone DNA polymerase fill-in of the gap created. c. Mismatch repair, followed by error-prone DNA polymerase fill-in of the gap created. d. All of the options are possible.

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Chapter 11 e. None of the options are possible.

ANSWER: d 11. SHM and CSR are both dependent on the activity of which of the following enzymes? a. AID b. RAG-1/2 c. DNA uridine glycosylase d. Both AID and RAG-1/2 are required for SHM and CSR. e. Both AID and DNA uridine glycosylase are required for SHM and CSR. ANSWER: e 12. A knockout of which of the following genes results in the inability to form germinal centers? a. Blimp-1 b. IRF-4 c. Pax-5 d. Bcl-6 e. NF-κB ANSWER: d 13. Which of the following is considered to be the "master regulator" of terminal plasma cell differentiation? a. Blimp-1 b. IRF-4 c. Pax-5 d. Bcl-6 e. NF-κB ANSWER: a 14. Blimp-1 represses the expression of which of the following transcription factors? a. Blimp-1 b. IRF-4 c. Pax-5 d. Bcl-6 e. NF-κB ANSWER: d 15. Which of the following factors is thought to induce expression of Blimp-1? a. IRF-4 b. Pax-5 c. Bcl-6 d. NF-κB e. None of the answers are correct.

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Chapter 11 ANSWER: a 16. Which of the following is a way in which follicular B cells can acquire antigen entering a lymph node via an afferent lymphatic? a. Direct capture of whole antigen that directly enters the follicle by passing between subcapsular sinus macrophages. b. Transfer of complement-bound antigen from surface receptors on subcapsular sinus macrophages to B cells. c. Passage of antigen from subcapsular sinus macrophages to follicular dendritic cells to B cells. d. Passage of antigen from DCs that reside near HEVs to B cells. e. All of the answers are possible.

ANSWER: e 17. Which of the following does NOT occur shortly following oligomerization of the BCR upon antigen binding? a. Movement of the BCR complex into areas of the membrane called "lipid rafts". b. Positioning of Ig α and Ig β to allow for phosphorylation of their ITAM motifs. c. Positioning of CD3 to allow for phosphorylation of its ITAM motifs. d. Formation of clathrin-coated pits around BCR complex. e. All of the answers occur.

ANSWER: c 18. After endocytosing its BCR cognate antigen, B cells a. upregulate CD80 b. upregulate CD86 c. upregulate CD40 d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 19. Which of the following is or appears to be controlled by Blimp-1 during plasma cell differentiation? a. Exit from the cell cycle. b. Transitioning from membrane-bound to secreted IgM. c. Loss of MHC class II from the cell surface. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 20. Which factors on the surfaces of B cells and T cells, through their interaction, are required to allow germinal center formation to occur? a. CD40 and CD40L. b. Fas and FasL. Copyright Macmillan Learning. Powered by Cognero.

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Chapter 11 c. CD28 and CD80/86. d. TCR and MHC class II. e. None of the answers are correct.

ANSWER: a 21. The follicular mantle zone consists primarily of which of the following? a. Follicular dendritic cells. b. Naïve IgD+ B cells that are not participating in the response against the antigen. c. TFH cells. d. Plasmacytoid dendritic cells. e. None of the answers are correct.

ANSWER: b 22. Which cells that are found within GC light zones are generally NOT found in the GC dark zones? a. Differentiating B cells. b. TFH cells. c. FDCs. d. Naïve IgD+ B cells that are not participating in the response to the antigen. e. None of the answers is correct.

ANSWER: c 23. The function of SHM is BEST described by which of the following statements? a. Increasing junctional diversity in IgH and IgL V regions. b. Increasing the affinity of immunoglobulins for their antigen. c. Irreversibly changing the isotype of immunoglobulin. d. Promoting alternative splicing of an immunoglobulin heavy chain transcript to produce different isotypes on the B-cell surface. e. None of the answers are correct.

ANSWER: b 24. To which compartment in the body can long-lived plasma cells potentially be retained for the lifetime of the individual? a. Medullary cords of the lymph node. b. Germinal center. c. Bone marrow. d. Red pulp of spleen. e. None of the answers are correct.

ANSWER: c 25. Post-germinal-center plasma cells that take up residence in the bone marrow can be found in close proximity Copyright Macmillan Learning. Powered by Cognero.

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Chapter 11 to which other type of immune cells that provide survival factors to the plasma cells? a. Macrophages b. DCs c. Monocytes d. Eosinophils e. All of the answers are correct.

ANSWER: d 26. Which immunoglobulin isotype CANNOT be produced by memory B cells? a. IgM b. IgG1 c. IgA2 d. IgE e. All of the answers can be produced by memory B cells.

ANSWER: a 27. Which of the following antigen types could be characterized as TI antigens? a. Soluble proteins b. Bacterial cell wall components c. Capsular polysaccharides d. Both bacterial cell wall components and soluble proteins e. Both bacterial cell wall components and capsular polysaccharides ANSWER: e 28. Which of the following is NOT true of T-independent antigens? a. They are rarely proteins. b. They may contain PAMPs. c. They may be heavily polymerized. d. They are rarely carbohydrates. e. All of the answers are true.

ANSWER: d 29. Which of the following statements are TRUE about

T cells and B-1 B cells?

a. Both can self-renew in the periphery and do not need to be replenished from primary lymphoid tissues. b. Both have identical lymphocyte receptors to one another. c. Both respond to their antigens via high-affinity receptor responses. d. All of the answers are true. e. None of the answers are true.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 11 30. Which of the following statements is TRUE about B-1 B cells and MZB cells? a. Both are self-renewing in the periphery, not requiring replacement from bone marrow. b. Both can respond to TI antigen. c. Both do not undergo SHM. d. Both are self-renewing in the periphery, not requiring replacement from bone marrow, and can respond to TI antigen. e. None of the answers are true.

ANSWER: d 31. What do SHP-1 and IL-10 have in common with regard to B-cell function? a. Both exert negative regulation of B-cell activity. b. Both exert positive regulation of B-cell activity. c. Both are B-cell survival factors. d. Both induce B-cell proliferation. e. None of the answers are correct.

ANSWER: a 32. Which of the following is a negative regulator of B cells? a. CD21 b. CD22 c. CD80 d. CD86 e. All of the answers are positive regulators.

ANSWER: b 33. What molecular events occur when a B cell encounters its cognate antigen for the first time? Describe the events occurring both inside and outside the cell membrane.

ANSWER: Outside of the cell, BCRs briefly spread over the surface of the antigen-presenting membrane and then contract, resulting in B-cell receptor clustering. This clustering leads to the formation of an immunological synapse between the B cell and its antigen - a cSMAC, which is surrounded by the pSMAC. This is followed by phosphorylation of tyrosine residues in the ITAMs of Ig α and Ig β by Src-family kinases inside the cell. What happens after that depends on the strength and duration of receptor binding.

34. How are Bcl-6 and BLIMP-1 related to B-cell fates? Which protein leads to which type of cell?

ANSWER: Bcl-6 and BLIMP-1 are antagonistic and lead to separate fates - high levels of Bcl-6 cause activated cells to migrate to germinal centers, whereas BLIMP-1 expression leads to high levels of antibody secretion.

35. What special role do follicular dendritic cells play in germinal centers, and how are they adapted for this role?

ANSWER: FDCs are reservoirs of antigen for B-cell activation. Specifically, due to high levels of Fc and complement receptors, they can retain antigens for long periods of time and provide antigens during Copyright Macmillan Learning. Powered by Cognero.

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Chapter 11 mutation, selection, and development.

36. What cells in our body typically have the HIGHEST rate of mutation? What is occurring in these cells?

Explain.

ANSWER: B cells, specifically in lymph node germinal centers, have a mutation rate of almost 1/1000 base pairs. These mutations occur specifically in the variable regions of antibody genes; these changes are then tested by our bodies to see if the new antibodies bind with a higher affinity to their antigen.

37. What is AID, what does it do, and what two B cell processes cannot happen without it?

ANSWER: AID is activation-induced cytidine deaminase. This enzyme acts on single-stranded DNA, where it deaminates deoxycytidine, leaving deoxyuridine. Without this enzyme, the processes of class-switch recombination (CSR) and somatic hypermutation (SHM) cannot take place.

38. Why is it advantageous for most plasma cells to die by apoptosis at the end of an infection?

ANSWER: There are many reasons. First, it clears physical space in lymph nodes for new B-cell clones.

Second, plasma cell division and antibody secretion waste energy if there is not an active infection.

Finally, it helps prevent immune mediated damage from inflammation and antigen-antibody complex hypersensitivity.

39. What is the MOST common type of activated B cell? What are three other types and what kind of antigens do they typically recognize?

ANSWER: Most of our circulating B cells are the B-2 type and need T-cell help for full activation. Other kinds of B-cell populations are B-1a, B-1b, and marginal zone B cells. These three have some characteristics of innate immune cells as well as adaptive immunity, and all tend to respond to Tindependent antigens.

40. What type of macromolecule is BEST able to produce a T-independent B-cell response? What are some common characteristics of TI antigens?

ANSWER: The majority of TI antigens are carbohydrate in nature; proteins usually require T-cell help. TI-1 antigens such as LPS stimulate innate immune receptors, whereas TI-2 antigens are heavily polymerized and can activate B cells by engaging many BCRs at once.

41. What are three different ways memory B cells can be regulated? Why is regulation of B-cell responses important?

ANSWER: Any three of these: Activation of CD22; FcγRIIb; CD5; and IL-10 from B-10 B cells. These mechanisms exist to prevent overactivation of B cells and reduce inflammatory responses.

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Chapter 12 1. What is the effector molecule of humoral immunity? a. Antibodies b. Cytotoxic T cells c. Dendritic cells d. Helper T cells e. Plasma cells ANSWER: a 2. The role of cell-mediated immunity is a. to find cells infected with intracellular pathogens. b. to find and eliminate cells infected with intracellular pathogens. c. to present antigens to TH cells. d. to produce memory B cells. e. to secrete antibodies.

ANSWER: b 3. Cell-mediated immunity includes a. antibodies. b. plasma cells. c. TC cells. d. both antibodies and TC cells. e. both plasma cells and TC cells.

ANSWER: e 4. Examples of cytotoxic effector cells include all of the following EXCEPT a. basophils. b. eosinophils. c. macrophages. d. NK cells. e. TC cells.

ANSWER: a 5. NK T cells (NKTs) express a. CD4. b. CD8. c. CD12. d. CD33. e. both CD4 and CD8.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 6. _____ describes the action of antibodies whereby antibodies bind to a pathogen and prevent the pathogen from interacting with cell receptors. a. Antibody-dependent cell-mediated cytotoxicity b. Antigen presentation c. Complement fixation d. Neutralization e. Opsonization ANSWER: d 7. _____ describes the recruitment of phagocytic cells by the Fab portion of an antibody. a. Antibody-dependent cell-mediated cytotoxicity b. Antigen presentation c. Complement fixation d. Neutralization e. Opsonization ANSWER: e 8. Lysis of a pathogen by MAC formation is an example of a. antibody-dependent cell-mediated cytotoxicity. b. antigen presentation. c. complement fixation. d. neutralization. e. opsonization.

ANSWER: c 9. Virally infected host cells are tagged with antigen-antibody complexes. These complexes recruit NK cells that trigger apoptosis in the infected host cell. This is an example of a. antibody-dependent cell-mediated cytotoxicity. b. antigen presentation. c. complement fixation. d. neutralization. e. opsonization.

ANSWER: a 10. Which class of antibodies is the FIRST to be produced during the primary immune response? a. IgA b. IgD c. IgE d. IgG e. IgM ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 11. IgA is typically found as a dimer in high levels of secretions such as milk, tears, and saliva. What is the primary function of IgA in secretions? a. To alert plasma cells of an invading pathogen b. To neutralize toxins and pathogens c. To secrete nonspecific enzymes such as lysozyme d. To stimulate the growth of normal microbiota (normal flora) species e. To trigger apoptosis in infected mucosal cells ANSWER: b 12. Which class of antibodies is good at fixing complement? a. IgA b. IgD c. IgE d. IgG e. IgM ANSWER: d 13. Monoclonal antibodies may be used to treat cancer in all of the following ways EXCEPT a. directly binding of monoclonal antibodies may trigger apoptosis or antibody-dependent cell-mediated cytotoxicity. b. monoclonal antibodies compete with growth factors to bind receptors on tumor cells. c. monoclonal antibodies may prevent the formation of new blood vessels to tumors. d. monoclonal antibodies may recruit TH cells to a developing tumor. e. monoclonal antibodies may serve as a vector to target tumor cells for toxin mediated therapy.

ANSWER: d 14. Fc-receptor molecules tend to have short cytoplasmic tails. How does this influence signaling events within the Fc-receptor cell? a. The Fc-receptor is adjacent to secondary messengers (e.g., MAP kinase) that translocate into the nucleus to affect transcription. b. The Fc-receptor is dependent upon a coreceptor (e.g., ITAM or ITIM) that will trigger signaling events within the cell. c. The Fc-receptor is not directly involved in a signaling event. d. The Fc-receptor serves only to enhance or dampen a signaling event. e. The Fc-receptor translocates into the cytoplasm where it will bind to secondary messengers.

ANSWER: b 15. Which Fc-receptor is responsible for triggering the release of histamine, proteases, and other inflammatory signals from IgE? a. Fc α receptor b. Fc ε receptor Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 c. Fc γ receptor d. Neonatal Fc-receptor e. Polymeric immunoglobulin receptor (pIgR) ANSWER: b 16. Why is IgM the class of antibody able to form large polymers? a. IgM is the strongest binding antibody class. b. IgM is considered the most important type of antibody. c. IgM has low affinity and benefits from having a large number of binding sites. d. IgM is used exclusively against parasites. e. IgM requires form polymers traveling through the body.

ANSWER: c 17. Which type of antibody is MOST effective against the largest variety of pathogens? a. IgM b. IgG c. IgA d. IgE e. IgD ANSWER: b 18. Cell-mediated effector cells include a. CTLs and NKT cells. b. Plasma cells and dendritic cells. c. TC cells and NK cells. d. TC cells, NKT cells, and NK cells. e. TC cells and memory TH cells.

ANSWER: d 19. The Fas ligand (FasL) represents a key signaling pathway among cell-mediated effector cells. What is the function of the Fas-FasL signaling pathway? a. Activation of the Fas-FasL signaling pathway triggers apoptosis. b. Binding of Fas to FasL induces phagocytosis by dendritic cells. c. Expression of Fas occurs only on naïve B cells. d. Fas-FasL binding recruits TH cells. e. TNF-α is released by NKT cells triggering histamine release in infected target cells.

ANSWER: a 20. At what location are naïve TC cells activated to become CTLs? a. Blood stream Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 b. Bone marrow c. Lymph node d. Site of infection e. Thymus ANSWER: c 21. CTLs mediate a powerful and lethal immune response to infected host cells. Which of the following steps is NOT involved with CTL activation and function? a. Antigen presented with MHC class I is recognized by CTLs. b. APC presentation occurs to both TC and TH cells. c. Fas-FasL signaling pathway is activated, triggering apoptosis. d. Histamine is released from cytoplasmic granules, recruiting macrophages to the site of infection. e. Perforin and granzymes are released, triggering apoptosis of infected cell.

ANSWER: d 22. Precursor CTLs are characterized by each of the following EXCEPT a. they do not divide. b. they do not express high affinity for CD25. c. they express CD4. d. they lack cytotoxic activity. e. they produce low amounts of IL-2.

ANSWER: c 23. Which of the following statements about NK T cells is TRUE? a. Activated NKT cells can act as both a TH and a TC cell. b. CD4 is expressed by all NKT cells. c. NKT cells rely on p53 expression to cause apoptosis in an infected host cell. d. NKT cells express most of the T cell lineage characteristics. e. The TCR on NKT cells recognizes antigens presented with MHC class I and class II molecules.

ANSWER: a 24. Licensing on an NK cells refers to a. activation of an NK cell by MHC class II displayed peptide antigen. b. expression of IFN-γ and TNF-α by NK cells. c. production of memory cells. d. suppressing the activity of a self-recognizing NK cell. e. testing an NK cell to ensure that it will not target healthy host cells.

ANSWER: e 25. In a recent experiment, NK cells were collect from an MCMV infected mouse and placed into a healthy mouse. Upon exposure to the MCMV virus, the healthy mouse quickly mounted an immune response. How Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 could these results BEST be interpreted? a. MCMV virus failed to infect the healthy mouse. b. NK cells show memory and are quickly able to recognize MCMV infected cells in the healthy mouse. c. Plasma cells were transferred along with NK cells and produced antibodies that target MCMV virus particles. d. TC cells were transferred along with the NK cells and have been targeting MCMV virus particles. e. TH cells were transferred to the healthy mouse instead of NK cells and have stimulated B cells to activate.

ANSWER: b 26. How many subpopulations of TC cells are there? a. One: TC b. Two: TC1 and TC2 c. Three: TC1, TC2, and TC3 d. Five: TCA, TCD, TCE, TCG, and TCM e. It varies depending on the type of infection that is found.

ANSWER: b 27. MHC tetramers a. are a novel way to detect and follow specific T-cell populations within an organism. b. are found only in mice though a parallel system in humans is under current investigation. c. describe high-functioning TC cells found in autoimmune response. d. represent novel immunotherapy for patients with Crohn's disease. e. use fluorescent staining to bind to MHC class I molecules on dendritic cells.

ANSWER: a 28. A new pathogenic bacterium has been discovered - it is an intracellular parasite and can prevent MHC molecules from being properly made in infected cells. Which of the following cell types would be MOST effective at fighting this pathogen? a. CTL b. NK cell c. B cell d. Dendritic cell e. Basophil ANSWER: b 29. Which of the following effector function components would have the GREATEST impact on a patient's cells if the cells were not functioning properly during a viral infection? a. Perforin Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 b. Granzyme B c. Fas d. MHC I e. FcR ANSWER: d 30. Which molecule can induce the GREATEST variety of effector functions? a. MHC I b. MHC II c. TCR d. Bound antibody e. NCRs ANSWER: d 31. Which two classes of antibodies are BEST at agglutinating pathogens? Explain.

ANSWER: IgM and IgA; both can form polymers, which increases the total number of antigen binding sites.

32. Compared to other effector functions, why is there such diversity in antibody FcR interactions?

ANSWER: Antibodies are unique among effector functions in that different antibody classes carry information about the nature of the pathogen to other cell types. Therefore, it makes sense that different effector cells would have their own subsets of FcR molecules to respond appropriately to different kinds of pathogens. As we have seen, the best and most appropriate responses are pathogen specific - for example, bound IgE will interact with FcεRI to produce antiparasitic responses, whereas FcγRI is used to facilitate phagocytosis after opsonization by IgG3.

33. Why were early monoclonal antibodies poor therapeutics? Support your answer by providing two ways that these antibodies were modified to make them more suitable for human use.

ANSWER: The first monoclonal antibodies were derived from murine B cells, which are immunogenic in humans. Current versions of these antibodies are "humanized" by replacing either their Fc region or everything except the antigen-binding site, or they are developed by screening phage display or yeast libraries for useful human antibodies.

34. What three steps must occur before a CTL is ready to kill target cells? Explain why these steps must occur.

ANSWER: To become activated, a CTL precursor must receive the following signals: high affinity binding to an antigen/MHC complex on a licensed APC by the T cell's TCR; a costimulatory signal from the same APC; and binding of IL-2 to its receptor on the CTL. All of this is necessary due to the destructive power of CTLs and the damage to the host that could occur if they were too easily activated.

35. What are the two means by which activated CTLs kill target cells? Explain the significance of both events.

ANSWER: CTLs can kill target cells by either activating a signaling pathway in the target cell or by directly releasing proapoptotic molecules. First, many CTLs release a combination of two molecules, perforin and granzyme. Perforin is a pore-forming molecule that is similar to the complement component C9. It polymerizes in endosomes and allows granzyme molecules to enter the cell. The Copyright Macmillan Learning. Powered by Cognero.

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Chapter 12 other method CTLs use is activation of the Fas molecule on a target cell with its ligand FasL on activated CTLs. Both of these actions activate caspases inside the target cell, leading to apoptosis.

36. What two properties of NK cells make them innate-like in their function? What two properties are more closely aligned with the adaptive immune system? Explain.

ANSWER: NK cells do not undergo rearrangement of receptor genes in development. They are also immediately able to target and signal cells to undergo apoptosis without activation by other cells. On the other hand, NK cells interact with MHC molecules on target cells, which are part of the adaptive immune response of T cells. Recently, it has also become known that NK cells are capable of forming "memory" cells.

37. Why are NK cells such an important component of the immune system?

ANSWER: NK cells serve as a counter to CTLs in a host. Although both cells are capable of direct cell killing, CTLs are not present in high numbers until 7-10 days after the start of an infection and are completely dependent on MHC/TCR interactions. In contrast, NK cells do not depend on as many signals to become activated, do not undergo genetic rearrangement in development, and use MHC as an inhibitory molecule instead of an activating one. They are also capable of killing cells via ADCC, which means using antibodies to recognize antigens outside of MHC complexes.

38. Identify the components of an NKT cell that are NK-like and those that are T-cell-like. Which components are like neither? Explain.

ANSWER: NKT cells display a TCR, induce apoptosis via Fas/FasL interactions, and have helper and cytotoxic populations like T cells. However, their surface proteins have more in common with NK cells, and they do not interact with either MHC I or MHC II. What makes NKT cells unique is their ability to interact with CD1 and recognize foreign lipid molecules.

39. Compare and contrast the ways in which antibodies and T cells interact with their cognate antigen. Explain how this benefits the host.

ANSWER: Both antibodies and T cells use genetic rearrangement to produce molecules that can recognize and bind antigen - small components of nonhost molecules. The variable region of an antibody binds directly to antigens in the environment, whereas the TCR is dependent on antigen presentation via MHC proteins. T cells also need helper proteins (either CD8 or CD4) to facilitate this interaction.

Antibodies can bind to many types of molecules, such as proteins and carbohydrates, and these can be either denatured or in a native confirmation. T cells can only recognize short, digest peptide fragments. This is advantageous for the host because it allows the immune system to monitor the extracellular environment with antibodies and inside its own cells with T cells.

40. The use of CAR therapy has been a major breakthrough in cancer treatment. CAR stands for "Chimeric Antigen Receptor," and it is a combination of the antigen-binding domain of an antibody and the intracellular domain of the TCR. What advantage might this construct have over endogenous cellular machinery?

ANSWER: A CAR molecule combines the versatility of antibodies with the direct cell-killing power of T cells.

CAR cells are able to recognize antigens without processing and presentation on MHC molecules.

Once the CAR binds its cognate antigen, it is able to induce apoptosis of the cancer cell directly using existing CTL pathways.

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Chapter 13 1. Which of the following is NOT a normal part of commensal microbiota? a. Bacteria b. Viruses c. Nematodes d. Fungi e. Protozoa ANSWER: e 2. Which part of our body is the BEST example of a barrier organ? a. Skin b. Liver c. Kidneys d. Lungs e. Spleen ANSWER: a 3. What mechanism is NOT used by epithelial cells to prevent the invasion of barrier tissues? a. Secretion of antimicrobial peptides. b. Phagocytosis of microbes. c. Production of mucus layer. d. Use of beating cilia. e. All of the answers are correct.

ANSWER: b 4. Peyer's patches and isolated lymphoid follicles are components of a. mucus. b. GALT. c. germinal centers. d. stomach lining. e. bronchial passages.

ANSWER: b 5. Which of the following is a tolerogenic cytokine? a. TGF-β b. IL-1 c. IL-10 d. Both TGF-β and IL-1 e. Both TGF-β and IL-10 ANSWER: e 6. MOST immune cells in the gut can be found in the Copyright Macmillan Learning. Powered by Cognero.

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Chapter 13 a. mucosa. b. submucosa. c. lamina propria. d. villi. e. crypts.

ANSWER: c 7. What is the meaning of the gut epithelial cells being "polarized"? a. They have distinct apical and basolateral sides. b. They have many tight junctions. c. They store positive and negative ions in vesicles. d. They contain deposits of metals. e. They diffract wavelengths of light.

ANSWER: a 8. Which of the following statements is TRUE regarding microfold (M) cells and goblet cells? a. Only M cells can transport antigens. b. Only goblet cells can transport antigens. c. Both M cells and goblet cells move antigens by transcytosis. d. Neither M cells nor goblet cells move antigens by transcytosis. e. None of the answers are correct.

ANSWER: c 9. What would you expect to observe in a suburban Philadelphia patient who was unable to make IgE antibodies? a. Recurrent norovirus infections b. Problems with chronic gut inflammation c. A lack of allergies and asthma d. Rampant helminthic infection e. Systemic typhoid fever ANSWER: c 10. Which of the following is NOT an antimicrobial molecule secreted into the intestinal lumen? a. Defensins b. AMPs c. REG3 family proteins d. Enterocyte e. Lysozyme ANSWER: d 11. Retinoic acid is Copyright Macmillan Learning. Powered by Cognero.

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Chapter 13 a. a metabolite of vitamin A. b. used to kill pathogens in the gut. c. released to produce a tolerogenic response. d. both a metabolite of vitamin A and used to kill pathogens in the gut. e. both a metabolite of vitamin A and released to produce a tolerogenic response.

ANSWER: e 12. Compared to the small intestine, the microbiome in the large intestine is a. identical. b. less diverse and larger. c. less diverse and smaller. d. more diverse and larger. e. more diverse but equivalent in size.

ANSWER: d 13. Both celiac disease and ulcerative colitis a. can lead to tumors. b. are caused by parasitic nematode infections. c. are inflammatory diseases that occur in the gut. d. are disorders of the small intestine. e. are the result of an overproduction of IL-10.

ANSWER: c 14. Which of the following is NOT a risk factor for inflammatory bowel disease? a. NOD2 mutations. b. Low tryptophan levels. c. CARD9 mutations. d. Increased levels of IL-23. e. All of the answers are risk factors.

ANSWER: e 15. Which of the following pathogens invades epithelial cells directly? a. Trichinella b. Salmonella typhimurium c. Clostridium difficile d. Lactobacillus e. None of the answers directly invades epithelial cells.

ANSWER: b 16. Which gut disease is MOST closely associated with antigen presentation? a. IBD Copyright Macmillan Learning. Powered by Cognero.

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Chapter 13 b. IBS c. Crohn's disease d. Celiac disease e. Ulcerative colitis ANSWER: d 17. Which of the following is ONLY found in the respiratory tract - and NOT the GI tract? a. Lamina propria b. Goblet cells c. A mucocilliary layer d. M cells e. All of the answers are correct.

ANSWER: c 18. Nasal-associated lymphoid tissue (NALT) MOST closely resembles a. BALT b. Peyer's patches c. Goblet cells d. Stem cells e. Lamina propria ANSWER: b 19. Which of the following is NOT a response to H. influenza infection? a. NK cells b. Type I IFNs c. TLR pathways d. Mast cells e. Alarmins ANSWER: d 20. When available, humans are able to receive an intranasal vaccine for which disease? a. Influenza b. Measles c. Mumps d. Chickenpox e. Smallpox ANSWER: a 21. Which of the following is the name for specialized skin epithelial cells? a. Enterocyte b. Keratinocyte Copyright Macmillan Learning. Powered by Cognero.

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Chapter 13 c. Langerhans cell d. Paneth cell e. Goblet cell ANSWER: b 22. A Langerhans cell is a type of a. T cell. b. NK cell. c. dendritic cell. d. B cell. e. epithelial cell.

ANSWER: c 23. Which of the following diseases would be the BEST candidate for an intranasal vaccine? a. Norovirus b. Malaria c. S. aureus d. Leishmania e. Parainfluenza ANSWER: e 24. Why is peripheral tolerance critical to barrier immunity? a. Because it counters inappropriate activation. b. Because overactivation can lead to chronic inflammation and disease. c. Because microbes that colonize areas like the skin and intestines are not harmful. d. Because it both counters inappropriate activation, and overactivation can lead to chronic inflammation and disease. e. None of the answers explains why peripheral tolerance is critical to barrier immunity.

ANSWER: d 25. Which is NOT a shared protective element observed in both the skin and the ileum? a. stratified epithelium b. ILCs c. mast cells d. lymphatic drainage ANSWER: a 26. You are an immunologist studying cytokine levels in the gut. Compared to a healthy control, the patient you are studying has the changes listed in the following table. Describe the clinical symptoms that could have contributed to this profile.

TGF-β

IL-10

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IgE Page 5

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Chapter 13 10% of control

15% of control

10% of control

200% of control

ANSWER: This patient has lower levels of tolerogenic cytokines and noninflammatory IgA while having an increased amount of IgE. This patient may, therefore, be suffering from gut inflammation, possibly due to a parasitic infection but also potentially due to a chronic condition such as IBD. 27. Provide three benefits of the microbiome inside of our bodies. Explain their significance.

ANSWER: Producing needed substances, metabolism of food products, honing the immune system.

28. There are antibodies present in the gut lumen, despite being produced in the lamina propria (on the other side of the epithelial layer). How is this possible? Explain.

ANSWER: Antibodies are released into the gut through the process of transcytosis. B cells in the lamina propria produce antibodies (including IgA) against antigens found in the lumen. These antibodies are brought into epithelial cells by polymeric Ig receptors, where they are carried by vesicles to the apical side and released.

29. What is an enterocyte, and what function does it serve within the immune system? In your response, provide an example of one mechanism that prevents it from reacting to harmless commensal organisms.

ANSWER: Enterocytes are the most common cell type in the small intestine. They are the cells responsible for transporting nutrients to capillaries and the lymphatic system. They are also able to communicate via cytokines to immune cells in the lamina propria. They have the ability to sense pathogens via PRRs such as those TLR4; however, they mostly express these receptors internally. This allows them to ignore commensals in the lumen and only be activated by invading pathogenic bacteria.

30. Which two antibody classes are MOST critical to the maintenance of gut immunity and appropriate tolerance? Explain their significance.

ANSWER: IgA and IgE. IgA is effective at being brought through epithelial cells in vesicles; it is released into the barrier space where it can clear potential pathogens. IgA is not pro-inflammatory like other classes of antibody. IgE is activated in response to parasitic infections. However, IgE can also a source of allergy and asthma - and indiscriminate gut inflammation can lead to diseases like IBD and ulcerative colitis. Therefore, it is important to maintain a balanced immune response.

31. What are the four different cell types that work together to maintain immune homeostasis in the gut?

Explain the function of each cell type and identify a chronic disease that can develop when these cells are not working properly.

ANSWER: TREGs, innate lymphoid cells (ILCs), IgA-producing B cells, and T follicular helper cells (Note: TH17 cells is also acceptable). Regulatory T cells release cytokines that suppress inflammation and the immune response. TFH cells induce isotype switching in B cells to IgA, which produce an inflammatory response. ILCs secrete signals that suppress inflammation and hyperactivity of the immune system. One disease that can arise from dysregulation of these cells types is inflammatory bowel disease (IBD).

32. Compare and contrast the barrier layers in both the gut and the lungs.

ANSWER: Both the lungs and the gut are in contact with spaces outside of the body (with immune system cells on the other side), in the lamina propria. As such, they must maintain a mucus layer for protection Copyright Macmillan Learning. Powered by Cognero.

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Chapter 13 and have the ability to transmit antigens across epithelial cells. Both systems have M cells and goblet cells. However, only the lung contains large numbers of ciliated epithelial cells, alveolar macrophages, and the multifunction club cell.

33. When pathogenic microbes invade barrier tissues (such as the lungs or gut), which cytokines are released in response? Explain the effect the cytokines have on the immune response.

ANSWER: Invasion by a small pathogen will trigger recognition of MAMPs by epithelial cells and nearby APCs. This will cause a release of pro-inflammatory cytokines such as IL-17, IL-23, and IL-1β.

This combination will then activate the appropriate TH1 and TH17 responses to fight the infection.

34. Explain how parasitic worms and asthma are related, in terms of an immunological response.

ANSWER: The immune response to parasitic helminth infections and asthma attacks are both based on TH2 activation. Specifically, IL-4, IL-5, and IL-13 are produced in conjunction with IgE antibodies from B cells. IgE bound to antigens can then signal mast cells to release histamine and other effector molecules. Although this response is useful at fighting large pathogens, it can also be triggered by harmless stimuli in individuals with asthma (e.g.microbes, pollen, abiotic environmental factors).

Interestingly, rates of asthma are highest where the rate of parasitic infections is low, suggesting that there may be a link between helminth infection and the ability to respond correctly to harmless antigens.

35. Provide two examples of commensal organisms providing protection against harmful pathogens.

ANSWER: S. epidermidis, a commensal microbe on the epidermis, can protect the host from more harmful infections (such as the protozoan Leishmania). S. epidermidis induces the production of antimicrobial peptides and initiates the release of cytokines which activate the TH17 response. In the gut, bacteriotherapy is used to introduce large numbers of commensal microbes to outcompete the pathogenic microbes such as C. difficile, thereby favoring resistance to harmful microbes.

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Chapter 14 1. After production, naïve lymphocytes travel briefly through the blood to the a. spleen. b. peripheral lymph nodes. c. mucosal associated lymphoid tissue. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 2. Continual lymphocyte circulation is needed because a. antigen is usually present in large amounts. b. lymphocytes have a small chance of recognizing a particular antigen. c. the chance of a naïve cell encountering its target antigen is moderately high. d. there are relatively few antigen-presenting cells in the lymph nodes compared to lymphocytes. e. All of the answers are correct.

ANSWER: b 3. Lymphocytes exit the blood and enter the lymph node by extravasating at the high-endothelial venules (HEVs) present in the lymph node cortex. Extravasation does NOT require which of the following? a. Homing b. Addressins c. Chemokines d. Dendritic cells e. All of the answers are required.

ANSWER: d 4. After extravasation, naïve lymphocytes enter the _____ to scan for antigen. a. thymic cortex b. lymph node medulla c. lymph node cortex d. high-endothelial venule e. None of the answers are correct.

ANSWER: c 5. Reticular networks in the lymph nodes a. are made of fibroblasts. b. guide T-cell movements. c. guide B-cell movements. d. regulate lymphocyte direction. e. All of the answers are correct.

ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 14 6. Naïve B cells do NOT depend on which of the following as they move through a lymph node? a. Follicular dendritic cells b. Fibroblastic reticular fibers c. Chemokines CCL21 and CCL19 d. The chemokine CXCL13 e. Naïve B cells do not depend on any of the answer choices provided.

ANSWER: c 7. S1P1 receptor is upregulated by naïve T cells and B cells after 12-18 hours if they fail to encounter antigen in the lymph node. This means all of the following EXCEPT a. the naïve cells have not been activated. b. the naïve cells have not encountered antigen. c. the naïve cells will exit the lymph node. d. space will be made for other cells to enter the lymph node. e. the naïve cells will die by apoptosis.

ANSWER: e 8. Pattern-recognition receptors on innate immune cells a. coordinate killing of pathogens. b. alert the adaptive immune system of an infection. c. recognize specific pathogen. d. both coordinate killing of pathogens and alert the adaptive immune system of an infection. e. both coordinate killing of pathogens and recognize specific pathogens.

ANSWER: d 9. Early in an infection, antigen-presenting cells a. become less effective at phagocytosis. b. become more effective at antigen processing. c. become less effective at cross presentation. d. recruit more adaptive immune cells than innate immune cells. e. remain at the site of infection.

ANSWER: b 10. Which of the following is the CORRECT sequence of events? a. Antigen uptake > antigen processing > APC migration to lymph nodes > antigen presentation b. APC migration to lymph nodes > antigen uptake > antigen processing > antigen presentation c. APC migration to lymph nodes > antigen presentation > antigen uptake > antigen processing d. Antigen uptake > antigen processing > antigen presentation > APC migration to lymph nodes e. APC migration to lymph nodes > antigen uptake > antigen presentation > antigen processing ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 14 11. As antigen is picked up in peripheral tissues by antigen-presenting cells, it is a. processed for presentation to B cells. b. processed for presentation to T cells. c. moved without processing over several hours to the lymph nodes. d. taken in unprocessed form for presentation to T cells. e. All of the answers are correct.

ANSWER: b 12. Which of the following mechanisms of travel to lymph nodes by unprocessed antigen is CORRECT? a. Small and soluble antigens travel through afferent lymphatics as opsonized particles. b. Small and soluble antigens travel directly through the bloodstream. c. Large particles and pathogens travel directly through the bloodstream. d. Opsonized pathogens travel directly through the bloodstream. e. Small particles are carried by macrophages.

ANSWER: b 13. Which of the following is the proper order of transfer for opsonized antigens? a. CD169+ macrophages > follicular dendritic cells > antigen nonspecific B cells b. Antigen nonspecific B cells > CD169+ macrophages > follicular dendritic cells c. CD169+ macrophages > antigen nonspecific B cells > follicular dendritic cells d. Antigen nonspecific B cells > follicular dendritic cells > CD169+ macrophages e. None of the answers are correct.

ANSWER: c 14. The use of complement receptor deficient cells has shown that a. normal B cells sample antigen on macrophages and leave it intact. b. normal B cells sample antigen on macrophages and take part of it. c. complement receptor-deficient B cells do not sample antigen on macrophages. d. complement receptor-deficient B cells sample antigen on macrophages and take part of it. e. None of the answers are correct.

ANSWER: b 15. Which of the following cell types is NOT likely to be present early on in an infection? a. Granulocytes b. Antigen-presenting cells c. Cytotoxic T cells d. Dendritic cells e. Neutrophils ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Chapter 14 16. During activation, naïve CD4+ T cells a. interact with antigen-presenting cells. b. reduce movement. c. begin to divide. d. move to interact with B cells. e. All of the answers are correct.

ANSWER: e 17. Although our understanding of the kinetics of T-cell activation has changed over time, we now believe that a. antigen availability does not affect T-cell/APC interactions. b. antigen quantity does not affect T-cell/APC interactions. c. optimal proliferation of helper T cells requires only relatively brief APC exposure. d. optimal proliferation of helper T cells requires several hours of APC exposure. e. dendritic cell activation does not affect T-cell activation.

ANSWER: d 18. B cells have been shown to need two signals for activation. Absent T-cell help, they will NOT activate because a. T cells provide signal 1 through the B-cell receptor. b. T cells provide signal 2 through the B-cell receptor. c. T cells activate B cells indirectly by activating follicular dendritic cells. d. T cells activate B cells through CD40 signaling. e. B cells will still activate because of dendritic cells.

ANSWER: d 19. Several types of T cells have been shown to be able to provide help for B cells during activation. Which of the following statements is TRUE? a. All produce the same chemokine to activate but provide different CD40 signals. b. All produce the same chemokine and the same CD40 signal as well. c. All provide CD40 signaling but produce different chemokines. d. All provide CD40 signaling but trigger distinct class switching. e. All provide CD40 signaling but produce different chemokines and trigger distinct class switching.

ANSWER: e 20. Activation of naïve B cells is a two-step process, during which a. antigen triggers B-cell production of CCR7, which leads it to interact with T cells. b. antigen triggers T-cell production of CCR7, which recruits B cells. c. T-cell help stimulates B cells to produce CCR7, then divide. d. macrophages trigger B-cell production of CCR7, which leads it to interact with T cells. e. None of the answers are correct.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 14 21. T-cell help of B cells will be impaired if the T cells lack CD28 because a. CD28 is needed to activate class switching by turning on AICD. b. CD28 is needed to interact with CD40 on the B cell. c. CD28 is needed to signal through the B-cell receptor. d. CD28 is needed to signal through the T-cell receptor. e. None of the answers are correct.

ANSWER: d 22. Visualization of B-cell traffic between the light and dark zones of the germinal center has shown that they migrate far less than had been predicted. This demonstrates that a. the traditional model of trafficking is inaccurate. b. the rate of hypermutation and selection does not require extensive movement. c. only brief contacts by the B cells with helper T cells are needed. d. both the traditional model of trafficking is inaccurate and only brief contacts by the B cells with helper T cells are needed. e. both the rate of hypermutation and selection does not require extensive movement and only brief contacts by the B cells with helper T cells are needed.

ANSWER: e 23. A major difference between naïve and effector lymphocytes is that effector lymphocytes a. follow chemokine trails. b. do not home in to the lymph nodes. c. do not require co-stimulation. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 24. In tissues, B cells seek out T cell help in a. bone marrow. b. afferent lymphatics. c. the follicle border of lymph nodes. d. the red pulp of the spleen. e. All of the answers are correct.

ANSWER: c 25. To avoid returning to the lymph nodes, effector cells a. up-regulate chemokine receptors to allow them to home in to site of infection. b. down-regulate L-selectin, so they do not enter the high-endothelial venules (HEVs). c. down-regulate chemokine receptors, so they do not enter the high-endothelial venules (HEVs). d. up-regulate chemokine receptors and downregulate L-selectin.

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Chapter 14 e. down-regulate both L-selectin and chemokine receptors.

ANSWER: d 26. Tracking of responses to a transgenic pathogen (toxoplasma) has shown that a. T-cell behavior followed patterns predicted by previous studies. b. dendritic cell behavior followed patterns predicted by previous studies. c. lymph-node architecture changed due to inflammation. d. T cells divided at the site of infection. e. All of the answers are correct.

ANSWER: c 27. Which of the following adaptive cell types' response is MOST similar to innate immunity? a. Central memory T cells. b. Effector memory T cells. c. Tissue-resident memory T cells. d. Memory B cells. e. None of the answers are correct.

ANSWER: c 28. Studies of graft rejection using cells labeled with fluorescent markers demonstrate that a. any infiltration of a skin graft depends on MHC mismatch. b. deep infiltration of a skin graft depends on MHC mismatch. c. host antigen-presenting cells enter the skin graft before migrating to lymph nodes. d. both any infiltration of a skin graft depends on MHC mismatch, and host antigen-presenting cells enter the skin graft before migrating to lymph nodes. e. both any infiltration of a skin graft depends on MHC mismatch and host antigen-presenting cells enter the skin graft before migrating to lymph nodes.

ANSWER: e 29. Listeria is able to persist in an infection because it a. avoids being broken down and presented as antigen. b. localizes quickly to lymph nodes and persists there. c. reproduces inside macrophages. d. is passed by dendritic cells to monocytes. e. None of the answers are correct.

ANSWER: d 30. The failure of cytotoxic T cells to eliminate tumors can be attributed to a. failure of tumor antigen presentation. b. failure of activation of tumor-specific T cells. c. failure of recruitment of T cells to the tumor.

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Chapter 14 d. failure of the T cells to produce cytotoxic effector molecules. e. All of the answers are correct.

ANSWER: a 31. Immune responses are often ineffective - in some cases, these responses can contribute to disease through which of the following conditions? a. Listeria b. Tissue grafts c. Solid tumors d. Type 1 diabetes e. All of the conditions are contributed to by immune responses.

ANSWER: e 32. What is extravasation, and what are its four primary steps?

ANSWER: Extravasation is the process of immune system cells leaving blood vessels by squeezing between endothelial cells. The four main steps are: rolling, activation, arrest/adhesion, and, finally, migration.

33. A line of mice develops wherein the S1P1 gene is excised following lymphocyte development. What effect would this have on the immune response?

ANSWER: S1P1 is important because it allows lymphocytes to leave tissues where they do not encounter their cognate antigen. This is important for two reasons: 1) the cells are then able to travel to new sites (where they can potentially encounter antigen), and 2) it creates space for new cells to enter the tissue. Mice with developed (but naïve) lymphocytes without S1P1 would have generally damped immune responses because their cells would not encounter their antigens as often as wild-type animals.

34. Explain the function of nonantigen-specific B cells during the early phases of the adaptive immune response.

ANSWER: When antigens are opsonized by complement fragments even noncognate B cells can be important players in immune activation and response. Specifically, these nonspecific B cells uptake antigen from CD169+ macrophages; these antigens are ultimately relayed to follicular dendritic cells and presented to naïve B lymphocytes.

35. Compare and contrast how a soluble toxin subunit and a malarial parasite (sporozoite) would travel through the body. How would each be recognized by the immune system?

ANSWER: Small, soluble antigens (such as the hypothetical soluble toxin) are able to travel via the bloodstream and end up in the lymph node, as a result. Larger moieties - up to and including single-cell parasites - can reach lymph nodes via afferent lymphatics. Antigens are then processed (often after being opsonized with complement) by macrophages and other antigen-presenting cells; they are then presented to lymphocytes.

36. How do CD4+ T cells provide physical help to CD8 T cells, given that they interact with different classes of MHC molecules?

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Chapter 14 ANSWER: Because of imaging studies, we know that CD4+ and CD8 T cells interact with the same antigenpresenting cell at the exact same time. These APCs, often licensed dendritic cells, express MHC I and MHC II and can display peptides to both sets of T cells.

37. What are the steps required for a naïve B cell to achieve activation in vivo? Explain the significance of each step.

ANSWER: B cells require two signals to activate: binding to antigen and costimulation from CD4+ T cells.

Antigen binding occurs first via the BCR; these cells then migrate to the border between the follicle and the paracortex of the lymph node by upregulating CCR7. At this border B and T cells establish an immunological synapse between the TH cell's clustered TCR, CD28, and CD40L and a B cell's class II MHC, class II-peptide, CD80/86, and CD40 molecules.

38. What are the three types of memory cells in the body? Where is each type located?

ANSWER: Memory cells are either central memory, resident memory, or effector memory. Central memory cells stay in secondary lymphoid tissues, resident memory cells live in specific tissues (often at barrier sites), and effector memory cells circulate through various tissues.

39. Explain how the immune system both responds to and controls Toxoplasma gondii infection in the brain.

ANSWER: Antigen-specific CD8+ T cells in the lymph node respond rapidly and form contacts with DCs. Crawling naïve antigen-specific T cells slow down considerably after encountering DCs that have been exposed to antigen. These cells collect in the lymph node's subscapular sinus before the CD8 T cells begin entering the brain by day 3. In an experimental model, some cells formed stable clusters near infected cells and appeared to be interacting with brain-resident APCs. Infection induced the appearance of a new reticular network.

40. Provide an example of the immune system helping to spread an infection throughout the body, including an analysis of how the infection is able to circulate.

ANSWER: There are many examples of pathogens exploiting the host's own immune response, but one that has been well visualized is bacterial Listeria infection. Listeria travels to lymph nodes after physiologic or experimental infection and is then able to actively infect and survive in the dendritic cells that phagocytize it. From there, it is able to "hitch a ride" inside these cells as they circulate, infecting distant regions of the body.

41. What is one component, activity, or interaction in the immune system of which you would want high-quality video? What might it assist you in evaluating? How would you apply this to your studies? Explain.

ANSWER: Answers will vary but the response should demonstrate knowledge of how the immune response is both initiated and ultimately carried out.

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Chapter 15 1. Hypersensitivity reactions to penicillin have been identified that correspond to which of the below types of reactions? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: e 2. Hypersensitivity reactions to cell surface antigens via IgG or IgM are classified as which type? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: b 3. Which of the following types of hypersensitivity reactions is associated with IgE? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: a 4. Which of the following types of hypersensitivity reactions includes the transfusion reaction? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: b 5. Which of the following reactions features mast cell degranulation as one of its key features? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 15 6. The Arthus reaction is considered to be which of the following hypersensitivity types? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: d 7. Formation of immune complexes between antibodies and soluble antigens is considered to be which type of hypersensitivity reaction? a. Type I hypersensitivity b. Type II hypersensitivity c. Type III hypersensitivity d. Type IV hypersensitivity e. All of the answers are correct.

ANSWER: c 8. A normal individual should only produce IgE in response to which of the following types of antigens? a. Antigens from extracellular bacterial antigens b. Antigens from intracellular bacterial antigens c. Viral antigens d. Parasite antigens e. All of the answers are correct.

ANSWER: d 9. Which of the following cell-surface receptors is MOST closely linked to activating type I hypersensitivity reactions? a. FcεRII b. FcγRIIB c. FcεRI d. LFA-1 e. None of the answers are correct.

ANSWER: c 10. Which of the following cell types are implicated in type I hypersensitivity reactions? a. Neutrophils b. Mast cells and basophils c. T cells d. Monocytes e. None of the answers are correct.

ANSWER: b Copyright Macmillan Learning. Powered by Cognero.

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Chapter 15 11. Which of the following is NOT packaged within basophil and mast cell granules? a. Prostaglandins b. Histamine c. Heparin d. Tryptase e. All of the answers are found in granules.

ANSWER: a 12. Which of the following cell types are targets of the products of mast-cell degranulation, as well as the mediators produced by mast cells following degranulation? a. Smooth muscle b. Nervous tissue c. Hematopoietic cells d. Epithelial cells e. All of the answers are correct.

ANSWER: e 13. The effects of histamine in allergic reactions are primarily attributable to its binding which of the following histamine receptors? a. H1 b. H2 c. H3 d. H4 e. None of the answers are correct.

ANSWER: a 14. Which of the following effects is NOT a result of histamine binding to histamine receptor H1? a. Intestinal smooth muscle contraction. b. Suppression of mast-cell degranulation. c. Increased vascular permeability. d. Increased mucous secretion. e. All of the answers result from histamine binding H1.

ANSWER: b 15. Which of the following cytokines is NOT generally associated with allergic reactions? a. TNF-α b. GM-CSF c. IL-4 d. TGF-β Copyright Macmillan Learning. Powered by Cognero.

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Chapter 15 e. All of the answers are associated with allergic reactions.

ANSWER: d 16. What cell type would be MOST instructive in classifying the type of reaction responsible for a skin rash? a. CD4+ T cells b. CD8+ T cells c. NK cells d. APCs e. Mast cells ANSWER: a 17. The immune response to a peanut allergy is MOST similar to a a. poison ivy rash. b. positive PPD test. c. bee sting. d. transfusion reaction. e. None of the answers are similar.

ANSWER: c 18. Desensitization therapy works by a. producing IgG antibodies that compete for antigen binding sites with IgE. b. producing IgG antibodies to activing ITIMs on other Fc receptors. c. switching the response from TH2 to TH1. d. inducing anergy of TH2 cells. e. All of the answers are correct.

ANSWER: e 19. Allergic responses may have evolved to a. protect us from spoiled food. b. break down venom from reptiles. c. keep us away from excess pollen. d. prevent blood transfusions. e. All of the answers are correct.

ANSWER: b 20. Which of the following is NOT a means by which type II hypersensitivity reactions occur? a. IgE binding to FcεRI on mast cells. b. IgM binding to cell-surface antigens, leading to complement fixation on the cell surface. c. Cytotoxic cells with Fc receptors for antibodies bound to the surface of a cell, leading to cytotoxic killing.

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Chapter 15 d. Antibody-antigen complexes that form opsonins, leading to phagocyte-driven cell killing. e. All of the answers are associated with type II hypersensitivity reactions.

ANSWER: a 21. The transfusion reaction involves which of the following antigens that are structurally similar to antigens on the surface of commensal bacteria? a. Fc receptors on the surface of mast cells b. Complement receptors on the surface of APCs c. Carbohydrates on the surface of erythrocytes d. Fc receptors on the surface of cytotoxic cells e. None of the answers are correct.

ANSWER: c 22. Which of the following BEST describes the difference(s) between types II and III hypersensitivity reactions? a. Direct recognition of cell-surface antigens by antibodies in type II reactions versus deposition of improperly cleared antibody-antigen complexes in type III reactions b. Direct recognition of cell-surface antigens by antibodies in type III reactions versus deposition of improperly cleared antibody-antigen complexes in type II reactions c. Cross-linking of FcεRI by IgE-opsonized pathogens d. Cross-linking of FcγRIIB by IgG-opsonized pathogens e. None of the answers are correct.

ANSWER: a 23. Which of the following is NOT an explanation for inefficient clearing of antibody-antigen complexes that could lead to type III hypersensitivity reactions? a. High affinity for tissues of particular antigens b. Antigens that are prone to formation of lattices when bound by antibodies c. Highly charged antigens d. Compromised phagocytic system e. All of the answers could explain inefficient clearing of antibody-antigen complexes.

ANSWER: e 24. An Arthus reaction refers to a. a localized type III reaction. b. a response to moldy hay or pigeon feces. c. an inflammatory response 4 to 10 hours after exposure. d. swelling and localized bleeding after a type I response. e. All of the answers are correct.

ANSWER: e 25. The tuberculin reaction is an example of which type of hypersensitivity?

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Chapter 15 a. Type I b. Type II c. Type III d. Type IV e. None of the answers are correct.

ANSWER: d 26. Which of the following cell types is NOT typically associated with type IV hypersensitivity reactions? a. B cells b. TH1 c. TH17 d. Langerhans cells e. None of the answers are typically associated with type IV hypersensitivity reactions.

ANSWER: a 27. Which of the following is a potential cause of chronic inflammation? a. Obesity b. Infectious agents c. Tissue damage d. Intestinal commensal microbiota components e. All of the answers are correct.

ANSWER: e 28. Which of the following cytokines is NOT generally found in increased concentrations in individuals with chronic inflammation? a. IL-10 b. TNF-α c. IL-1 d. IL-6 e. All of the answers are generally elevated in chronic inflammation.

ANSWER: a 29. Which of the following is NOT involved in the development of Type II diabetes? a. Antibodies against pancreatic islet cells. b. Signaling from IL-6R. c. Inactivation of components involved in signaling from the insulin receptor by JNK. d. All of the answers are involved in the development of Type II diabetes. e. None of the answers are involved in the development of Type II diabetes.

ANSWER: a Copyright Macmillan Learning. Powered by Cognero.

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Chapter 15 30. Chronic stimulation of the tissue regeneration function of the inflammatory response primarily involves which of the following cells? a. T cells b. Fibroblasts c. B cells d. Basophils e. None of the answers are correct.

ANSWER: b 31. Which of the following is present during both acute and chronic inflammation? a. Monocytes b. Macrophages c. Lymphocytes d. Neutrophils e. Fibroblasts ANSWER: d 32. What two features are common across many allergens? Explain why scientists believe these features potentially make molecules MORE likely to be allergenic.

ANSWER: There are "rules" for what can be an allergen, but these molecules commonly have protease activity and/or have at least one PAMP associated with them. Molecules with protease activity may be able to break through host defenses at the barrier level and interact with immune cells deeper in tissues.

Molecules that have PAMPs will also trigger activation of the immune system once recognized.

33. You are studying mice that have a mutation in the FcεRI signal cascade: their ITAM motifs cannot be phosphorylated. What types of immune reactions would be affected by the mutation? Explain the effect the mutation would have on the mice.

ANSWER: FcεRI receptors are responsible for both binding IgE and inducing allergic/anti-parasitic effector functions. These mice would still be able to bind to the Fc portion of IgE. However, because the ITAM motifs would not be able to be activated, there would neither be downstream signaling nor the release of histamine and other effector molecules. In short, these mice would be immune to developing allergies but would be extremely susceptible to parasitic infections.

34. One treatment for serious allergies involves injecting a monoclonal antibody as a drug. If allergies are caused by antibodies, how can this treatment be effective?

ANSWER: The initial event leading to an allergic reaction is IgE binding to a foreign substance, but more important, this IgE complex must bind to Fc receptors on mast cells. The drug omalizumab works by preventing this interaction through binding to the Fc region of IgE antibodies and, therefore, signaling events leading to degranulation.

35. Explain how desensitization immunotherapy works. In your response, provide and evaluate at least two of its primary mechanisms.

ANSWER: Desensitization therapy is the practice of injecting small (but increasing) doses of an allergen or group of allergens to reduce symptoms. There are multiple proposed mechanisms for its Copyright Macmillan Learning. Powered by Cognero.

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Chapter 15 effectiveness, which include producing IgG antibodies to compete with existing IgE and stimulating an inhibitory response from Fc receptors, switching the response from TH2 to TH1, and even inducing anergy or apoptosis of TH2 cells.

36. Describe two different hypersensitivity reactions caused by antibiotics such as penicillin.

ANSWER: Penicillin can cause a type I anaphylactic reaction where it is bound by IgE. It can also cause a type II reaction by absorbing nonspecifically to red blood cells, where it is then bound by IgG or IgM. The blood cell is then destroyed by either complement activation or antibody-mediated cytotoxicity (ADCC).

37. Describe a type III hypersensitivity reaction. What are two sources of antigens that can cause this response?

ANSWER: A type III reaction occurs when antigens and antibodies form large complexes that can damage tissues in the body. The Fc regions present can bind to Fc receptors on mast cells, neutrophils, and others - this causes vasodilation and localized inflammation. The antigens that cause the reactions can be foreign (i.e., from pathogens) or in some cases, from autoantigens.

38. Describe one positive and one negative outcome of the DTH reaction in response to TB infection in the lungs. Explain.

ANSWER: TB is an intracellular bacterial parasite that can infect the lungs. The DTH response is able to fight this bacteria by having CD4+ TH1 T cells recruit and activate macrophages to the infected area. In some cases, the macrophages are able to destroy the bacteria via an increase in phagocytic activity and the secretion of lytic enzymes to surrounding tissues. If unchecked, this response can lead to granulomas – a mass of macrophages that assumed epithelioid shape and fused cells together. The resulting mass can displace and damage normal tissues.

39. What causes the rash that some people contract when exposed to poison ivy? Can this rash be spread?

ANSWER: The poison ivy rash is a type IV hypersensitivity reaction: these reactions are marked by a slow (>24 hour) recruitment of T cells to a site, as well as a recruitment and activation of macrophages. This response can be protective against certain pathogens (such as Mycobacterium tuberculosis), but the potential for tissue damage by the activated macrophages is high. Following exposure to poison ivy, oils from the plant break down and attach themselves to host molecules, making them appear as "nonself" upon MHC presentation. Once sensitized, a person will repeatedly break out when exposed to oils called pentadecylcatechols, but because the rash is caused by the immune system, it is (as a result) not directly caused by the oils and, therefore, not contagious nor transmissible.

40. How is chronic inflammation different from regular, acute inflammation? Describe both two causes of chronic inflammation and two different diseases that can be caused or exacerbated by it.

ANSWER: Chronic inflammation is characterized by many of the same hallmarks as regular inflammation (such as IL-1, IL-6, and TNF-α) but persists over a much longer period of time. It can be caused by nonresolving infections or noninfectious conditions, such as mechanical damage and obesity.

Important, this can lead to either type II diabetes or encourage the growth of tumors.

41. Why, after millions of years of evolution, are human beings still susceptible to so many types of hypersensitivity reactions that lead to serious illness or death?

ANSWER: Although they can be harmful, all of the hypersensitivity reactions covered in this chapter of the text Copyright Macmillan Learning. Powered by Cognero.

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Chapter 15 are related to helpful and necessary components of a robust immune system. Type I reactions are caused by the same cells (B and mast cells) and molecules (IgE, histamine) that protect us from parasites and venom. Type II, III, and IV responses are also closely related to protective responses to pathogens, and Type III may actually occur during a normal response as serum sickness.

Therefore, to prevent susceptibility to allergies, asthma, and other hypersensitivities, we would risk crippling our entire immune system.

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Chapter 16 1. Central tolerance a. is the first step of tolerance mechanisms. b. affects both T cells and B cells. c. deletes cells that are autoreactive. d. occurs in the bone marrow and thymus. e. All of the answers are correct.

ANSWER: e 2. Which of the following statements does NOT describe tolerogens accurately? a. They can be the same molecules as immunogens. b. They lead cells to become unresponsive. c. They are part of peripheral tolerance. d. They only affect B cells. e. All of the answers describe tolerogens.

ANSWER: d 3. The tolerogenic response a. is not antigen specific. b. leads to apoptosis but not anergy. c. results in cells becoming nonresponsive. d. depends on the presentation context. e. affects T cells only.

ANSWER: c 4. Tolerance is promoted by all of the following circumstances EXCEPT a. high doses of antigen. b. persistent antigen. c. oral introduction of antigen. d. presence of adjuvant. e. low levels of costimulation.

ANSWER: d 5. Tolerance is promoted by a. induction of anergy. b. induction of apoptosis. c. regulation of activity of cells. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 6. Apoptosis is Copyright Macmillan Learning. Powered by Cognero.

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Chapter 16 a. similar to necrosis. b. important in peripheral but not central tolerance. c. important in central but not peripheral tolerance. d. impaired in Fas-deficient systems. e. None of the answers are correct.

ANSWER: d 7. Maintaining immunologically protected sites, such as the eye, a. allows sequestration of antigens. b. reduces central tolerance. c. can lead to autoreactivity secondary to injury. d. can reduce background reactivity. e. All of the answers are correct.

ANSWER: e 8. Central tolerance employs all but which of the following mechanisms? a. Apoptosis b. Receptor editing c. Positive selection d. Negative selection e. Clonal deletion ANSWER: c 9. Peripheral tolerance a. is caused by costimulation without TCR-MHC + peptide interaction. b. is caused by TCR-MHC + peptide interaction without costimulation. c. leads to anergy. d. both leads to anergy and is caused by costimulation without TCR-MHC + peptide interaction. e. both leads to anergy and is caused by TCR-MHC + peptide interaction without costimulation.

ANSWER: e 10. Which molecule is MOST closely associated with inhibitory responses to antigen? a. TCR b. MHCI c. CTLA-4 d. CD80 e. All of the answers are equally associated with inhibitory responses to antigen.

ANSWER: c 11. CD8+ TREG cells can counteract autoimmune diseases in mice deficient in Copyright Macmillan Learning. Powered by Cognero.

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Chapter 16 a. AIRE. b. CD4+ TREGs. c. IL-10. d. plasma cells. e. lymphocytes.

ANSWER: a 12. Which of the following events PRIMARILY drives the need for tolerance? a. Organ transplants b. V(D)J recombination in lymphocyte development c. HLA polymorphisms d. All of the answers are correct. e. None of the answers are correct.

ANSWER: b 13. What are the three main methods through which our body prevents immune responses against itself?

ANSWER: One of the methods involves partial partitioning of antigens away from immune circulation.

14. Speculate as to why regulatory T cells may have evolved, despite us having negative selection of lymphocytes during development. Explain your answer.

ANSWER See the figure. :

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Chapter 16

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Chapter 16 15. What is the PRIMARY difference between how central and peripheral tolerance are developed?

ANSWER See the figure. :

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Chapter 16

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Chapter 16 16. Autoimmune diseases a. involve a failure of central tolerance. b. involve a failure of peripheral tolerance. c. lead to tissue destruction. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 17. Hashimoto's thyroiditis targets the thyroid and a. is more common in men than in women. b. shows juvenile onset. c. is primarily T-cell mediated. d. leads to hypothyroidism. e. All of the answers are correct.

ANSWER: d 18. Insulin-dependent diabetes a. usually shows juvenile onset. b. is more common in men that in women. c. interferes with fat metabolism. d. seems to be triggered by antibodies. e. None of the answers are correct.

ANSWER: a 19. Myasthenia gravis is an autoimmune disease that a. is triggered by antibodies. b. targets the neuromuscular junction. c. leads to destruction of muscle cells. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 20. Systemic lupus erythematosus a. is more common in women than in men. b. is antibody mediated. c. targets multiple organs. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: e Copyright Macmillan Learning. Powered by Cognero.

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Chapter 16 21. Multiple sclerosis a. does not seem to have an environmental component. b. seems to have some genetic component. c. is more common in Europe than North America. d. seems to be primarily mediated by antibodies. e. All of the answers are correct.

ANSWER: b 22. Rheumatoid arthritis a. seems to be T-cell mediated, with cytotoxic T cells being primarily responsible. b. is more common in men than in women. c. targets the joint capsules. d. is characterized by juvenile onset. e. All of the answers are correct.

ANSWER: c 23. Individuals who express HLA-B27 are 90 times more likely to develop the autoimmune disorder ankylosing spondylitis than individuals with a different HLA allele at this locus. This leads to the conclusion that a. HLA-B27 causes ankylosing spondylitis. b. individuals with HLA-B27 will develop ankylosing spondylitis. c. autoimmune disorders must have genetic components. d. patients with ankylosing spondylitis express HLA-B27. e. None of the answers are correct.

ANSWER: e 24. Many autoimmune disorders are treated with immunosuppressive drugs, which produce other problems.

Antigen-specific immunotherapy would be much better because a. they would target only the autoreactive cells. b. they would not induce general suppression of the immune system. c. they would produce a general reduction in inflammation. d. they would both target only the autoreactive cells and not induce general suppression of the immune system. e. they would target only the autoreactive cells and produce a general reduction in inflammation.

ANSWER: d 25. Autografts will be rejected only rarely because of all but which of the following? a. They are from the same individual. b. They are MHC matched. c. They do not trigger an immune response. d. They have TH17 cells. e. All of the answers are correct.

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Chapter 16 ANSWER: d 26. Isografts are NOT usually rejected because a. they are between genetically identical individuals. b. they are MHC matched. c. they do not trigger an immune response. d. they are syngeneic. e. All of the answers are correct.

ANSWER: e 27. Rejection of allografts a. does not depend on MHC mismatching. b. demonstrates immunological specificity. c. demonstrates immunological memory. d. both demonstrates immunological specificity and does not depend on MHC mismatching. e. both demonstrates immunological specificity and immunological memory.

ANSWER: e 28. Because T cells are essential in graft rejection, nude mice, which lack a thymus a. will reject grafts the same as wild-type mice. b. will reject grafts more vigorously than wild-type mice. c. will not reject grafts as they lack T cells. d. will not reject grafts as they lack B cells. e. will not reject grafts because of peripheral tolerance.

ANSWER: c 29. Kidney transplant infiltrates show both CD4+ and CD8+ T cells. This suggests that to reduce graft rejection a. CD4+ T cells should be depleted. b. CD8+ T cells should be depleted. c. Both CD4+ and CD8+ cells should be depleted. d. Inflammatory cells should be depleted. e. None of the answers are viable treatments.

ANSWER: e 30. Although MHC matching is important for transplantation, ABO blood group matching is also critical because a. ABO antigens are expressed on nervous tissue. b. ABO antigens are expressed on muscle cells. c. complement will cause rapid lysis of ABO mismatched cells. d. All of the answers are correct.

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Chapter 16 e. None of the answers are correct.

ANSWER: c 31. Minor histocompatibility locus genes can cause tissue rejection a. only if major histocompatibility genes also cause rejection. b. even if major histocompatibility genes match properly. c. more quickly than MHC-mediated rejection. d. at the same rate as MHC rejection. e. None of the answers are correct.

ANSWER: b 32. Allografts can be accepted without use of immunosuppressive drugs if a. they lack alloantigens, such as cartilage. b. cells are grafted to a site that is immunologically privileged. c. tolerance has been induced previously, such as nonidentical twins. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 33. Graft rejection consists of a. sensitization, when T cells are stimulated, and effector, when they attack the graft. b. sensitization, when B cells are stimulated, and effector, when they attack the graft. c. recognition, when T cells are stimulated, and effector, when they attack the graft. d. recognition, when B cells are stimulated, and effector, when they attack the graft. e. None of the answers are correct.

ANSWER: a 34. Transplantation of organs and tissues is challenging (even between relatives) for all of the following reasons EXCEPT a. HLA alleles must be completely nonoverlapping. b. HLA alleles must be all or nearly matched. c. ABO blood groups must be matched. d. Immunosuppression is needed. e. All of the answers are correct.

ANSWER: a 35. In transplantation, CsA, rapamycin, and FK506 are all used to a. decrease the odds of rejection. b. inhibit the activation of resting T cells. c. improve the survival odds for the patient. d. All of the answers are correct.

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Chapter 16 e. None of the answers are correct.

ANSWER: d 36. What is the MOST important gene (or group of genes) for the development of autoimmunity? Explain.

ANSWER: There are a wide variety of genes that can leave a person at risk for developing autoimmune diseases, but the most important are those that encode for MHC molecules. These genes (known as "HLA" in humans) are critical because they are responsible for which antigens are presented to all T cells. For example, the HLA allele B-27 is responsible for a substantial increase in the risk of developing ankylosing spondylitis.

37. What causes the diseases APS-1 and IPEX? Explain why the conditions are grouped together despite being caused by different mutations.

ANSWER: APS-1 is caused by mutations in the AIRE gene, whereas IPEX occurs when FoxP3 is mutated.

However, because these two mutations control the beginning and the end stages of tolerance they are grouped together. With either mutation the ability to generate tolerance and prevent autoimmunity is greatly impacted, so both APS-1 and IPEX are associated with the development of many different autoreactive diseases.

38. In immunotherapy, there has been a great deal of success through the use of tailored approaches and gene therapy – for example, engineering T cells that target a patient's unique cancer cells. With this in mind, what might a similar approach look like for autoimmune diseases?

ANSWER: Option 1: CAR therapy that recognizes the specific TCRs or BCRs causing the autoimmune response; these are then targeted for apoptosis and/or anergy.

Option 2: Rationally designed TREG cells that bind the target autoantigen and induce tolerance/anergy in other nearby reactive immune cells.

39. Small animal models (for example, Drosophila) have afforded profound insights into both biology and genetics. Your classmate wants to propose an inexpensive lab studying autoimmunity by using this insect.

Predict what will happen next. Will the funding be received?

ANSWER: Small animal model systems can be excellent tools for studying immunology, but the classmate's proposal does not have a strong case. Human immunity is caused by the random recombination of antigen-binding genes in our lymphocytes - this process is unique to the adaptive immunity of vertebrates. Drosophila will not experience autoimmunity in the same way that a human being will.

40. Why is type 1 diabetes considered an autoimmune disorder despite being caused by a lack of insulin in the body? Explain.

ANSWER: Insulin is produced by beta cells in the pancreas. A common cause of type 1 diabetes is these cells being destroyed by autoreactive T cells produced by the host's own immune system. These CTLs recruit macrophages, which leads to a DTH response that destroys the body's source of insulin.

41. What are three different ways to prevent rejection following organ transplantation?

ANSWER: Answers will vary, but possible responses include transplanting an autograft (self-tissue), using immunosuppressive drugs, transplanting a tissue that does not contain alloantigens (such as cartilage), transplanting in a privileged site, or enclosing the transplanted cells in a protective barrier.

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Chapter 16 42. A transplantation doctor is observing her notes for an upcoming surgery. She sees the following information about the donor and recipient of a heart transplantation: HLA: 11/12 [genes matched] Donor blood type: A+ Recipient blood type: BWhat are the chances of success for this operation? Provide your prognosis.

ANSWER: Finding a donor organ that has 11/12 HLA genes matched up is rare (and quite exciting). However, the lack of a blood type match is concerning. There is a high chance that this patient will experience hyperacute rejection of the new organ due to complement deposition and damage incurred from mismatched blood type antigens. This surgery should not proceed as planned.

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Chapter 17 1. Viruses, like many good pathogens, have adapted to survive in their hosts. Which of the following scenarios would be MOST favorable to viral transmission and long-term survival of the viral species? a. Virus X enters a host cell, produces many progeny viruses (virions), and lyses the host cell. b. Virus X enters the host cell and merges viral DNA with the host DNA so that the virus is copied into all progeny host cells. c. Virus X enters the host cells, merges viral DNA with the host DNA until the host cell is stressed, and then begins to produce many virions eventually lysing the host cell. d. Virus X enters the host cell and consistently makes virions at a low level so that all host cell functions are not disrupted. e. Virus X enters the host cell, makes many progeny virions, and releases virions through exocytosis so that each virion is wrapped in the host cell plasma membrane. The host cell will eventually die or be targeted by the immune system for apoptosis.

ANSWER: d 2. Which of the following is NOT important for controlling infections at either barrier or mucosal sites? a. TH2 CD4+ T cells b. IL-4 c. IgA d. IgG e. IgE ANSWER: d 3. Which of the following is recognized by the innate immune system and triggers an immune response that will produce antiviral cytokines and trigger effector molecules? a. Complement b. IgA c. IL-2 d. PAMPs e. TNF-α ANSWER: d 4. One mechanism that viruses use to avoid the immune response is to bind up immune effector molecules. All of the following methods are used by antibodies to block viral infection EXCEPT a. antibodies bind to and coat virus particles, preventing viral ligands from binding to cell receptors. b. antibodies trigger complement, which can lyse viral particles or recruit opsonins. c. antibodies stimulate activation of cytotoxic T cells. d. antibodies aid in phagocytosis. e. antibodies compete for binding with viral ligands.

ANSWER: c 5. Viruses such as Epstein-Barr virus, cytomegalovirus, and HIV are capable of suppressing the immune system by Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 a. binding antibodies but avoiding an immune response. b. infecting lymphocytes or phagocytic cells. c. production of cytokine antagonists. d. wrapping progeny viral particles in the host-cell plasma membrane. e. both infecting lymphocytes or phagocytic cells and production of cytokine antagonists.

ANSWER: e 6. By which mechanisms can bacterial pathogens evade a host immune response? a. Avoiding phagocytosis by the production of a capsule. b. Escape of the phagolysosome within phagocytic cells. c. Neutralization of digestive enzymes found within phagocytic cells. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 7. Which pathogen would be LEAST affected by a host complement attack? a. Rotavirus (nonenveloped virus) b. Influenza (enveloped virus) c. HIV (enveloped virus) d. Gram-negative bacteria e. Gram-positive bacteria ANSWER: a 8. Each of the following is a step in bacterial infection EXCEPT a. attachment to host cells. b. the host feels tired or uncomfortable. c. invasion of host tissue. d. proliferation of bacterial cells. e. toxin-induced damage to host cells.

ANSWER: b 9. _____ is/are known as an endotoxin. a. C3a b. Capsular proteins c. Flagellar proteins (H antigen) d. Lipid A of the LPS in gram-negative cells e. Peptidoglycan in gram-positive cells ANSWER: d 10. Anaphylatoxins stimulate a localized inflammatory response, which includes mast-cell degranulation, vasodilation, and recruitment of lymphocytes and phagocytic cells. What is the purpose of this localized Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 immune response? a. Mast cells contain histamine, which triggers vasodilation, which will increase blood flow to an infected area so that higher numbers of white blood cells will be recruited. b. Serum proteins contain specific and nonspecific immune effector molecules to bind up and neutralize the invading pathogen and any toxins. c. Vasodilation locally increases the temperate of an infected area so that bacterial proteins become denatured. d. Vasodilation increases tenderness at the site of infection and causes edema (swelling) to that the host is careful not to overuse or tax the infected area. e. All of the answers are correct.

ANSWER: e 11. Which of the following are anaphylatoxins? a. C1 and MASP-1 b. C3a and C5a c. C3b and C5b d. C4b and factor D e. C5b and the MAC ANSWER: b 12. Parasitic infections include a. protozoans. b. protozoans and helminthes. c. prions and viruses. d. prions, viruses, and bacteria. e. protozoans, helminthes, prions, viruses, and bacteria.

ANSWER: b 13. Sleeping sickness and Chagas's disease are caused by members of the genus Trypanosoma, protozoans that reside in the bloodstream. What is the principle way trypanosomes evade the immune response? a. Antagonistic cytokines are produced by the trypanosome. b. Periodic changes in the surface antigen (VSG) of trypanosomes ensures that at least some cells will survive antibody mediated attacks. c. Trypanosomes are human pathogens and thus immune to human immune responses. d. Trypanosomes invade the brain and red blood cells so that immune effector cells such as macrophages and dendritic cells cannot phagocytize trypanosomes. e. Vaccines are readily available to people in trypanosome infested areas.

ANSWER: b 14. How do Plasmodium cells avoid immune clearance? a. Antagonistic cytokines are produced by the Plasmodium cells. b. Periodic changes in the surface antigen (VSG) of Plasmodium ensures that at least some cells will Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 survive antibody mediated attacks. c. Plasmodium cells show multidrug resistance. d. Plasmodium invades red blood cells so that immune-effector cells such as macrophages and dendritic cells cannot phagocytize Plasmodium cells. e. TNF-α is produced in large amounts by Plasmodium, thus overwhelming the immune response and creating a cytokine storm.

ANSWER: d 15. Schistosomiasis is a debilitating and potentially fatal disease caused by the helminthic parasite Schistosoma.

Which antibody is specific for helminth response? a. IgA b. IgD c. IgE d. IgG e. IgM ANSWER: c 16. Leishmaniosis is a disease that can either be fatal to its host or will be cleared by the immune response of the host. Which pathway is responsible for clearing leishmaniosis? a. Memory B cells b. Complement c. Plasma cells d. TC cells e. TH cells ANSWER: e 17. Some species of fungi are part of the normal microbiota or normal microbial flora of a host organism. How does the immune system differentiate between "good" fungi and "bad" fungi? a. Good fungi only reside in certain places and thereby will not trigger an immune response. b. Good fungi are weakly virulent, whereas bad fungi are highly virulent. c. Fungi are differentiated based on their cytokine production. d. Low levels of any fungi are ignored by the immune system. e. PAMPs such as motifs in peptidoglycan are used to mark fungal cells.

ANSWER: b 18. Cryptococcus may spread throughout an infected host. By what mechanism is Cryptococcus controlled by the acquired immune system? a. Activation of TH cells b. Degranulation of eosinophils and IgE c. Expression of TNF-α d. Granuloma formation Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 e. Plasma cell activation ANSWER: d 19. Primary virulence in fungi indicates a. an aggressive fungal infection. b. infection in a healthy person by a fungal species with high pathogenicity. c. infection by an opportunistic fungal species with low pathogenicity. d. infection by a multidrug-resistant fungal species. e. infection by multiple fungal species at once.

ANSWER: b 20. People encounter fungi on a daily basis, yet few healthy individuals develop fungal infections. Each of the following are mechanisms of the innate immune system that help prevent or limit fungal infections in healthy individuals EXCEPT a. neutrophils are especially good at phagocytizing fungal cells. b. normal microbial flora (commensals) limit fungal growth by toxin (antimicrobial) production. c. normal microbial flora use available nutrients and colonization space on the host, which makes the host an inhospitable environment for fungal cells. d. PAMPs such as β-glucans, mannans, and chitin are recognized by innate immune cells. e. several species of fungi are able to block PRR binding.

ANSWER: e 21. Acquired fungal immunity is supported by a. multiple antifungals and vaccines that are available. b. normal flora species that produce new antimicrobial compounds. c. plasma-cell and memory B-cell activation. d. TH1 and IFN-γ production. e. TNF-α and TC production.

ANSWER: d 22. Which type of pathogen mutates at the HIGHEST rate? a. HIV b. Influenza c. E. coli d. Plasmodium falciparum e. Candida sp.

ANSWER: a 23. Which of the following is NOT considered to be a newly emerging infectious disease? a. Ebola b. Legionnaires disease (Legionella) Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 c. Multidrug-resistant tuberculosis d. SARS e. West Nile ANSWER: c 24. Re-emerging infectious diseases present a major problem worldwide. What actions can be taken to prevent the spread of re-emerging infectious diseases such as whooping cough (Bordetella pertussis)? a. Create new antibiotics, antifungals, and antivirals to treat existing strains of pathogen and limit development of multidrug resistances. b. Ensure proper precautions during travel, especially for airborne pathogens. c. Maintain rigorous vaccination programs for all healthy individuals. d. Provide herd immunity during outbreaks. e. All of the answers are good preventive actions.

ANSWER: e 25. What is herd immunity? a. A global vaccination day established by the World Health Organization to ensure every person on the planet is vaccinated against a particular pathogen. The last herd immunity day was in the early 1980s with smallpox. b. A vaccination program started by progressive nations to prevent the spread of prion diseases such as Mad Cow (BSE). c. Herd immunity refers to a special vaccination method whereby immunocompromised individuals are given vaccines made only of antibodies. d. Receiving all government recommended vaccines in one day. This produces the strongest immune response possible but frequently leaves the person being vaccinated experiencing malaise (generally feeling bad) and feeling feverish. e. Vaccinating the majority of a population to protect immunocompromised individuals from a particular pathogen.

ANSWER: e 26. Which is an example of a fomite? a. a shared computer keyboard b. a mosquito c. sewage-contaminated water d. an infected rodent e. an infected human ANSWER: a 27. Which disease is spread via the oral-fecal route? a. cholera b. tetanus c. chlamydia Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 d. COVID-19 e. bubonic plague ANSWER: a 28. Physical barriers are an important (and often effective) defense against various types of potential invaders.

Summarize one method by which many different pathogens have evolved to use other organisms to bypass this layer of protection.

ANSWER: Many diseases are spread by vectors, or a third species that spreads disease into a host. These vectors are often parasitic insects that feed on blood meals and have specialized feeding organs that are able to break through the skin and other physical barriers. Examples of vector-borne diseases include Leishmania, Zika virus, and malaria — all of which are transmitted via different insects.

29. What are two different types of infections that can be cleared using IgA? Explain their functions.

ANSWER: IgA is used inside the body to clear viruses when in between host cells; it is also critical in maintaining barrier immunity at mucosal sites at the start of an infection. This occurs because IgA can be placed there by being translocated across cells by the poly-Ig receptor.

30. What are three different ways viral and bacterial pathogens can evade our immune systems? Provide species-specific examples in your response.

ANSWER: Answers will vary; Potential responses include: HIV and HSV can prevent antigens from being presented on MHC molecules, influenza is constantly mutating, and EBV can suppress the T-cell response via cytokine-mimicking molecules. In bacteria, Bordetella secretes adhesion molecules that prevent clearance; Streptococcus pneumonia has an extracellular capsule that prevents phagocytosis; and Pseudomonas species cleave active components of the complement system into inactive fragments.

31. What are three ways in which Plasmodium, the causative agent of malaria, is able to overcome our immune systems and medical treatment? Explain.

ANSWER: Plasmodium parasites are antigenically varied, making vaccine development difficult. Plasmodium parasites have developed resistance to many drug treatments. Plasmodium parasites live inside of red blood cells for part of their infectious cycle, making them inaccessible to much of our immune system.

32. You are analyzing the immune response of an ill patient. The patient's serum contains low levels of IgG and interferon molecules but is dominated by IgE antibodies and the production of the cytokine IL-4. What type of infection is MOST closely associated with this immune response? Explain.

ANSWER: This pair of responses is associated with TH2 infections, which are effective against large, multicellular parasites. Most commonly, this type of an immune response would be seen in a patient who is infected with a helminthic parasite.

33. Why is developing an effective response to trypanosome infection challenging for our immune system?

ANSWER: Trypanosoma is covered in molecules of VSG, or variable surface glycoprotein. Our bodies can develop a strong antibody response to VSG, which in turn clears most of the pathogens. However, the parasite encodes many copies of the gene for VSG, and the copy actively being expressed shifts randomly during the course of an infection. In summation, this means that every few weeks the host Copyright Macmillan Learning. Powered by Cognero.

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Chapter 17 needs to "restart" and develop a new primary immune response.

34. Define "emerging disease," and provide an example of one.

ANSWER: An emerging disease is a disease that has only been around for less than 20 years, or where the number of cases has significantly increased during that time. There are many examples, such as Ebola, Zika virus, West Nile virus, and a new strain of the Candida fungus. Reemerging diseases (like polio and TB) were previously controlled but now have increasing case numbers due to changing human behavior, drug resistance, and/or travel.

35. In efforts to cut funding for basic research, lobbyists and politicians will often frame said research as being wasteful, or without purpose. You are studying a harmless virus that exclusively affects bats. Using an example from the text, pose a counter argument defending the importance of your research.

ANSWER: There are many new diseases emerging in the 21st century. Often, these diseases are viral in nature and "jump" to humans from their natural, animal hosts. Consider the SARS coronavirus: this virus made an unpredictable jump to humans (zoonotic spread) in 2003. However, because researchers had been studying other less pathogenic coronaviruses for years prior, they had the ability to quickly identify and contain the source of this outbreak.

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Chapter 18 1. In what situation is a toxoid vaccine an effective strategy? What special care has to be taken when preparing them? Explain.

ANSWER: Toxoid vaccines are useful against a specific subset of diseases caused by bacterial pathogens.

These diseases, such as diphtheria or tetanus, are caused by a specific toxin produced by the pathogen; if it is neutralized by an effective antibody response that pathogen becomes virulent.

These vaccines can be very effective, but special care must be taken when inactivating the toxin protein - it can no longer cause the symptoms associated with the disease but still must be close enough to the original structure to produce an effective immune response.

2. Vaccines are MOST readily made against a. bacteria, because their cell walls remain relatively unchanged from generation to generation. b. fungi, because several species of fungi are commensals, therefore priming the immune response to readily produce antibodies to the new vaccine. c. helminths, because they are large organisms and make for easy targets. d. prions, because they are new microbe so there is much research effort to stop prion-related diseases. e. viruses, particularly RNA viruses, because their cell receptors are unchanging and bind human cell receptors.

ANSWER: a 3. Modern-day vaccines try to elicit an immune response from a. memory B cells. b. cytotoxic T cells. c. hematopoietic stem cells. d. innate immune cells. e. naïve B cells and TH cells.

ANSWER: e 4. Which of the following is an example of a passive immunization? a. Antibodies against rabies given to someone who was bitten by a potentially rabid dog b. Heat-killed flu antigen grown in chicken eggs c. Live viral antigen given on a sugar cube to protect against polio d. All of the answers are correct. e. None of the answers are correct.

ANSWER: a 5. Which maternal antigens are protective against diseases such as diphtheria, tetanus, streptococcal infections, and measles? a. IgA and IgE b. IgA and IgG c. IgD and IgE d. IgG and IgM e. All classes of immunoglobulins.

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Chapter 18 ANSWER: b 6. Why does active immunity produce long-term immunity better than passive immunity? a. Active immunity always leads to having the illness though in a milder form than an unvaccinated individual. b. Antibodies do not produce long-term immunity because they break down after two weeks. c. During active immunity, antigens for the disease are presented to the immune system through classical antigen presentation mechanisms, so an active B-cell response and immunologic memory develop. d. Long-term storage of antibodies maintains vaccine integrity; however, antigens cannot be stored long term. e. All of the answers are correct.

ANSWER: c 7. Several vaccines are combination vaccines and are used to vaccinate people against two or more pathogens.

One example of a combination vaccine is the TDaP vaccine (tetanus, diphtheria, and pertussis). How does a combination vaccine develop immunologic memory to more than one pathogen? a. Allergic reactions are less common with combination vaccines than with single-antigen vaccines. b. Combination vaccines develop immunity against very similar or the same (broad spectrum) antigens. c. Combination vaccines are more economical to produce than single vaccines. d. Each antigen target included in the combination vaccine must be different enough so that the immune system can recognize the target antigen on the pathogen cell. e. Similar antigens can be chemically modified so that the immune system will recognize each antigen as unique.

ANSWER: c 8. What would happen if a person who is undergoing chemotherapy were given a live virus vaccine against polio? a. The cancer patient would likely develop a strong immune response to the vaccine because a live viral antigen was used. b. The cancer patient would likely develop polio because the immune system is compromised and would not be able to fight off the live virus. c. The chemotherapy the cancer patient is receiving would inactivate the vaccine by killing the live polio virus. d. There would be no effect, as the cancer patient does not produce a high number of immune cells for the polio virus to interact with. e. Using a live viral antigen in a vaccine is lethal to immunocompromised people because their immune system would be overwhelmed and toxic shock would occur.

ANSWER: b 9. Which infectious disease is the BEST example of "original antigenic sin?" a. HIV b. Influenza Copyright Macmillan Learning. Powered by Cognero.

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Chapter 18 c. Measles d. Tapeworms e. Toxoplasma ANSWER: b 10. What type of vaccine would be MOST effective against tuberculosis, a disease that requires a strong CD4+ T-cell response? a. Toxoid b. DNA c. Subunit d. Inactivated e. Live attenuated ANSWER: e 11. Which of the following vaccine types is used in the prevention of pertussis or, “Whooping cough,” caused

by Bordetella pertussis? a. subunit (toxoid) b. subunit (polysaccharide) c. live, attenuated d. viral vector e. mRNA ANSWER: a 12. The initial vaccines used to protect against SARS-CoV-2 were _____. a. monovalent b. bivalent c. trivalent d. pentavalent ANSWER: a 13. Which of the following vaccines is NOT part of the early childhood immunization schedule (birth-to-12 months)? a. human papilloma virus (HPV) b. measles, mumps, and rubella (MMR) c. Haemophilus influenzae type b (Hib) d. inactivated poliovirus (IPV) e. hepatitis B (HepB) ANSWER: a 14. The increased immunogenicity conferred by live, attenuated vaccines can minimally require how many immunizations before full protection is achieved?

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Chapter 18 a. 1 b. 2 c. 3 d. 4 e. 5 ANSWER: a 15. Live, attenuated vaccines should have all of the following characteristics EXCEPT: a. an ability to replicate in host cells b. an ability to adhere to host cell plasma membranes c. antigens that can be presented by host MHC class I molecules d. antigenic similarity to fully virulent strains e. can be internalized by host target cells ANSWER: a 16. Which of the following tissue types would be ideal for the administration of a live, attenuated influenza vaccine? a. upper respiratory mucosa b. skeletal muscle (intramuscular) c. the skin (intradermal) d. oral mucosa e. all of these are equally appropriate ANSWER: a 17. Which are added to vaccines to increase their immunogenicity? a. adjuvants b. toxoids c. attenuated particles d. lipid nanoparticles e. protein-polysaccharide conjugates ANSWER: a 18. Vaccination with a polysaccharide-protein conjugates confers protection against which disease? a. Haemophilus influenzae type b meningitis b. whooping cough (Bordetella pertussis) c. influenza type A d. tetanus e. measles ANSWER: a 19. Protection against which disease is conferred by immunization with a toxoid-based vaccine?

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Chapter 18 a. tetanus b. influenza c. rotavirus d. COVID-19 e. poliomyelitis ANSWER: a 20. Passive immunization would be preferable to an active immunization approach resulting in lymphocyte activation in which situation? a. an adult is bitten by a black widow spider b. an immune competent individual is exposed to an emerging influenza strain c. a child receives periodic controlled injections of allergens to reduce their allergy symptoms d. an individual is exposed to a strain of bacteria that is responsive to commonly used antibiotics e. None of these situations favor passive immunization over active immunization.

ANSWER: a 21. Which disease has NOT been either preventively controlled or eliminated altogether by widespread vaccine utilization? a. AIDS b. tetanus c. diphtheria d. rabies e. influenza ANSWER: a 22. The depot effect refers to the ability of an adjuvant to: a. slow the rate of antigen movement away from the site of injection. b. induce leukocyte secretion of proinflammatory cytokines. c. aggregate antigens and promote their phagocytosis. d. increase expression of MHC class II molecules on cell surfaces. e. encourage lymphocytes to mature and migrate to lymph nodes.

ANSWER: a 23. List the major types of vaccines. Which is the strongest? The weakest? Explain why it is often necessary to develop weaker vaccines.

ANSWER: [From strongest to weakest] live attenuated, inactivated, subunit, conjugated, recombinant, toxoid, and DNA vaccines. Although live vaccines can provide the longest-lasting and most effective protection, they are the most dangerous. When a safer formulation of a vaccine is produced, it is typically preferable.

24. Explain the importance of the antibody isotype(s) produced in response to immunization against viral pathogens.

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Chapter 18 ANSWER: Ideally, the vaccine will induce the isotypes/sub-classes that can directly protect the individual at the anatomical location where the pathogenic virus initially gains access to the body. For example, if a virus normally gains entry via mucosal surfaces in the upper respiratory system, the ideal antibody response would involve dimeric secreted IgA on mucosal surfaces where it can neutralize infectious particles before they interact with their receptors and cause disease.

25. How are attenuated viral vaccines against human diseases produced?

ANSWER: Attenuated vaccines are commonly produced either through genetic engineering or adaptive passaging. When genetic engineering is used, at least one gene required for virulence and/or survival in host cells is removed. Depending on which gene or genes were removed, these viruses may be able to infect cells but not cause illness or replicate in host cells.

When adaptive passaging is used, infectious viral particles are cultured under unusual conditions, such as in non-human primate cells, and allowed to acclimate to those conditions. Over time, the viruses adapt to reproduce under the unusual growth conditions and lose their ability to reproduce in human cells. When administered to humans, the attenuated viral particles are capable of binding to the cellular receptors that pathogenic viruses use to gain entry to human cells, but cannot reproduce.

In both cases, the attenuated viral components can be broken down by normal mechanisms and presented via MHC class I proteins to provoke a strong CTL response, as well as TH1 and antibody responses.

26. Explain how the DTaP vaccine differ from the live, attenuated influenza vaccine (FluMist). Be sure to discuss the components and properties of each vaccine, the sites of administration, and how each vaccine induces immunity.

ANSWER: The DTaP vaccine contains inactivated toxins (toxoids) from three bacterial pathogens, Corynebacterium diphtheriae, Bordetella pertussis, and Clostridium tetani. It is used to induce strong neutralizing antibody responses against the illness-causing toxins rather than the pathogen. In contrast, the live, attenuated influenza vaccine (FluMist) confers protection against a few strains of influenza by inducing a strong cell-mediated immune response at the normal site of infection, the upper respiratory tract. The viral particles in this vaccine are adapted to grow under colder than usual conditions and cannot replicate in the human body.

The antigenic components of the vaccines also differ in their ability to enter host cells and the antigen-processing pathways used. Particles from the live, attenuated influenza vaccine can enter host cells, and antigen peptides are produced by the endogenous antigen processing pathway before presentation on MHC class I molecules. The toxoid components of the DTaP vaccines cannot enter cells; instead, the proteins are processed by the exogenous antigen processing pathway and presented on MHC class II molecules.

The DTaP vaccine is introduced into the body through intramuscular injection, whereas the live, attenuated influenza vaccine is introduced intranasally using an aerosolized mist. Both can be used to induce systemic immunity, but the live, attenuated influenza vaccine can also theoretically induce mucosal immunity.

27. Following the initial development of a vaccine candidate in preclinical stages, what are the next phases of clinical trials required for approval of the vaccine by the United States Food and Drug Administration (FDA)?

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Chapter 18 ANSWER: Before obtaining approval by the United States FDA, a vaccine candidate must progress through phase I, II, and III clinical trials. Each phase evaluates the vaccine against different criteria. Phase I trials evaluate the vaccine's safety in small groups of trial volunteers, whereas phase II trials evaluate the vaccine's efficacy, i.e., its ability to confer protection in a volunteer pool. Larger phase III trials evaluate the effectiveness of the vaccine against specific clinical benchmarks. A subsequent phase, phase IV, occurs after approval. During this final phase, officials monitor patient data, looking in particular for side effects that could not necessarily have been observed in the smaller phase I–III test cohorts. In some cases, the FDA may grant emergency-use authorization (EUA) for a vaccine before all phase I–III clinical trials are complete. In these cases, the vaccine is approved for specific uses while clinical trial data is still being collected because the potential benefits outweigh the potential risks.

28. What specific type(s) of additives can be used to elicit improved recruitment of immune system elements to the site of injection, and what receptor(s) would most likely be involved in the recognition of these additives?

ANSWER: PAMPs can be included in vaccines to improve the recruitment of immune system components to the site of injection. These PAMPs should be ligands for PRRs that are known to elicit a proinflammatory response. For example, the incorporation of bacterial PAMPs into adjuvants or other vaccine components allows for activation of TLRs such as TLR-2 heterodimers, TLR-4, and others that activate NF-κB. This results in the secretion of pro-inflammatory cytokines like TNF-α that can activate both resident immune cells and non-immune cells near the site of injection to recruit innate immune cells from within the tissue and the bloodstream, produce acute phase proteins, and stimulate further leukocyte production. All of these contribute to the improved delivery of formulated vaccine antigens to appropriate secondary lymphoid tissue sites, leading to more vigorous adaptive immune responses.

29. Explain whether vaccine boosters stimulate primary or secondary immune responses, and under what circumstances it may be appropriate to use boosters.

ANSWER: Boosters stimulate secondary immune responses because the immunized individual's immune system has already been primed against the antigen by the initial exposure. The booster response takes advantage of the pre-formed immunological memory conferred by the first exposure.

Booster doses are appropriate in cases in which the targeted pathogen has a high mutation rate and/or the most prevalent strain(s) change on a regular basis. In these cases, the vaccine may be updated to better tailor protection to circulating pathogens.

Boosters are also appropriate when using component vaccines that yield responses that wane over time. In such cases, the immunized individuals can lose protective immunity conferred by the vaccine when protective antibody titers fall below the threshold required for full protection. Finally, the age and immune status of the individual being vaccinated factor into the use of boosters, particularly in the cases of very young children and older adults. In these groups, for different reasons, the immune responses may not be as vigorous as would otherwise be seen.

30. Compare and contrast conjugate vaccines and adjuvants.

ANSWER: Conjugate vaccines and adjuvants are both designed to increase the overall immune response of the individual being vaccinated. Conjugate vaccines require the mildly-to-non-immunogenic antigens from a pathogen to be covalently attached to a carrier protein that is more immunogenic. Adjuvants take advantage of non-covalent interactions within the antigen preparation to be injected that lead to Copyright Macmillan Learning. Powered by Cognero.

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Chapter 18 prolonged exposure to the antigen once it has been injected and elevated recruitment of the immune system of the injected individual. By stimulating an inflammatory response at the injection site that can lead to improved antigen trafficking to nearby draining lymph nodes, it becomes possible to achieve a more vigorous adaptive immune response.

31. Explain the rationale behind investigation into engineering strains of Salmonella typhimurium with genes from Vibrio cholerae as a potential vaccine candidate. How does this differ from other currently existing vaccinations against other bacterial toxins?

ANSWER: Salmonella species that cause disease in humans normally do so by colonizing the gut mucosa.

Since cholera toxin is the primary virulence factor in cholera, by engineering segments of the genes encoding cholera toxin, as well as other potential targets into attenuated strains of Salmonella typhimurium that normally infect gut epithelium, it becomes possible to deliver cholera antigens directly to the tissues where they normally cause disease. Specific targeting of the affected tissue can lead to production of secreted IgA and, thus, the direct protection of that tissue instead of the generalized neutralizing antibody responses that are seen from other toxoid vaccines like TDaP. 32. Explain the rationale behind using a conjugate vaccine against Haemophilus influenzae type b (“Hib”) instead of a more traditional subunit vaccine.

ANSWER: H. influenzae type b possesses a polysaccharide glycocalyx on its outer surface that is both weakly immunogenic and effectively masks the more immunogenic antigens normally found on the outer surfaces of the bacterial cells, preventing their recognition by host PRRs. By linking the weakly immunogenic polysaccharide components with more highly immunogenic proteins in a conjugate vaccine, the immune system can be more efficiently directed toward the bacterium than would occur with a subunit vaccine against this pathogen.

33. With regard to their valency, how do the original COVID-19 mRNA vaccines differ from traditional influenza vaccines (either injected subunit vaccines or intranasal live-attenuated influenza vaccines)?

ANSWER: The original mRNA COVID-19 vaccines are monovalent in their protection as they stimulate an immune response against one version of the spike protein antigen of the SARS-CoV-2 viral particle.

Traditional influenza vaccines are multivalent, typically directed at three or four distinct strains of influenza type A and type B in a single administration, whether administered via intramuscular injection or intranasal mist.

Updated, bivalent COVID-19 vaccines have become available. These vaccines stimulate an immune response against two versions of the spike protein; however, as of late 2022, these bivalent vaccines are used only for booster doses.

34. Why is it important that toxoid vaccines like DTaP not be introduced to children younger than 12 months?

ANSWER: The transfer of maternal IgG1 across the placenta means that the newborn infant has a full cohort of circulating antibodies against whatever the mother had previously responded to up to and throughout the pregnancy. Since there is a high likelihood of the mother having been previously exposed to one or more versions of this vaccine prior to becoming pregnant, it could be reasonably expected that there should be neutralizing antibodies against the toxoid components of the vaccine among those passively transferred in utero. If B cells in the infant possess BCRs specific for the components of the toxoid while maternal neutralizing IgG remains present, those B cells can be inhibited from responding to the vaccine. By 12 months of age, enough of the maternal IgG should have been degraded to ensure that the infant will respond appropriately to the vaccine and actively Copyright Macmillan Learning. Powered by Cognero.

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Chapter 18 produce antibodies and memory cells of its own.

35. Antivenoms are tools of passive immunization that can be used in emergency situations when an individual has been bitten or stung by a venomous reptile, insect, or other such organisms. Briefly explain how these drugs could be developed.

ANSWER: Venom harvested from the source of interest must be injected into animals other than humans such that the active protein components of the venom can be taken up by the immune system of the animal and cause minimal harm to the animal. Over a course of initial exposure followed by multiple boost inoculations, high titers of neutralizing antibodies specific for the venom components can be generated in the animals. The antisera can be collected and venom-specific antibodies can be isolated. Injection of these isolated antibodies into an individual that has been bitten or stung allows the toxic components to be neutralized before binding their receptors, thus mitigating further damage to the individual.

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Chapter 19 1. Primary immunodeficiencies a. are inherited. b. are severe. c. alter the complement pathway. d. affect a range of cell types. e. are contagious.

ANSWER: a 2. Primary immunodeficiencies are NOT a. are the most common primary immunodeficiencies. b. are generally not especially severe. c. do not impair complement fixation. d. both are the most common primary immunodeficiencies and are generally not especially severe. e. both are the most common primary immunodeficiencies and do not impair complement fixation.

ANSWER: d 3. Primary immunodeficiencies affecting T cells tend to be MORE severe than those affecting B cells because a. T cells control the innate immune response. b. T cells regulate antigen presentation. c. T cells regulate the adaptive immune response. d. T cells can trigger apoptosis. e. None of the answers are correct.

ANSWER: c 4. Primary immunodeficiencies that affect B cells are often characterized by a. T cells help fully activate B cells. b. T cells help trigger class switching. c. T cells help regulate antigen presentation by dendritic cells. d. T cells help to both fully activate B cells and trigger class switching. e. T cells help to both fully activate B cells and regulate antigen presentation by dendritic cells.

ANSWER: d 5. Severe combined immunodeficiency (SCID) a. is a result of the absence of macrophages or B cells. b. affects only part of the adaptive immune response. c. can be caused by failure of TAP transporters. d. can be caused by failure of V(D)J recombination. e. All of the answers are correct.

ANSWER: d 6. Severe combined immunodeficiency (SCID) can be caused by Copyright Macmillan Learning. Powered by Cognero.

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Chapter 19 a. failure of V(D)J recombination. b. failure of cytokine receptors. c. failure of T-cell receptor signaling. d. failure of lymphoid progenitor survival. e. All of the answers are correct.

ANSWER: e 7. Children born with SCID often first become infected with fungi or viruses because a. their T cells function well enough to handle bacterial infection. b. maternal antibodies provide protection against bacteria for several months. c. their macrophage function is not impaired, and it can contain bacterial pathogens. d. complement lysis of bacteria, especially by the alternative pathway, is sufficient protection. e. None of the answers are correct.

ANSWER: b 8. Deficiency in the common γ chain of cytokine receptors is a particularly severe problem because a. it is encoded on the X chromosome, so males are hemizygous. b. it is used by several cytokine receptors. c. it leads to defects in T cells, B cells, and NK cells. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 9. Adenosine deaminase deficiency leads to SCID, even though a. cells have alternate pathways to use. b. it primarily affects dendritic cells. c. it is only used in adults. d. the gene is not part of the immune system. e. None of the answers are correct.

ANSWER: d 10. Bare lymphocyte syndrome does NOT a. produce a phenotype like SCID. b. result from a defect in the TAP transporter. c. lead to a lack of MHC class II. d. result in a deficiency of cytotoxic T cells. e. increase susceptibility to viral infections.

ANSWER: c 11. Hyper IgM syndrome a. is autosomal.

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Chapter 19 b. is a result of a helper T-cell defect. c. includes normal affinity maturation. d. has impaired cytotoxic T-cell responses. e. None of the answers are correct.

ANSWER: b 12. X-linked agammaglobulinemia (X-LA) a. is more common in women than men. b. has increased IgG levels. c. has increased susceptibility to fungal infections. d. can be treated with antiviral medication. e. results from a B-cell signaling defect.

ANSWER: e 13. A defect in NADPH is associated with which of the following disorders? a. Job syndrome b. Chronic granulomatous disease c. Severe combined immunodeficiency d. X-linked agammaglobulinemia e. None of the answers are correct.

ANSWER: c 14. Defects in which cell type are commonly associated with increased cancer risk? a. NK cells b. T cells c. B cells d. Macrophages e. Granulocytes ANSWER: a 15. Which of the following is NOT a good candidate for immunodeficiency replacement therapy? a. Immunoglobulin b. IFN-γ c. Hematopoietic stem cells d. Defective genes e. All of the answers are good candidates.

ANSWER: e 16. Which primary immunodeficiency has been co-opted in mice to study a secondary immunodeficiency? a. SCID b. RAG knockout Copyright Macmillan Learning. Powered by Cognero.

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Chapter 19 c. RAG/IL-2 γ chain knockout d. APECED e. Bare-lymphocyte syndrome ANSWER: c 17. Secondary immunodeficiencies a. can be brought on by multiple factors. b. can be contagious. c. can be inherited. d. can be both brought on by multiple factors and contagious. e. can be both brought on by multiple factors and inherited.

ANSWER: d 18. Hypogammaglobulinemia differs from common variable immunodeficiency in that it a. is not heritable. b. is characterized by low levels of IgG. c. can be treated by IV-gamma globulin. d. is relatively mild. e. All of the answers are correct.

ANSWER: a 19. Agent-induced immunodeficiency does NOT a. lead to an immunosuppressed state. b. accompany transplant treatments. c. come about after radiation treatment. d. get passed on in gametes. e. All of the answers are true.

ANSWER: d 20. Which of the following is NOT an acquired immunodeficiency? a. HIV b. Malnutrition c. Acquired hypogammaglobulinemia d. SCID e. Extremes of age ANSWER: d 21. HIV-1 a. is a retrovirus. b. belongs to the lentivirus family. c. integrates as a provirus.

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Chapter 19 d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 22. HIV-1 and HIV-2 are very similar EXCEPT that a. HIV-2 progresses far more quickly. b. HIV-2 is resident in high percentages in some populations. c. HIV-1 is thought to have arisen from FIV, Feline Immunodeficiency Virus. d. HIV-2 is more widespread. e. All of the answers are true.

ANSWER: b 23. HIV-1 is NOT a. most often transmitted by sexual contact. b. most often transmitted by blood products. c. able to be transmitted from mother to children during birth. d. treatable by antiviral drugs. e. able to progress over the course of many years.

ANSWER: b 24. Which of the following routes is thought NOT to be a major factor in HIV-1 early infection? a. Transmission by Langerhans cells b. Activation of local CD4+ cells c. Transmission by macrophages d. Transmission by dendritic cells e. All of the answers are major factors.

ANSWER: c 25. The HIV-1 pol protein encodes a. a protease. b. an integrase. c. a reverse transcriptase. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 26. Because reverse transcriptase is an error-prone enzyme, it follows that a. HIV-1 will have a high mutation rate. b. drugs targeting HIV will affect only part of any population. c. treatment of HIV will produce temporary results only.

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Chapter 19 d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 27. Because the gp120 protein on HIV-1 interacts with both CD4+ and CCR5, it is NOT reasonable to conclude that a. CD4+ cells will not be infected. b. CCR5 cells will not be infected. c. CCR5 deficiency should confer HIV-1 resistance. d. blocking CCR5 should provide some protection. e. blocking CD4+ is a useful therapeutic approach.

ANSWER: e 28. Multidrug treatment of HIV-1 is preferred over single-drug treatment because a. the high mutation rate of HIV-1 means that many drugs are not likely to work against it. b. multidrug treatment places a more challenging selective pressure on the virus; to survive requires multiple mutations. c. protecting itself against one drug makes the virus less able to protect itself against the others. d. the drugs work synergistically with each other. e. one drug makes the virus more susceptible to the others.

ANSWER: b 29. Which of the following does NOT improve prognosis after exposure or infection with HIV? a. Antiviral therapy b. Infection with HIV-2 c. A strong antibody response d. A strong and varied CD8+ T-cell response e. A deletion in the host gene for CCR5 ANSWER: c 30. What is often the FIRST clue that an individual may have a primary immune deficiency? Explain why it takes time for the deficiency to manifest, despite being inherited and present at birth.

ANSWER: The first clue is often recurring illnesses in childhood, sometimes combined with early evidence of autoimmune diseases. These illnesses do not start immediately because newborn infants are protected by maternal antibodies during the first months of life.

31. Define SCID and list three of its MOST common causes.

ANSWER: SCID stands for "Severe Combined Immunodeficiency Disorder." It refers to immunodeficiencies that affect both B and T cells. SCID has many causes, including reticular dysgenesis, premature death of lymphoid precursors, defects in V(D)J rearrangement, cytokine signaling, or CD3 function.

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Chapter 19 32. How can a variety of single-gene mutations all lead to the same condition of MSMD, or Mendelian inheritance of susceptibility to mycobacterial diseases? Explain.

ANSWER: Control of the intracellular mycobacterial infections TB and leprosy requires a specific immune response. Macrophages and dendritic cells are alerted to infection via PPRs (such as TLR2 and TLR4). These cells then activate and produce IL-12 and IL-23, which cause TH and NK cells to produce IFN-γ, IL-17, and TNF-α. Failure at any of these steps, including internal signaling events, can lead to lack of control and MSMD. So far, mutations in the genes for IL-12, IL-12R, the IFN-γ receptor, and multiple signaling molecules have all been implicated.

33. Some immunodeficiencies can also be the cause of autoimmune diseases. Explain how this paradox is possible.

ANSWER: A critical aspect of the immune response is self-tolerance; if genes important for preventing immune responses against self-antigens are impaired, the overall result can be autoimmune disease. One example is APECED, a disease that is caused by mutations in the AIRE gene. AIRE is critical for negative selection of autoreactive lymphocytes - without it, individuals are more likely to develop autoimmune diseases. Other genes in this category are FoxP3 and CTLA4.

34. Explain how HIV enters a new host. Once inside, how is HIV then able to enter and replicate inside of host cells?

ANSWER: HIV is only spread through direct contact with infected body fluids (such as semen, vaginal secretions, blood, and breast milk). HIV is a retrovirus that infects CD4+ cells; once it has entered a cell, a viral enzyme called "reverse transcriptase" turns HIV's single-stranded RNA genome into a double-stranded DNA molecule. This new DNA genome is then inserted into a host chromosome via the viral integrase enzyme, creating a provirus. Viral genes are now expressed from here and new virions are assembled and released.

35. Characterize the three clinical phases of untreated HIV infection, starting with initial infection.

ANSWER: The first weeks of infection are considered the acute phase, wherein viral load spikes and CD+ Tcell levels crash. This phase may be clinically asymptomatic or be accompanied by a flulike set of symptoms. After this, the host develops virus-specific CD8+ T cells and controls the infection by lowering viral loads to a lower set point. This phase is clinically asymptomatic and may last for months or years. During this time, however, viral levels are slowly rising and CD4+ T-cell counts are slowly dropping. The host develops AIDS, which is defined by a T-cell population of < 200 cells/μL of blood and 1 or more opportunistic infections. This phase is followed by death in the absence of treatment.

36. Name two different classes of drugs that can prevent HIV replication. How are there so many drugs that work against the virus? Explain.

ANSWER: There are many options: nucleoside reverse transcriptase inhibitors (AZT), nonnucleoside inhibitors of the same enzyme, drugs designed to interfere with the viral protease (preventing new viruses from maturing), integrase (or, "preventing integration") enzymes, and drugs that prevent entry at the cell surface. Multiple HIV gene products do not have close homologs in people, making them attractive drug targets. Also, HIV is causing a pandemic globally and is intensely studied - this increases the chances of successfully developing a new drug(s).

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Chapter 19 37. Developing a vaccine against HIV is challenging - explain why. Describe two failures and one potential success.

ANSWER: There are multiple factors that make a successful HIV vaccine so difficult to develop. First, the virus has a great deal of genetic diversity - a vaccine that protects against one isolate may not be effective against others. Second, the virus mutates rapidly in both populations and within patients, so critical antigens are always changing. Third, because HIV is a retrovirus that integrates into the host's genome, any infection becomes life-long. One early vaccine trial that tried to develop neutralizing antibodies failed for the first two reasons provided. A later trial emphasizing cellular immunity increased infections; the reasons are not entirely understood, but T cells activated by the vaccine may have potentially provided targets for infection. In 2009, however, a combination DNA vaccine prime and canarypox vector-boost provided some degree of protection in a clinical trial.

38. Identify three nondrug conditions that can lead to a person NOT developing AIDS after being exposed to HIV. Explain.

ANSWER: First, the patient may have a deletion in the HIV coreceptor CCR5 that renders that protein nonfunctional. These patients are essentially immune to infection. Second, the patient may have been exposed to HIV-2, which is less virulent and does not always progress clinically to AIDS. Finally, the patient may be a long-term nonprogressor - one of the 2% of patients whose immune systems are able to control HIV for long periods of time.

39. Explain the relationship between the HIV receptors CD4+, CCR5, and CXCR4.

ANSWER: All of these are host molecules that the HIV virion and GP120 use to bind to and enter cells. All HIV particles must first bind to CD4+ on immune system cells. Next, GP120 binds either to CCR5 or CXCR4 — these molecules are known as coreceptors, as a result. Scientists have identified a region on the viral glycoprotein that determines which coreceptor is utilized. CCR5 and CXCR4 are located on different populations of cells, so "R5" tropic viruses initiate infection of a new host, whereas "X4" viruses emerge later and are responsible for progression to AIDS.

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Chapter 20 1. The major difference between benign and malignant tumors is that a. benign tumors are capable of metastasis. b. malignant tumors do not invade surrounding tissue. c. benign tumors are not neoplasms. d. malignant tumors are capable of uncontrolled growth. e. All of the answers are correct.

ANSWER: d 2. The MOST common kind of cancers are carcinomas, which a. are derived from epithelial tissue. b. include breast and colon cancer. c. include leukemia. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: c 3. Metastasis is NOT which of the following? a. A property of benign tumors b. Invasion of new sites by tumor cells c. The production of secondary tumors d. A property of malignant tumors e. Extremely dangerous ANSWER: a 4. Hematopoietic tumors include all but which of the following? a. Lung cancer b. Leukemia c. Lymphoma d. Myeloma e. All of the answers are hematopoietic tumors.

ANSWER: a 5. Leukemias can be defined as a. either acute or chronic, where chronic is longer lasting. b. either acute or chronic, where chronic involves less mature cells. c. either lymphocytic or myelogenous, where lymphocytic involves lymphocytes. d. either lymphocytic or myelogenous, where lymphocytic involves any white blood cell. e. both acute/chronic and lymphocytic/myelogenous.

ANSWER: c 6. Malignant transformation of cells usually means that they Copyright Macmillan Learning. Powered by Cognero.

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Chapter 20 a. grow in a density-independent fashion. b. have reduced dependence on growth factors. c. are not anchorage dependent. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 7. Carcinogens are NOT a. agents that induce DNA mutations. b. agents that induce transformation. c. energy such as ionizing radiation. d. viruses such as Epstein-Barr virus. e. chemicals such as formaldehyde.

ANSWER: d 8. Oncogenes a. can be found in some viruses. b. have been found to be normal parts of cellular function. c. often regulate cell growth. d. are mutated or dysregulated in cancer. e. All of the answers are correct.

ANSWER: e 9. Tumor-suppressor genes are NOT a. normally regulators of cell growth. b. called anti-oncogenes. c. causes of cancer when they become inactive. d. causes of cancer when they become activated. e. either normally regulators of cell growth or causes of cancer when they become inactive.

ANSWER: d 10. Hallmarks of tumor transformation include all of the following EXCEPT a. growth-factor independence. b. dependence of tumor suppressors. c. angiogenesis. d. evasion of apoptotic signals. e. All of the answers are hallmarks of tumor transformation.

ANSWER: c 11. Which of the following is NOT a gene class that can lead to cancer? a. Host oncogenes Copyright Macmillan Learning. Powered by Cognero.

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Chapter 20 b. Viral oncogenes c. Apoptotic genes d. Tumor-suppressor genes e. Tumor-activator genes ANSWER: a 12. Which of the following is a gene that is commonly mutated in cancers? a. Ras b. TP53 c. ADA d. RAG e. Both Ras and TP53 are commonly mutated in cancers.

ANSWER: e 13. MOST tumor antigens a. are products of viruses. b. target the tumor for immune recognition. c. are not recognized as self-antigens. d. are oncogene products. e. All of the answers are correct.

ANSWER: d 14. T cells can recognize tumor antigens from each of the following classes, EXCEPT a. antigens encoded by genes exclusively expressed by tumors (e.g., viral genes). b. antigens encoded by variant forms of normal genes that are altered by mutation. c. antigens that are expressed at lower than normal levels. d. antigens normally expressed only at certain stages of development. e. antigens that are overexpressed in particular tumors.

ANSWER: c 15. Tumor-specific antigens a. trigger T-cell killing of the tumor. b. can be difficult to identify. c. are strongly selected against by the immune system. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 16. Tumor-associated antigens a. are not normal cellular proteins. b. are viral proteins.

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Chapter 20 c. have abnormal expression patterns. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: c 17. Alpha-fetoprotein (AFP) is a. normally expressed by embryos. b. normal for pregnant women. c. expressed aberrantly by some cancers. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 18. What is the definition of an oncofetal tumor antigen? a. An oncogene fused to a fetal gene. b. An antigen derived from a reactivated fetal gene. c. An antigen found in a nonviable pregnancy. d. An antigen which is not immunogenic. e. All of the answers are correct.

ANSWER: b 19. The immune system does NOT control cancer with which of the following mechanisms? a. Elimination of transforming viruses. b. Elimination of tumor inflammation. c. Induction of apoptosis in cancer cells. d. Induction of anergy in cancer cells. e. All of the answers are mechanisms used.

ANSWER: d 20. The theory that the immune system actively monitors and eliminates cancer cells is supported by the observation(s) that a. AIDS patients have higher rates of some types of cancer than other populations. b. transplant patients on immunosuppressive therapy have higher rates of some types of cancer than other populations. c. patients who are deficient in adenosine deaminase and on immunosuppressive therapy have higher rates of some types of cancer than other populations. d. both AIDS patients and transplant patients have higher rates of some types of cancer than other populations. e. both AIDS patients and patients who are deficient in adenosine deaminase and on immunosuppressive therapy have higher rates of some types of cancer than other populations.

ANSWER: d Copyright Macmillan Learning. Powered by Cognero.

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Chapter 20 21. Immunoediting does NOT a. lead to more aggressive tumors by natural selection. b. lead to elimination of tumor cells. c. consist of elimination, equilibrium, and escape. d. extend over a period of several to many years. e. All of the answers describe immunoediting.

ANSWER: e 22. Variability in the immune response to cancer leads to observations that a. NK cells and dendritic cells can control cancer cells directly. b. NK cells and dendritic cells can activate a helper T-cell response to control cancer. c. NK cells and dendritic cells can activate a cytotoxic T-cell response to control cancer. d. TH17 cells can activate a response to control cancer. e. All of the answers are correct.

ANSWER: c 23. A key role for natural killer cells in controlling cancer is NOT supported by the a. observation that NK-deficient mice have higher than normal rates of sarcoma development. b. observation that NK cells can kill cancer cells in vitro. c. observation that many tumors down-regulate MHC genes, including NK receptors. d. observation that cellular stress up-regulates many NK receptors. e. All of the answers support the role.

ANSWER: d 24. Responses of the immune system that can promote cancer include all of the following EXCEPT a. chronic inflammation. b. inhibition of TH1 responses. c. myeloid-derived suppressor cells (MDSCs). d. CTL activation. e. All of the answers promote cancer.

ANSWER: d 25. Immunotherapy designed to target B-cell lymphoma with a monoclonal antibody is easier to administer than other immunotherapies because a. the lymphoma is more prone to apoptosis. b. an anti-idiotypic monoclonal antibody won't target bystander cells. c. the lymphoma is able to conduct class switching. d. the lymphoma is localized to specific organs. e. All of the answers are correct.

ANSWER: b Copyright Macmillan Learning. Powered by Cognero.

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Chapter 20 26. Immunotoxins work by a. inducing apoptosis in the target cells. b. recruiting complement to kill the target cells. c. delivering chemicals specifically to the target cells. d. recruiting NK cells. e. None of the answers are correct.

ANSWER: c 27. Cytokine treatment of cancer has proven problematic because a. cytokines can show in vivo toxicity. b. dosages are very hard to control properly. c. cytokines can regulate the production of other cytokines. d. cytokines exert effects on a large number of target cells. e. All of the answers are correct.

ANSWER: e 28. The use of tumor-specific T cells reintroduced to patients requires all of the following EXCEPT a. tumor-specific cells being isolated. b. tumor-specific cells being activated to overcome tumor-induced anergy. c. the patient being lympho-depleted to facilitate reintroduction. d. tumor-specific cells being depleted of autoreactive clones. e. All of the answers are required steps.

ANSWER: d 29. Manipulation of costimulatory signals has potential to treat tumors because a. tumors that do not provide costimulation induce anergy instead. b. it is relatively easy to isolate and introduce genes to tumor cells. c. modified tumors with increased costimulatory activity can be reintroduced to patients. d. blockage of CTLA-4 on tumors will increase T-cell activation. e. All of the answers are correct.

ANSWER: e 30. Which of the following is NOT a standard therapy for cancer? a. Chemotherapies b. Hormonal therapies c. Targeted therapies d. Immunotherapies e. Homeopathic remedies ANSWER: e 31. Which of the following is NOT a cancer immunotherapy?

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Chapter 20 a. Therapeutic vaccines b. mAb therapy c. Checkpoint inhibitors d. Ex vivo expansion of TIL e. Radiation therapy ANSWER: e 32. Is it better to be diagnosed with an acute lymphoma or a chronic lymphoma? Explain your answer.

ANSWER: Somewhat counterintuitively, patients diagnosed with acute lymphomas have a better clinical diagnosis. These definitions have to do with the course of the disease in the absence of treatment, and acute lymphomas often react better to treatment and can result in long-term or even permanent remission.

33. Why can a conventional vaccine for human papilloma virus also be effective at preventing cancer? Explain.

ANSWER: This vaccine is designed to prevent infection from a handful of important strains of the virus. It has the additional benefit of preventing cervical and many other types of cancer. This is possible because HPV infection is what leads to these cancers developing, meaning that HPV either contains a viral oncogene or can interfere with tumor suppressors.

34. What are the three classifications of cancer - which one is the MOST common?

ANSWER: Carcinoma, sarcoma, and blood cell cancers - a group containing myelomas, lymphomas, and leukemias. Carcinomas are by far the most common group.

35. What are the three types of host genes that, when mutated, can lead to tumor formation and cancer? For each type of gene, how do mutations lead to neoplasms? Explain.

ANSWER: The three types of host genes are oncogenes, tumor-suppressor genes, and apoptosis genes.

Oncogenes are normally involved in cell growth, so mutations upregulate their expression and/or activity. Mutations that deactivate tumor suppressors and apoptosis genes, on the other hand, are what causes cancer in those cells.

36. A tumor does not appear from normal cells overnight. Describe the series of steps that leads to transformation in vivo.

ANSWER: The first change that occurs is initiation, the starting mutation or mutations that lead to cancer. This is followed by promotion, the local accumulation of cells that contain mutations. Progression is the next step and also a combination of the first two steps - rapid growth leads to additional mutations accumulating. After one more round of mutation, metastasis occurs: the loss of adhesion and the invasion of other areas of the body.

37. Compare and contrast tumor-specific antigens and tumor-associated antigens.

ANSWER: Both TSAs and TAAs can be found in and used to identify cancer cells. The difference lies in where else these antigens can be found. Tumor-specific antigens, as their name implies, are new non-selfantigens (or epitopes). Tumor-associated antigens, on the other hand, are derived from normal host gene sequences. However, their expression pattern has changed from normal tissues - either they are only expressed in fetal development or they may be overexpressed in cancer cells. Important, both sets of antigens can be used as targets for the immune system and clinical therapy.

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Chapter 20 38. Evaluate the immune response to cancer. Why is it a "double-edged sword" that can prevent disease in some instances but inversely lead to disease in others?

ANSWER: The immune response to cancer is largely similar to that against pathogens, except that in this case, it is searching for and destroying altered self-antigens instead of non-self-antigens. In some cases, the immune response is enough to clear the tumor, but in others a phenomenon occurs known as immunoediting. In this case, less harmful or more immunogenic tumor cells are weeded out and invasive and/or poorly immunogenic cells are selected.

39. Gene sequencing from primary tumor cells has revealed a novel mutation in the p53 oncogene.

WT: MEEPQSDPS Tumor: MEDPQSDPS Interestingly, this new sequence is well displayed on the cancer patient's own HLA molecules. What two ways could this be an advantage for the patient? Explain.

ANSWER: First, because this is a mutation, the host may be able to recognize this new epitope as foreign via Tcell/MHC interactions and selectively kill the tumor cells. Also, the peptide bound to host antigenpresentation molecules may be a good candidate for recognition and destruction by CAR-T-cell therapy.

40. What are two different ways antibodies can be used as treatments for cancer? Explain.

ANSWER: First, monoclonal antibodies can be used to direct and focus the host's own immune response. These antibodies can be directed against a molecule specific to the cancer or to markers only found on the cancer's cell type. One example of the latter is CD20 on B cells for lymphomas of that cell type.

Antibodies can also be used as checkpoint inhibitors. Antibodies that bind and inhibit CTLA-4 and PD-1 can indirectly improve the host's immune response.

41. If an individual announces that they have discovered the "cure for cancer," why should you be suspicious?

Explain.

ANSWER: In this chapter of the text, we have learned that "cancer" isn't one disease but a collection of many separate diseases with some similarities. For one, there are many ways in which normal cells can mutate and begin to act like cancer cells (such as changes to p53 and K-ras). There are also multiple cell and tissue types that can turn cancerous (such as carcinomas, sarcomas, and lymphomas). For these reasons it should not be a surprise that the best treatment for one person's cancer may be substantially different from another's. There are a large and growing number of options, from traditional chemotherapy to cancer vaccines and multiple types of immunotherapy. Prognoses hopefully will continue to improve, but it is unlikely that there will ever be a single "cure."

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Experimental Systems 1. Polyclonal antibodies differ from monoclonal antibodies in all ways EXCEPT which of the following? a. They generally have fewer cross-reactivities. b. They are generally better for immunoprecipitation. c. They generally have lower affinity. d. They can vary from preparation to preparation. e. All of the answers are ways in which they differ.

ANSWER: a 2. Monoclonal antibodies make effective research tools because a. as products of a single B cell, they all have the same specificity. b. their specificity is stable over time. c. their cross-reactivity can be well characterized. d. they are produced by transformed cells and, therefore, can be produced in large quantities. e. All of the answers are correct.

ANSWER: e 3. Which of the following is NOT required to generate a B-cell hybridoma? a. Myeloma cell line b. Primary plasma cell c. Chemical fusogens d. HGPRT selection e. None of the answers are required to generate a B-cell hybdridoma.

ANSWER: e 4. Immunoprecipitation does NOT a. allow characterization of molecules bound to cells. b. take place in gel matrices. c. work well in solution. d. require the use of a monoclonal antibody. e. All of the answers are characteristics of immunoprecipitation.

ANSWER: d 5. Immunoprecipitation can be used a. with Western blotting to assess its efficiency. b. with Western blotting to determine protein abundance. c. with secondary antibodies to ascertain protein-protein interactions. d. to purify proteins. e. All of the answers are correct.

ANSWER: e 6. All of the following concerning agglutination reactions are true EXCEPT Copyright Macmillan Learning. Powered by Cognero.

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Experimental Systems a. they are used only with red blood cells. b. they only detect molecules on the surface of cells. c. they require a high degree of expertise to interpret. d. they should be done with titrations of antibodies. e. All of the answers are true.

ANSWER: c 7. Hemagglutination inhibition reactions are used to detect a. responses to bacteria. b. responses to viruses. c. proteins on the surface of red blood cells. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: b 8. ELISPOT assays a. are modifications of Western blotting. b. are used to detect individual cells. c. involve the use of "capture" antibodies. d. both involve the use of "capture" antibodies and are modifications of Western blotting. e. both involve the use of "capture" antibodies and are used to detect individual cells.

ANSWER: e 9. Design of an effective ELISA can be challenging because a. different detection systems have sensitivity that ranges over five orders of magnitude. b. the number of replicates required for any ELISA is quite high. c. the anticipated concentration of targets must be estimated to determine the sensitivity required of the assay. d. signal amplification by the assay conditions can impair interpretations. e. All of the answers are correct.

ANSWER: c 10. Which of the following does NOT describe equilibrium dialysis? a. It is used to quantitate binding between antibody and antigen. b. It depends on the ligand being able to cross a semipermeable membrane. c. It measures the amount of antibody-bound ligand compared to unbound ligand. d. It requires an enzyme amplification step. e. All of the answers describe equilibrium dialysis.

ANSWER: d 11. Surface plasmon resonance Copyright Macmillan Learning. Powered by Cognero.

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Experimental Systems a. is a relatively recently developed technique. b. depends on the molecules close to a reflective surface. c. requires that both binding and dissociation be evaluated. d. All of the answers are correct. e. None of the answers are correct.

ANSWER: d 12. Immunohistochemistry and immunocytochemistry do NOT share which of the following characteristics? a. Use of antibodies to recognize specific targets. b. Use of enzymes to amplify the signal. c. Use of irrelevant proteins, such as milk, to reduce nonspecific binding. d. Use of detergent to permeabilize the membrane. e. They do share all of these characteristics.

ANSWER: d 13. Immunohistochemistry and immunocytochemistry differ from each other in that a. immunocytochemistry analyzes tissue sections. b. immunohistochemistry analyzes individual cells. c. immunohistochemistry uses electron-gold microscopy. d. Immunocytochemistry analyzes individual cells. e. None of the answers are correct.

ANSWER: d 14. Immunofluorescence-based imaging a. allows fine-scale visualization of subcellular localization. b. has been enhanced by the availability of multiple dyes. c. has been simplified by genetic engineering to tag GFP onto target proteins. d. can take advantage of molecules that do not need antibodies to bind targets. e. All of the answers are correct.

ANSWER: e 15. Confocal microscopy improves on immunofluorescence in that it a. increases the resolution of the image. b. allows construction of three-dimensional images. c. allows detection of multiple molecules. d. is the only technique that allows use of living cells. e. None of the answers are correct.

ANSWER: b 16. Multiphoton microscopy is a variation on what type of technique? a. Confocal microscopy Copyright Macmillan Learning. Powered by Cognero.

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Experimental Systems b. FACS c. MACS d. Electron microscopy e. Immunohistochemistry ANSWER: a 17. In flow cytometry, in addition to fluorescent markers, forward (FSC) and side (SSC) scatter are measured, and a. side scatter is a reflection of the size of the cell. b. forward scatter is a measure of the amount of DNA in the cell. c. side scatter is a measure of the amount of DNA in the cell. d. forward scatter is a reflection of the internal complexity of the cell. e. None of the answers are correct.

ANSWER: e 18. Intracellular staining is a major advance in cell sorting that a. requires permeabilization of the cell membrane. b. allows detection of molecules inside the cell instead of simply at the cell surface. c. allows subcellular localization of molecules. d. both requires permeabilization of the cell membrane and allows detection of molecules inside the cell instead of simply at the cell surface. e. both requires permeabilization of the cell membrane and allows subcellular localization of molecules.

ANSWER: d 19. The major distinction between FACS and MACS is that a. MACS is not as precise as FACS. b. MACS does not use a fluorescent marker. c. MACS can be used with living cells. d. MACS can be used for intracellular staining. e. All of the answers are correct.

ANSWER: b 20. You might want to use MACS instead of FACS if you a. have a very small number of cells to sort. b. are working with cells that are especially fragile. c. are working with a very large number of cells. d. need a very high degree of accuracy. e. are using multiple antibodies.

ANSWER: c Copyright Macmillan Learning. Powered by Cognero.

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Experimental Systems 21. Which of the following is TRUE regarding propidium iodide and cell cycle analysis? a. Apoptotic cells will have more DNA than normal G1 content. b. S-phase cells will have the same DNA content as G1 cells. c. G2 cells will have more DNA than normal G1 cells. d. M cells will have the same DNA content as normal G1 cells. e. All of the answers are true.

ANSWER: c 22. Carboxyfluorescein succinimidyl ester (CFSE) can be used to track cell division because a. after pulsing the cells with it, dividing cells will incorporate more into their DNA. b. after pulsing cells with it, dividing cells will incorporate more into their proteins. c. its intensity is cut in half, approximately, when DNA replicates. d. its intensity is cut in half, approximately, when the cell divides. e. None of the answers are correct.

ANSWER: d 23. In chromium release assays, or more recently in CFSE release assays, cells that die release the marker if they a. die by apoptosis only. b. die by necrosis only. c. die by either apoptosis or necrosis. d. divide before dying. e. replicate DNA before dying.

ANSWER: c 24. Annexin-V staining of cells identifies a. a failure of membrane integrity. b. broken ends of chromosomes produced during DNA fragmentation. c. necrotic but not apoptotic cells. d. both apoptotic and necrotic cells. e. a breakdown of membrane asymmetry.

ANSWER: e 25. The following can be used to analyze chromatin structure in intact cells. a. flow cytometry b. ChIP c. 3C d. 3C and ChIP only e. 3C and flow cytometry only ANSWER: d Copyright Macmillan Learning. Powered by Cognero.

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Experimental Systems 26. CRISPR-Cas9 technology can be used to a. remove targeted sequences of DNA. b. induce recombination and introduction of mutations. c. repair genetic diseases. d. tag specific DNA for imaging. e. All of the answers are correct.

ANSWER: e 27. The use of inbred lines of mice a. reduces genetic heterogeneity. b. reduces experimental variables. c. increases similarity among individuals. d. leads to syngeneic animals. e. All of the answers are correct.

ANSWER: e 28. Congenic strains are NOT a. identical genetically at almost all loci. b. distinct at only one locus. c. useful for adoptive transfer experiments. d. equivalent to identical twins. e. All of the answers are congenics.

ANSWER: d 29. The Cre/lox system is NOT able to a. delete a gene in a specific tissue type. b. delete a gene when a drug is introduced. c. express a gene only in specific tissues. d. enable study of embryonic lethal gene alterations. e. All of the answers are correct.

ANSWER: d 30. How do monoclonal and polyclonal antibodies differ from one another? Explain, and provide two advantages in using each type of antibody in assays.

ANSWER: Polyclonal antibodies are essentially purified serum from a vaccinated animal (or animals) that contains many different species of antibody against the target antigen. Monoclonal antibodies, on the other hand, all come from the same B-cell clone that has been fused to an immortal cancer cell.

Because all monoclonal antibodies come from the same Ig clone, these antibodies are more consistent and specific. However, polyclonal antibodies can be generated more quickly and, due to their variation, can be more useful in agglutination assays.

31. Compare and contrast indirect and sandwich ELISA assays. Which requires multiple types of antibodies Copyright Macmillan Learning. Powered by Cognero.

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Experimental Systems against the target antigen? Explain.

ANSWER: ELISAs test for the presence of antibodies or antigens on coated surfaces. Enzyme-conjugated secondary antibodies are used in the presence of a substrate to determine the amount of antigen or primary antibody present in the sample. Indirect ELISAs start with plate-bound antigen to determine how much cognate antibody is present in a sample. Sandwich ELISAs start with antibodies on the plate to trap antigens. After the sample is added, a second antibody, specific for a different epitope on the antigen, is added to provide a readout.

32. Explain how an ELISPOT works. What does it most commonly measure?

ANSWER: ELISPOT assays are variations of the basic ELISA principle modified to test for secreted cytokines from cells. Immune system cells are added to an antibody-coated plate, stimulated, and washed off.

A second antibody is then added that is linked to an enzyme; addition of that enzyme's substrate results in a colored precipitate that is visible as the titular "spot". Each spot can then be read as one cell in a population that secreted your cytokine of interest.

33. What are two methods used to measure the affinity of antibodies to antigen? Which method is newer?

Explain.

ANSWER: Both equilibrium dialysis and surface plasmon resonance can be used. SPR is newer, and more rapid and sensitive, but it requires the use of more specialized equipment than the older equilibrium dialysis.

34. What are two useful techniques for visualizing the intracellular location of a protein in groups of cells in intact tissues? What links them? Explain.

ANSWER: The two best techniques for this kind of experiment are 1) immunohistochemistry and 2) immunofluorescence (IF) microscopy. Both use linked antibodies (enzymes in histology and fluorescent dyes in IF), so individual proteins can be stained and viewed. Both of these techniques can also be performed on tissue sections, preserving larger morphology.

35. You are studying the localization of stored granzyme and an internal membrane marker in activated T cells.

How could you image groups of these two molecules together when they are located all over the 3-D space inside of cells? Explain.

ANSWER: Immunofluorescent techniques are best when the ability to visualize specific proteins is needed. To solve the problem of resolving multiple objects in three dimensions, confocal microscopy is the best choice and either two- or multiphoton imaging will provide the greatest resolution and clarity. In these assays, more than one photon must hit the target to excite the probe, reducing photobleaching and giving the clearest possible picture.

36. What simpler technique from immunology is the basis for modern flow cytometry, and how does it improve on the earlier assays? Explain.

ANSWER: Flow cytometry (and FACS) is based on the same principles behind immunofluorescence microscopy. However, flow experiments are able to 1) take measurements for many different parameters at once, thanks to multiple lasers, dyes with narrow emission spectra, and electronic signal compensation, and 2) take these measurements in a quantitative way and do it for each individual cell.

37. List and evaluate three ways to measure cell death experimentally.

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Experimental Systems ANSWER: The first assay to do this reliably was the 51Cr release assay, where cells were incubated in sodium chromate and release of that chemical into the media was measured upon exposure to effector cells.

Labeled annexin-V binds to and can be used to assay phosphatidyl serine, which is a phospholipid that is only found on the exterior of cells that are undergoing apoptosis. TUNEL assays measure the breakdown of chromosomal DNA into fragments during apoptosis, and caspase enzymatic activity can also be used to measure the same process.

38. Using what you have learned in the text, explain the excitement surrounding the technological innovation(s) behind CRISPR-Cas9. In your answer, describe how CRISPR-Cas9 works.

ANSWER: CRISPR is a system originally found in bacteria that lets scientists very easily manipulate and replace specific DNA sequences in vitro and in vivo. It originally evolved as a sort of adaptive immunity in prokaryotes. Sequences from invading bacteriophages would be clipped out of the virus's genome and stored in a special region of the host chromosome. The Cas9 enzyme could then recognize these sequences if they appeared again and use its nuclease activity to degrade the invading DNA. In the hands of modern researchers, CRISPR-Cas9 has been used to knock out genes, introduce new sequences, and even repair genetic defects in some cells.

39. Imagine you want to study Promoter X, which controls many of the genes in B cells that you believe are important for controlling viral infections. You want to generate a transgenic mouse line with a mutation in this promoter that makes it expressed at low levels. Unfortunately, after all of your work, you learn that your mutation is "embryonic lethal." Describe the strategies/techniques that could be used to circumvent this problem.

ANSWER: One technique you could use is the Cre/lox system. Cre is a bacteriophage recombinase that recognizes loxP sites in the genome — genes in between two such sites can be excised by the enzyme. Crucially, Cre can be placed under the control of any promotor, so in this case it could be engineered to only activate after gestation.

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