TEST BANK for Cellular and Molecular Immunology 10th Edition by Abbas A, Lichtman Andrew, Pillai Shi

TEST BANK Cellular and Molecular Immunology 10th Edition Abul K. Abbas; Andrew H. Lichtman; Shiv Pillai

TABLE OF CONTENTS Chapter 1: Properties and Overview of Immune Responses Chapter 2: Cells and Tissues of the Immune System Chapter 3: Leukocyte Circulation and Migration Into Tissues Chapter 4: Innate Immunity Chapter 5: Antibodies and Antigens Chapter 6: Antigen Presentation to T Lymphocytes and the Functions of Major Histocompatibility Complex Molecules Chapter 7: Immune Receptors and Signal Transduction Matching Chapter 8: Lymphocyte Development and Antigen Receptor Gene Rearrangement Matching Questions Chapter 9: Activation of T Lymphocytes Chapter 10: Differentiation and Functions of CD4+ Effector T Cells Chapter 11: Differentiation and Functions of CD8+ Effector T Cells Chapter 12: B Cell Activation and Antibody Production Chapter 13: Effector Mechanisms of Humoral Immunity Matching Chapter 14: Specialized Immunity at Epithelial Barriers and in Immune Privileged Tissues

Chapter 15: Immunologic Tolerance and Autoimmunity Chapter 16: Immunity to Microbes Chapter 17: Transplantation Immunology Chapter 18: Tumor Immunology Chapter 19: Hypersensitivity Disorders Chapter 20: Allergy Chapter 21: Primary and Acquired Immunodeficiencies

Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 1: Properties and Overview of Immune Responses Multiple Choice The principal function of the immune system is: A. Defense against cancer B. Repair of injured tissues C. Defense against microbial infections D. Prevention of inflammatory diseases E. Protection against environmental toxins ANS: C. The immune system has evolved in the setting of selective pressures imposed by microbial infections. Although immune responses to cancer may occur, the concept that “immunosurveillance” against cancer is a principal function of the immune system is controversial. Repair of injured tissues may be a secondary consequence of the immune responses and inflammation. Although the immune system has regulatory features that are needed to prevent excessive inflammation, prevention of inflammatory diseases is not a primary function. The immune system can protect against microbial toxins, but it generally does not offer protection against toxins of nonbiologic origin.

2.

Which of the following infectious diseases was prevented by the first successful vaccination?

A. Polio B. Tuberculosis C. Smallpox D. Tetanus E. Rubella ANS: C. In 1798, Edward Jenner reported the first intentional successful vaccination, which was against smallpox in a boy, using material from the cowpox pustules of a milkmaid. In 1980, smallpox was reported to be eradicated worldwide by a vaccination program. Effective vaccines against tetanus toxin, rubella virus, and poliovirus were developed in the 20th century and are widely used. There is no effective vaccine against Mycobacterium tuberculosis.

3.

Which of the following is a unique property of the adaptive immune system?

A. Highly diverse repertoire of specificities for antigens B. Self-nonself discrimination C. Recognition of microbial structures by both cell-associated and soluble receptors D. Protection against viral infections E. Responses that have the same kinetics and magnitude on repeated exposure to the same microbe

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ANS: A. Highly diverse repertoires of specificities for antigens are found only in T and B lymphocytes, which are the central cellular components of the adaptive immune system. Both the innate and the adaptive immune systems use cell-associated and soluble receptors to recognize microbes, display some degree of self-nonself discrimination, and protect against viruses. On repeated exposure to the same microbe, the adaptive immune response becomes more rapid and of greater magnitude; this is the manifestation of memory.

4.

Antibodies and T lymphocytes are the respective mediators of which two types of immunity?

A. Innate and adaptive B. Passive and active C. Specific and nonspecific D. Humoral and cell-mediated E. Adult and neonatal ANS: D. Both B and T lymphocytes are principal components of adaptive immunity. B lymphocytes produce antibodies, which are the recognition and effector molecules of humoral immune responses to extracellular pathogens. T cells recognize and promote eradication of intracellular pathogens in cell-mediated immunity. Passive and active immunity both can be mediated by either B or T lymphocytes. Specific immunity is another term for adaptive immunity.

Both B and T lymphocytes participate in adult adaptive immunity but are still developing in the neonatal period.

5.

A. B. C. D. E.

The two major functional classes of effector T lymphocytes are: Helper T lymphocytes and cytotoxic T lymphocytes Natural killer cells and cytotoxic T lymphocytes Memory T cells and effector T cells Helper cells and antigen-presenting cells Cytotoxic T lymphocytes and target cells

ANS: A. T cells can be classified into effector subsets that perform different effector functions.

Most effector T cells are either helper T lymphocytes, which enhance the responses of other immune cells, including phagocytes and B cells, to infections, or cytotoxic T lymphocytes, which directly kill infected cells. Natural killer cells are not T lymphocytes. Antigen-presenting cells usually are not T cells. Memory T cells are not effector T cells.

6.

A. B. C. D. E.

Which of the following cell types is required for all adaptive humoral immune responses?

Natural killer cells Dendritic cells Cytolytic T lymphocytes B lymphocytes Helper T lymphocytes

ANS: D. Humoral immune responses are antibody-mediated immune responses, and all antibodies are made by B lymphocytes and no other cell type.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 2: Cells and Tissues of the Immune System Matching Questions 1-5 Match each of the descriptions in questions 1-5 with the appropriate name (A-M) of an anatomic feature of lymphoid tissues.

A. Periarteriolar lymphoid sheath B. Thymic medulla C. Thymic cortex D. Parafollicular cortex of lymph node E. Hematopoietic bone marrow F. Afferent lymphatic G. Efferent lymphatic H. Marginal zone I. Red pulp of spleen J. White pulp of spleen K. Epidermis L. Dermis M. Peyer’s patch 1.

Location of most T lymphocytes in the spleen

ANS: A. The periarteriolar lymphoid sheath surrounds the central arteries in the spleen and is the T cell zone in this organ.

2.

Vessels that drain lymph away from a lymph node

ANS: G. Efferent lymphatic vessels drain lymph away from lymph nodes; afferent vessels drain lymph into lymph nodes.

3.

Site of least mature T cell precursors in the thymus

ANS: C. Bone marrow–derived T cell precursors first enter the thymic cortex and migrate into the medulla as they become more mature.

4.

Location of Langerhans cells

ANS: K. Langerhans cells are dendritic cells in the epidermis of the skin that develop from fetal macrophages.

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5.

Lymphoid aggregate of the mucosal immune system

ANS: M. Peyer’s patches are B cell–rich lymphoid aggregates located in the submucosa of the small intestine.

Multiple Choice 6.

A. B. C. D. E.

Which of the following is the generative (primary) lymphoid organ for T lymphocytes?

Bone marrow Spleen Lymph node Thymus Tonsil

ANS: D. Generative (primary) lymphoid organs are the organs where lymphocytes first express antigen receptors and attain functional maturity. Although T cell precursors arise in the bone marrow, these precursors migrate to the thymus, where maturation takes place. In contrast, B cells mature in the bone marrow. Spleen, lymph node, and tonsil are secondary lymphoid organs populated by mature B and T cells.

7. Which of the following statements about tissue-resident macrophages is correct?

A. They are all derived from blood monocytes that enter tissues during infections B. Many of these cells first populate tissues during fetal development C. They differentiate from different kinds of epithelial cells in each tissue D. They constantly recirculate between different tissues E. They are professional antigen-presenting cells that activate naive T cells that migrate into tissues ANS: B. Many tissue-resident macrophages are derived from fetal yolk sac and fetal liver precursors and establish residence in the different tissues during fetal development. Other tissueresident macrophages are derived from bone marrow–derived blood monocytes that enter tissues under normal conditions or during infections. Epithelial cells do not differentiate into macrophages. Once in the tissue, tissue-resident macrophages cells do not leave to recirculate.

Naive T cells do not usually enter non-lymphoid tissues, and tissue-resident macrophages have no role in presenting antigen to naive T cells.

8. Which type of leukocyte is the most abundant in the blood of a healthy adult?

A. Monocytes B. B lymphocytes C. T lymphocytes D. Polymorphonuclear leukocytes E. Basophils

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ANS: D. Polymorphonuclear leukocytes (or neutrophils) are the most abundant blood leukocyte (~ 4,000/mm3), about twice the number of B and T lymphocytes combined.

9. Which of the following is a feature of fibroblastic reticular cells (FRCs)?

A. They line the lumens of lymphatics entering lymph nodes B. They are derived from hematopoietic precursors C. They play a critical role in establishing where lymphocytes are located in lymph nodes D. They secrete cytokines that stimulate T cell proliferation E. They are phagocytic cells of innate immunity that kill microbes ANS: C. FRCs are mesenchymal-derived (not haematopoietically-derived) cells with properties of muscle and fibroblast (myofibroblasts) that drive formation of secondary lymphoid organs during embryonic development and contribute to the anatomic segregation and movement of lymphocytes and dendritic cells in secondary lymphoid organs. They are not phagocytic, have no direct antimicrobial effector functions, do not secrete IL-2 or other T cell growth factors, and do not line lumens of lymphatics.

10. Which type of cell is most important in capturing protein antigens of microbes that enter through epithelial barriers and presenting them to naive T cells in secondary lymphoid organs?

A. Classical dendritic cells B. Plasmacytoid dendritic cells C. Plasma cells D. Macrophages E. Follicular dendritic cells ANS: A. Classical (or conventional) dendritic cells (DCs) are the main cell type that brings microbial antigens from infected tissues into draining lymph nodes and presents peptides derived from these antigens to naive T cells that circulate though the lymph nodes. Plasmacytoid DCs secrete type 1 interferons in response to viral infection. Plasma cells are antibody-secreting cells derived from B cells and do not present antigen to T cells. Macrophages can present antigen to effector T cells, but they are not efficient activators of naive T cells. Follicular dendritic cells display antigens to B cells on lymphoid follicles.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 3: Leukocyte Circulation and Migration Into Tissues Multiple Choice 1.

In naive T cell recirculation, entry of the cells into lymph nodes occurs through which specialized vessel?

A. Efferent lymphatic B. Thoracic duct C. Central artery D. High endothelial venule E. Sinusoid ANS: D. The high endothelial venule is a specialized vessel in the lymph node paracortex that expresses adhesion molecules that mediate the binding and transmigration of naive T cells into lymph node tissue. The efferent lymphatic is a route of exit of T cells from the lymph node. The thoracic duct is a major site of drainage of lymph back into the blood circulation. A central artery is a vessel in the spleen around which are T cell lymphoid aggregates (periarteriolar lymphoid sheath). Sinusoids are blood channels in the spleen lined by fenestrated endothelium and phagocytic cells.

Matching Questions 2-6 For each description of a molecule involved in lymphocyte migration in questions 2-6, choose the lettered description (A-I) that most closely matches it.

A. Peripheral lymph node addressin B. Intercellular adhesion molecule-1 (ICAM-1) C. Integrin a4b1( (VLA-4) D. E-selectin E. P-selectin ligand F. CCR7 G. CXCR5 H. MadCAM-1 I. Vascular cell adhesion molecule-1 (VCAM-1) 2.

This molecule binds chemokines CCL19 and CCL21 and is involved in naive T cell migration into interfollicular zones of lymph nodes ANS: F. CCL19 and CCL21 are the chemokines that bind to CCR7 on naive T lymphocytes and dendritic cells and direct their migration into lymph nodes.

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3.

The expression of this molecule is induced on endothelial cells in inflamed tissues, and it mediates rolling of T cells along the endothelial surface ANS: D. E-selectin expression is induced on endothelial cells by cytokines and microbial products, and it mediates rolling interactions of T cells and other leukocytes.

4.

This molecule is expressed on activated endothelium, is a member of the immunoglobulin superfamily, and binds to b1 integrins on activated T cells ANS: B. Intercellular adhesion molecule-1 (ICAM-1) on endothelial cells binds to the integrin LFA-1 on activated T cells.

5.

This vascular addressin binds to integrins on T cells and mediates their homing to intestinal mucosa ANS: H. MadCAM-1 is expressed on vessels in the intestine and binds to a4b1 integrins on guthoming T cells.

6.

This receptor is expressed on naive B cells and promotes their migration into lymph node follicles ANS: G. CXCR5 is a chemokine receptor on naive B cells that binds chemokines made in lymphoid follicles.

Questions 7-12 For each of the following descriptions (questions 7-12) of a chemokine or chemokine receptor, select the chemokine or chemokine receptor (A-G) that most closely matches it.

A. CXCL8 (IL-8) B. CXCL10 (IP-10) C. CCL19 (ELC) D. CCL11 (Eotaxin) E. CCR5 F. CXCR1 G. CXCL13 7.

Mediates neutrophil recruitment into tissues

ANS: A. Interleukin-8, a CXC family chemokine, is one of the major chemokines that attracts neutrophils into tissues. Neutrophils respond to several other CXC chemokines but not CC chemokines.

8.

Binds to interleukin-8

ANS: F. CXCR1, the only CXCR family receptor listed, binds interleukin-8, a CXC family chemokine.

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9.

Binds chemokines important in T cell recruitment into peripheral inflammatory sites

ANS: E. CCR5 is expressed on Th1 T cells and binds at least three CC chemokines, including RANTES (CCL5), MIP-1a (CCL3), and MIP-1b (CCL4), which are produced at sites of infection.

10.

Important in dendritic cell and T cell localization in lymph nodes

ANS: C. ELC (CCL19) and SLC (CCL21) are produced by stromal cells in the parafollicular zones of lymph nodes. Dendritic cells and T cells express the CCR7 receptor that binds these chemokines.

11.

Important mediator of inflammatory component of immediate hypersensitivity reactions

ANS: D. Eotaxin (CCL11) is produced at sites of allergic inflammation and binds to CCR3 on eosinophils, thereby stimulating eosinophil migration into these sites.

12.

Important for attracting B cells and Tfh cells into B cell follicles

ANS: G. CXCL13 is produced within B cell follicles and binds CXCR5 on B cells and Tfh cells.

CXCL13 and CXCR5 are essential for T-dependent B cell responses, including the germinal center reaction.

Multiple Choice 13. Which of the following binds to the integrin VLA-4, promoting T cell recruitment into inflammatory sites?

A. B7-1, B7-2 B. Class II MHC C. LFA-3 D. VCAM-1 E. Sialylated Lewis X ANS D. VLA-4, an integrin expressed on T cells, binds to VCAM-1, an Ig superfamily member expressed on activated endothelium. VLA-4–VCAM-1 interactions promote T cell recruitment into inflammatory sites.

14. Which of the following is expressed on the surface leukocytes and mediates their rolling on venular endothelial cells?

A. B. C. D. E.

CCR7 B7-1 LFA-3 VCAM-1 Sialylated Lewis X

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ANS: E. Sialylated Lewis X is a carbohydrate structure on glycoprotein ligands of selectins expressed by endothelial cells (E-selectin and P-selectin) or leukocytes (L-selectin). Selectin binding to sialylated Lewis X structures mediates leukocyte rolling interactions with activated endothelium.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 4: Innate Immunity Multiple Choice 1.

Which of the following statements about the innate immune system is NOT true?

A. Innate immunity is present in all multicellular organisms, including plants and insects B. Deficiencies in innate immunity markedly increase host susceptibility to infection, even in the setting of an intact adaptive immune response C. Innate immunity is better suited for eliminating virulent, resistant microbes than is adaptive immunity D. The innate immune response can be divided into recognition, activation, and effector phases E. The innate immune response against microbes influences the type of adaptive immune response that develops ANS: C. Innate immunity is the first line of defense against infections, yet many pathogenic microbes have evolved strategies to resist innate immunity. Adaptive immunity, being more potent and specialized, plays a critical role in defending against these virulent microbes. Innate immunity is the phylogenetically oldest mechanism of microbial defense, and it is present in all multicellular organisms, including plants and insects. Studies have shown that hampering effector mechanisms of innate immunity renders hosts much more susceptible to infection, even with a functional adaptive immune system. It is also true that, like the adaptive response, the innate immune response consists of recognition, activation, and effector phases. Although it provides the initial, rapid response against microbes, innate immunity can influence adaptive immune responses to tailor them against particular microbes.

2.

Which of the following comparisons of the innate and adaptive immune systems is FALSE? A. The innate immune system is more likely to recognize normal self, and therefore cause autoimmunity, than is the adaptive immune system B. Receptors used for recognition in innate immunity are encoded in the germline, whereas those of the adaptive immune system are encoded by genes generated via somatic recombination of germline receptor gene loci C. The innate and adaptive immune systems share some of the same effector mechanisms D. Both the innate and adaptive immune systems can recognize nonmicrobial substances E. The innate immune system has less long-lived memory than the adaptive immune system does

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ANS: A. Innate immune system receptors are encoded by germline genes that have evolved to recognize microbial structures or molecules produced by stressed self, and therefore there is little chance of innate immune responses to normal self. Because the specificities of adaptive immune system receptors (Ig or T cell receptor molecules) are randomly generated by somatic recombination and junctional-diversity mechanisms, there is a greater chance that the adaptive immune system receptors may recognize normal self molecules, leading to autoimmunity.

Mechanisms of tolerance minimize this possibility, but these mechanisms can fail. The adaptive immune system receptors can recognize nonmicrobial structures. Although most innate immune system receptors recognize microbial structures, some Toll-like receptors and activating receptors of natural killer cells do recognize nonmicrobial self proteins expressed by stressed, damaged, or infected cells. Memory is a major property of the adaptive but not the innate immune system.

3.

Toll-like receptors (TLRs) are a family of homologous receptors expressed on many cell types and are involved in innate immune responses. Some TLRs are expressed on the plasma membrane, Others are expressed on endosomal membranes inside the cells. Which of the following is a shared property of the TLRs in the endosomes?

A. Recognition of nucleic acids B. Recognition of bacterial cell wall molecules C. Signaling by JAK-STAT pathways D. Inhibition of inflammatory responses E. Secreted into the blood ANS: A. More than 10 mammalian TLRs have been identified, and each recognizes a different set of structures. TLRs located in endosomes (TLRs 3, 7, and 9) recognize forms of nucleic acids. TLR3 recognizes double-stranded RNA produced by viruses. TLR9 binds ssRNA. TLR9 binds unmethylated cytosine guanosine (CpG) motifs typical of bacterial and protozoan DNA. Cell surface TLRs, TLR2 and TLR4, recognize the components of bacterial cell walls, lipoteichoic acid and lipopolysaccharide, respectively. Endosomal TLRs signal via MyD88-NFkB or TRIF-IRF pathways, not JAK-STAT pathways, which promote inflammatory and anti-viral responses. Cells do not secrete TLRs. 4.

The signaling pathways triggered by Toll-like receptors (TLRs) typically result in activation of which of the following pairs of transcription factors?

A. NFAT and T-BET B. AP1 and GATA-3 C. FOS and STAT6 D. NF-kB and IRFs E. LCK and JUN ANS: D. The predominant signaling pathway used by TLRs results in the activation of the NFkB and immune regulatory factors (IRFs), which regulate promote expression of inflammatory genes and type 1 interferon genes, respectively. T-BET and GATA-3 are transcriptional regulators involved in helper T cell differentiation. FOS is a component of AP1, and STAT6 is a

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transcription factor activated by IL-4 binding to cells. LCK is not a transcription factor but rather a tyrosine protein kinase involved in antigen-receptor signaling in T cells.

5.

Cytosolic DNA sensors are a large group of molecules that detect microbial dsDNA in the cytosol of infected cells and stimulate innate responses. Most of these sensors signal though a pathway that includes which protein?

A. Mitochondrial antiviral-signaling protein (MAVS) B. Cytochrome C C. RIG-like receptors (RLRs) D. TLR9 E. Stimulator of interferon genes (STING) ANS: E. STING is present in the endoplasmic reticulum (ER) membrane of most cells and functions as an adaptor protein that responds to various cytosolic dsDNA sensors, including the enzyme cGAS (cyclic GMP-AMP synthase), which generates a signaling molecule called cGAMP (cyclic GMP-AMP) that binds to STING. STING then interacts with other molecules to generate signals that activate IRF transcription factors and type interferon gene expression.

MAVS are involved in signaling initiated by RLR binding to cytosolic ssRNA. TLR9 is an endosome membrane DNA sensor. Cytochrome C is a mitochondrial protein involved in cellular energy metabolism but stimulates apoptosis when released into the cytosol.

6.

A. B. C. D. E.

Which of the following is an enzymatic function of most types of inflammasomes?

Generate active granzyme B from an inactive precursor Generate an active form of the inflammatory cytokine IL-1b from an inactive precursor Proteolytically inactivate caspase 1 Degrade dsDNA Phosphorylate interferon regulatory factors (IRFs)

ANS: B. There are several forms of inflammasomes, all of which are multiprotein complexes that form in the cytosol of cells in response to stimuli related to infection, toxins, or cell stress.

When they form, inflammasomes incorporate an inactive precursor of the enzyme caspase 1, which is proteolytically cleaved to form active caspase 1, which goes on to proteolytically cleave an inactive precursor of IL-1b to generate active IL-1b.

7.

Toll-like receptors (TLRs) and other receptors are potent activators of various components of the innate immune system. All of the following proteins are expressed in response to signaling by these receptors EXCEPT: A. Interleukin-12 B. E-selectin C. Tumor necrosis factor D. Inducible nitric oxide synthase (iNOS) E. CD28 ANS: E. CD28, the activating receptor for B7-1 and B7-2 costimulatory molecules, is constitutively expressed on the surface of many T cells and is not induced by TLR signaling.

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TLR signaling does induce expression of B7-1 and B7-2 on antigen-presenting cells. Other genes expressed in response to TLR signaling encode proteins important in many different components of innate immune responses. These include inflammatory cytokines such as tumor necrosis factor-á (TNF-á), interleukin-1 (IL-1), and IL-12; endothelial adhesion molecules such as Eselectin; and proteins involved in microbial killing mechanisms, including iNOS. The specific genes expressed depend on the cell type of the responding cell.

Matching Questions 8-12 For each of the descriptions of a component of the innate immune system in questions 6-10, select the term that best matches it (A-J).

A. Defensin B. Opsonin C. Natural antibody D. Adjuvant E. Complement F. Inflammation G. C-reactive protein H. Mannose-binding lectin I. Reactive oxygen species J. Inducible nitric oxide synthase 8.

Superoxide anion, hydroxyl radical, or hydrogen peroxide, produced by activated phagocytes ANS: I. Reactive oxygen species (ROS) are generated by enzymes in phagocytes, such as phagocyte oxidase and myeloperoxidase. They have unpaired electrons in their outer orbitals and induce oxidative damage to cellular membranes and DNA. ROS can kill microbes, but they also damage host cells.

9.

Plasma protein that serves as a soluble pattern recognition receptor binding to microbial cells but not to mammalian cells ANS: H. Mannose-binding lectin is a C-type lectin found in the serum that binds microbial surface carbohydrates with terminal mannose residues and mediates phagocytosis and activation of the lectin complement pathway.

10.

Produced by B-1 cells, protects against microbes that succeed in penetrating epithelial barriers ANS: C. Natural antibodies are IgM antibodies produced by B-1 B cells. They have very limited diversity and bind to commonly encountered microbial structures, such as phosphoryl choline.

11.

Acute-phase reactant produced by the liver and released into blood

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ANS: G. C-reactive protein, a member of the pentraxin family of plasma proteins, is an acute phase reactant that is rapidly up-regulated by hepatocytes in response to inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor.

12.

Broad-spectrum antibiotic present in the skin and in neutrophil granules; its synthesis is increased in response to inflammatory cytokines ANS: A. Defensins are a family of vertebrate antimicrobial peptides found in epithelial barrier cells and neutrophil granules. They are toxic to a wide variety of microorganisms and may work by perturbing the permeability of limiting membranes of microbes.

Questions 13-17 The tumor necrosis factor (TNF) family of proteins includes several soluble and membrane proteins that share structural homologies. All members of this family bind to members of the TNF-receptor (TNF-R) family of molecules expressed on cell surfaces. TNF-R family members are structurally homologous to one another and utilize similar signal transduction pathways. For each description of a TNF or TNF-R family member in questions 1-5, select the term (A-E) that best matches it.

A. TNF-RI B. CD40 C. FAS ligand D. RANK E. Lymphotoxin 13.

Produced by T cells and binds to the same receptors as does TNF produced by macrophages ANS: E. Lymphotoxin (LT) shares 30% sequence homology with TNF made by macrophages; it binds to the same receptors as TNF and thus has the same biologic effects. The quantity of LT secreted by antigen-stimulated T cells is much less than TNF secreted by activated macrophages, and therefore LT does not have systemic effects. LT is considered to be an important link between T cell activation and acute inflammation, and it is also critical for the architectural development of lymphoid organs.

14.

Expressed on macrophages and B lymphocytes, this receptor plays an important role in the helper T cell–mediated effector functions ANS: B. CD40 is a member of the TNF-R family expressed by B cells and macrophages. CD40 binds CD40 ligand on activated helper T cells, and ligand binding initiates signaling pathways that activate macrophages and B lymphocytes. CD40-mediated macrophage activation leads to enhanced phagocytic and microbicidal functions, and CD40-mediated B cell activation is essential for T follicular helper cell–dependent Ig isotype switching and affinity maturation.

15.

Expressed on osteoclasts, this receptor is important in remodeling bone

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ANS: D. RANK, also known as osteoprotegerin receptor, is a TNF-R family member expressed on osteoclasts and some macrophages. RANK is involved in bone resorption, both in health and in disease states such as rheumatoid arthritis.

16.

Expressed on many cells types, its cytoplasmic tail includes a death domain, binds TNFR associated death domain (TRADD), and initiates a pro-apoptotic signaling cascade ANS: A. TNF-RI is one of two receptors for TNF-a expressed on a wide variety of cell types.

TNF-RI, like FAS, is directly linked to apoptotic pathways because it contains a death domain in the cytoplasmic tail.

17.

Expressed as a membrane molecule on the surface of activated T cells, it binds to a receptor found on many cell types, including T cells, and induces apoptosis ANS: C. FAS ligand (FASL, CD178) is a member of the TNF family and binds FAS on T cells and other cell types. FAS-FAS ligand-dependent apoptosis of T cells is important for T cell homeostasis; deficiencies of FASL, FAS, or signaling molecules downstream of FAS cause autoimmune disease.

Multiple Choice 18.

A. B. C. D. E.

Which of the following is a major effect of interleukin-6 (IL-6)?

B cell Ig class switching Acute phase protein expression Macrophage activation T cell proliferation Th2 differentiation

ANS: B. The cytokines IL-1, tumor necrosis factor (TNF), and IL-6 are the major inducers of acute phase proteins. Acute phase proteins (or reactants) are proteins whose concentration in the blood goes up when there is an acute inflammatory response occurring somewhere in the body.

Acute phase reactants are synthesized mainly by the liver in response to inflammatory cytokine released during the innate immune response to infections or tissue injury. Examples of acute phase proteins include C-reactive protein, serum amyloid A, complement proteins, and fibrinogen. Several cytokines, but not IL-6, drive B cell class switching, including IL-21, IL-4 and TGF-b. Interferon (IFN)-g is the major cytokine that activates macrophages. IL-2 is the major cytokine that stimulates T cell proliferation. IL-4 is required for Th2 differentiation.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 5: Antibodies and Antigens Matching Questions 1-5 Match each of the descriptions in questions 1-5 with the correct lettered antibody isotype (A-E).

(Answers may be used more than once.)

A. IgA B. IgD C. IgE D. IgG E. IgM 1. The secreted form of this isotype forms pentamers around a J chain ANS: E. IgM is secreted as a J chain–linked pentamer.

2. The most abundant Ig isotype in the blood ANS: D. The blood IgG concentration is about 3.5 mg/mL and includes four subtypes (IgG1 to IgG4).

3. The isotype only found in membrane-bound form on naive B cells ANS: B. Very little IgD is secreted, and in membrane form it is only on the surface of naive B cells; its function is not well understood 4. The isotype found predominantly in mucosal secretions ANS: A. IgA accounts for almost two thirds of the 3 g of antibody produced each day by an adult, most of which is produced in the gastrointestinal-associated lymphoid tissues and secreted into the gut lumen.

5. The isotype most closely associated with immediate hypersensitivity (allergic) disease ANS: C. Most IgE that is secreted is bound to mast cells, and it plays a role in the activation of mast cells during allergic reactions.

Questions 6-10

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Match each description in questions 6-10 with the appropriate lettered term (A-I).

A. Conformational determinant B. Linear determinant C. Neoantigenic determinant D. Hinge region E. Immune complex F. Fab G. Fc H. Tail piece I. Hapten 6. A proteolytic fragment of an antibody molecule that contains a single intact antigen-binding site ANS: F. Fab fragments, derived from enzymatic cleavage of Ig molecules, are composed of one intact light chain covalently linked to the N-terminal region of one heavy chain and include a single intact antigen-binding site.

7. A three-dimensional shape, formed by a portion of a macromolecule, to which an antibody binds ANS: A. Conformational determinants will usually be destroyed by physicochemical disruption of macromolecules, such as by denaturation or proteolysis of proteins.

8. A small chemical group recognized by an antibody that is attached to a larger macromolecule ANS: I. Although haptens can be recognized by antibodies, they are not, by themselves, able to stimulate an antibody response (i.e., they are not immunogens). Antibody responses to haptens can be induced when the hapten is attached to a macromolecule, called a carrier.

9. The proteolytic fragment of an antibody molecule that contains the heavy chain constant region ANS: G. The Fc fragment, generated by proteolytic cleavage of an antibody molecule, is composed of the C-terminal end of the heavy chain and lacks the antigen-binding region. This region of an intact Ig molecule, which can interact with Ig receptors and complement, is called the Fc region.

10. A region of an antibody molecule that permits bivalent binding of antibodies to pairs of surface epitopes varying in distance from one another ANS: D. The hinge region, located between the two N-terminal Ig domains of the heavy chains of most isotypes, is flexible, permitting variations in the distance between the two antigenbinding sites.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 6: Antigen Presentation to T Lymphocytes and the Functions of Major Histocompatibility Complex Molecules Matching Questions 1-5 Match the description in questions 1-5 with the lettered item (A-I) related to antigen-presentation pathways.

A. T cell receptor on CD4+ T cells B. Endosomes C. Endoplasmic reticulum D. Invariant chain E. Class II–associated invariant chain peptide (CLIP) F. LMP2 and LMP7 G. Acidic proteases H. T cell receptor on CD8+ T cells I. HLA-DM 1.

Site of proteolysis of antigens in the class II MHC pathway

ANS: B. Endosomes are membrane-bound acidic vesicles in which internalized proteins are proteolytically degraded in the class II MHC pathway by cathepsins and other proteases.

2.

A protein that binds to newly synthesized class II MHC molecules in the endoplasmic reticulum (ER), which blocks the peptide-binding site and directs transport of the class II MHC molecule to endosomes ANS: D. The invariant chain prevents peptides generated in the ER from binding to class II MHC, but the invariant chain must be removed in the endosome in order to allow peptides there to bind to the class II MHC. 3.

The molecule that binds to the final product of the class II antigen-processing pathway

ANS: A. The final product of the class II MHC pathway of antigen presentation is a peptideclass II MHC complex. This is displayed on the antigen-presenting cell surface, where it can be recognized by T cell receptors on CD4+ T cells.

4.

Required for proteolytic generation of class I MHC-binding peptides

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ANS: F. LMP2 and LMP7 are subunits of the proteasome that are needed to efficiently generate peptides of the correct length and composition for optimal binding to class I MHC molecules.

The expression of these proteasomal subunits is induced by innate immune responses.

5.

Site of peptide loading of class I MHC molecules

ANS: C. Peptides generated in the cytoplasm by the proteasome are pumped into the endoplasmic reticulum via the transporter associated with antigen-processing (TAP) 1/2 pump and bind to newly formed class I MHC molecules in the lumen of the endoplasmic reticulum.

Questions 6-9 Match each of the definitions in questions 6-9 with the MHC nomenclature (A-E).

A. HLA-A1, -B7, -C4, -DP5, -DQ10, and -DR8 B. H-2 C. HLA-DQ D. HLA-B5 E. HLA-DR4A 6.

Human class I MHC allele

ANS: D. There are three human class I genes, HLA-A, HLA-B, and HLA-C, and each gene has many allelic forms, designated by numbers following A, B, or C. 7.

Mouse major histocompatibility complex

ANS: B. The mouse MHC is called the H-2 complex.

8.

Human MHC haplotype

ANS: A. An MHC haplotype is a group of MHC genes on one chromosome, inherited from one parent. A human MHC haplotype (or HLA haplotype) includes single alleles of HLA-A, HLA-B, and HLA-C genes encoding class I MHC molecules and HLA-DP, HLA-DQ, and HLA-DR genes, encoding class II MHC molecules. These are tightly linked genes, which are usually inherited en bloc from a parent.

9.

Gene encoding one chain of a human class II MHC molecule

ANS: E. The genes encoding human class II molecules include HLA-DP, HLA-DQ, and HLA-DR genes. Class II MHC molecules are heterodimers of one alpha chain and one beta chain. The alpha chain in encoded by the A genes, and the beta chains are encoded by B genes. So, HLADR2A encodes the alpha chain of the class II MHC molecule HLA-DR2.

Questions 10-13

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For each region of a class I MHC molecule listed in questions 10-13, match the lettered label (AD) from the diagram shown below.

10.

Peptide-binding groove

ANS: C. The peptide-binding groove of class I MHC molecules is formed by approximately 90 amino acids of the N-terminal a heavy chain, which includes the a1 and a2 domains. This groove is composed of a floor of b-pleated sheet and two parallel strands of a helix.

11.

CD8-binding site

ANS: A. Class I MHC molecules bind to CD8 on T cells via the á3 Ig domain of the á heavy chain. This is a region of the protein that is the same among different alleles (i.e., it is a nonpolymorphic part of the protein).

12.

b2-Microglobulin

ANS: D. b2-Microglobulin is a separate nonpolymorphic polypeptide containing a single Ig domain, which is noncovalently associated with the extracellular region of the a heavy chain of class I MHC molecules.

13.

Polymorphic region

ANS: B. All the polymorphic residues of class I MHC molecules are in the walls or floor of the peptide-binding groove.

Multiple Choice 14.

The chance that two non-twin children of the same genetically unrelated patents have identical HLA molecules is: A. 75% B. 50%

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C. D.

25% <1%

ANS: C. Because the HLA genes on one chromosome are tightly linked and inherited en bloc, they are inherited as haplotypes in a Mendelian fashion—one haplotype from each parent. As with single genes, the chances of two children inheriting the same two haplotypes is 25%.

15.

Which of the following statements about HLA genes is correct?

A. Each individual inherits hundreds of different HLA genes B. There are thousands of different HLA alleles in human populations C. Each cell in the body expresses only class I MHC genes or only class II MHC genes, but not both D. Class II MHC genes are expressed by all nucleated cells E. Class I MHC molecules are less polymorphic than class II MHC genes ANS: B. HLA (human MHC) genes are the most polymorphic genes in the human genome, meaning there are many thousands of alleles in the population. However, any one individual inherits on average only two alleles of the six different types of HLA-genes. Class I MHC genes are expressed as proteins in all nucleated cells, while class II MHC gene expression is limited mainly to antigen-presenting cells, and those cells that express class II genes also express class I genes. The most polymorphic HLA genes are the class I genes (HLA-A, -B, and -C).

16.

Antigen-presenting cells (APCs) perform which of the following functions in adaptive immune responses?

A. Display major histocompatibility complex (MHC)–associated peptides on their cell surfaces for surveillance by B lymphocytes B. Initiate T cell responses by specifically recognizing and responding to foreign protein antigens C. Display MHC-associated peptides on their cell surfaces for surveillance by T lymphocytes D. Display polysaccharide antigens on their cell surfaces for surveillance by B lymphocytes E. Secrete peptides derived from protein antigens for binding to T cell antigen receptors ANS: C. APCs degrade proteins derived from the extracellular environment or synthesized by the APC. They form complexes of peptide fragments of these proteins with MHC molecules and display these complexes on their cell surfaces, where T cells can “see” them. Neither processing nor MHC association of protein or polysaccharide antigens is required for recognition by B cell antigen receptors. APCs do not distinguish between self and foreign proteins and will display peptides derived from a sampling of all cytoplasmic and extracellular proteins. APCs do not secrete peptide antigens, and T cell antigen receptors do not bind free peptides.

17.

A child who suffers from a persistent viral infection is found to have a deficiency in lymphocyte production and very few T and B cells. Other bone marrow–derived cells are produced in normal numbers, and major histocompatibility complex (MHC) molecule expression on cells appears normal. Transfusion of mature T cells from an unrelated donor who had recovered from a previous infection by the same virus would not be expected to help the child

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clear his infection. Which one of the following is a reasonable explanation for why this therapeutic approach would fail?

A. Clearance of viral infections requires antibodies and T cells B. The patient’s own immune system would destroy the transfused T cells before they could respond to the viral infection C. T cells recognize peptides, not viral particles D. Donor T cell viral antigen recognition is restricted by MHC molecules not expressed in the patient E. In responding to the previous infection, the donor would have used up all his T cells specific for that virus ANS: D. T cells are “self MHC restricted,” meaning they specifically recognize infected cells that display microbial peptides displayed by self MHC molecules. There may be no MHC molecules shared by the donor and patient, and therefore the transfused T cells would not recognize virus-infected cells in the patient. Because the patient has very few B cells and T cells, his immune system is unlikely to be able to recognize and destroy (i.e., “reject”) the transfused T cells. T cells do not recognize structures on intact viral particles but rather peptides derived from viral proteins bound to MHC molecules. Prior viral infection in the donor would be expected to generate memory T cells specific for the virus.

18.

Many vaccines in current use include highly purified, recombinant, or synthetic peptide antigens. Given alone, the antigens in these vaccines would be less immunogenic than vaccines containing intact killed or live microbes. Adjuvants are substances added to purified protein or peptide vaccines to enhance their ability to elicit T cell immune responses. Which of the following statements about these adjuvants is NOT correct?

A. They induce local inflammation, thereby increasing the number of antigen-presenting cells (APCs) at the site of immunization B. They stimulate the expression of costimulators on local APCs C. They enhance local production of cytokines that promote T cell activation D. They prolong the expression of peptide-MHC complexes on the surface of APCs E. They bind to T cell antigen receptors and promote their proliferation ANS: E. Adjuvants are not necessarily T cell antigens. Some adjuvants may be T cell antigens, but their adjuvant activity is unrelated to their ability to be recognized, in peptide form, by T cells. Adjuvants are surrogates of the innate immune response to a microbe, required along with the antigen component of a vaccine for naive T cell activation. Adjuvants stimulate local inflammation, influx of APCs, and activation of APCs to secrete cytokines and express costimulatory molecules, and they prolong peptide-MHC expression on the APC membrane.

19.

The cell type shown below is found between follicles in lymph nodes and expresses B71, B7-2, and class II MHC. What type of cell is this?

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A. B. C. D. E.

B cell Follicular dendritic cell Thymic epithelial cell Dendritic cell Plasma cell

ANS: D. Dendritic cells have delicate cytoplasmic extensions, which may serve to enhance interactions with T cells. They express molecules required for naive T cell activation, and they migrate from infected tissues into the parafollicular (T cell) areas of lymph nodes.

20.

Which of the following best describes events that occur during cross-presentation by antigen-presenting cells (APCs)?

A. Viral proteins expressed in the cytosol of an infected APC are pumped into endosomes for processing and presentation by the class II MHC pathway B. APCs ingest extracellular viral proteins into endosomes, then deliver the proteins into the cytosol where they are processed and presented by the class I MHC pathway.

C. Viral proteins expressed in the cytosol of an infected cell are processed by proteasomes into peptides, which are then then pumped into endoplasmic reticulum (ER). where they bind to newly synthesized class I MHC molecules.

D. Viral proteins from outside an APC are internalized into endosomes, processed into peptides by endosomal proteases, and are then presented on class II MHC molecules.

ANS B: Cross-presentation is a mechanism by which microbial protein antigens can be processed and presented via the class I pathway to naive CD8+ T cells, even when the microbes do not infect the DC and the microbial proteins are not made in the cytosol of the DC. Crosspresentation does not apply to presenting cytosolic proteins via the class II MHC pathway.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 7: Immune Receptors and Signal Transduction Matching Questions 1-4 Match the description in questions 1-4, related to T cell antigen receptors, with the lettered item (A-E) A. Antigen-binding site B. Immunoreceptor tyrosine-based activation motif (ITAM) C. CD3 protein D. z protein E. TCR beta chain 1. Six hypervariable loops in two Ig V domains ANS: A. TCR antigen-binding sites are composed of three hypervariable loops (or complementarity-determining regions) each of the a- and b-chain N-terminal V domains.

2. Ig superfamily protein that does not vary between different T cell clones ANS: C. The CD3 proteins are three highly homologous Ig super family members, d, e, and g, that are noncovalently associated with the T cell ab heterodimer, are invariant, and act as signaling molecules 3.

A T cell membrane protein that is expressed as a homodimer, is noncovalently associated with the TCR ab heterodimer, and has a short extracellular domain and a long cytoplasmic domain ANS: D. z proteins have ITAMs in their cytoplasmic tails and function, along with CD3 proteins, to transduce signals that activate the T cell after antigen binding to the TCR. 4. Present in the cytoplasmic tails of CD3 and z proteins ANS: B. ITAMs are signaling motifs present in the cytoplasmic tails of the CD3 and z proteins.

Tyrosine residues within ITAMs become phosphorylated after antigen binding to the TCR and serve as docking sites for ZAP-70 (z-associated protein of 70 kD).

Questions 5-8 For each of the descriptions in questions 1-4, select the B cell signaling molecule (A-I) that most closely matches it.

A. Iga Copyright © 2022 Elsevier Inc. All rights reserved.

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B. C. D. E. F. G. H. I.

Igb C3b C3d CR2 CD19 CD81 FYN SYK

5.

A protein tyrosine kinase homologous to ZAP70, which phosphorylates several adaptor proteins and enzymes ANS: I. The tyrosine kinase SYK binds through its SH2 domains to the phosphotyrosine residues on the cytoplasmic tails of Iga and Igb. On activation, SYK, in turn, activates numerous downstream signaling molecules, including B cell linker protein (BLNK). BLNK serves as a scaffolding protein for the activation of different pathways, including the RAS-MAP kinase pathway, the phospholipase C pathway with calcium release, and BTK activation. Ultimately, many of the same transcription factors that are important in T cell activation also mediate B cell activation, including NFAT, AP1, and NF-kB. 6.

A Src family kinase that phosphorylates immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of B cell receptor complex proteins ANS: H. On antigen-mediated cross-linking of the B cell receptor (BCR), the ITAMs of Iga and Igb are phosphorylated by SRC family kinases, including FYN, LYN, and BLK. This initiates the signaling cascade for B cell activation.

7.

A protein that is the cell surface receptor for Epstein-Barr virus (EBV)

ANS: E. Complement receptor 2 (CR2; gp140) is the cell surface receptor for EBV and mediates EBV entry into the cell. CR2 also serves as a coreceptor with the B cell receptor, mediating complement-dependent enhancement of B cell activation.

8.

A protein that covalently binds to microbes and serves as a ligand for a coreceptor that enhances B cell responses to antigen ANS: D. C3d is a complement protein fragment that binds covalently to microbial surfaces. C3d serves as the link between the B cell receptor (BCR), which binds directly to the microbe, and the CR2 coreceptor. This cross-linking between the BCR and CR2 serves to amplify the B cell response 1000-fold when compared with immune responses in which CR2 is not recruited. CR2 forms a complex with two other proteins, CD19 and CD81, on the B cell surface. When CD19 is brought into proximity with BCR-associated kinases, the cytoplasmic tail of CD19 is rapidly phosphorylated. CD19 then activates several signaling pathways, including PI3-kinase.

Multiple Choice

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9.

Which of the following groups of cytokine receptors signal through JAK-STAT pathways?

A. Receptors for tumor necrosis factor (TNF), lymphotoxin, and BAFF B. Receptors for IL-8, CXCL13, and CCL11 C. Receptors for IL-17 D. Receptors of IL-2, IL-4, and interferon (IFN)-g ANS: D. IL-2 and IL-4, are members of the type 1 cytokine family, and interferon-g is a member of the type 2 cytokine family. Receptors for type 1 and 2 cytokine families signal by JAK-STAT pathways. IL-8, CXCL13, and CCL11 are chemokines, and all chemokine receptors are Gprotein, calcium-mobilizing receptors. IL-17 receptors signal though unique ACT1/TRAF pathways. TNF, lymphotoxin, and BAFF are members of the TNF superfamily, all of which bind to TNFR superfamily receptors that signal through TRAF/NF-kB pathways.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 8: Lymphocyte Development and Antigen Receptor Gene Rearrangement Matching Questions 1-3 A block in the stage of lymphocyte development described in questions 1-3 will be caused by a mutation in which of the genes listed (A-F)?

A. RAG2 B. Ikaros C. l5 surrogate light chain D. CD3e E. TAP-1 F. Jak3 1. Stem cell to committed B or T lineage precursor ANS: B. Ikaros is a transcription factor required for transition of a pluripotent stem cell to a cell committed to either B or T lymphocyte lineages.

2. Pro-B cell to pre-B cell ANS: A. Pro-B to pre-B transition requires expression of Ig µ heavy chains. Functional µ heavy chain genes are formed by RAG-1– and RAG-2–dependent VDJ recombination.

3. CD4+CD8+ thymocyte to a single positive CD8+ thymocyte ANS: E. Maturation to a single positive CD8+ thymocyte requires positive selection of cells whose TCRs recognize self class I MHC-peptide complexes on other cells in the thymus. TAP-1 and TAP-2 are needed to deliver peptides that participate in the assembly of class I-peptide complexes into the endoplasmic reticulum. Mutations in RAG-2, Ikaros, CD3e, or JAK3 would block development before the double positive thymocyte stage.

Questions 4-7

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The figure depicts the germline organization of gene segments of the Ig heavy chain locus on chromosome 14. Choose the lettered label on the figure (A-E) that best matches the description in questions 4-7.

4. Encodes the isotype of antibodies made by naive B cells ANS: D. Naive B cells produce IgM and IgD antibody isotypes. The IgM isotype is a characteristic of the heavy chain constant region, encoded by the C µ gene segment.

5. A segment that encodes Ig domains that form part of the antigen-binding region of an Ig molecule ANS: A. One variable (V) gene segment, from as many as 45 possible V gene segments, is used in each functional Ig heavy chain gene. This V gene segment encodes an Ig domain that includes complementarity-determining regions (CDRs) 1 and 2 of the antigen-binding region of the heavy chain.

6. This type of gene segment encodes part of the third complementarity=determining region (CDR3) of Ig heavy chains and TCR b chains but not Ig light chains or TCR a chains ANS: B. Diversity (D) segments are found in the Ig heavy chain and TCR b chain loci but not in the Ig light chain or the TCR a chain loci. D segments are joined to V and J segments through somatic recombination and encode part of CDR3.

7.

A type of gene segment involved in somatic recombination events in Ig heavy chains and light chains as well as TCR a and b chain gene loci ANS: C. Joining ( J) segments are found in all antigen receptor loci. In the first somatic recombination event in Ig heavy chain and TCR b chain loci, J segments are joined to D segments. In the only somatic recombination event in the Ig light chain and the TCR a chain loci, J segments are joined to V segments.

Multiple Choice 8. Which of the following is NOT a required step in B and T lymphocyte maturation?

A. Proliferative expansion of precursor cells B. Cell surface expression of complete antigen receptor complexes Copyright © 2022 Elsevier Inc. All rights reserved.

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C. D. E.

Positive selection Activation of precursors by foreign antigens Pre-antigen receptor expression

ANS: D. Foreign antigens are not likely to be present in the generative lymphoid organs where lymphocytes mature and thus are not involved in the process. Both B cell and T cell maturation include sequential steps, including cytokine-induced proliferation and expansion of immature precursors, somatic recombination of Ig heavy chain or T cell receptor (TCR) b chain genes, expression of Ig µ heavy chain or TCR b chain with a surrogate nonvariable partner to form a pre-BCR or pre-TCR, somatic recombination of Ig light chain or TCR a chain genes, expression of complete antigen receptors and associated signaling molecules, and positive selection by recognition of self antigens.

9. Which of the following is NOT an example of a checkpoint in lymphocyte maturation that contributes to the selective maturation of cells with useful antigen receptors?

A. B cell precursors that cannot express Ig g heavy chains die by apoptosis B. T cell precursors that cannot express TCR b chains die by apoptosis C. Immature B cells that bind to self antigen with high affinity die by apoptosis D. Developing T cells that fail to express TCR b chains die by apoptosis E. Developing T cells that recognize self major histocompatibility complex (MHC) molecules with high affinity die by apoptosis ANS: A. B cell precursors must express Ig µ heavy chains (not Ig g heavy chains) to survive. The l chains associate with surrogate light chains in pre-B cells, which allows for the generation of survival signals. Otherwise, the cells die by a default apoptotic pathway. A similar checkpoint exists in T cell precursors, which must express TCR b chains that associate with pre-Ta chains to avoid apoptotic death. Developing T cells must progress to express TCR b chains and form ab TCRs to be positively selected and continue to survive. Both immature B cells and developing T cells will undergo apoptosis if they express high-affinity receptors that bind to self antigens. In the case of developing T cells, high-affinity binding to self MHC will lead to apoptotic death.

10. Which of the following statements about negative selection during lymphocyte development is most accurate?

A. The mechanism of negative selection is the death of cells whose antigen receptors are not stimulated by self antigens B. The mechanism of negative selection is apoptosis actively induced by antigen-receptor recognition of self antigens C. Negative selection ensures a self major histocompatibility complex (MHC)–restricted repertoire of T lymphocytes D. Negative selection occurs only in T cell maturation and not in B cell maturation E. The major mechanism of negative selection is inhibition of antigen receptor expression ANS: B. Negative selection is a mechanism that promotes a self-tolerant lymphocyte repertoire for both B and T cells. It occurs in the generative lymphoid organs (bone marrow and thymus) when developing lymphocytes express antigen receptors that bind strongly to self antigens. The major mechanism is actively induced apoptosis; immature lymphocytes that receive strong antigen Copyright © 2022 Elsevier Inc. All rights reserved.

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receptor–mediated signals are particularly susceptible to death by apoptosis. Positive selection in the thymus promotes a self MHC–restricted T cell repertoire.

11. Which of the following is NOT a property of the V(D)J recombinase?

A. Recognizes specific DNA sequences flanking gene segments in the antigen receptor gene loci B. Introduces double-stranded nicks in the DNA between recombination signal sequences and the adjacent V, D, or J coding sequences C. Promotes joining V-to-J, D-to-J, and V-to-D D. Repairs double-stranded DNA breaks E. Splices out intronic sequences from primary RNA transcripts ANS: E. The V(D)J recombinase is an enzyme complex that includes the lymphocyte-specific RAG-1 and RAG-2 proteins as well as other more widely expressed DNA repair enzymes. This recombinase acts on DNA in the antigen receptor gene loci but does not mediate RNA splicing.

The RAG-1 protein binds to recombination signal sequences (RSSs), cleaves the adjacent DNA, and promotes alignment of the different segments to be joined. Other enzymes in the complex ligate the cleaved DNA ends to form the functional gene, encoding a chain of the antigen receptor.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 9: Activation of T Lymphocytes Multiple Choice 1.

A helper T cell response to a protein antigen requires the participation of antigenpresenting cells that express which of the following types of molecules?

A. Class II major histocompatibility complex (MHC) and costimulators B. Class I MHC and CD4 C. Class II MHC and CD8 D. CD4 and costimulators E. Class II MHC and CD4 ANS: A. Helper T cells are almost always CD4+. The activation of naive CD4+ T cells requires T cell receptor recognition of class II MHC-peptide complexes and the binding of costimulators, both on the antigen-presenting cell (APC) surface. CD4+ helper T cells bind to class II MHC molecules on the APC, not to class I MHC molecules. CD4 or CD8 expression on the APC surface has no known relevance to T cell activation.

2.

Which of the following molecules are expressed on antigen-presenting cells and are costimulators, required in addition to antigen for activation of naive T cells?

A. Class I and class II MHC B. IL-1 receptor and IL-2 receptor (CD250) C. B7-1 (CD80) and B7-2 (CD86) D. CD28 and CTLA-4 E. CD40 and tumor necrosis factor (TNF) receptor ANS: C. B7-1 and B7-2 on antigen-presenting cells bind to CD28 on naive T cells, generating costimulatory signals in the T cells.

3. Which of the following molecules expressed on the surface of activated T cells generates signals that drive clonal expansion A. Class I MHC B. PD-1 C. FAS-ligand D. CD40 ligand E. IL-2 receptor (CD25) ANS E. CD25 is part of the high-affinity IL-2 receptor, which binds IL-2 secreted by the same or nearby activated T cells and signals the T cell to undergo mitosis, generating more T cells of the same antigen specificity (clonal expansion). Class II MHC is not involved in signaling in the T Copyright © 2022 Elsevier Inc. All rights reserved.

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cells. PD-1 inhibit T cell proliferation. FAS-ligand and CD40-ligand bind to receptors on other cells and do not directly signal into the T cell to drive proliferation 4. Which of the following best describes the molecule CTLA-4 A. Inhibits T cell activation by binding to PD-1 B. Binds to B7-1 and B7-2 and blocks T cell costimulation C. Mediates CD8+ T cell killing of infected cells D. Is a receptor for the cytokine IL-4 E. Binds to CD28 and promotes T cell costimulation ANS: B. CTLA-4 on T cells binds to B7-1 and B7-2 on antigen-presenting cells, which prevents the B7 molecules from binding to CD28 and thus blocks costimulation of the T cells.

5.

Which of following describes the function of CD4 in T cell activation?

A. Serves as an adhesion molecule, stabilizing T cell interactions with antigen-presenting cells B. Is a cytokine receptor needed for responses to T cell growth factors C. Brings cytoplasmic tyrosine kinases close to signaling motifs of the TCR complex D. Binds to PD-L1 and inhibits T cell activation E. Binds to peptides displayed by major histocompatibility complex (MHC) molecules, activating the antigen-presenting cells ANS: C. CD4 on T cells binds to a nonpolymorphic region of class II MHC during T cell recognition of antigen. This is not a strong adhesive interaction but results in bringing tyrosine kinases attached to the cytoplasmic tail of CD4 in vicinity of immunoreceptor tyrosine-based activation motifs (ITAMs) of TCR complex and promotes signaling events required for T cell activation.

6.

How does CD40 ligand (CD40L) expression on activated T cells enhance the response of the T cells to antigen?

A. CD40L binds to CD40 on dendritic cells, inducing upregulation of B7 molecules B. CD40L binds to CD40 on B cells, stimulating Ig isotype switching C CD40L binds to CD40 on macrophages, enhancing generation of reactive oxygen species D. CD40L binds to CD40 on regulatory T cells, enhancing TGF-b secretion E. CD40L binds to CD40 on endothelial cells, causing migration of the T cells into lymph nodes ANS: A. CD40L can induce the expression of costimulatory molecules by dendritic cells that are presenting antigen to the T cell, which enhances the activation of the T cell.

7. Which of the following is a consequence of B7-1 and B7-2 biding to CD28 on a naive T cell during antigen presentation?

A.

Increased production of anti-apoptotic molecules BCL-XL and BCL-2

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B. C D. E.

Increased expression of cell cycle inhibitors Reduced differentiation into memory T cells Reduced expression of IL-2 Reduced differentiation into effector cells

ANS: A. B7-1 and B7-2 binding to CD28 results in biochemical signals that enhance the expression of BCL family proteins that block cell death and also enhance IL-2, IL-2 receptor, and cyclin expression, while at the same time decrease expression of cell cycle inhibitors. All of these changes result in enhanced T cell proliferation, leading to clonal expansion. Other signals generated by B7’s binding to CD28 increase differentiation of effector and memory T cells.

8. Which of the following statements about the cytokine IL-2 is correct?

A. B. C D. E.

It is required for proliferation and maintenance of CD4+ but not CD8+ T cells It induces apoptosis of macrophages It binds to a single polypeptide receptor called CD25 It is only produced about 7 days after antigen activation of naive T cells It is required for proliferation and maintenance of regulatory T cells

ANS: E. IL-2 is a T cell growth factor required for effector T cell clonal expansion (both CD4+ and CD8+) and regulatory T cell differentiation and survival. It binds to a trimeric receptor that includes CD25 and two other polypeptide chains. IL-2 is expressed within hours after antigen stimulation of naive T cells. IL-2 does not have significant effects on macrophages.

9. Which of the following statements about clonal expansion of T cells is correct?

A. The number of effector T cells generated from a single naive CD8+ cell is usually less than the number generated from a single naive CD4+ cell B. Most of the effector T cells generated during clonal expansion during an infection survive and become memory T cells C. The number of effector T cells generated from a single naive T cell is often 1000 or more D. The cytokine that drives T cell clonal expansion is IL-17 E. T cell clonal expansion usually occurs at the site of infection ANS: C. T cell clonal expansion occurs in secondary lymphoid organs draining sites of infection and is driven by the cytokine IL-2, and 1000 to 50,00 effector cells can be generated from a single naive precursor. CD8 T cell expansion is usually greater than CD4 T cell expansion. Most of the effector T cells generated die by apoptosis as the inciting antigens are cleared.

10.

CTLA-4-Ig, a soluble fusion protein consisting of the extracellular domain of CTLA-4 and the Fc portion of human IgG, binds to B7-1 and B7-2. In which of the following types of

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diseases would CTLA-4-Ig be useful as a treatment?

A. Cancers that evade anti-tumor T cell responses B. Autoimmune diseases mediated by T cells C. T cell immunodeficiency diseases such as acquired immunodeficiency syndrome (AIDS) D. Diseases caused by defects in T cell migration E. Psychiatric diseases ANS: B. CTLA-4-Ig acts as an inhibitor of T cell costimulation by competitively blocking B7 binding to CD28, and thus it can reduce severity of T cell–mediated autoimmune diseases. It would not be useful in diseases where there is too little T cell immunity, such as in some cancers or immunodeficiency states. Note that anti-CTLA-4 is a different drug that blocks the function of CTLA-4, thereby enhancing T cell costimulation, and is used in cancer immunotherapy. There is no known basis for treating psychiatric disease with CTLA-4-Ig.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 10: Differentiation and Functions of CD4+ Effector T Cells Matching Questions 1-4 Match the descriptions of helper T cell subset differentiation in questions 1-4 with the appropriate cytokine or transcription factor (A-H).

A. Interleukin (IL)-10 B. IL-12 C. RORgT D. STAT6 E. STAT4 F. IL-4 G. IL-10 1.

This cytokine is required for Th1 differentiation

ANS: B. Th1 differentiation requires antigen plus IL-12 stimulation of naive T cells. IL-12, secreted by dendritic cells, binds to its receptors on T cells and activates the JAK kinases, which phosphorylate and activate STAT4.

2.

This intracellular signaling molecule and transcription factor is required for differentiation of Th2 cells and for responses of other cells to Th2 cells ANS: D. STAT6 is an intracellular signaling molecule that is activated by IL-4 via JAK kinases.

IL-4 activation of STAT6 is required for the differentiation of naive T cells into the Th2 phenotype, as well as for the effects of IL-4 on other cell types, such as isotype switching to IgE in B cells.

3.

This intracellular signaling molecule and transcription factor is required for Th17 differentiation ANS: C. RORgT is the master regulator of Th17 differentiation and function. Its expression is induced by antigen activation of naive T cells in combination with other cytokines such as IL-6.

4.

This cytokine is required for Th2 differentiation

ANS: F. IL-4 is required for Th2 differentiation, as well as for Th2 function. IL-4 induces the transcription GATA3, the master regulator of Th2 cells.

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Questions 5-7 For each of the descriptions in questions 5-7, select the molecule involved in Th subset function (A-L).

A. IL-5 B. CD40 ligand (CD40L) C. CD40 D. IL-17 E. IL-22 F. IL-4 G. Interferon (IFN)-g 5.

This membrane molecule is expressed on the surface of activated Th1 cells and promotes macrophage activation ANS: B. CD40L (CD154), a member of the tumor necrosis factor (TNF) family of proteins, is expressed on Th1 cells after antigen-induced activation and binds to CD40, a member of the TNF receptor family, on macrophages. The signals generated by CD40 promote macrophage activation. IFN-g, also produced by helper T cells, synergizes with CD40L in activating macrophages.

6.

This product of Th2 cells promotes immunity to helminthic infections

ANS: A. IL-5 is a cytokine produced by Th2 cells that stimulates production of eosinophils in the bone marrow and promotes eosinophil activation. Eosinophil granules contain molecules, such as major basic protein, that are particularly toxic to helminths.

7.

This cytokine promotes acute inflammation during helper T cell responses to extracellular microbes ANS: D. IL-17 produced by Th17 cells acts on hematopoietic cells in the bone marrow, on endothelial cells, and on innate cells in tissues, all to promote neutrophil-rich inflammation, which is required for protection against extracellular fungi and bacteria.

Questions 8-12 For each of the descriptions of a biologic function in questions 8-12, select the T cell–derived cytokine (A-E) that matches it.

A. Interferon (IFN)-g B. Interleukin (IL)-13 C. IL-5 D. Transforming growth factor (TGF)-b E. IL-17 8.

Stimulates growth and activation of eosinophils

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ANS: C. IL-5 is secreted by helper T cells of the Th2 subset and promotes inflammatory responses rich in eosinophils. The protective function of eosinophils is against helminth infections, but, more commonly, eosinophils are associated with allergic disease.

9.

Induces B cell isotype switching to IgE production

ANS: B. IL-13 is secreted by a subset of Tfh cells and promotes IgE production by B cells. Il-4 also has this activity. IgE contributes to antigen-induced mast cell degranulation and immediate hypersensitivity reactions. Therefore, IL-4 production contributes to allergic disease.

10.

Stimulates expression of class II MHC on various cell types

ANS: A. IFN-g is a proinflammatory cytokine secreted by helper T cells of the Th1 subset and natural killer (NK) cells. This cytokine induces class II MHC expression on various cell types, thereby enhancing antigen presentation to CD4+ T cells. Other important biologic activities of IFN-g are induction of class I MHC expression, macrophage activation, and B cell Ig isotype switching.

11.

Inhibits proliferation and differentiation of T cells and the activation of macrophages

ANS: D. TGF-b is produced by various cell types. The principal function of TGF-b is inhibition of T cell differentiation and proliferation, as well as inhibition of macrophage activation. TGF-b is secreted by regulatory T cells. TGF-b is also an IgA isotype switch factor.

12.

Enhances acute inflammation

ANS. E. IL-17, produced by Th17 cells, promotes acute inflammatory responses to bacteria and fungi that live outside cells.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 11: Differentiation and Functions of CD8+ Effector T Cells Multiple Choice 1.

The differentiation of naive CD8+ T cells into cytotoxic T lymphocytes (CTLs) requires expression of which of the following transcription factors?

A. GATA3 B. RORgT C. FOXP3 D. T-bet E. PAX3 ANS: D. Two critical transcription factors needed for CTL differentiation are T-bet (which is also required for Th1 differentiation) and eomesodermin, which is related to T-bet. GATA3, RORgT, and FOXP3 are required for Th1, Th17, and regulatory T cell differentiation, respectively, but not CTL differentiation. PAX3 is required for embryonic development of some nonlymphoid tissues.

1.

The cDC1 subset of dendritic cells (DCs) is especially important for immunity to viruses because this type of DC is efficient at cross-presenting antigens. Why is the ability to crosspresent antigen important?

A. It allows DCs to present peptide fragments of viral proteins bound to class I MHC even when the viral proteins are not synthesized in the DC cytosol B. It allows virally infected DCs to present peptide fragments of viral proteins bound to class II MHC to CD4+ helper T cells C. It allows DCs to efficiently carry viral antigens from infected tissues to lymph nodes D. It allows DCs to present viral antigens to B cells E. It allows DCs to transfer viral antigens to macrophages, which then present the antigens to CD8+ T cells ANS: A. Cross-presentation is the process of a DC taking up protein antigens made by microbes or by other cells into endosomes and then delivering the antigens from the endosomes into the DC cytosol so they can be processed and presented by the class I MHC pathway to CD8+ T cells.

This allows DCs to simulate cytotoxic T lymphocyte (CTL) responses to viral antigens, which is necessary for anti-viral defense, even though the DC may not have been infected by the virus.

2. What is the mode of death of cells targeted by cytotoxic T lymphocytes (CTLs)?

A. Necrosis B. Pyroptosis C. Netosis D. Apoptosis

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E.

Osmosis

ANS: D. CTL killing of target cells depends on release of CTL granule contents, including perforin and granzymes. Perforin damages the target cell membrane, allowing the granzymes to enter the cytosol where they initiate apoptotic pathways by proteolytically activating proapoptotic caspases. Pyroptosis is a form of death induced by inflammasomes activation. Netosis is a mode of neutrophil death in which cell content, including DNA, is actively extruded.

Necrosis is a common form of death due to toxins, loss of blood supply, and other causes, which results in global loss of cell function and structure with passive release of cell contents. Osmosis is not a form of death but may contribute to cell death when plasma membrane function fails.

4.

Cytotoxic T lymphocyte (CTL) killing of virus-infected target cells depends on which of the following molecules?

A. Interferon (IFN)-g B. Complement C9 C. Perforin D. Interleukin (IL)-17 E. CD40L ANS: C. When a CTL recognizes viral peptide-MHC on an infected cell surface, it is activated to release the contents of its cytosolic granules, which contain perforin and granzymes. Perforin is a membrane-disrupting protein that inserts into the infected cell plasma membrane and facilitates entry of the granzymes into the cytosol of the infected cell. Granzymes then activate apoptosis of the infected cell.

5.

Cytokines made by other cells contribute to the differentiation of CD8+ T cells into cytotoxic T lymphocytes (CTLs) for generation of memory cells. Two of these are: A. Interleukin (IL)-1 and IL-9 B. IL-4 and IL-5 C. Tumor necrosis factor (TNF) and IL-6 D. IL-12 and IL-15 E. IL-17 and IL-13 ANS: D. IL-12, produced by dendritic cells, is required for CTL differentiation, and IL-15, produced by dendritic cells (DCs) and other cell types, is important for the survival of memory CD8+ T cells. IL-1, IL-6, and TNF are inflammatory cytokines made by macrophages and other cell types and important in innate immune responses. IL-4, IL-5, and IL-13 are produced by Th2 cells and contribute to anti-parasite defense and to allergic responses. IL-17 is a proinflammatory cytokine made by Th17 cells.

6.

Which of the following is the major cytokine secreted by activated cytotoxic T lymphocytes (CTLs) and contributes to the effector functions of CTLs? A. Interleukin (IL)-4 B. IL-12 C. IL-15

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D. E.

IL-21 Interferon (IFN)-g

ANS: E. IFN-g is the major cytokine secreted by activated CTLs and works to activate antimicrobial functions of macrophages. IL-4, IL-12, IL-15, and IL-21 are not secreted by CTLs. 7.

Which of the following is a correct description of exhausted cytotoxic T lymphocytes (CTLs)?

A. CTLs with elevated expression of various inhibitory molecules and inability to functionally respond to antigen activation B. CTLs that have recently been activated by antigen and have emptied the contents of all their granules C. Dysfunctional CTLs found in the blood of sleep-deprived individuals D. CTLs that cannot migrate out of lymph nodes because they lack enough metabolic energy E. Dysfunctional CTLs found in the blood of patients suffering from carbon monoxide poisoning ANS: A. Exhausted CTLs develop after repeated stimulation in patients with chronic viral infections or cancers. Exhausted CTLs have various functional defects, including decreased proliferation, interferon (IFN)-γ production, and cytotoxic activity. These cells express increased levels of multiple inhibitory receptors, such as PD-1 and CTLA-4.

8.

Which of the following is a major way in which cytotoxic T lymphocyte (CTL) responses to infection can cause disease?

A. CTLs can cause significant tissue damage by killing infected cells, even when the microbe itself does not cause cell death.

B. Released granzymes kill many healthy bystander cells when the CTLs kill infected cells C. Interferon (IFN)-g released by activated CTLs causes death of macrophages D. CTLs kill infected CD4+ T cells, causing immunodeficiency disease ANS: A. In some infectious diseases, such as viral myocarditis and viral hepatitis, the viruses are often not cytopathic (i.e., they do not kill the cells they infect), but in fact the CTL response is the cause of death of the cells, resulting in organ dysfunction. There is little bystander injury of cells when a CTL kills an infected cell because the granule contents are released into small immune synapse spaces between the tightly opposed CTL and target cell. IFN-g released by activated CTLs causes macrophage activation, not death. In the case of human immunodefiency virus (HIV) infection, the virus infects CD4+ T cells, and CTLs do kill infected CD4+ T cells, perhaps contributing to immunodeficiency, but most viruses do not infect CD4+ T cells.

8.

A. B. C. D

Which of the following is a manifestation of genetic deficiency of the perforin protein?

Increased eosinophil in tissues Reduced numbers of CD8+ T cells in blood Decreased release of interferon (IFN)-g by activated cytotoxic T lymphocytes (CTLs) Systemic excess macrophage activation

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ANS: D. Perforin deficiency, caused by mutations in the perforin genes, leads to a severe systemic inflammatory disease called familial hemophagocytic lymphohistiocytosis (fHLH) characterized by excessive macrophage activation. It is thought that perforin-deficient, virusspecific CTLs can be activated by virus- infected cells to secrete IFN-g, but the CTLs cannot kill those cells, resulting in prolonged excess IFN-g secretion and resultant macrophage activation.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 12: B Cell Activation and Antibody Production Multiple Choice 1.

A child is infected with a virus, mounts antibody responses to a viral protein, and recovers. A year later, the child is exposed to the same type of virus and mounts a memory response specific for the same viral protein. Which one of the following statements comparing the (primary) antibody response to the viral protein and the memory response a year later is true?

A. The antibodies in primary responses were of lower affinity for viral protein than those produced in memory responses B. The peak blood levels of antibodies during the primary response was higher than in the memory response C. T follicular helper (Tfh) were mainly required during the memory response, and not in the primary response D. Antibodies specific for the viral protein were only produced by plasma cells in the memory response E. In the primary response, mainly IgG was produced, whereas in the memory responses mainly IgM was produced ANS: A. In a primary immune response, short-lived plasma cells are generated which secrete low affinity IgM antibodies against the protein antigens, but as the response develops, Tfh cells induce isotype switching, production of IgG with high affinity for antigen, memory B cells, and long lived plasma cells. In the memory response, memory B cells are rapidly activated to become plasma cells that produce high levels of high affinity IgG. 2. Which one of the following statements about humoral immune responses is true?

A. Naive B cells are required for initiation of primary responses and memory B cells are required for initiation of secondary responses.

B. Antibody responses to bacterial polysaccharide antigens require CD4+ helper T cells.

C. Heavy chain isotype switching typically occurs in response to bacterial polysaccharide antigens.

D. Affinity maturation does not require T follicular helper T cells.

E. Antibody-secreting cells generated during a humoral immune response live for only a few hours.

ANS: A. Humoral responses require antigen-dependent activation of B cells through binding of the antigen to membrane Ig on naive B cells or on memory B cells, for primary or secondary responses, respectively. In most cases, nonprotein antigens do not stimulate isotype switching or affinity maturation because these changes require T cell help, and only protein antigens can stimulate T cells. For both nonprotein and protein antigens, antibody-secreting cells that are generated may live for months, often in the bone marrow.

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3. The initiation of a B cell response to an antigen requires that antigens are presented to naive B cells. Various types of cells, including macrophages and follicular dendritic cells, are involved in presenting the antigens. Which of the following statements about the antigen that is presented to B cells is correct?

A. It is usually in its intact, native conformation and is not processed by antigen-presenting cells.

B. It is always a protein, which is processed into peptides by the presenting cell before recognition by B cells C. The antigen must be a carbohydrate in order to be recognized by B cells D. The antigen must be synthesized by infected antigen-presenting cells ANS: A. In most cases, the antigen that is presented to B cells is generally in its intact, native conformation. The antigen can be any form of molecule, not just protein, and it can bind to the surface of the presenting cell, without requirement of being internalized, in contrast to antigen presentation of protein to T cells, which requires internalization and proteolytic processing. The antigen-presenting cell does not need to be infected, and the molecule does not have to be synthesized by the antigen-presenting cell.

4. Complement activation can enhance naive B cell responses to antigen. Which of the following correctly describes the molecules that are involved?

A. The C3d fragment of complement binds to the microbial antigen and to complement receptor 2 (CD21) on the B cell B. The membrane attack complex (C5-C9) on a microbial surface promotes release of microbial antigens that can be recognized by B cells C. C1 binds to membrane Ig on the B cells D. The C3a and C5a fragments released by C3 and C5 convertases, respectively, bind to receptors on the B cell ANS: A. B cells express the complement receptor CR2 (also called CD2. When a microbe activates complement, C3dg fragments are generated that bind to the microbes and is recognized

by CR2/CD21, which transduces signals that enhances the strength of B cell receptor (BCR) signaling.

5. Which property of many carbohydrates, lipids, and nucleic acids allows them to activate B cells and induce antibody responses without the help of T cells?

A. Water solubility B. Negative charge C. Low molecular weight D. Multivalency ANS: D. T-independent antigens, such as polysaccharides, contain multiple identical epitopes on each molecule that can cross-link many BCRs, and this results in signaling by the BCR leading to B cell activation and functional responses, without the need for helper T lymphocytes. Most globular protein antigens have only one copy of each epitope per molecule and, in their

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monovalent form, cannot cross-link multiple Ig molecules and directly fully activate BCR signaling.

Matching Match each description of an event in T-dependent B cell responses in questions 6-10 with the appropriate lettered term (A-I).

A. Antigen presentation by B cells to T cells in the extrafollicular focus and upregulation of ICOS, BCL6, PD1, and IL-21 B. Downregulation of chemokine receptor CXCR5 and upregulation of CCR7 and EBI2 C. B cells stop dividing and shut off expression of the CXCR4 chemokine receptor D. Downregulation of chemokine receptor CCR7 and upregulation of chemokine receptor CXCR5 E. Activated B cells in extrafollicular focus triggered by Tfh cell interactions to downregulate EBI2 6. Generation of follicular helper T cells (Tfh) ANS: A. Tfh cells are generated from helper T cells (Th) cells previously derived from naive CD4+ T cells activated by antigen presented by dendritic cells in the T cell zone. B cells in the extrafollicular focus present the same antigen to the Th cells and provide signals that drive differentiation of the Th cells into Tfh cells. Tfh differentiation depends on the transcription factor BCL6 and is characterized in part by expression of ICOS, PD1, and IL-21.

7. Migration of antigen-activated helper T cells (Th) toward B cell follicles ANS: D. After antigen activation, helper T cells downregulate the chemokine receptor CCR7 and increase the expression of CXCR5 and, as a result, leave the T cell zone and migrate toward the follicle in response to CXCL13 secreted by follicular dendritic cells (FDCs) and other cells in the follicle.

8. Migration of B cells out of follicles and toward the T cell zone ANS: B. B cells respond to antigen triggering of BCR signaling by reducing cell surface expression of chemokine receptor CXCR5 and increasing expression of CCR7 and the receptor EBI2. EBI2 responds to oxysterols, which draws the B cells to the edge of follicle, and then the B cells migrate towards the T cell zone in response to CCL19 and CCL21, the ligands for CCR7.

9. Generation of the germinal center ANS E: The germinal center is formed by the migration of B cells and Tfh cells from the extrafollicular focus into to the center of a follicle, followed by further Tfh:B cell interactions, leading to exuberant B cell proliferation and differentiation. Entry of B cells into the follicle is triggered by Tfh cells through CD40L-CD40 interactions, causing B cells to downregulate EBI2 and move to the center of the follicle.

10. B cell migration from the dark zone to the light zone ANS C. B cells in the dark zone, which have undergone somatic mutation, stop dividing and shut off expression of the CXCR4 chemokine receptor. The CXCR4 ligand, CXCL12, is more

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abundant in the dark zone than in the light zone, and the loss of CXCR4 expression results in the migration of these heavily mutated non-dividing B cells to the adjacent light zone that contains Tfh cells and FDCs. These non-dividing dark zone B cells still express CXCR5 and are drawn towards the higher concentration of CXCL13 in the light zone.

Multiple Choice 11. A genetic deficiency of CD40-ligand (CD40L) results in which of the following pair of B cell-related immune defects?

A. Elevated blood IgG; no germinal centers B. Decreased blood IgG; no germinal centers C. Elevated blood IgE; large germinal centers D. Elevated blood IgM; high affinity IgM E. Low blood IgM; no IgE ANS: B. CD40L on T follicular helper cells is required to induce expression of activationinduced cytidine deaminase (AID) in B cells, and AID is required for isotype switching and the germinal center reaction where affinity maturation takes place. Children with CD40L deficiency make IgM but very little IgG, and the IgM and IgG are of low affinity. Histology of lymphoid tissues shows these children do not make well-formed germinal centers.

12. During B cell isotype switch recombination, which of the following occurs?

A. Ig heavy chain locus V-D-J recombination resulting in a change in the V-D-J gene cassette used to encode the Ig heavy chain V domain B. Single nucleotide mutations in a previously formed V-D-J gene cassette encoding the heavy chain V domain C. Ig heavy chain locus DNA recombination resulting in use of a different heavy chain constant gene but the same V-D-J gene cassette D. Alternative splicing of Ig heavy chain mRNA resulting in expression of a different heavy chain isotype ANS: C. Class switch recombination involves activation-induced cytidine deaminase (AID)– mediated DNA recombination, including double-stranded DNA breaks, deletion of DNA, and religation to bring a previously rearranged heavy chain V-D-J cassette in proximity to a new constant region gene in the same locus. The result is that the B cell will express Ig with a different heavy chain isotype than before but have the same antigen specificity.

13. Which of the following does not take place in a germinal center reaction?

A. Generation of long-lived plasma cells B. Generation of longed lived plasma cells C. Isotype switching D. Somatic hypermutation of V genes.

E. V-D-J recombination in Ig heavy chain locus.

ANS: E. V-D-J recombination occurs during B cell development in the bone marrow.

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14. Which of the following is a role of follicular dendritic cells (FDCs) in antibody responses to infections?

A. FDCs transport antigens from infected tissues into lymph nodes B. FDCs trap antigen in the subcapsular sinuses of lymph nodes and display them to naive B cell in adjacent follicles C. FDCs display antigen to B cells in germinal centers, which results in deletion of B cells expressing high-affinity B cell receptors D. FDCs display antigen to B cells in germinal centers, which results in selective survival of B cells expressing high-affinity B cell receptors E. FDCs present peptide antigen bound to class II CD4+ T cells, leading to T cell differentiation into T follicular helper (Tfh) cells ANS: D. FDCs are essential for affinity maturation in the germinal center reactions. The FDCs display intact B cell antigens on their cell surface for positive selection of high-affinity B cells.

FDCs do not express class II MHC and cannot present peptide-MHC antigens to CD4+ T cells.

FDCs are only located only in B cell follicles of secondary lymphoid organs but not in infected tissues or the subcapsular sinus of lymph nodes.

15. Antibody feedback is a physiologic control mechanism in humoral immune responses that is triggered by secreted antibody and blocks further antibody production. Antibody feedback inhibition of B cell responses is mediated by which of the following events?

A. Antigen-antibody complexes simultaneously interact with the B cell antigen receptor through the antigen and the inhibitory IgG Fc receptor (FcγRIIB) through the antibody B. Antibodies with antigen -binding sites specific for the inhibitory IgG Fc receptor (FcγRIIB) on B cells bind to FcγRIIB, inducing inhibitory signals in the B cells C. Antibodies activate complement, and Ig-C3d complexes simultaneously bind to the B cell antigen receptor through the antigen and complement receptor 2 (CR2) on B C3d D. Antigen-antibody complexes deposit in walls of blood vessels supplying the spleen, leading to vasculitis and damage to the spleen E. Antigen-antibody complexes simultaneously interact with the B cell antigen receptors through the antigen and with activating IgG Fc receptors (FcγRI) on macrophages through the antibody, causing macrophage activation and phagocytosis of the B cells ANS: A. IgG antibodies inhibit B cell activation by forming complexes with the antigen, and these complexes bind to a B cell receptor for the Fc portions of the IgG, called the Fcγ receptor II (FcγRIIB, or CD32). FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail, and when this receptor is engaged, the ITIM is phosphorylated, initiating a phosphatase-mediated inhibitory signaling cascade that blocks further activation of the B cell by antigen.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 13: Effector Mechanisms of Humoral Immunity Matching Questions 1-5 For each of descriptions in questions 1-5, select the Ig isotype (A-E) that most closely matches it.

(Answers may be used more than once.)

A. IgM B. IgD C. IgG D. IgE E. IgA 1.

An allergic reaction ANS: D. IgE antibodies play an essential role in immediate-type hypersensitivity reactions (e.g., allergies), asthma, and helminthic infections. Mast cells express plasma membrane Fcå receptors, which bind IgE antibodies specific for allergens that were produced after a prior exposure to allergens. On re-exposure to an allergen that binds to some of the IgE antibodies bound to the mast cell, the mast cells are activated and rapidly release histamine and other vasoactive and inflammatory molecules.

2.

Phagocytosis ANS: C. Phagocytosis is primarily mediated by neutrophils and macrophages during an immune response to an infection. Both cell types express Fcg receptors, which bind to the constant regions of IgG antibodies that have bound to microbes. The Fcg receptors then activate the cells to phagocytose the antigen-coated microbes.

3.

Unclear functional role ANS: B. IgD is expressed mainly as a membrane but not secreted Ig by naive B cells, and its function is unclear.

4.

Binds to receptors in the placenta for delivery into the fetal blood ANS: C. Neonatal immunity is mediated in large part by maternal antibodies, which are transported into the fetal blood by specific Fc receptors expressed in the placenta. These receptors are specific for the IgG isotype and are called FcRn (“n” for “neonatal”). Maternal IgGs acquired in utero are a primary mode of immunity for the first 6 months of life before the infant has produced significant amounts of antibody on its own.

5.

T cell–independent antigens

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ANS: A. All B cells initially make IgM and IgD and not other isotypes. Most isotype switching from IgM to other isotypes depends on T cell help. Therefore, in responses to T cell–independent antigens, which are non-protein antigens, the main isotype is IgM. Questions 6-9 For each of the descriptions in questions 6-9, select the Fc receptor (A-G) that best matches it.

A. FcgRI (CD64) B. FcgRIIB (CD32) C. FcgRIIIA (CD16) D. FceRI E. FceRII (CD23) F. FcaR (CD89) G. FcRn 6.

High-affinity Ig receptor on mast cells important in immediate hypersensitivity reactions

ANS: D. FceRI is a high-affinity IgE receptor expressed on mast cells and basophils. Although serum IgE levels are relatively very low, FceR1 receptors are fully occupied by IgE because of the high affinity of the receptor. Cross-linking of this receptor by allergen binding to the IgE leads to mast cell activation, which includes granule exocytosis with release of mediators such as histamine, as well as production of lipid mediators and cytokines.

7.

High-affinity Ig receptor on macrophages and neutrophils important for phagocytosis and activation ANS: A. FcgRI (CD64) is a high-affinity IgG1 and IgG3 receptor that mediates phagocytosis of opsonized organisms and delivers signals that enhance microbicidal activity of the phagocytes.

8.

Low-affinity Ig receptor on natural killer (NK) cells that mediates antibody-dependent cell-mediated cytotoxicity ANS: C. FcgRIIIA (CD16) is a low-affinity IgG receptor that targets NK cells to bind and IgGopsonized target cells and signals the NK cell to release cytotoxic granules that kill.

9.

Ig receptor on B cells that mediates feedback inhibition

ANS: B. FcgRIIB (CD32) is a low-affinity IgG receptor expressed on B lymphocytes. When antigen-IgG complexes simultaneously bind to membrane Ig and FcgRIIB, phosphatases that bind to immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytosolic tail of FcgRIIB become activated and block activating signals from the B cell antigen receptor complex.

Questions 10-14 For each of the functions described in questions 10-14, select the complement system protein (AF) that best matches it.

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A. B. C. D. E.

C3b iC3b C3d C5b C5a

10.

Generated by Factor I–mediated proteolysis, this complement fragment binds to complement receptor 2 (CR2) on B cells and enhances B cell activation ANS: C. C3d is covalently bound to cell surface and is produced by sequential Factor I–mediated proteolytic processing of C3. It binds to CR2 on B cells simultaneously with antigen binding to membrane Ig. CR2 is part of a coreceptor complex, which also includes CD19 and CD21. CD19 transduces signals that synergize with the B cell receptor complex signals to activate the B cell.

11.

Generated by Factor I–mediated proteolysis, this opsonizing complement fragment binds to CR3 on phagocytes ANS: B. iC3b is covalently bound to cell surfaces and is produced by sequential Factor I– mediated proteolytic processing of C3. iC3b binds to CR3 and CR4, which are integrins expressed by phagocytes.

12.

Produced by C3 convertases, this opsonin promotes phagocytosis of microbes

ANS: A. C3b is the larger fragment of C3 convertase-mediated cleavage of C3, which becomes covalently bound to cell surfaces and is recognized by complement receptor 1 (CR1) on phagocytes.

13.

This complement fragment is a chemoattractant for neutrophils

ANS: E. C5a is a small soluble fragment generated by C5 convertase-mediated cleavage of C5.

C5a binds to a G protein–coupled serpentine receptor on neutrophils and stimulates chemotaxis.

The C5a receptor is also expressed on other cell types, and C5a has several proinflammatory functions, including mast cell and endothelial cell activation. C3a and C4a have similar biologic activities as C5a, but they are not as potent. Together, C5a, C4a, and C3a are called anaphylatoxins.

14.

This complement fragment is a component of the membrane attack complex

ANS: D. C5b is the larger fragment of C5 generated by C5 convertase. It is the initial component in the formation of the membrane attack complex, which includes C5, C6, C7, C8, and several C9s.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 14: Specialized Immunity at Epithelial Barriers and in Immune Privileged Tissues Multiple Choice 1.

A. B. C. D. E.

Which epithelial barrier has the largest surface area in the body?

Intestinal mucosa Skin Bronchopulmonary mucosa Genitourinary tract Conjunctiva

ANS: A. The combined surface area of the mucosa of the small and large bowel is about 200 m2 (the size of a tennis court), most of which is accounted for by the small intestinal villi and microvilli. The skin has the second largest epithelial barrier surface.

2.

Which one of the following statements about the mucosal immunity is correct?

A. There are more bacteria normally living on the skin than at any other anatomic site B. There are about 1014 bacteria normally living in the intestines C. There are more species of viruses than other types of microbes in the normal intestines D. The bacteria found on the skin are mostly pathogens, while those in the gut are mostly commensals E. The bronchopulmonary tree is normally free of any microbes ANS: B. More than 500 to 1000 different species of bacteria, amounting to approximately 1014 cells, live in the human gut (more than any other site in the body), many of which are ingested along with food and most of which are continuously growing as commensals. The bacteria normally found on the skin, gut, and other barrier sites are mostly commensals. Pathogens are numerically very rare. The bronchi normally do contain bacteria, fungi, and some viruses, but the alveoli are usually sterile.

3. Which of the following statements about mucus in the gut is correct?

A. The mucus has a slow turnover and a uniform chemical composition over time B. Most of the bacteria in the gut are kept from direct contact with the intestinal epithelium by the mucus layer C. The source of most of the mucus in the small bowel are Paneth cells found in the crypts between villi D. Mucus is composed of a mixture of secreted protein-free oligosaccharides E. The mucus layers in the small bowel and the large bowel are indistinguishable

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ANS: B. Intestinal mucus is produced by specialized epithelial cells called goblet cells and is composed of glycoproteins called mucins that have many different O-linked oligosaccharides. In the small bowel, the mucus forms a single layer, and most of the bacteria are in the outer portion of the mucus; bacteria rarely make direct contact with small intestine epithelial cells. Colonic mucosa has an outer layer that is colonized by bacteria and an inner denser layer that is attached to the epithelium and is bacteria free. The mucous barrier undergoes constant turnover and chemical changes in response to various environmental and immune signals, which allow rapid increases in mucosal barrier function.

Matching For each feature of innate intestinal mucosal immunity described in questions 4-8, choose the term (letters A-F) that most closely matches it A. α-defensins, HD5, and HD6 B. β-defensins C. Regenerating islet-derived proteins (REGIII) D. IL-17 E. IL-13 F. IL-25 1.

Secreted by type 2 innate lymphoid cells (ILC2s) and acts on intestinal goblet cells to increase mucus production ANS: E. ILC2s play a role in intestinal innate immunity against helminths. In response to the cytokines IL-33 and IL-25 released from epithelial cells, ILC2s secrete IL-5 and IL-13. IL-5 activates eosinophils, which secrete enzymes that degrade the outer integument of helminths, and IL-13 increases mucus production, contributing to expulsion of the worms.

2. Antimicrobial peptides secreted by small intestine Paneth cells as an inactive precursor that is proteolytically activated by trypsin ANS: A. The α-defensins, including human defensin 5 (HD5) and HD6, are produced constitutively as inactive precursor proteins by Paneth cells located at the base of crypts between microvilli in the small bowel, and are activated by proteolytic cleavage mediated by trypsin, also produced by Paneth cells.

6. C-type lectins secreted by Paneth cells, which block bacterial colonization of the epithelial surface by binding to Gram-positive bacterial peptidoglycan ANS: C. Paneth cells secrete C-type lectins called regenerating islet-derived proteins (REGIII), which block bacterial colonization of the epithelial surface.

7. Secreted by specialized intestinal epithelial cells called the tuft cells in response to helminths, which stimulates ILC2s to secrete IL-13 ANS: F. Tuft cells are activated by helminths to secrete abundant IL-25, which stimulates ILC2s to secrete IL-13, which in turn stimulates the differentiation of mucus-secreting goblet cells and more tuft cells from intestinal crypt stem cells.

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8. Secreted by type 3 innate lymphoid cells (ILC3s) and acts on intestinal epithelial cells to enhance defensin production and increase tight junctions ANS: D. Most of the ILC3s in the body are found in the gut, and they respond to IL-1 and IL-23 by secreting IL-17 and IL-22. IL-17 promotes acute inflammatory response to the microbes, and both IL-17 and IL-22 enhance intestinal mucosal barrier function by stimulating production of defensins and by enhancing epithelial tight junction function.

Multiple Choice 9. Specific homing of lymphocytes from blood into intestinal mucosa is mediated by which of the following pairs of integrin and chemokine receptor?

A. α4β7 and CCR7 B. VLA-4 (α4β1) and CXCR3 C. LFA-1 and CCR9 D. α4β7 and CCR9 E. LFA-1 and CCR10 ANS: D. The major integrin on gut-homing B and T lymphocytes is α4β7, which binds to the MadCAM-1 protein expressed on postcapillary venular endothelial cells in the gut lamina propria. Gut homing requires the chemokine receptor CCR9 on the B and T lymphocytes and its chemokine ligand CCL25, which is produced by intestinal epithelial cells. The combined expression of MadCAM-1 on endothelium and CCL25 in tissues is restricted to the gut.

10. Which Ig isotype is the most abundantly produced by the human immune system?

A. IgD B. IgM C. IgG D. IgA E. IgE ANS: D. IgA is produced in higher amounts than any other antibody isotype. A normal 70-kg adult secretes about 2 g of IgA per day, which is 60% to 70% of the total Ig production.

11. Which of the following descriptions of the poly-IgA receptor is correct?

A. It mediates transcytosis of IgA and IgM through the placenta into the fetal circulation B. It mediates secretion of IgA into the intestinal lumen and into breast milk C. It mediates IgA uptake from the gut lumen of nursing children into blood D. It is a pentameric version of IgA held together with a J chain E. It is a proteolytic enzyme that cleaves IgA dimers to form IgA monomers that are secreted into the gut lumen ANS: B. IgA and Ig that is produced in lymphoid tissues in the gut are transcytosed across the intestinal epithelium by the poly-IgA receptor. IgA produced by plasma cells in lymphoid tissue

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in the mammary gland is secreted into colostrum and mature breast milk through poly-Ig receptor–mediated transcytosis and mediates passive mucosal immunity in breastfed children.

The poly-IgA receptor is not involved in transplacental Ig transport, is not a form of IgA, and has no proteolytic activity. The poly IgA receptor is cleaved by proteases at the lumenal side of intestinal epithelial cells to release dimeric IgA with a fragment of the poly IgA receptor, called the secretory component, attached.

12. Which of the following is the major function of microfold (M) cells in the gut epithelium?

A. Secretion of antimicrobial defensins B. Phagocytosis and killing of viruses and bacteria in the gut lumen.

C. Secretion of mucus D. Processing and presentation of protein antigens to lamina propria T cells E. Transcellular transport of antigens from the gut lumen to antigen-presenting cells in Peyer’s patches ANS: B. The main function of M cells is transcellular transport of antigens from the lumen of the intestine across the epithelial barrier to underlying antigen-presenting cells in Peyer’s patches.

They do not process antigens and do not perform directly antimicrobial effector functions.

13. In addition to defending against pathogens, the intestinal immune system must maintain tolerance to commensal organisms and ingested food. One of many studies addressing how this tolerance is maintained used mice with selective deletion of the IL-10 gene only in FOXP3expressing T cells. These mice severe develop inflammatory bowel disease, but not when the mice were bred in sterile (“germ-free”) conditions. These experimental findings are consistent with which of the following conclusions?

A. IL-10 produced by regulatory T cells (Treg) promotes growth of intestinal microbes, which are necessary for tolerance to food B. Treg that cannot produce IL-10 become inflammatory T cells that attack intestinal tissues C. IL-10 produced by Th17 cells are essential in maintaining tolerance to commensal organisms D. IL-10 produced by Treg are essential in maintaining tolerance to commensal organisms E. IL-10 produced by Th1 cells are essential in maintaining tolerance to commensal organisms ANS: B. Mouse studies, and some evidence from studies of patients with inflammatory bowel disease, indicate that several cytokines are required for mucosal tolerance, including IL-2, IL-10, and TGF-b. Mice in which cytokines, cytokine receptors, and cytokine receptor signaling are genetically ablated only in specific cell types have been used to address which cells are critical.

FOXP3+ is expressed mainly in Treg and not Th1 or Th17 cells. Selective deletion of the genes encoding IL-10 or TGF-b in FOXP3+ cells leads to severe colitis, but not in germ-free mice, consistent with the critical role of Treg-produced IL-10 in maintaining tolerance to commensals in the gastrointestinal tract.

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Matching For each of the regional immune functions described in questions 14-18, select the molecule (AF) that best matches it.

A. Surfactant proteins A (SP-A) and D (SP-D) B. IL-1b C. Langerin (CD207) D. Cutaneous lymphocyte antigen (CLA) E. FOXP3 F. Indoleamine 2,3-dioxygenase (IDO) 14.

Expression of this molecule in the immune system evolved at the same time as placental mammals ANS E. Eutherian mammals have evolved a change in a regulatory sequence of the Foxp3 gene that allows these species to generate stable peripheral regulatory T cells (Treg). This suggests Tregs may be required for maternal tolerance to the allogeneic fetus in human and other eutherian mammals.

15.

These molecules provide innate immune defense to prevent microbial pneumonia ANS A. SP-A and SP-D, which are secreted into the alveolar spaces, are members of the collectin family and bind to carbohydrate PAMPs on the surface of many pathogens. They are involved in viral neutralization and clearance of microbes from the alveoli.

16.

This protein is expressed by the main type of dendritic cell (DC) found in the epidermis ANS: C Langerhans cells, which express a C-type lectin receptor called langerin (CD207), are the most abundant DCs in the epidermis. The dendrites of Langerhans cells form a dense meshwork between the keratinocytes of the epidermis. Langerhans cells perform sentinel functions in innate responses to skin infection, as well as antigen processing and presentation functions to initiate T cell responses.

17.

This T cell protein is an E-selectin ligand involved in recruitment of T cells to the skin ANS: D. Migration of effector or memory T cells into the skin depends on T cell expression of cutaneous lymphocyte antigen (CLA), which is an E-selectin–binding carbohydrate moiety displayed on various glycoproteins on the endothelial cell plasma membrane. When naive T cells are activated by antigens and differentiate into effector T cells in skin-draining lymph bodes, they are induced to express CLA, which imparts a skin-homing phenotype to these effector cells.

18.

This enzyme likely contributes to maternal tolerance to the allogeneic fetus ANS: F. Fetuses express paternal allo-antigens, and therefore mechanisms must exist to suppress maternal immune responses that could reject the fetus. Such responses may be regulated by local concentrations of tryptophan and its metabolites in the decidua, which inhibit T cells. The enzyme indoleamine 2,3-dioxygenase (IDO) is expressed in the placenta and catabolizes tryptophan, generating a byproduct called kynurenine. Tryptophan is required for proliferating cells, including lymphocytes, and kynurenine is toxic to these cells. T cell responses to the fetus may be normally blocked because decidual tryptophan levels are kept low or the levels of toxic metabolites produced by IDO are high.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 15: Immunologic Tolerance and Autoimmunity Multiple Choice 1.

Immunologic tolerance is defined as: A. The removal of an antigen, or the microbes expressing the antigen, by the immune system so that the host can tolerate the infection B. Activation of only B cells, and not T cells, on exposure to an antigen C. Unresponsiveness of the immune system to an antigen, which is induced by previous exposure to that antigen D. The production of memory B cells and T cells on primary exposure to an antigen, which allows the host to tolerate a secondary exposure to the antigen E. Vaccination of individuals against particular pathogens to prevent subsequent infections ANS: C. Immunologic tolerance refers to the unresponsiveness of the immune system to particular antigens and develops on previous exposure to the antigen. Although the exact requirements for inducing tolerance have not been clearly defined, factors that do influence tolerance include the concentration of antigen, the mode of administration of the antigen, and the presence of costimulatory molecules on antigen-presenting cells for peptide antigens.

2.

A. B. C. D. E.

Failure of self-tolerance is the cause of which one of the following types of diseases?

Allograft rejection Autoimmunity Atopy Anergy Acne

ANS: B. Autoimmunity is an immune reaction against self (autologous) antigens. For this reaction to occur, normal mechanisms of tolerance must fail. Allograft rejection is an immune reaction against allogeneic, not autologous, antigens. Atopy is the name for allergic diseases that are caused by IgE and mast cell–mediated immune responses to foreign antigens. Acne is an infection of hair follicles in the skin and was included as a choice because it begins with the letter “a”; it is not an autoimmune disease.

3.

Which of the following statements about induction or maintenance of T cell tolerance is NOT true?

A. Central tolerance is induced when immature developing T cells in bone marrow or thymus encounter self antigens B. Peripheral T cell tolerance results when mature naive T cells recognize antigens without adequate B7-1– or B7-2–mediated costimulation

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C. Peripheral T cell tolerance results when T cells recognize antigen in the setting of an innate immune response to the antigen D. Peripheral T cell tolerance to some antigens is induced when mature T cells recognize antigen and bind B7-1 or B7-2 via the inhibitory CTLA-4 receptor E. Peripheral T cell tolerance to an antigen may be induced by persistent and repeated stimulation of lymphocytes by that antigen in tissues ANS: C. Innate immune responses are usually required for induction of adaptive immune responses and may actually contribute to breaking tolerance to self antigens. Central tolerance occurs because of the susceptibility of immature lymphocytes to death in response to antigen receptor signals. Autoreactive lymphocytes that are not deleted during development must be regulated by a mechanism of peripheral tolerance, which is induced in T cells by antigen receptor stimulation without costimulation, with CTLA-4–mediated inhibition, by repeated and persistent stimulation by antigen, and by suppression by regulatory T cells.

4.

The AIRE protein is expressed by thymic medullary epithelial cells and is required for tolerance to many self antigens. Which one of the following statements about how AIRE functions is correct?

A. AIRE is secreted by thymic medullary epithelial cells and then binds and blocks the T cell receptors on developing T cells B. AIRE suppresses MHC expression by thymic medullary epithelial expression C. AIRE is secreted by thymic medullary epithelial cells and binds to soluble self antigens D. AIRE is required for thymic medullary epithelial expression of peripheral tissue antigens, which are then presented to immature T cells E. AIRE stimulates expression of immunosuppressive cytokines by thymic medullary epithelial cells ANS: D. AIRE induces thymic medullary epithelial cell expression of proteins otherwise only expressed in selected tissues, such as insulin in the pancreatic islets. These proteins are then processed and presented as peptide-MHC antigens to immature T cells, leading to the death of the T cells specific for the self antigens or their development into regulatory T cells (Treg). The result is T cell tolerance to these peripheral tissue antigens.

5.

CTLA-4, expressed by regulatory T cells and activated effector T cells, is crucial for selftolerance as well as regulation of T cell responses of foreign antigens. Which of the following is a property of CTLA-4 that is important for its function?

A. CTLA-4 binds to CD28 and blocks its function B. CTLA-4 binds B7-1 and B7-2 with high affinity, blocking their binding to CD28 C. CTLA-4 binds class I MHC and blocks it ability to bind peptides D. CTLA-4 binds IL-2, preventing IL-2 binding to the IL-2 receptor E. CTLA-4 binds to IgG, preventing IgG biding to antigens ANS: B. CTLA-4 expressed on the surface of Treg or on recently activated naive T cells competitively binds the B7 proteins on dendritic cells and prevents B7 proteins from binding to CD28. Therefore, the naive T cells are not co-stimulated, leading to anergy or death of the T cells. CTLA-4 does not bind CD28, MHC proteins, IL-2, or IgG.

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6.

Which of the following sets of proteins (among others) are typically expressed by most regulatory T cells (Treg)?

A. CD8, CD3, Perforin, IL-2, and T-bet B. CD4, PD-L1, IL-2, and GATA3 C. CD4, CD3, CD25 (IL-2 receptor), and FOXP3 D. CD4, CD3, CLTA-4, and AIRE E. CD4, TGF-b, CD25 (IL-2 receptor), and IL-2 ANS: C. Treg express the transcription factor FOXP3, which is essential for their development and function. They express the high-affinity IL-2 receptor chain CD25 but not IL-2, and they are dependent on IL-2 from other sources for growth and survival. Treg are mostly CD4 positive and express a class II MHC-restricted T cell receptor, with associated CD3 and zeta chain signaling molecules. Most Treg do express CTLA-4 but do not express perforin, T-bet, GATA3, or AIRE. 7.

The most commonly identified alleles that are associated with risk for autoimmune diseases encode which type of the following proteins?

A. T cell costimulatory molecules (e.g., B7-1) B. T cell inhibitory molecules (e.g., CTLA-4) C. Class I MHC (e.g., HLA-B27) D. Class II MHC (e.g., HLA-DR2) E. Complement proteins (e.g., C3) ANS: D. For common autoimmune diseases, multiple genes contribute to risk; among these genes, the most common are MHC alleles, and class II risk alleles are more common than class I. Furthermore, MHC alleles carry a much higher risk than other identified risk genes. Although there are some variants of T cell inhibitory molecules and other immune effector and regulatory molecules that carry increased risk for development of autoimmunity, they are rarer than class II MHC. Matching Questions 8-14 For each feature of self-tolerance described in questions 4-10, choose the term (letters A-K) that most closely matches it.

A. Immature (IgM+IgD−) B. Thymic cortex C. Bone marrow D. Antigen recognition without T cell help E. Receptor editing F. Activation-induced cell death G. Regulatory T cell–mediated suppression H. Antigen recognition with costimulation I. Double positive (CD4+CD8+) J. Anergy

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K.

Thymic medulla

8.

Tolerance-sensitive stage of T cell maturation

ANS: I. Central T cell tolerance is induced largely by clonal deletion (negative selection) in the thymus at the CD4+CD8+ stage of T cell maturation.

9.

Mechanism of peripheral tolerance for T cells but not B cells

ANS: G. Regulatory T cells are known to suppress T cells but not B cells. Helper T cell– dependent B cell responses may be indirectly suppressed by this mechanism.

10.

Mechanism of central tolerance of B cells

ANS: E. If an immature B cell in the bone marrow recognizes self antigen, RAG gene expression may be induced and additional Ig light chain V(D)J recombination events may occur. This will change the antigen specificity of the expressed Ig. 11.

Mechanism of peripheral tolerance induction of B cells but not T cells

ANS: D. B cell recognition of antigen in the periphery without concomitant helper T cell– derived signals may render the B cells anergic or unable to enter follicles for further differentiation.

12.

Tolerance-sensitive stage of B cell maturation

ANS: A. Tolerance induction of B cells and T cells requires antigen receptor expression, but it occurs most readily before full maturation is completed. For B cells, IgM+ IgD− immature B cells are the most sensitive to tolerance induction.

13.

Mechanism of peripheral tolerance of B cells and T cells

ANS: J. Anergy, which is a block in signaling that prevents full activation of lymphocytes, is a mechanism of peripheral tolerance for both B and T lymphocytes.

14.

Site of central T cell tolerance induction

ANS: B. Double-positive T cells, which are the cells susceptible to central T cell tolerance induction, are found in the thymic cortex. The developing T cells that are not deleted at the double-positive stage mature into single-positive (CD4+ or CD8+) thymocytes and migrate into the medulla before exiting the thymus.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 16: Immunity to Microbes Matching For each of the descriptions of immune mechanisms in questions 1-4, select the immune mechanism (A-D) that correctly matches it.

A. Type I interferons (IFN-a, IFN-b) B. CD8+ cytolytic T lymphocyte C. Antibody D. Natural killer (NK) cell 1.

Innate immune mechanism for preventing viral infection of cells

ANS: A. One of the key innate immunity responses that can prevent viral infection is the production of type I interferons (IFNs), which are secreted by various cell types in response to double-stranded RNA interacting with endosomal Toll-like receptors, ssRNA binding to cytoplasmic Rig-like receptors, and dsDNA binding to cytosolic DNA sensors. Type I IFNs induce an antiviral state in cells, which makes them resistant to host viral replication.

2.

Adaptive immune mechanism for eradicating established viral infection

ANS: B. Once viruses have infected cells, they produce cytoplasmic proteins that are processed and presented by the class I MHC pathway. CD8+ cytotoxic T lymphocytes recognize viral peptide-class I MHC complexes on the surface of infected cells and kill these cells. The killing mechanism leads to apoptosis, which ensures degradation of viral DNA as well as host cell DNA. 3.

Innate immune mechanism for eradicating virally infected cells

ANS: D. NK cells are innate immunity effector cells that can kill infected cells by mechanisms similar to cytotoxic T lymphocytes (CTLs). However, they are activated by different receptors than are CTLs, and they are inhibited by receptors that bind class I MHC on other cells. Viruses have the ability to evade detection by CTLs by inhibiting class I MHC expression on their host cell surfaces. When this occurs, NK cells may provide a backup defense mechanism because they are activated by host cells that lack normal class I MHC expression.

4.

Adaptive immune mechanism for preventing a viral infection

ANS: C. Antibodies can neutralize viruses before they infect cells. Immunity imparted by many antiviral vaccines is due to antibodies.

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Questions 5-9 Match the description of a vaccine in questions 5-9 with the correct type of vaccine (A-G).

A. Live attenuated or killed bacteria B. Live attenuated oral virus C. Synthetic viral subunit vaccines D. Conjugate vaccines E. Recombinant viral vectors F. DNA vaccines G. Purified subunit vaccines 5.

Good induction of mucosal immunity but risk of developing a viral disease, especially in immunocompromised hosts ANS: B. Live attenuated viral vaccines infect recipient cells, and viral proteins are processed and presented to T cells. This method of vaccination induces good T cell–dependent antibody responses. Attenuation makes risk of serious disease from the vaccine very low. Live attenuated oral poliovirus vaccines, which induced good IgA responses in the gastrointestinal tract, are no longer used routinely in the United States because of low but definable risk of vaccine-associated cases of paralytic polio.

6.

Induction of a T cell–dependent antibody response to polysaccharides, such as Haemophilus influenzae B and pneumococcal capsular polysaccharides ANS: D. Conjugate vaccines are composed of bacterial capsular polysaccharides covalently coupled to proteins. This hapten-carrier arrangement promotes T cell–dependent responses to the polysaccharides, which are required for protective IgG memory responses with high affinity IgG and long-lived memory. Polysaccharides alone do not activate T cells and therefore do not induce robust isotype switching, affinity maturation, or memory cell generation.

7.

Composed of viral proteins synthesized from recombinant viral genes

ANS: C. Synthetic subunit viral vaccines are composed of viral proteins synthesized from recombinant genes. The hepatitis B virus vaccine, now in widespread use, was the first synthetic viral subunit vaccine to be developed and contains the recombinant hepatitis B surface antigen (HBsAg).

8.

Composed of antigens purified from microbes or inactivated toxins, such as the tetanus toxoid vaccine ANS: G. The most commonly used purified subunit vaccines are the diphtheria and tetanus toxoid vaccines, which induce protective antibody responses against toxins produced by the bacteria.

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9.

Composed of a recombinant nonpathogenic virus carrying genes of a pathogenic virus, such as human immunodeficiency virus (HIV) ANS: E. Genes encoding immunodominant epitopes of a pathogenic virus can be cloned into the genome of nonpathogenic viruses, and the resulting recombinant virus can be used as a vaccine against the pathogenic virus. This is one of the approaches under development for HIV vectors.

Multiple Choice 10.

A common strategy by which microbes survive the host’s immune responses involves changing the structures of the molecules they produce so that they are no longer recognized by the host’s immune system. This strategy, called antigenic variation, is most likely to allow evasion of which type of immune recognition?

A. Toll-like receptor–dependent recognition of microbes by cells of the innate immune system B. Mannose receptor–dependent recognition of microbes by cells of the innate immune system C. Antibody recognition of microbial cell surface molecules D. Natural killer (NK) cell inhibitory receptor recognition of class I major histocompatibility complex (MHC) molecules on infected cells E. T cell receptor recognition of microbial cell wall lipid antigens ANS: C. Antigenic variation allows microbes to evade adaptive immune recognition, usually by antibodies but also by T cells. Antigenic variation usually involves mutations or recombination events in microbial genes encoding cell surface proteins or encoding enzymes involved in synthesis of cell surface sugars. The result changes microbial surface antigens. This is an effective strategy because many of the microbial antigenic structures that the adaptive immune system recognizes are not essential for survival or virulence of the microbe. In contrast, most structures recognized by receptors of the innate immune system (e.g., Toll-like receptor and scavenger receptor ligands) are essential for microbial survival and, as such, cannot undergo antigenic variation. Although some viruses may block class I MHC expression by infected cells, this renders the cells more susceptible to NK cell–mediated killing and is not antigenic variation by the virus. Only a small subset of T cells recognizes lipid antigens, usually in association with CD1 molecules. There is no evidence for antigenic variation of the lipid antigens recognized by these T cells.

11.

Some viruses evade cytotoxic T lymphocyte (CTL)–mediated immunity by expressing molecules that have which of the following actions?

A. Inhibition of the TAP peptide transporter B. Inhibition of proteolysis of the invariant chain C. Stimulation of proteasome activity D. Activation of immune regulatory factors (IRFs) E. Inhibition of IL-5 production ANS: A. CTL killing of virus-infected cells requires presentation of viral peptide-class I major histocompatibility complex (MHC) complexes on the cell surface. The class I MHC pathway of antigen presentation, which generates the peptide-class I MHC complexes, depends on TAP

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transporter. TAP pumps cytosolic peptides, generated by the proteasome, into the endoplasmic reticulum (ER) where they bind to newly translated class I MHC molecules. Many viruses carry genes that encode inhibitors of different parts of the class I MHC pathway, including TAP transporter, the proteasome, and others. Proteolysis of the invariant chain is required for the class II MHC pathway of antigen presentation. Activation of IRFs would enhance CTL-mediated immunity by upregulating class I MHC expression. IL-5 does not influence CTL activity.

12.

Protection against extracellular bacterial infections, such as with staphylococci, and extracellular fungi, such as with Candida, is in part mediated by which of the rolling types of T cell responses?

A. Cytotoxic T lymphocytes (CTLs) B. Th1 cells C. Th2 cells D. Th17 cells E. Regulatory T cells (Treg) ANS: D. Extracellular microbes may be readily killed after ingestion by neutrophils. Th17 responses enhance neutrophilic responses to infection by secreting IL-17, which increases bone marrow production of neutrophils and induces tumor necrosis factor (TNF) production that in turn increases expression of chemokine and adhesion molecules that increase neutrophil recruitment to sites of infection.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 17: Transplantation Immunology Multiple Choice 1.

Allogeneic immune responses lead to graft rejection. Which of the following best defines an allogeneic immune response in human-to-human transplantation?

A. An innate immune response mounted by an individual against transplanted cells or tissues derived from an unrelated individual B. An adaptive immune response mounted by an individual against transplanted cells or tissues derived only from an unrelated individual C. An adaptive immune response mounted by an individual against transplanted cells or tissues derived from a genetically non-identical individual D. An innate or adaptive immune response mounted by an individual against transplanted cells or tissues derived from a genetically non-identical individual E. An adaptive immune response mounted by an individual against transplanted cells or tissues derived from a genetically identical individual ANS: C. Allogeneic immune responses are against molecules that are different between graft donor and graft recipient. Within species, molecular differences are largely due to genetic differences (i.e., polymorphisms of genes encoding the same molecules). Other than identical twins, all humans, including other family members, have many different variants (i.e., alleles) of genes encoding the same proteins. These differences are detected by the adaptive immune system in graft recipients and stimulate allogeneic immune responses. The innate immune system does not recognize allogeneic differences.

2.

Which type of molecules are the most frequent target of allogeneic immune responses against transplanted organs and why?

A. Endothelial adhesion molecules, because they are present in the blood vessels of grafted organs, where donor lymphocytes can interact with them B. Human leukocyte antigens (HLA), because they are the most polymorphic proteins in the organs C. Lipids, because they easily cross through the membranes of lymphocytes D. Polymorphic cytosolic proteins, because they are readily processed into peptides that can bind class I MHC molecules E. Blood group antigens, because they are expressed on all red blood cells and endothelial cells ANS: B. The genes encoding HLA molecules, which include class I and class II major histocompatibility complex (MHC) proteins are the most polymorphic genes in the genome, with thousands of different alleles in the population. Therefore, allogeneic responses against HLA proteins are more likely to occur than any against other type of molecules, including endothelial

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adhesion molecules or cytosolic proteins. Since HLA molecules are present on graft endothelial cell membranes, they are also easily seen by recipient antibodies and T cells. Differences in blood group antigens between donor and recipient are screened for, and transplantation between blood group incompatible individuals is rarely performed.

3.

A kidney is transplanted into a patient with renal failure due to diabetes, and within 15 minutes after the recipient blood supply to the graft is established, the graft becomes pale and stops functioning. Microscopic analysis of the failed graft shows death of cells due to lack of blood flow (“ischemic necrosis”). What is the most likely cause of this graft failure?

A. Acute rejection due to stimulation of the recipient B and T cells specific for graft alloantigens B. Chronic rejection, with narrowing of the graft blood vessels by vascular smooth muscle cells and fibrous tissue C. A leaky surgical connection between the recipient and graft blood vessels D. Hyperacute rejection, with thrombosis (clotting) of graft blood vessels due to previously formed antibodies in the recipient specific for recipient HLA molecules E. Damage to the graft because of the patient’s diabetes ANS: D. The rapid development of ischemic necrosis in the graft is diagnostic of hyperacute rejection, which is always caused by antibodies against graft endothelial antigens already circulating in the recipient before the transplantation. The preexisting antibodies may be natural anti–blood group antigens, if the donor and recipient are of incompatible blood types, or antiHLA antibodies, if the recipient has had previous pregnancies or received transfusions or transplants in the past. Acute rejection requires the recipient T and B cells to be activated over the course of several days. Chronic rejection takes months to develop. Damage to kidneys due to diabetes takes years to develop.

4.

Which of the following is a correct description of direct T cell recognition of allogeneic major histocompatibility complex (MHC) molecules by graft recipients?

A. Recipient T cells recognize soluble donor MHC molecules shed from the graft cells B. Recipient T cells recognize peptides derived from allogeneic MHC molecules that are bound to the recipient’s own MHC molecules on recipient antigen-presenting cells C. Recipient T cells recognize intact allogeneic MHC molecules on graft cells, without the need for processing those MHC proteins into peptides and presenting them on self-MHC molecules D. Donor T cells in the graft recognize recipient peptides bound to recipient MHC molecules E. Recipient T cells act as antigen-presenting cells to donor T cells ANS: C. Many T cells in any individual can recognize and be activated by intact allogeneic MHC molecules, whether or not the peptides bound to the allogeneic MHC are polymorphic and different from self-peptides. This can be considered a cross-reaction of T cells that normally would recognize microbial peptides bound to self-MHC. The high frequency of T cells that can directly recognize allogeneic MHC is one reason why allogeneic T cell responses are so frequent

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and strong in graft recipients. Indirect allogeneic MHC recognition, described in answer B, also occurs in graft recipients.

Matching Questions 5-8 For each of the descriptions in questions 5-8, choose the blood group antigen (A-E) that best matches it.

A. A B. B C. O D. RhD E. AB 5.

Antibodies specific for this blood group found in a person with type A blood

ANS: B. People make natural antibodies to blood groups they do not express. Type A people make anti-B, type B people make anti-A, type O people make both anti-A and anti-B, and type AB people do not make either anti-A or anti-B. 6.

The blood group of a red blood cell blood donor that can be transfused to recipients of any ABO blood type without an anti-ABO transfusion reaction ANS: C. Group O donors have neither A or B antigen on their red blood cells, and therefore, preformed anti-A or anti-B antibodies in any recipient will not bind to and cause lysis of the donor cells.

7.

Blood group of a person whose red blood cells can only transfused to a person with the same blood group ANS: E. AB blood can only be transfused into people with no anti-A or anti-B antibodies, which are only type AB people.

8.

Nonglycosylated red cell membrane protein missing or mutated in 15% of humans

ANS: D. About 15% of individuals do not express the RhD protein and therefore mount immune responses to RhD+ cells introduced by transfusion or during pregnancy. RhD is the major antigen associated with hemolytic disease of the newborn.

Questions 9-13 For each of the descriptions in questions 9-13, choose the immunosuppressive or tolerance induction therapy for allograft rejection (A-I) that best matches it.

A. Azathioprine B. Cyclosporine

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C. D. E. F. G. H. I.

Mycophenolate mofetil (MMF) Rapamycin Anti-CD40L antibody Anti-IL-2R antibody CTLA4-Ig Anti-thymocyte globulin Corticosteroids

9.

Inhibits a lymphocyte-specific isoform of inosine monophosphate dehydrogenase, an enzyme that is required for the synthesis of guanine nucleotides ANS: C. MMF, like azathioprine, inhibits the maturation and proliferation of T cells. MMF is metabolized to mycophenolic acid, which blocks a lymphocyte-specific form of an enzyme required for the de novo synthesis of guanine nucleotides.

10.

Blocks calcineurin-dependent activation of NFAT

ANS: B. Cyclosporine is a cyclic fungal peptide that inhibits calcium-dependent calcineurin and thus prevents the dephosphorylation of NFAT. NFAT is an essential transcription factor for numerous T cell cytokine genes, including interleukin-2.

11.

Inhibits macrophage cytokine secretion

ANS: I. Corticosteroids are potent antiinflammatory agents that are thought to block the synthesis and secretion of cytokines, primarily tumor necrosis factor (TNF) and interleukin-1, by macrophages. Inhibition of these cytokines results in reduced graft endothelial cell activation and inflammatory cell recruitment. Corticosteroids are also thought to block other effector functions of macrophages, such as the production of reactive oxygen intermediates and nitric oxide.

12.

Inhibits mammalian target of rapamycin (mTOR) and thereby inhibits IL-2–driven cell cycle progression in T cells ANS: D. Rapamycin is an antibiotic that binds to FK506 binding protein (FKBP) and inhibits T cell proliferation. The rapamycin-FKBP complex does this by binding another cellular protein, the MTOR, which regulates cell cycle progression. Note that FK506, another immunosuppressive drug, also binds FKBP, and the complex binds and inhibits calcineurin, as does cyclosporine.

13.

Can block T cell activation through inhibition of costimulatory signaling

ANS: G. CTLA4-Ig is a fusion protein that binds to B7-1 and B7-2 and therefore blocks B7 binding to CD28. This is a method of blocking costimulation. If, at the time of transplantation, alloantigens provide signal 1 to alloreactive T cells, while signal 2 is blocked by CTLA4-Ig, the alloreactive T cells may become anergic.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 18: Tumor Immunology Multiple Choice 1.Which of the following statements about adaptive immune responses to cancers is true?

A. T cell responses only occur when the cancers harbor oncogenic viruses B. Antibody responses only occur when the cancer is harboring an oncogenic virus C. Both T cell and B cell responses often occur in patents with common forms of cancer, but those immune responses are usually ineffective in stopping progression of the cancer D. In patents with common forms of cancer, T cell responses often occur, which are usually effective in stopping progression of the cancer E. There is no evidence of T cell or antibody responses occurring to human tumors without immunotherapy ANS: C. Adaptive immune responses specific for antigens made by tumor cells can be detected in many cancer patients, yet these response may often not be effective in stopping tumor progression without therapeutic intervention that enhance these responses.

2. Which of the following description of T cell responses to tumor antigens is correct?

A. Most anti-tumor T cell responses are specific for mutant peptides bound to class II MHC molecules B. Most T cell responses to tumors are specific for unmutated but overexpressed tumor cell surface proteins C. Cancer patients whose tumors have relatively high mutation burdens are less likely to mount effective anti-tumor T cell responses D. The majority of anti-tumor T cell responses in cancer patients are specific for mutations, which contribute to the malignant phenotype of the cancer, including mutated cellular oncogenes and tumor suppressor genes E. The majority of anti-tumor T cell responses in cancer patents are specific for randomly mutated cellular proteins, which do not contribute to the malignant phenotype of the cancer ANS: D. Cancer cells are genetically unstable and over time accumulate large numbers of random mutations, most of which are not “oncogenic” mutations relevant to the malignant behavior of the cancer. The majority of T cell responses against tumors appear to be specific for peptides derived from these mutant proteins, bound to either class I or class II MHC molecules.

In fact, the higher the number of mutations, the more likely there will be effective anti-tumor T cell responses, albeit most clearly seen in the context of patents receiving checkpoint blockade immunotherapy.

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3. A pathologist analyzes a resected colon with carcinoma, and she determines the tumor has penetrated deep into the colonic wall. Furthermore, there are a higher number of CD8+ T cells in and around the cancer compared to most colon cancers analyzed in this way. What is the significance of the T cell finding?

A. Worse prognosis B. Better prognosis C. No correlation with prognosis D. More likely respond to anti-PD-1 therapy E. Patient likely to develop autoimmunity ANS: B. The presence of relatively high numbers of CD8+ CTL and CD4+ Th1 cells in and around resected colon cancers is correlated with a better prognosis after surgery, and this is thought to reflect more effective anti-tumor T cell responses against residual tumor cells in the patient. Surprisingly, the presence of high numbers of T cells does not correlate with responsiveness to checkpoint blockade therapy, and most colon cancer patients do not respond to anti-PD-1 therapy.

4. Which of the following is a correct description of checkpoint blocking drugs used in tumor immunotherapy?

A. Soluble Ig-fusion proteins that contain the extracellular domains of T cell inhibitory molecules B. Blocking monoclonal antibodies specific for T cell growth factor IL-2 C. Small molecule inhibitors of JAK kinases involved in cytokine activation of T cells D. Blocking monoclonal antibodies specific for T cell molecules that normally inhibit T cell activation E. Blocking monoclonal antibodies specific for T cell molecules that normally enhance T cell activation ANS: D. Checkpoint blockers bind to and block the function of T cell inhibitory molecules, such as PD-1 and CTLA-4. The result is inhibiting the inhibitors, leading to enhanced activation of anti-tumor T cells. The drugs listed in all the other choices would inhibit activators of T cell activation and thus inhibit anti-tumor T cell responses.

5. The most common adverse effects of anti-PD-1 and anti–CTLA-4 therapy for tumors is which of the following?

A. Infections B. Autoimmune organ dysfunction C. Hypoglycemia D. Stroke E. Asthma ANS: B. The targets of checkpoint blockade (e.g. PD-1 and CTLA-4) are required to maintain self-tolerance. Therefore, their use leads to excess activation of self-reactive T cells as well as anti-tumor T cells. A wide range of autoimmune disorders is associated with these therapies, involving gut, lung, endocrine organs, and heart. Immunodeficiency leading to infections is not

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usually a complication. Diabetes with hyperglycemia (not hypoglycemia) due to autoimmune attack on pancreatic islets and loss of insulin production is observed in some patients receiving checkpoint blockers. Neither stroke nor asthma is associated with these therapies.

6. Which of the following is not a feature of chimeric antigen receptors (CARs) used in CAR-T cell therapy for cancers A. B. C. D. E.

MHC restricted antigen recognition Costimulatory receptor signaling domains ITAM motifs Ig variable domains for antigen binding Expressed by viral vectors

ANS: A. Unlike the endogenous T cell antigen receptors of T cells, CARs contain Ig heavy and light chain variable domains cloned from antibody genes and are not MHC restricted.

Matching For each of the descriptions of tumor antigens in questions 7-10, select the example (A-D) that correctly matches it.

A. Cancer testis antigen B. HER2/NEU C. PD-L1 D. CD20 7. A differentiation antigen present on both normal and malignant cells of a particular lineage ANS: D. CD20 is present on both normal B cells and on B cell–derived leukemia and lymphoma cells. Therefore, immunotherapy that targets this antigen will deplete normal B cells as well as kill tumor cells.

8. An unmutated tumor antigen normally expressed only during fetal life or in adults on testis or ovary, but frequently expressed on cancer cells derived from various lineages ANS: A. Cancer testis antigens frequently induce T cell responses in cancer patients, although it is not clear that these responses are protective.

9. A signaling molecule overexpressed in a subset of breast carcinomas, which is the target of monoclonal antibody therapy ANS: B. HER2/NEU acts as an oncogene when overexpressed due to gene amplification in breast cancers. Monoclonal antibodies specific for Her2/neu are widely used to treat breast cancers with high expression of the protein.

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ANS: C. PD-1 inhibits anti-tumor CTL killing of tumor cells by binding to PD-L1 expressed on the tumor cells. Biopsies of cancers, especially lung cancers, are analyzed for PD-L1 expression in order to restrict anti-PD-1 therapy to the patients with PD-L1 on their tumors, who are therefore most likely to respond.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 19: Hypersensitivity Disorders Multiple Choice 1.

A. B. C. D. E.

All of the following are effector mechanisms of antibody-mediated disease EXCEPT: Opsonization and phagocytosis of cells FAS-dependent apoptosis of cells Complement- and Fc receptor–mediated inflammation and tissue injury Antibody stimulation of cell surface receptors in the absence of the physiologic ligands FceR crosslinking

ANS: B. FAS-dependent apoptosis is a regulatory mechanism in T cell–mediated responses and may be involved in T cell–mediated damage to other cells, but the FAS pathway is not stimulated by antibodies. Antibody-mediated (types I to III) hypersensitivity diseases involve four main effector mechanisms: (1) IgE coats mast cells and links the presence of allergens with mast cell activation and release of inflammatory mediators, (2) antibody-mediated opsonization of cells and activation of complement promotes phagocytosis of cells through phagocyte Fc or C3 receptors, (3) antibody binding to tissues can promote activation of leukocytes via binding to Fc receptors on leukocytes or by activation of complement with release of chemotactic byproducts, and (4) autoantibodies specific for cell surface receptors either stimulate receptor activity in the absence of the physiologic ligand or inhibit binding of physiologic ligands to their receptors.

2.

The figure shows histologic and immunofluorescence images of a kidney biopsy specimen taken from a 53-year-old man with acute-onset renal failure and hemoptysis (coughing up blood). The histologic section is notable for glomerular inflammation in a crescentic distribution. Staining, using fluorescently tagged anti-IgG antibody, shows linear deposits of IgG along the glomerular basement membrane. Urinalysis is positive for moderate proteinuria and red cell casts. A chest radiograph shows pulmonary infiltrates. Which of the following is the most likely diagnosis?

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A. Systemic lupus erythematosus B. Graves’ disease C. Chronic allograft rejection D. Goodpasture’s syndrome E. Poststreptococcal glomerulonephritis ANS: D. Goodpasture’s syndrome is a type II hypersensitivity disease in which IgG antibodies against the glomerular basement membrane (GBM) of the kidney deposit in a linear distribution, causing complement- and Fc receptor–mediated inflammation and subsequent nephritis. These anti-GBM antibodies cross-react with pulmonary alveolar basement membranes to produce the typical clinical scenario of pulmonary hemorrhages associated with renal failure. Note that the pathology here contrasts to that seen in glomerulonephritis caused by type III hypersensitivity diseases (e.g., systemic lupus erythematosus, poststreptococcal glomerulonephritis) in that deposits are linear and smooth (antibody) versus granular and coarse (antigen-antibody immune complex). Chronic allograft rejection more closely resembles a type IV hypersensitivity reaction.

Graves’ disease does not directly involve the kidney.

3.

Which type of hypersensitivity disease is caused by deposition of antigen-antibody complexes in blood vessel walls?

A. Type I B. Type II C. Type III D. Type IV E. Type V ANS: C. Hypersensitivity diseases are often categorized by numerical designation. Type III is immune complex disease. Type I is immediate hypersensitivity (allergic) disease. Type II is disease caused by antibodies binding to antigens in tissues. Type IV is T cell–mediated disease.

There is no type V hypersensitivity.

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4.

Which of the following statements about immune complex–mediated diseases is NOT true?

A. Immune complexes may contain antibodies bound to either self or foreign antigens B. Immune complex–mediated diseases generally show systemic manifestations C. Pathologic features of immune complex diseases are determined by the cellular source of the antigen D. Small complexes are deposited in vessels more than large complexes, which are usually efficiently phagocytosed E. Complexes containing cationic antigens are more likely to produce severe, long-lasting injury by depositing in blood vessels and renal glomeruli ANS: C. A hallmark of immune complex–mediated disease is that pathologic features reflect the site of immune complex deposition and are not determined by the cellular source of the antigen.

As such, immune complex–mediated diseases tend to be systemic, with little or no specificity for particular tissues. Immune complexes that cause disease may be composed of either self antigens or foreign antigens with bound antibodies. These complexes are produced during normal immune responses, but they cause disease only when they are produced in excessive amounts or are not efficiently cleared so that they become deposited in tissues. Small complexes are often not phagocytosed and tend to be deposited in vessels more readily than large complexes, which are usually cleared by phagocytes. Complexes containing cationic antigens bind tightly to negatively charged components of basement membranes of blood vessels and kidney glomeruli, typically producing long-lasting injury.

5.

In which of the following disorders is the underlying pathogenic mechanism NOT due to antibody-mediated damage to cells or tissues?

A. Pernicious anemia B. Autoimmune hemolytic anemia C. Pemphigus vulgaris D. Acute rheumatic fever E. Hyperacute allograft rejection ANS: A. Pernicious anemia is caused by neutralizing autoantibodies specific for intrinsic factor, which is a secreted protein required for absorption of vitamin B12 in the gastrointestinal tract.

The lack of vitamin B12 absorption leads to decreased erythropoiesis, with subsequent anemia.

Autoimmune hemolytic anemia is caused by opsonizing antibodies specific for erythrocyte membrane antigens, leading to their destruction by phagocytes. Pemphigus vulgaris occurs when autoantibodies specific for epidermal cell intracellular junctions cause inflammatory disruption of the skin, leading to formation of skin vesicles. Acute rheumatic fever is caused by antistreptococcal cell wall antibodies that cross-react with myocardial antigens, leading to inflammation and damage to the myocardium. Hyperacute allograft rejection is caused by antibodies specific for alloantigens on graft endothelial cells, leading to blood vessel wall damage and thrombosis.

6.

Which of the following is NOT associated with increased relative risk of developing systemic lupus erythematosus (SLE)?

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A. B. C. D. E.

Female gender Deficiency in complement protein C2 African-American ethnicity Presence of HLA-DR3 Defect in B cell maturation

ANS: E. SLE is a chronic, remitting and relapsing, multisystem disease that affects predominantly women, with an incidence of 1 in 700 in women between the ages of 20 and 60 years. Incidence increases to about 1 in 250 in African-American women. The female-to-male ratio is 10:1. Deficiencies of classical complement proteins, especially C2 or C4, are seen in about 10% of patients with SLE; abnormal complement levels may result in defective clearance of immune complexes. Individuals with the class II DR2 or DR3 HLA allele have a five-fold higher probability of developing SLE. In contrast, patients with defects in B cell maturation would typically have impaired antibody synthesis; thus it is unlikely that these patients would develop an autoimmune disease characterized by the production of autoantibodies.

Matching For each of the clinical scenarios in questions 7-10, choose the hypersensitivity type (A-D) that best matches the associated immunologic disease. (Answers may be used more than once.)

A. Type I hypersensitivity B. Type II hypersensitivity C. Type III hypersensitivity D. Type IV hypersensitivity 7.

A 5-year-old girl is taken to the emergency department with lethargy, confusion, vomiting, abdominal pain, and flushed skin that is warm to the touch. Respirations are fast and shallow and emanate a strong, fruity odor. The mother notes that the child has been excessively thirsty over the past week and that she began wetting her bed during naps. Urine dipstick testing reveals markedly elevated levels of glucose and ketones.

ANS: D. This patient is in diabetic ketoacidosis, a serious complication of her previously undiagnosed insulin-dependent diabetes mellitus (type 1). Her insulin deficiency results from destruction of the insulin-producing beta cells of the islets of Langerhans in the pancreas. Several mechanisms may contribute to beta cell destruction. Prominent among these mechanisms are type IV (delayed-type) hypersensitivity reactions mediated by CD4+ Th1 cells reactive with islet antigens, and cytotoxic T lymphocyte (CTL)–mediated lysis of islet cells.

8.

A 60-year-old man is evaluated for shortness of breath, lightheadedness, diarrhea, abdominal pain, and tingling in his fingers and toes. A blood smear from the patient is shown in the figure. Antibodies to intrinsic factor are detected in his serum.

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ANS: B. This patient has pernicious anemia, a type II hypersensitivity disease in which autoantibodies against intrinsic factor of gastric parietal cells lead to neutralization of intrinsic factor, which is required for intestinal absorption of vitamin B12. Deficiency in vitamin B12 leads to abnormal erythropoiesis with macrocytic anemia and hypersegmented neutrophils (as shown in the figure).

9.

A 29-year-old woman gives birth to an infant who is lethargic, jaundiced, and severely anemic and has an enlarged liver and spleen. The mother is RhD negative and the father is homozygous RhD positive. This is their second child.

ANS: B. This condition, called erythroblastosis fetalis, is a severe form of hemolytic disease of the newborn that occurs when an Rh-negative mother gives birth to an infant who is Rh positive (since the father is homozygous Rh positive). In this disease, the mother produces IgG antibodies against Rh-positive cells to which she has been previously exposed (i.e., during the delivery of her first Rh-positive child). Because the mother’s immune system recognizes Rh antigen as “foreign,” she produced large amounts of anti-Rh antibody when she encountered the antigen during the second pregnancy. This antibody crossed the placenta and mediated cellular injury in the second infant. Therefore, this is an example of type II hypersensitivity. Note that the most commonly involved antigen in erythroblastosis fetalis is RhD. 10.

A 23-year-old medical student is taken to the emergency department because of diffuse facial erythema (redness), tightness of the chest, and difficulty breathing. He reports that the symptoms began shortly after he ate a shellfish dinner at a nearby Thai restaurant. On physical examination, he appears to be in acute distress, with elevated heart rate and respiratory rate and a dangerously low blood pressure. He is treated with epinephrine.

ANS: A. This young man is in anaphylactic shock secondary to systemic exposure to shellfish antigens, to which he produced IgE antibodies when he was previously exposed. This is a classic example of type I (immediate) hypersensitivity.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 20: Allergy Multiple Choice 1.

Which of the following is the most common disorder of immunity, affecting 20% of all individuals in the United States?

A. Atopy B. Diabetes mellitus C. Leukemia D. IgA deficiency E. Latent tuberculosis infection ANS: A. Atopy, or allergy, is the most common disorder of immunity and affects 20% of all individuals in the United States. Within this category, allergic rhinitis is perhaps the most common allergic disease and is a consequence of immediate hypersensitivity reactions to common allergens, such as plant pollen or house dust mites, localized to the upper respiratory tract by inhalation. Selective IgA deficiency is the most common known primary immunodeficiency.

2.

A. B. C. D. E.

All of the following are key mediators of immediate hypersensitivity reactions EXCEPT: Mast cells Basophils IgE Macrophages Th2 cells

ANS: D. The main cellular mediators of immediate hypersensitivity reactions are mast cells, basophils, and eosinophils. IgE antibody plays a major role in sensitizing these cellular mediators for subsequent activation. Activation of Th2 cells is required for appropriate release of cytokines, such as interleukin (IL)-4 and IL-13, which stimulate IgE class switching in B cells. In contrast, macrophages are effector cells in delayed-type hypersensitivity reactions.

3.

Immediate hypersensitivity differs from delayed-type hypersensitivity (DTH) in which one of the following ways?

A. Immediate hypersensitivity is a CD4+ T cell–mediated disease B. Immediate hypersensitivity does not require previous exposure to an antigen C. Immediate hypersensitivity does not involve inflammation D. Immediate hypersensitivity is driven by cytokines such as interleukin (IL)-4, IL-5, and IL-13 E. Immediate hypersensitivity typically leads to granuloma formation

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ANS: D. In contrast to DTH, which is a Th1-mediated disorder, immediate hypersensitivity is driven by cytokines, such as IL-4, IL-5, and IL-13 and is therefore a Th2-mediated disorder. Note that both types of hypersensitivity reactions involve CD4+ T cells (Th1 vs. TH1), although DTH also involves CD8+ T cells. Importantly, both types of hypersensitivity reactions occur only after prior exposure to an antigen, and they are both characterized by inflammation. Granuloma formation, as a chronic response to persistent microbes, is a pathologic feature more typical of DTH than immediate hypersensitivity.

Matching Questions 4-10 Match the definitions in questions 4-10 with the mast cell mediator (A-G) that most closely matches it.

A. Histamine B. Tryptase C. Prostaglandin D2 D. Leukotriene C4 E. Platelet-activating factor F. Interleukin-5 G. Tumor necrosis factor 4.

Lipoxygenase-pathway product of arachidonic acid metabolism that causes prolonged bronchoconstriction, mucus secretion, and increased vascular permeability ANS: D. Leukotriene C4 (LTC4) is rapidly synthesized by the lipoxygenase pathway of arachidonic acid metabolism in activated mast cells. It is one component of a so-called slowreacting substance of anaphylaxis, which also includes LTD4 and LTE4. These leukotrienes are major mediators of bronchoconstriction in allergic asthma.

5.

Soluble factor that promotes eosinophil maturation and activation

ANS: F. Interleukin-5 is a cytokine synthesized by activated mast cells (as well as Th2 cells) and promotes eosinophilia and eosinophilic inflammation, which are characteristic of chronic immediate hypersensitivity conditions.

6.

Vasoactive amine that transiently increases vascular permeability and smooth muscle contraction ANS: A. Histamine, one of several vasoactive amines in mast cell granules, is partly responsible for the rapid increases in vascular permeability, causing wheals (or hives), and for the smooth muscle contraction in bronchi and intestines, causing some of the pulmonary and gastrointestinal symptoms of immediate hypersensitivity reactions.

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7.

Cyclooxygenase-pathway product of arachidonic acid metabolism that causes vascular dilatation, smooth muscle contraction, and neutrophil chemotaxis ANS: C. Prostaglandin D2 (PGD2) is the major arachidonic acid product of the cyclooxygenase pathway in mast cells. PGD2 causes vasodilation and bronchoconstriction, which contribute to the early signs and symptoms of immediate hypersensitivity reactions. It also is a chemoattractant for neutrophils, which accumulate in tissues as part of the late-phase inflammatory response to allergens.

8.

Protein constituent of granules that contributes to tissue damage in immediate hypersensitivity reactions ANS: B. Tryptase is a neutral serine protease stored in mast cell granules. When released into the extracellular matrix, this enzyme cleaves fibrinogen and activates collagenases, contributing to tissue damage.

9.

Soluble factor that promotes inflammation and late-phase reaction and activates endothelial expression of adhesion molecules critical for sequential neutrophilic infiltrate ANS: G. When tumor necrosis factor is released during IgE-mediated mast cell activation, it activates endothelial expression of the adhesion molecules, accounting for subsequent infiltration of neutrophils. As such, it is critical for inflammation and the late-phase allergic reaction.

10.

Membrane phospholipid derivative that causes bronchoconstriction, retraction of endothelial cells, and relaxation of vascular smooth muscle ANS: E. Platelet-activating factor (PAF) is synthesized after mast cell activation by acylation of a membrane phospholipid derivative. It acts on bronchial smooth muscle cells and endothelial cells. Genetic deficiency of an enzyme that inactivates PAF is associated with asthma.

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Abbas, Lichtman, and Pillai: Cellular and Molecular Immunology, 10th Edition Test Bank Chapter 21: Primary and Acquired Immunodeficiencies Multiple Choice 1.

A. B. C. D. E.

All of the following may result in an acquired immunodeficiency EXCEPT: Malnutrition Treatment with corticosteroids Disseminated cancer Inherited defect in B cell maturation Infection with human immunodeficiency virus (HIV)

ANS: D. An inherited defect in B cell maturation is, by definition, a primary immunodeficiency, not an acquired immunodeficiency. In particular, abnormalities in B lymphocyte development and function result in deficient antibody production and increased susceptibility to infection by extracellular microbes. In contrast, malnutrition, treatment with corticosteroids, disseminated cancer, and infection with HIV would all result in acquired, or secondary, immunodeficiencies.

Administration of corticosteroids to intentionally create an immunosuppressive state, such as in the treatment of inflammatory diseases or the prevention of tissue allograft rejection, is referred to as iatrogenic immunosuppression.

2.

Which one of the following is typically NOT associated with most T cell immunodeficiencies?

A. Cancer B. Viral infection C. Autoimmunity D. Infection with intracellular microbes E. Infection with pyogenic bacteria ANS: E. B cell, not T cell, immunodeficiencies are associated with increased incidence of infection with pyogenic bacteria. In contrast, increased incidence of cancer is most often seen in T cell immunodeficiencies because T cells are critical for surveillance against oncogenic viruses and the tumors they cause. Defects in cell-mediated immunity lead to infection by viruses and other intracellular microbes. Interestingly, certain immunodeficiencies are associated with increased incidence of autoimmunity; the mechanism for this phenomenon may reflect a deficiency of regulatory T cells that normally serve to maintain self-tolerance.

3.

Mutations in the gene encoding which of the following proteins is most likely to be associated with increases susceptibility to opportunistic intracellular infections such as with atypical mycobacterium but not to extracellular microbes such as Candida and Staphylococci ?

A. IL-4 B. IL-17

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C. D. E.

Integrin protein CD11a Interferon gamma receptor Ig heavy chain

ANS: D. Inherited deficiencies in molecules required for Th1/interferon gamma immunity cellular immunity lead to selectively impaired defense against microbes that live inside phagocytes, such as mycobacterial species. These disorders are called Mendelian susceptibility to mycobacterial disease and are caused by mutations in genes encoding chains of IL-12, IL-12 receptor, interferon receptor, STAT1, and others. Deficiencies in IL-4 have not been described.

Deficiencies in IL-17, B cell development as would occur with Ig heavy chain mutations, and defects in integrins would all be expected to increase susceptibility to extracellular microbial infections such as Candida and Staphylococci.

4.

A generalized deficiency in the ability to mount delayed-type hypersensitivity (DTH) responses, as described in question 3, is called: A. Clinical atopy B. Clonal ignorance C. Clinical anergy D. Clonal deletion E. Seroconversion ANS: C. A generalized deficiency in DTH responses is called clinical anergy. Note that clonal (or lymphocyte) anergy refers to the failure of clones of T or B cells to react to antigen. Anergy may be a mechanism of maintaining immunologic tolerance to self. Atopy refers to allergic disease.

Clonal ignorance and clonal deletion are mechanisms of tolerance to antigens. Seroconversion refers to the appearance in the serum of antibodies specific for a particular antigen after infection or immunization.

Matching Questions 5-9 Match each of the following descriptions in questions 5-9 with the appropriate disease (A-G).

A. X-linked agammaglobulinemia B. X-linked hyper-IgM syndrome C. X-linked lymphoproliferative syndrome D. Class II MHC deficiency E. Chronic granulomatous disease (CGD) F. Leukocyte adhesion deficiency-1 (LAD-1) G. Leukocyte adhesion deficiency-2 (LAD-2) 5.

Impaired CD4+ T cell development and activation, resulting in defective cell-mediated immunity and impaired T cell–dependent humoral immunity ANS: D. Class II MHC deficiency is a form of severe combined immunodeficiency disease (SCID) caused by inherited mutations in genes encoding factors required for class II MHC transcription. The absence of class II MHC in the thymus results in a lack of positive selection and maturation of CD4+ T cells.

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6.

Defect in leukocyte adhesion-dependent functions, resulting from mutations in the gene encoding the CD18 integrin β chain and leading to recurrent bacterial and fungal infections ANS: F. LAD-1 is a rare disorder in which integrins with the CD18 chain, such as LFA-1, are not expressed. Migration and function of neutrophils, monocytes, and lymphocytes are all impaired.

7.

Defect in lymphocyte activation due to mutations in the gene encoding the SAP adapter protein required for inhibition of signaling by the SLAM molecule; lack of SAP results in uncontrolled B cell proliferation, hypogammaglobulinemia, and B cell lymphoma in the setting of Epstein-Barr virus (EBV) infection ANS: C. X-linked lymphoproliferative syndrome is characterized by a severe CD8+ T cell response to EBV, the virus that causes infectious mononucleosis. In a way, this is an example of a lethal exaggerated response to an infection, rather than a true immunodeficiency.

8.

Defect in B cell maturation at the pre-B cell stage caused by mutations in the gene encoding the B cell tyrosine kinase (BTK), resulting in undetectable levels of serum Ig ANS: A. BTK is required for pre-B cell receptor signaling and maturation from pre-B to immature B cells. In females carrying the mutated BTK gene on one X chromosome, the B cells that do mature have all inactivated the X chromosome carrying the mutant allele; thus, these individuals do not show a clinical phenotype. This disease, called X-linked agammaglobulinemia, is effectively controlled by injections of pooled gamma globulin.

9.

Defect in phagocyte microbicidal activity as a result of defective production of reactive oxygen intermediates, most commonly from a mutation in the gene encoding cytochrome b558 ANS: E. Chronic granulomatous disease (CGD) is a disorder of the innate immune system. The failure to generate reactive oxygen intermediates (free radicals) leads to persistent intracellular bacterial infections, with chronic T cell stimulation of macrophages and development of granulomas.

Multiple Choice 10.

The progression of human immunodeficiency virus (HIV) infection to acquired immunodeficiency syndrome (AIDS) is most directly due to which of the following?

A. A loss of CD4+ T cells to numbers insufficient to prevent infections B. Reduction in serum IgG levels to levels insufficient to prevent infections C. Increased amount of virus in the blood D. Loss of weight E. Reduction in CD8+ CTLs specific for HIV ANS: A. AIDS is most often diagnosed based on a finding of a CD4+ T cell count below 200 cells/mm and certain opportunistic infections. The incidence of infections and other Copyright © 2022 Elsevier Inc. All rights reserved.

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manifestations of AIDS including cancers, weight loss, and encephalopathy increase significantly when the blood CD4+ T cell count drops, which reflects an even greater loss of T cells in lymphoid organs.

11.

Which of the following is not a valid explanation for why patients cannot eradicate human immunodeficiency virus (HIV) infections?

A. HIV does not stimulate a CD8+ CTL response B. HIV mutation rate is high, leading to evasion of immune recognition C. A reservoir of latently infected cells invisible to the immune system is established rapidly after infection D. CD4+ T cells are destroyed, impairing the immune response to the virus ANS: A. Patients infected with HIV typically mount a strong early CD8+ T cell response against viral antigens and an antibody response to various HIV antigens. However, for the reasons given in the other choices, these responses are not sufficient to eradicate the infections.

12.

Which molecules on the T cell surface are directly involved in human immunodeficiency virus (HIV) infection?

A. CD4 and CD25 B. CCR5 and CD25 C. CD3 and CD4 D. CD8 and CCR5 E. CD4 and CCR5 ANS: E. HIV infects CD4+ T cells by a mechanism that involves the HIV envelope gp120 protein binding to CD4, followed by conformational changes in gp120 promoting CCR5 binding.

The importance of CCR5 is indicated by the fact that rare individuals who lack CCR5 are resistant to HIV infection.

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