TEST BANK for Basic Immunology;Functions & Disorders of the Immune System 7th Ed by Abbas|Pillai

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Basic Immunology-Functions and Disorders of the Immune System 7th Edition by Abul K. Abbas, Andrew H. Lichtman & Shiv Pillai

ISBN-10: 0443105197 ISBN-13: 978-0443105197 Test bank for Basic Immunology-Functions and Disorders of the Immune System 7th Edition by Abul K. Abbas, Andrew H. Lichtman & Shiv Pillai

ISBN-10 : 0443105197 ISBN-13 : 978-0443105197

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TABLE OF CONTENTS Chapter 1. Introduction to the Immune System: Nomenclature, General Properties, and Components

Chapter 2. Innate Immunity: The Early Defense Against Infections

Chapter 3. Antigen Capture and Presentation to Lymphocytes: What Lymphocytes See

Chapter 4. Antigen Recognition in the Adaptive Immune System: Structure of Lymphocyte Antigen

Chapter 5. T Cell–Mediated Immunity: Activation of T Lymphocytes by Cell-Associated Antigens

Chapter 6. Effector Mechanisms of T Cell–Mediated Immunity: Functions of T Cells in Host Defense

Chapter 7. Humoral Immune Responses: Activation of B Lymphocytes and Production of Antibodies

Chapter 8. Effector Mechanisms of Humoral Immunity: Elimination of Extracellular Microbes and Toxins

Chapter 9. Immunological Tolerance and Autoimmunity: Self–Nonself Discrimination in the Immune System and Its Failure

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Chapter 10. Immune Responses Against Tumors and Transplants: Immunity to Noninfectious Transformed and Foreign Cells

Chapter 11. Hypersensitivity: Disorders Caused by Immune Responses

Chapter 12. Congenital and Acquired Immunodeficiencies: Diseases Caused by Defective Immunity

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Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 1: Introduction to the Immune System: Nomenclature, General Properties, and Components 1. What are the two types of adaptive immunity, and what types of microbes do these

adaptive immune responses combat? a. Humoral immunity (extracellular microbes) and cell-mediated immunity (intracellular) via T lymphocytes b. Both primarily combat extracellular microbes. c. Humoral Immunity: i. Also called antibody – mediated immunity ii. Antibodies are produced by plasma B cells with the help of helper T cells.

1. Antibodies kill the target iii. Combats pathogens that are circulating freely or occur outside the infected cells.

1. Example: viruses and bacteria d. Cell – Mediated Immunity: i. Mediated by T – lymphocytes ii. Occurs inside the infected cells. iii. Antigen of a pathogen is expressed on APCs. iv. Cytokines secreted by helper T cells help the T lymphocytes to bind to the infected cells through MHC. 1. Leads to differentiation of T lymphocytes into cytotoxic T cells. v. Infected cells die of lysis vi. Destroy intracellular pathogens and infected host cells to prevent further expansion of the disease.

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.

A previously healthy 8-year-old boy is infected with an upper respiratory tract virus for the first time. During the first few hours of infection, which one of the following events occurs?

A. The adaptive immune system responds rapidly to the virus and keeps the viral infection under control.

B. The innate immune system responds rapidly to the viral infection and keeps the viral infection under control.

C. Passive immunity mediated by maternal antibodies limits the spread of infection.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

D. B and T lymphocytes recognize the virus and stimulate the innate immune response.

E. The virus causes malignant transformation of respiratory mucosal epithelial cells, and the malignant cells are recognized by the adaptive immune system.

ANS: B The innate immune response to microbes develops within hours of infection, well before the adaptive immune response. B and T lymphocytes are components of the adaptive immune response, and they would not be able to respond to a newly encountered virus before the innate immune response. An 8-year-old boy would no longer have maternal antibodies from transplacental passive transfer and is unlikely to be breast-feeding, which is another potential source of maternal antibodies. Malignant transformation takes months or years to develop.

4.

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

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.

5.

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.

6.

A standard treatment of animal bite victims, when there is a possibility that the animal was infected with the rabies virus, is administration of human immunoglobulin preparations containing anti–rabies virus antibodies. Which type of immunity would be established by this treatment?

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

A. Active humoral immunity B. Passive humoral immunity C. Active cell-mediated immunity D. Passive cell-mediated immunity E. Innate immunity ANS: B Humoral immunity is mediated by antibodies. The transfer of protective antibodies made by one or more individuals into another individual is a form of passive humoral immunity. Active immunity to an infection develops when an individual’s own immune system responds to the microbe. Cell-mediated immunity is mediated by T lymphocytes, not antibodies, and innate immunity is not mediated by either antibodies or T lymphocytes.

7.

At 15 months of age, a child received a measles-mumps-rubella vaccine (MMR). At age 22, she is living with a family in Mexico that has not been vaccinated and she is exposed to measles. Despite the exposure, she does not become infected. Which of the following properties of the adaptive immune system is best illustrated by this scenario?

A. Specificity B. Diversity C. Specialization D. Memory E. Nonreactivity to self ANS: D Protection against infections after vaccination is due to immunologic memory of the adaptive immune system. Memory is manifested as a more rapidly developing and vigorous response on repeat exposure to an antigen compared with the first exposure. Specificity and diversity are properties related to the range of antigenic structures recognized by the immune system, and specialization is the ability of the adaptive immune system to use distinct effector mechanisms for distinct infections.

8.

A vaccine administered in the autumn of one year may protect against the prevalent strain of influenza virus that originated in Hong Kong that same year, but it will not protect against another strain of influenza virus that originated in Russia. This phenomenon illustrates which property of the adaptive immune system?

A. Specificity B. Amnesia C. Specialization D. Cultural diversity E. Self-tolerance ANS: A Adaptive immune responses are highly specific for distinct molecular structures, which may be present in a vaccine and be produced by one strain of virus but not by a closely related strain.

Amnesia, although generally not used in immunology, implies lack of memory, but the efficacy of the vaccine against the Hong Kong strain implies it has induced memory. The same effector mechanisms would be required to combat different strains of influenza, and therefore failure of a vaccine to protect against two different strains of virus is not related to specialization of effector functions.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

9.

The two major functional classes of effector T lymphocytes are: A. Helper T lymphocytes and cytotoxic T lymphocytes B. Natural killer cells and cytotoxic T lymphocytes C. Memory T cells and effector T cells D. Helper cells and antigen-presenting cells E. 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 promote macrophage and B cell responses 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.

10.

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

A. Natural killer cells B. Dendritic cells C. Cytolytic T lymphocytes D. B lymphocytes E. Helper T lymphocytes

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

11.

During a humoral immune response to a newly encountered bacterial infection, B cells are first stimulated to proliferate and then secrete antibodies specific for the bacterium. The antibodies may then bind to the bacteria and facilitate ingestion of the microbes by phagocytic cells. In what phase of the humoral immune response does the binding of secreted antibodies to bacteria occur?

A. Recognition phase B. Activation phase C. Effector phase D. Homeostatic phase E. Memory phase ANS: C The effector phase of an immune response occurs when cells or molecules eliminate the microbe or microbial toxin. In a humoral immune response, the effector phase includes secretion of antibody, binding of the antibody to the microbe or toxin, and subsequent antibody-dependent elimination of the microbe or toxin. The recognition phase is the initial binding of the antigen by the naive lymphocyte. The activation phase includes proliferation and differentiation of lymphocytes in response to antigen recognition. The homeostatic phase follows the effector phase, during which the response wanes. In the memory phase, memory B cells and antibodies secreted by long-lived antibody-secreting cells are “waiting” for a repeat exposure to the microbe.

12.

Which of the following statements is consistent with the process of clonal selection?

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

A. The specificity of a lymphocyte antigen receptor changes to accommodate the structure of an antigen that binds to it.

B. Many different antigen receptors with different specificities are expressed on each lymphocyte.

C. Lymphocytes do not express antigen receptors on their cell surfaces until after exposure to antigen.

D. The diversity of the lymphocyte repertoire for antigens is very small before exposure to antigen but increases significantly after antigen exposure.

E. The diversity of the lymphocyte repertoire for antigens is very large before exposure to antigen, with millions of different clones of lymphocytes, each having a different specificity.

ANS: E The clonal selection hypothesis accurately predicted that individuals possess large numbers of different clones of lymphocytes before antigen exposure, with cells in each clone expressing antigen receptors with a single identical specificity, but with different specificities from other clones. Thus, the diversity of the lymphocyte repertoire is very large even before antigen exposure. These receptors are expressed before antigen exposure, and their specificities generally do not change in response to antigen.

13.

Which of the following best describes clonal expansion in adaptive immune responses?

A. Increased number of different lymphocyte clones, each clone specific for a different antigen during the course of an infection B. Increased number of different lymphocyte clones, each clone specific for a different antigen during development of the immune system, before exposure to antigen C. Increased number of lymphocytes with identical specificities, all derived from a single lymphocyte due to nonspecific stimuli from the innate immune system D. Increased number of lymphocytes with identical specificities, all derived from a single lymphocyte stimulated by a single antigen E. Increased size of the lymphocytes of a single clone due to antigen-induced activation of the cells

ANS: D Clonal expansion occurs during the activation phase of an adaptive immune response. A single lymphocyte is stimulated to divide by antigen, and the progeny go through several rounds of division until there are many lymphocytes, all with identical specificities, all derived from one cell. The number of different clones is not influenced by antigen exposure. Expansion does not refer to the size of the cells, although activated lymphocytes are larger than their naive precursors.

14.

The estimated number of distinct structures that can be recognized by the mammalian adaptive immune system is A. 1-10 B. 102-103 C. 103-105 D. 107-109 E. ∞ ANS: D

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Although the theoretical number of antigen specificities of the adaptive immune system is higher, estimates of the actual number of different antibody and T cell antigen receptor specificities are in the range of 107-109. This number is large enough to accommodate most of the diversity in molecular structures that the microbial world is capable of producing.

15.

Which of the following statements best describes the “two-signal requirement” for naive lymphocyte activation?

A. Lymphocytes must recognize two different antigens to become activated.

B. Lymphocytes must recognize the same antigen at two sequential times to become activated.

C. Lymphocytes must recognize antigen and respond to another signal generated by microbial infection to become activated.

D. Both naive B and naive T lymphocytes must simultaneously recognize antigen for either to be activated.

E. When lymphocytes recognize antigen, the antigen receptors must activate two-signal transduction pathways to become activated.

ANS: C Naive lymphocytes will not become activated by antigen alone (signal 1). In addition, they require “costimulatory” signals (signal 2), which are either microbial products or molecules on host cells induced by microbial infection. The molecules that provide signal 2 bind to receptors on the lymphocytes that are distinct from the clonally distributed antigen receptors. Each lymphocyte cannot generally recognize more than one antigen. Although lymphocyte activation may require recognition of antigen molecules by more than one antigen receptor, the two-signal requirement does not refer to this. There is no general requirement for both T and B cells to recognize the same antigen for activation of either to occur. The two-signal requirement does not refer to antigen receptor–associated signal transduction pathways.

16.

In addition to T cells, which cell type is required for initiation of all T cell–mediated immune responses?

A. Effector cells B. Memory cells C. Natural killer cells D. Antigen-presenting cells E. B lymphocytes ANS: D T cell–mediated immune responses are initiated when naive T cells are activated. Antigenpresenting cells, such as dendritic cells, are required to display antigens (peptide-MHC molecule complexes) for naive T cell recognition and to express costimulatory molecules also needed for T cell activation. Memory cells, cytotoxic T cells, and B lymphocytes are not involved in the initial activation of naive T lymphocytes.

17. What are the principal classes of lymphocytes, and how do they differ in function? a. Lymphocytes aka white blood cells i. Main cells of body’s defense mechanism b. B-cells- express surface immunoglobulin, which are antigen receptors.

Humoral immunity: can differentiate into plasma cells that secrete antibodies

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

or memory cells that improve immune responses. i. Neutralization of microbe, phagocytosis, complement activation. ii. Recognize soluble or cell surface antigens. c. T-lymphocytes express helper T or cytotoxic T cells. After activation, they express MHC, which present protein antigens from ingested microbes. i. Helper- CD4 1. Activation of macrophages, inflammation, activation of B lymphocytes 2. Identify antigens on APCs. 3. Secrete cytokines.

4. Initiate immune responses. ii. Cytotoxic-CD8 1. Killing of infected cell 2. Identify antigens on the surface of the infected cells and destroy them via lysis. iii.

Regulatory 1. Suppression of immune response d. NK Cells i. Elimination of infected/ malignant cells ii. Recognize certain surface proteins characteristic to: 1. Viruses 2. Bacteria 3. Cancers iii.

Control viral infections by secreting interferons.

1. Interferons – signaling proteins which are displayed by those cells which are infected by viruses.

18. What are the important differences among naive, effector, and memory T and B lymphocytes? a. Naive cells -> mature T or B cells that are not activated by a microbe antigen yet. i. Pass through circulation in lymph nodes or wait in the tissue. ii. All lymphocytes which exit the main lymphoid organs are naïve iii. Mobilized through the peripheral lymphoid organs in order to encounter and eliminate foreign antibodies. b. Effector cells -> are activated by a pathogen and elicit an antimicrobial defense to protect or eliminate pathogens. (Most die, but some can live on.) i. Functional lymphocytes that have encountered an antigen. ii. Example: cytotoxic T lymphocyte iii.

Effector T – lymphocytes: 1. Travel to peripheral locations of infection and eliminate disease causing microorganisms. iv.

Effector B – Lymphocytes: 1. Stay in the lymphoid organs and bone marrow.

2. Secrete antibodies that pass into the circulation and eradicate the pathogens. c. B cells - secrete antibodies that bind to antigens, or initiate the complement

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

system. d. T cells - recognize, ingest, and destroy microbes, display their peptides to B cells activating their humoral response. e. Memory B cells--> live even after the immune response dies down. They change isotopes of antibody immunoglobulin to improve affinity and specialize for antigens. Improve reaction to second exposure. i. Crucial for launching the secondary immune response if the same pathogen attacks the body later in life.

19. Where are T and B lymphocytes located in lymph nodes, and how is their anatomic separation maintained? a. Lymph Node: i. Made of the outer cortex and inner medullar zone.

1. Cortex contains primary and secondary follicles. b. B lymphocytes in follicles in peripheral lymphoid organs i. Secondary Follicles c. T lymphocytes in T cell zone of cortex of lymph nodes i. Parafollicular cortex (aka paracortical areas) d. Kept there by cytokines called chemokines, which are secreted by stromal cells in the follicle and the parafollicular cortex. i. Chemokines – proteins which act as attractants and are secreted by the endothelial cells of the lymph nodes. e. Lymphocytes are transported to the lymph nodes or organs through specialized organs aka HEV’s (high endothelial venules). i. Directed towards different areas of the lymph nodes via chemokines.

20. How do naive and effector T lymphocytes differ in their patterns of migration? a. Naive T lymphocytes flow through the peripheral organs and recirculate until activated by an antigen. b. Effector T lymphocytes are activated in the lymph node but go to the marginal or peripheral site of infection where the antigen may be located.

MULTIPLE CHOICE

1.

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

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

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.

A previously healthy 8-year-old boy is infected with an upper respiratory tract virus for the first time. During the first few hours of infection, which one of the following events occurs?

A. The adaptive immune system responds rapidly to the virus and keeps the viral infection under control.

B. The innate immune system responds rapidly to the viral infection and keeps the viral infection under control.

C. Passive immunity mediated by maternal antibodies limits the spread of infection.

D. B and T lymphocytes recognize the virus and stimulate the innate immune response.

E. The virus causes malignant transformation of respiratory mucosal epithelial cells, and the malignant cells are recognized by the adaptive immune system.

ANS: B The innate immune response to microbes develops within hours of infection, well before the adaptive immune response. B and T lymphocytes are components of the adaptive immune response, and they would not be able to respond to a newly encountered virus before the innate immune response. An 8-year-old boy would no longer have maternal antibodies from transplacental passive transfer and is unlikely to be breast-feeding, which is another potential source of maternal antibodies. Malignant transformation takes months or years to develop.

4.

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

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,

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

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.

5.

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.

6.

A standard treatment of animal bite victims, when there is a possibility that the animal was infected with the rabies virus, is administration of human immunoglobulin preparations containing anti–rabies virus antibodies. Which type of immunity would be established by this treatment?

A. Active humoral immunity B. Passive humoral immunity C. Active cell-mediated immunity D. Passive cell-mediated immunity E. Innate immunity ANS: B Humoral immunity is mediated by antibodies. The transfer of protective antibodies made by one or more individuals into another individual is a form of passive humoral immunity. Active immunity to an infection develops when an individual’s own immune system responds to the microbe. Cell-mediated immunity is mediated by T lymphocytes, not antibodies, and innate immunity is not mediated by either antibodies or T lymphocytes.

7.

At 15 months of age, a child received a measles-mumps-rubella vaccine (MMR). At age 22, she is living with a family in Mexico that has not been vaccinated and she is exposed to measles. Despite the exposure, she does not become infected. Which of the following properties of the adaptive immune system is best illustrated by this scenario?

A. Specificity B. Diversity C. Specialization D. Memory E. Nonreactivity to self ANS: D

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Protection against infections after vaccination is due to immunologic memory of the adaptive immune system. Memory is manifested as a more rapidly developing and vigorous response on repeat exposure to an antigen compared with the first exposure. Specificity and diversity are properties related to the range of antigenic structures recognized by the immune system, and specialization is the ability of the adaptive immune system to use distinct effector mechanisms for distinct infections.

8.

A vaccine administered in the autumn of one year may protect against the prevalent strain of influenza virus that originated in Hong Kong that same year, but it will not protect against another strain of influenza virus that originated in Russia. This phenomenon illustrates which property of the adaptive immune system?

A. Specificity B. Amnesia C. Specialization D. Cultural diversity E. Self-tolerance ANS: A Adaptive immune responses are highly specific for distinct molecular structures, which may be present in a vaccine and be produced by one strain of virus but not by a closely related strain.

Amnesia, although generally not used in immunology, implies lack of memory, but the efficacy of the vaccine against the Hong Kong strain implies it has induced memory. The same effector mechanisms would be required to combat different strains of influenza, and therefore failure of a vaccine to protect against two different strains of virus is not related to specialization of effector functions.

9.

The two major functional classes of effector T lymphocytes are: A. Helper T lymphocytes and cytotoxic T lymphocytes B. Natural killer cells and cytotoxic T lymphocytes C. Memory T cells and effector T cells D. Helper cells and antigen-presenting cells E. 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 promote macrophage and B cell responses 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.

10.

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

A. Natural killer cells B. Dendritic cells C. Cytolytic T lymphocytes D. B lymphocytes E. Helper T lymphocytes

ANS: D

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

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

11.

During a humoral immune response to a newly encountered bacterial infection, B cells are first stimulated to proliferate and then secrete antibodies specific for the bacterium. The antibodies may then bind to the bacteria and facilitate ingestion of the microbes by phagocytic cells. In what phase of the humoral immune response does the binding of secreted antibodies to bacteria occur?

A. Recognition phase B. Activation phase C. Effector phase D. Homeostatic phase E. Memory phase ANS: C The effector phase of an immune response occurs when cells or molecules eliminate the microbe or microbial toxin. In a humoral immune response, the effector phase includes secretion of antibody, binding of the antibody to the microbe or toxin, and subsequent antibody-dependent elimination of the microbe or toxin. The recognition phase is the initial binding of the antigen by the naive lymphocyte. The activation phase includes proliferation and differentiation of lymphocytes in response to antigen recognition. The homeostatic phase follows the effector phase, during which the response wanes. In the memory phase, memory B cells and antibodies secreted by long-lived antibody-secreting cells are “waiting” for a repeat exposure to the microbe.

12.

Which of the following statements is consistent with the process of clonal selection?

A. The specificity of a lymphocyte antigen receptor changes to accommodate the structure of an antigen that binds to it.

B. Many different antigen receptors with different specificities are expressed on each lymphocyte.

C. Lymphocytes do not express antigen receptors on their cell surfaces until after exposure to antigen.

D. The diversity of the lymphocyte repertoire for antigens is very small before exposure to antigen but increases significantly after antigen exposure.

E. The diversity of the lymphocyte repertoire for antigens is very large before exposure to antigen, with millions of different clones of lymphocytes, each having a different specificity.

ANS: E The clonal selection hypothesis accurately predicted that individuals possess large numbers of different clones of lymphocytes before antigen exposure, with cells in each clone expressing antigen receptors with a single identical specificity, but with different specificities from other clones. Thus, the diversity of the lymphocyte repertoire is very large even before antigen exposure. These receptors are expressed before antigen exposure, and their specificities generally do not change in response to antigen.

13.

Which of the following best describes clonal expansion in adaptive immune responses?

A. Increased number of different lymphocyte clones, each clone specific for a different antigen during the course of an infection

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

B. Increased number of different lymphocyte clones, each clone specific for a different antigen during development of the immune system, before exposure to antigen C. Increased number of lymphocytes with identical specificities, all derived from a single lymphocyte due to nonspecific stimuli from the innate immune system D. Increased number of lymphocytes with identical specificities, all derived from a single lymphocyte stimulated by a single antigen E. Increased size of the lymphocytes of a single clone due to antigen-induced activation of the cells ANS: D Clonal expansion occurs during the activation phase of an adaptive immune response. A single lymphocyte is stimulated to divide by antigen, and the progeny go through several rounds of division until there are many lymphocytes, all with identical specificities, all derived from one cell. The number of different clones is not influenced by antigen exposure. Expansion does not refer to the size of the cells, although activated lymphocytes are larger than their naive precursors.

14.

The estimated number of distinct structures that can be recognized by the mammalian adaptive immune system is A. 1-10 B. 102-103 C. 103-105 D. 107-109 E. ∞ ANS: D Although the theoretical number of antigen specificities of the adaptive immune system is higher, estimates of the actual number of different antibody and T cell antigen receptor specificities are in the range of 107-109. This number is large enough to accommodate most of the diversity in molecular structures that the microbial world is capable of producing.

15.

Which of the following statements best describes the “two-signal requirement” for naive lymphocyte activation?

A. Lymphocytes must recognize two different antigens to become activated.

B. Lymphocytes must recognize the same antigen at two sequential times to become activated.

C. Lymphocytes must recognize antigen and respond to another signal generated by microbial infection to become activated.

D. Both naive B and naive T lymphocytes must simultaneously recognize antigen for either to be activated.

E. When lymphocytes recognize antigen, the antigen receptors must activate two-signal transduction pathways to become activated.

ANS: C Naive lymphocytes will not become activated by antigen alone (signal 1). In addition, they require “costimulatory” signals (signal 2), which are either microbial products or molecules on host cells induced by microbial infection. The molecules that provide signal 2 bind to receptors on the lymphocytes that are distinct from the clonally distributed antigen receptors. Each

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

lymphocyte cannot generally recognize more than one antigen. Although lymphocyte activation may require recognition of antigen molecules by more than one antigen receptor, the two-signal requirement does not refer to this. There is no general requirement for both T and B cells to recognize the same antigen for activation of either to occur. The two-signal requirement does not refer to antigen receptor–associated signal transduction pathways.

16.

In addition to T cells, which cell type is required for initiation of all T cell–mediated immune responses?

A. Effector cells B. Memory cells C. Natural killer cells D. Antigen-presenting cells E. B lymphocytes ANS: D T cell–mediated immune responses are initiated when naive T cells are activated. Antigenpresenting cells, such as dendritic cells, are required to display antigens (peptide-MHC molecule complexes) for naive T cell recognition and to express costimulatory molecules also needed for T cell activation. Memory cells, cytotoxic T cells, and B lymphocytes are not involved in the initial activation of naive T lymphocytes.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 2: Innate Immunity: The Early Defense Against Infections 1. How may ethics be best described? a. b. c. d.

The philosophical study of morality The process of value clarification The beliefs and norms of a society The application of ethical principles to moral issues ANS: A

Feedback A Correct! Ethics, the philosophical study of morality, is a comprehensive approach to the systematic exploration of what is morally right and wrong.

B Incorrect—Value clarification is a process through which individuals come to understand the values they hold and the relative importance of each of these values and hence come to understand the various and shared perspectives they hold.

C Incorrect—The beliefs and norms of a society influence ethical perspectives and are explored in the study of ethics.

D Incorrect—Applying ethical principles to moral issues helps provide frameworks for ethical decision making and is a component of the study of ethics.

DIF:

Cognitive level: Knowledge

2. Which of the following is the focus of normative ethics? a. b. c. d.

The analysis of morality without taking a moral position The question of what is right or wrong Explaining how moral attitudes and beliefs differ from person to person Distinguishing between what is normal and what is not

ANS: B Feedback A Incorrect—This is a focus of descriptive ethics.

B Correct! Normative ethics focuses on the reasons, principles, or arguments that guide decisions about what is right and wrong. Basic principles and virtues are identified to guide morality and provide coherent, systematic, and justifiable answers to moral questions.

C Incorrect—A person’s differing moral attitudes and beliefs help to shape his or her personal values; and influence views about what is right or wrong.

D Incorrect—People’s ideas of normal and abnormal could be based on values, but these distinctions are not necessarily ethical.

DIF:

Cognitive level: Comprehension

3. Which of the following fields of ethics applies ethical theories and principles to actual moral problems? a. b. c. d.

Philosophical ethics Biomedical ethics Nursing ethics Applied ethics

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

ANS: D Feedback A Incorrect—Ethics in general is a philosophical study.

B Incorrect—Biomedical ethics explores moral issues and ethical questions associated with health care.

C Incorrect—Nursing ethics focuses on moral questions within all domains of nursing.

D Correct! Applied ethics is a specific field of ethics where theories and principles are applied to actual moral problems to assist in guiding decision making.

DIF:

Cognitive level: Knowledge

4. Which of the following exists when mutually exclusive alternatives can both be supported by strong moral reasons? a. b. c. d.

Moral distress An ethical dilemma A value conflict An ethical violation

ANS: B Feedback A Incorrect—Moral distress results when a person is faced with ethical issues or conflicting values and cannot deal effectively with them or is obstructed from doing so.

B Correct! An ethical dilemma arises when the best course of action is unclear and there are strong moral reasons supporting each opposing position.

C Incorrect—A value conflict occurs when people encounter other individuals or groups whose value system are in conflict with their own.

D Incorrect—An ethical violation occurs when actions and behaviours contradict what is clearly the right action or fail to meet an ethical standard or code of ethics.

DIF:

Cognitive level: Comprehension

5. What is the result when a nurse believes that a course of action is correct, but is prevented (e.g., through a law or policy) from carrying out that action or influencing the decision, resulting in feelings of guilt? a. b. c. d.

An ethical dilemma Moral distress Ethical reasoning Moral irresponsibility

ANS: B Feedback A Incorrect—An ethical dilemma arises when the best course of action is unclear and there are strong moral reasons supporting each opposing position.

B Correct! Moral distress results when a person is faced with ethical issues or conflicting values and cannot deal effectively with them.

C Incorrect—Ethical reasoning is the process of ethical decision making, not the result of a situation.

D Incorrect—Moral responsibility refers to the duty to act in accordance with the moral principles that guides groups or society. Moral irresponsibility would occur if a nurse disregarded professional or organizational ethical standards or codes of ethics.

DIF:

Cognitive level: Comprehension

6. What is the correct term to describe a framework of principles and guidelines that helps to identify ethical issues and reconcile conflicts?

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

a. b. c. d.

Metaethics Ethical theory Ethical values Descriptive ethics ANS: B

Feedback A Incorrect—Metaethics analyzes the meanings of concepts, such as right, obligation, good, and virtue, and attempts to distinguish between what is moral and what is not—for example, the difference between a moral rule and a social rule.

B Correct! Ethical theory is the study of the nature and justification of general ethical principles that can be applied to moral problems.

C Incorrect—Ethical values are ideals and may vary across individuals, groups, or populations; they do not resolve conflicts but help in understanding various perspectives on an issue.

D Incorrect—Descriptive ethics encompasses explanations and factual descriptions of moral behaviour and beliefs; it does not identify ethical issues or resolve conflicts.

DIF:

Cognitive level: Knowledge

7. Which of the following best describes the concept of equality for all Canadians? a. b. c. d.

A belief A value A principle A moral dilemma ANS: B

Feedback A Incorrect—A belief is individual and is something felt to be true; the concept of equality is not simply an individual belief.

B Correct! Equality for all is a societal value; the majority of Canadians subscribe to this ideal.

A value has significant meaning to an individual, group, or society.

C Incorrect—Principles help to guide moral decisions; the concept of equality is based on the principle of justice.

D Incorrect—A moral dilemma occurs when the right course of action is not clear.

DIF:

Cognitive level: Application

8. A nurse’s support of client autonomy is based on which of the following? a. b. c. d.

An “a priori” principle A personal value A professional value A legal requirement

ANS: C

Feedback A Incorrect—Ethical principles are considered “prima facie”; that is, their application may be relative to another principle that may have more weight or priority in a given situation. They are not considered “a priori” or binding.

B Incorrect—A nurse’s support of client autonomy may be an example of a personal value, but not exclusively.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

C Correct! Professional values build and expand on personal values. The value of client autonomy is a professional (and possibly personal) value and is evident in codes of ethics and professional standards for nurses.

D Incorrect—Some legal doctrines, such as informed consent, are based on the principle of autonomy, but generally, supporting client autonomy is not a legal requirement.

DIF:

Cognitive level: Comprehension

9. Which of the following theories may guide nurses to choose actions that will lead to the best consequences, outcomes, or results? a. b. c. d.

Utilitarian Deontological Normative Relative ANS: A

Feedback A Correct! Utilitarianism is a teleological theory in which the ethical choice is the one with the best consequences, outcomes, or results.

B Incorrect—Deontological theories make explicit the duties and principles that should guide people’s actions; they do not focus on the consequences of actions.

C Incorrect—Normative theories are intended to provide frameworks and rules to guide decisions about what is right or wrong, but they do not focus on the consequences of actions.

D Incorrect—Relativism states that there are no moral absolutes and that the concept of morality varies across cultures and among individuals; it does not provide a guide to choosing the best actions.

DIF:

Cognitive level: Knowledge

10. What is the main principle underlying a rule-based theory of utilitarianism? a. b. c. d.

The theory is always deontological.

The theory considers individual acts.

The theory considers general patterns of behaviour.

The theory is the foundation of nursing ethics.

ANS: C Feedback A Incorrect—Deontological theory (which includes the belief that standards for moral behaviour exist independently of means or ends) includes both rule- and act-based theories but is not the main underlying principle.

B Incorrect—Rule-based theories consider general patterns of behaviour, whereas act-based theories consider individual acts.

C Correct! General patterns of behaviour are the foundation of rule-based theories. Rule-based theories consider general patterns of behaviour, whereas act-based theories consider individual acts. Both rule- and act-based theories are utilitarian (in which the best choice is the one with the best outcomes).

D Incorrect—Such approaches as caring ethics and ethical principles, not rule-based theories, are the foundation of nursing ethics.

DIF:

Cognitive level: Comprehension

11. Which of the following is the basis for ethical decision-making frameworks? a. Ethical reasoning

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

b. Ethical values c. Ethical dilemmas d. Ethical principles ANS: D

Feedback A Incorrect—Ethical reasoning is a process of ethical decision making using a framework.

B Incorrect—Ethical values are beliefs held by an individual or a group and may evolve over time; they are not the basis for ethical decision-making frameworks.

C Incorrect—Ethical dilemmas arise when the best choice of action is unclear and when strong moral reasons support each position; they are not the basis for ethical decision-making frameworks.

D Correct! Ethical principles serve as rules to guide moral conduct and provide a framework for ethical decision making.

DIF:

Cognitive level: Knowledge

12. What is the main difference between deontological and teleological theories? a. Teleological theory focuses on the use of principles to choose the correct actions. b. Deontological theory focuses on ends or outcomes and consequences of decisions. c. Deontological theory suggests that standards for moral behaviour are independent of the ends or outcomes of actions. d. All teleological theories are rule based.

ANS: C Feedback A Incorrect—Teleological theory is focused on the end results or outcomes of actions.

B Incorrect—Deontological theory is focused on acts and rules that support principles or duties, not on the ends or outcomes of decisions.

C Correct! Deontological theory suggests that standards for moral behaviour are independent of the ends or outcomes of actions, whereas teleological theory focuses on the outcomes and consequences of actions.

D Incorrect—Teleological theory is focused on the end results or outcomes of actions. Although rule utilitarianism, a teleological theory, considers the utility of general patterns of behaviour rather than that of specific actions.

DIF:

Cognitive level: Comprehension

13. Which of the following ethical principles is the foundation of informed consent? a. b. c. d.

Beneficence Justice Nonmaleficence Autonomy

ANS: D Feedback A Incorrect—Beneficence holds that one must make a positive move to produce some good or benefit for another; it is not the foundation of informed consent.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

B Incorrect—Justice is based on the notions of fairness and equity; it is not the foundation of informed consent.

C Incorrect—Nonmaleficence obliges people to act in such a way as to prevent or remove harm; it is not the foundation of informed consent.

D Correct! Autonomy, or self-determination (including the right to choose one’s own path), is the foundation of informed consent.

DIF:

Cognitive level: Analysis

14. Which of the following influenced the shift in ethical thinking away from abstract rules that reinforce a deductive reasoning process? a. b. c. d.

Patricia Benner Maternalistic attitudes Feminine ethics The principle of nonmaleficence

ANS: C Feedback A Incorrect—Patricia Benner observed the value of a nurse’s intuition and proposed that emotions are central to perception and rationality; she did not influence this shift in ethical thinking.

B Incorrect—Maternalistic attitudes have not influenced shifts in ethical thinking.

C Correct! Feminine ethics argues for an inductive process in which the starting point is the individual’s circumstances or personal story. It has influenced the shift in ethical thinking away from abstract rules that reinforce a deductive reasoning process.

D Incorrect—Nonmaleficence is an ethical principle meaning “do no harm.” This longstanding principle was also present during periods when abstract rules reinforced a deductive reasoning process.

DIF:

Cognitive level: Knowledge

15. Which of the following considers the influence of the nurse–patient relationship on ethical decision making? a. b. c. d.

Social Justice Autonomous ethics Feminine ethics Relational ethics

ANS: D Feedback A Incorrect—Social justice addresses equity and fairness within a society. Nurses advocate for strategies that address the societal issues that affect the health and well-being of persons in Canadian society.

B Incorrect—Autonomy is an ethical principle; however, “autonomous ethics” is not a recognized form of ethics.

C Incorrect—Feminine ethics emphasizes relational ethics, but relational ethics is not the main focus of feminine ethics.

D Correct! Relational ethics considers the influence of the nurse–patient relationship on ethical decision making. If the entire focus is on ethical principles and the relationship between the nurse and the patient is ignored, then relational ethics is not present and the nurse may become disengaged.

DIF:

Cognitive level: Comprehension

16. Which of the following aligns with the use of the narrative in nursing ethics?

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

a. b. c. d.

Ethic of care Relational ethics Value clarification Moral perspectives of Indigenous peoples

ANS: D Feedback A Incorrect—An ethic of care offers an approach to ethics that values feelings, emotions, empathy, and care. It recognizes the importance of relationships and the uniqueness and context of particular situations. It recognizes the value of knowing the person and his or her context; however, the use of narrative is not the major focus.

B Incorrect—Relational ethics considers the influence of the nurse–patient relationship on ethical decision making. Although understanding a person’s story is part of relationship building, it is not the major focus.

C Incorrect—Value clarification assists individuals in understanding the values they hold and the perspectives they may share with others.

D Correct! The use of stories to uncover the complexity of moral issues is part of the rich oral Indigenous culture. Through stories, shared from generation to generation, they have created a strong system of knowledge and mythology that guides their moral thinking and actions. In nursing narrative ethics encourages the sharing of stories to gain a clearer understanding of the ethical issues and challenges embedded in them.

DIF:

Cognitive level: Comprehension

TRUE/FALSE 1. Rationality is related to the notion of thinking and reasoning. It is associated with comprehension, intuition, and intelligence.

ANS: F Feedback Correct Rationality is associated with comprehension, intelligence, or inference; intuition is not considered a component of rational thinking.

Incorrect Rationality is associated with comprehension, intelligence, or inference; intuition is not considered a component of rational thinking.

DIF:

Cognitive level: Comprehension

2. Ensuring open visiting for those important to the person is an expression of a Canadian value.

ANS: T Feedback Correct Canadians value equity, individual rights, health and well-being, quality of life, and human dignity. Most Canadians, whatever their cultural background may be, value their family and friends—those closest to them. It is the person’s choice to make as to who should be present with them when they are unwell. Of course, this has to be balanced with the rights of others in the same setting.

Incorrect Canadians value equity, individual rights, health and well-being, quality of life, and human dignity. Most Canadians, whatever their cultural background may be, value their family and friends—those closest to them. It is the person’s choice to make as to who should be present with them when they are unwell. Of course, this has to be balanced with the rights of others in the same setting.

DIF:

Cognitive level: Synthesis

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

3. Cultural relativists value democracy is the most ethical way to govern.

ANS: F Feedback Correct Relativists believe that the moral values and principles of one culture do not govern the conduct of others. What may be considered moral in one culture may be considered immoral in another. Although some societies value democracy, others disagree and value utilitarian regimes, which may be the most appropriate, or the best, for that particular society.

Incorrect Relativists believe that the moral values and principles of one culture do not govern the conduct of others. What may be considered moral in one culture may be considered immoral in another. Although some societies value democracy, others disagree and value utilitarian regimes, which may be the most appropriate, or the best, for that particular society.

DIF:

Cognitive level: Comprehension

4. W. D. Ross identified prima facie duties as those duties that one must always act upon unless they conflict with duties of equal or stronger obligation.

ANS: T Feedback Correct Ross proposed that “right” choice or action is the one consistent with all the rules.

When all of the duties are consistent, then the choice is based on preference. When there is conflict, then one appeals to the higher rule to resolve the conflict (e.g., sanctity of life versus veracity).

Incorrect Ross proposed that “right” choice or action is the one consistent with all the rules.

When all of the duties are consistent, then the choice is based on preference. When there is conflict, then one appeals to the higher rule to resolve the conflict (e.g., sanctity of life versus veracity).

DIF:

Cognitive level: Knowledge

5. Indigenous peoples have a consistent view of morality, and this is embedded in their rich oral tradition.

ANS: F Feedback Correct Not all Indigenous communities hold to one philosophical view, religious belief, or moral code; however, all share an oral tradition that transmits history, traditions, and culture across generations.

Incorrect Not all Indigenous communities hold to one philosophical view, religious belief, or moral code; however, all share an oral tradition that transmits history, traditions, and culture across generations.

DIF:

Cognitive level: Comprehension

1. How does the specificity of innate immunity differ from that of adaptive immunity? a. Innate immunity is directed against common molecular patterns shared by different microbes and the products of damaged cells and is mediated by cell surface receptors and secreted proteins of limited diversity. i. Recognizes and eliminates dead cells and microbes. b. Adaptive immunity uses an extremely diverse set of antigen receptors to recognize a wide range of microbial and nonmicrobial antigens.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

2. What are examples of microbial substances recognized by the innate immune system, and what are the receptors for these substances? a. Lipopolysaccharide recognized by toll-like receptor-4 (TLR-4) b. Flagellin recognized by TLR-5. c. Microbial DNA recognized by TLR-9. d. Viral RNAs recognized by TLR-3, -7, and –8. e. Bacterial peptidoglycans recognized by NOD-like receptors. f. Mannans recognized by mannose receptor and mannose binding protein.

3. What is the inflammasome, and how is it stimulated? a. The inflammasome is a multiprotein complex found in the cytoplasm of phagocytes, dendritic cells, and other cell types. It proteolytically cleaves a precursor of the cytokine interleukin-b (IL-1b), generating an active proinflammatory form of IL-1b that is released from the cell. The inflammasome has a NOD family molecule called NLRP3 and the proteolytic enzyme caspase 1.

NLRP3 responds to many different stimuli that show cell infection or injury, leading to activation of caspase-1, which then cleaves the IL-1b precursor. Stimuli that activate the inflammasome include various microbial products, crystals such as sodium urate, reduced potassium concentration, and reactive oxygen species.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

4. What are the mechanisms by which the epithelium of the skin prevents the entry of microbes? a. The skin supplies an impermeable epithelial barrier by virtue of a surface layer of keratin and by tight junctions between keratinocytes. These epithelial cells secrete antimicrobial peptide antibiotics, and the skin also has protective intraepithelial lymphocytes. b. The continuous epithelia also protect the gastrointestinal tract, genitourinary tract, respiratory tract, and skin. c. Contents of the epithelia: i. Tight adhering cells 1. Provide mechanical support ii. Mucosal Epithelial cells 1. Produce keratins which prevents microbes from infecting the epithelial cells iii. Peptide antibiotics 1. Produce by epithelial cells (defensins and cathelicidins) iv. Intraepithelial T lymphocytes 1. Act against infectious pathogens that breach epithelia 5. How do phagocytes ingest and kill microbes? a. Phagocytes have a range of receptors that recognize microbial carbohydrates and Fc receptors that recognize microbes coated (opsonized) by antibodies. i. Microbes that bind to these receptors are internalized into phagosomes, which fuse with lysosomes, where the microbes are destroyed by reactive oxygen and nitrogen species and lysosomal enzymes. b. The mechanism of phagocytosis begins with the adherence of the phagocytes to the microbes. (Note - in the case of bacteria, phagocytes adhere with the help of opsonin's) 6. What is the role of MHC molecules in the recognition of infected cells by NK cells, and what is the physiologic significance of this recognition? a. NK cells recognize pathogen infected cells and later respond by killing the infected cells via the secretion of IFN-gamma (macrophage activating cytokine). b. NK cells express inhibitory receptors that recognize MHC class I molecules on host cells and can then inhibit NK cell activation. In virally infected cells, MHC class I molecules are downregulated and therefore fail to engage inhibitory receptors, and at the same time, ligands for activating NK cell receptors are expressed. As a result, NK cells are activated to kill these infected cells.

7. What are the roles of the cytokines TNF, IL-12, and type I interferons in defense against infections? a. TNF stimulates inflammation in part by helping to recruit neutrophils and monocytes to sites of infection. IL-12 made by macrophages and dendritic cells

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

contributes to NK cell and T cell activation. Type I interferons inhibit viral replication (inducing an antiviral state). i. TNF are mainly involved in employing monocytes in blood neutrophils to the site of infection. ii. TNF possess systemic effects comprising fever by reacting on the hypothalamus. iii. Thrombus formation is promoted by TNF at high concentrations which reduces blood pressure. iv. Severe clinical and pathologic manifestation of septic shock is caused by high levels of TNF. v. IL-12 Really activates NK cells, which in turn activates macrophages. vi. Type –I interferons are produced by dendritic cells upon infection by the virus. This cytokine inhibits viral replication and prevents infection spread.

8. How do innate immune responses enhance adaptive immunity? a. Innate immune responses induce the expression of costimulators on dendritic cells that can provide second signals for T cell activation. Innate immune cells also make cytokines that promote the adaptive immune response. Complement activation as part of the innate immune response can lead to the generation of complement fragments that enhance B lymphocyte activation.

9. 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.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

10. A 4-year-old girl stepped on a rusty nail in her backyard. Two days later, she is taken to the pediatrician because her heel is painful, red, and swollen and is warm to the touch. All of the following are mechanisms of innate immunity that may be protecting the patient against pathogenic microbes in the heel wound EXCEPT: a. Epithelial barrier function of the skin of her foot b. Intraepithelial lymphocytes present in the skin c. Circulating neutrophils migrating to the site of the wound d. Soluble cytokines that induce a local inflammatory response e. Circulating anti-tetanus toxin antibodies ANS: E Secreted antibodies against protein antigens are effectors of humoral immunity, a component of the adaptive immune system. All other mechanisms listed are part of the innate immune system. Intact epithelial surfaces prevent microbial entry, and epithelial

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

cells express anti-microbial factors, such as defensins. Neutrophils are effector cells that function in early phagocytosis and killing of microbes. Cytokines that mediate inflammation (e.g., tumor necrosis factor, interleukin-1, chemokines) are components of innate immunity. Intraepithe-lial T lymphocytes present in the epidermis and mucosal epithelia express a limited diversity of antigen receptors; as such, they are considered effector cells of innate immunity and function in host defense by secreting cytokines, activating phagocytes, and killing infected cells.

11. 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 does not have memory but the adaptive immune system does.

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 unique property of the adaptive and not the innate immune system.

12. Toll-like receptors (TLRs) are a family of homologous receptors expressed on many cell types and are involved in innate immune responses. Ten different mammalian TLRs have been identified, and several ligands for many of these receptors are known. Which of the following is a TLR ligand? a. Single-stranded RNA b. Transfer RNA c. Double-stranded DNA d. Unmethylated CpG DNA e. Heterochromatin ANS: D

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

More than 10 mammalian Toll-like receptors (TLRs) have been identified, and each appears to recognize a different set of structures that are found in pathogenic microbes but not in mammalian cells. Such structures are called pathogen-associated molecular patterns (PAMPs). Unmethylated cytosine guanosine (CpG) motifs are typical of bacterial and protozoan DNA, but not mammalian DNA, and are therefore PAMPs. TLR9 binds CpG DNA. Transfer RNA, single-stranded RNA, double-stranded DNA, and heterochromatin are all normal components of mammalian cells and are not recognized

by TLRs. Double-stranded RNA is produced by some viruses but not by mammalian cells and is recognized by TLR3.

13. A 67-year-old homeless man is brought to the emergency department after being found behind a neighborhood bar in freezing weather. On arrival, he has a shaking chill, fever, and cough productive of blood-tinged sputum. A chest radiograph shows lobar consolidations consistent with bacterial pneumonia. Blood cultures are positive for Streptococcus pneumoniae. Which of the following molecular patterns recognized by Toll-like receptors expressed on the surface of this patient’s phagocytes is important for activating his innate immune system against this gram-positive bacterial infection? a. Peptidoglycan b. Double-stranded RNA c. Lipopolysaccharide (LPS) d. Lipoarabinomannan e. Phosphatidylinositol dimannoside ANS: A Gram-positive bacteria contain cell walls rich in peptidoglycan. When shed by bacteria such as Streptococcus pneumoniae, peptidoglycan serves as a ligand that binds Toll-like receptor 2 (TLR2), stimulating an innate immune response. The other choices listed are also ligands that stimulate TLRs, but they are not present in gram-positive bacteria.

Double-stranded RNA is found in replicating viruses, lipopolysaccharide (LPS) is a component of the outer cell wall of gram-negative bacteria, and both lipoarabinomannan and phosphatidylinositol dimannoside are present in mycobacteria.

14. The signaling pathways triggered by Toll-like receptors typically result in activation of which of the following pairs of transcription factors? a. NFAT and T-bet b. AP-1 and GATA-3 c. Fos and STAT-6 d. NFB and AP-1 e. Lck and Jun ANS: D The predominant signaling pathway used by Toll-like receptors (TLRs) results in the activation of the NF-B transcription factor. Ligand binding to the TLR at the cell surface leads to recruitment of several cytoplasmic signaling molecules through specific domaindomain interactions, resulting in degradation of IB and subsequent activation of NFB. In some cell types, certain TLRs also engage other signaling pathways, such as the MAP kinase cascade, leading to activation of the AP-1 transcription factor. T-bet and GATA-3

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

are transcriptional regulators involved in helper T cell differentiation. Fos is a component of AP-1, and STAT-6 is a 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.

15. Toll-like receptors 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 Toll-like receptor (TLR) signaling. 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- (TNF-), interleukin-1 (IL-1), and IL-12; endothelial adhesion molecules such as E-selectin; and proteins involved in microbial killing mechanisms, including inducible nitric oxide synthase (iNOS). The specific genes expressed depend on the cell type of the responding cell.

16. Which of the following is a receptor on macrophages that is specific for a structure produced by bacteria but not by mammalian cells? a. CD36 (scavenger receptor) b. Fc receptor c. Complement receptor d. Mannose receptor e. ICAM-1 ANS: D The macrophage mannose receptor binds to terminal mannose and fucose residues on bacterial glycoproteins and glycolipids. Mammalian cells do not typically contain these residues. CD36 binds many different ligands, including microbial and self molecules. Fc receptors, complement receptors, and ICAM-1 are receptors for mammalian complement fragments, Ig, and LFA-1, respectively.

17. Which one of the following comparisons between neutrophils and macrophages is true? a.

Neutrophils that enter inflammatory sites can survive for days, but macrophages are very short lived and only survive for hours. b.

Both neutrophils and macrophages are phagocytic and can kill internalized microbes.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

c.

Neutrophils proliferate at inflammatory sites, but macrophages are terminally differentiated and cannot proliferate. d.

Neutrophils, but not macrophages, express the high-affinity FcRI receptor, which recognizes specific opsonins bound to microbes and facilitates phagocytosis. e.

Both neutrophils and macrophages contain abundant cytoplasmic granules containing lysozyme, collagenase, and elastase.

ANS: B Neutrophils and macrophages can both actively phagocytose and kill microbes, and both express opsonin receptors, such as FcRI or complement receptors that enhance phagocytosis. Neutrophils are short lived, whereas macrophages can survive for days or weeks. Macrophages are not terminally differentiated and can undergo cell division at inflammatory sites, but neutrophils cannot. Only neutrophils have cytoplasmic granules filled with enzymes, including lysozyme, collagenase, and elastases; these are called specific granules.

18. A 43-year-old man with a history of kidney transplantation is on immunosuppressive drugs. He presents to the emergency department 84 days after transplantation with a slight fever, accompanied by violent shaking chills, rapid heart rate, and dangerously low blood pressure. Blood cultures are positive for gram-negative bacteria, including Klebsiella and Pseudomonas. Although the patient was initially alert and responsive to fluids and antibiotic therapy, his condition rapidly deteriorates into disseminated intravascular coagulation (DIC), hypoglycemia, and cardiovascular failure. Which of the following is an essential mediator of this patient’s condition?  Transforming growth factor-  Tumor necrosis factor- c. Interleukin (IL)-2 d. IL-10 e. IL-3 ANS: B This patient is suffering from septic shock, characterized by the clinical triad of disseminated intravascular coagulation (DIC), hypoglycemia, and cardiovascular failure.

This condition is most often initiated by endotoxin, also known as lipopolysaccharide (LPS), a component of the outer cell walls of gram-negative bacteria. LPS is a potent stimulus for tumor necrosis factor (TNF)- secretion by mononuclear phagocytes and other cell types. Most of the biologic effects of LPS are mediated through TNF-.

Transforming growth factor- (TGF-) and interleukin (IL)-10 are anti-inflammatory cytokines, IL-2 is a T cell growth factor, and IL-3 is a hematopoietic cytokine. These cytokines are not mediators of septic shock.

19. Macrophages and neutrophils express several enzymes that are involved in biochemical mechanisms that kill ingested microbes. Which of the following is NOT an enzyme expressed by these cells? a. Inducible nitric oxide synthase (iNOS) b. Granzyme B c. Phagocyte oxidase

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

d. Myeloperoxidase e. Lysozyme ANS: B Granzyme B, a proteolytic enzyme component of cytolytic T lymphocyte (CTL) and natural killer (NK) cell granules, is involved in initiating caspase-dependent CTL killing of target cells. Granzyme B is not involved in phagocyte killing of ingested microbes.

Inducible nitric oxide synthase (iNOS) generates NO in macrophages, and NO is toxic to microbes. Phagocyte oxidase and myeloperoxidase are involved in generating free radical species that kill ingested microbes in phagocytes. Lysozyme is a proteolytic enzyme in neutrophil granules that contributes to microbial killing.

20. All of the following molecules are opsonins that facilitate efficient phagocytosis of microbes by neutrophils and macrophages EXCEPT: a. C3b b. C5a c. C-reactive protein d. IgG e. Mannose-binding lectin ANS: B C5a is a peptide released after cleavage of C5 protein during the complement cascade. It stimulates the influx of neutrophils to the site of infection, thus acting as a chemoattractant, not as an opsonin. C3b (covalently bound to microbes on which complement activation has taken place) and IgG bound to antigen, are particularly potent opsonins, because phagocytes have receptors for both C3b and the Fc region of IgG. Creactive protein and mannose-binding lectin also can coat microbes and be recognized by phagocyte receptors; thus they serve as opsonins.

21. A 3-year-old boy, who is small for his age, has a history of pyogenic (pus-producing) infections and cutaneous skin abscesses. Physical examination is remarkable for high fever, enlarged liver and spleen, and swollen cervical lymph nodes. A culture from an abscess on his arm reveals Staphylococcus aureus, a gram-positive bacteria that is also catalase-positive. Immunoglobulin and complement levels are normal. Results of the nitroblue tetrazolium test are consistent with a diagnosis of chronic granulomatous disease (CGD). The boy’s immunodeficiency involves impaired generation of which of the following? a. C5a b. C-reactive protein c. Mannose-binding lectin d. Reactive oxygen intermediates e. Membrane attack complex ANS: D Chronic granulomatous disease (CGD) is a rare, inherited immunodeficiency disease associated with a defective intracellular respiratory burst in phagocytes. It consists of a group of heterogeneous disorders of oxidative metabolism in which the pathways

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

required for generation of toxic reactive oxygen species (ROIs) are impaired. In patients with CGD, phagocytosis occurs normally, but the engulfed microbes are not killed and they multiply within the cell. In this way, patients are susceptible to recurrent infections with organisms such as Staphylococcus, which are of low virulence in normal hosts.

22. A 4-year-old-girl sees her physician because of a severe necrotizing, oropharyngeal herpes simplex viral (HSV) infection. She has a past medical history of cytomegalovirus (CMV) pneumonitis and cutaneous HSV infection. Phenotypic analysis of her blood cells shows an absence of CD56+ and CD16+ cells. There are normal numbers of CD4+ and CD8+ cells in the blood, and serum antibody titers are normal. The patient’s CD8 + T cells were able to kill virally infected target cells in vitro. Which of the following is NOT characteristic of this girl’s immunodeficiency disease? a.

Lack of cells whose activation is normally inhibited by self class I major histocompatibility complex (MHC) b. Impaired granzyme B–dependent killing of virally infected target cells c. Lack of cells that are activated by IL-15 d. Impaired interferon (IFN)- production during early phases of viral infection e. Failure to form viral peptide-class I MHC complexes ANS: E The presence of normal numbers of CD8+ T cells and the ability of these cells to kill virally infected target cells indicates that the class I major histocompatibility complex (MHC) pathway of viral peptide antigen presentation is intact. The patient’s immunodeficiency is due to a lack of natural killer (NK) cells. NK cells express CD56 and/or CD16. NK cells are activated by interleukin-15 (IL-15) and IL-12, are normally inhibited by recognizing class I MHC on other cells, kill target cells with altered class I MHC expression through a granzyme B–dependent mechanisms (similar to cytolytic T lymphocyte killing), and produce interferon- as part of the early innate response to viral infection.

23. Which one of the following statements about inhibitory receptors on natural killer (NK) cells is true? a. Inhibitory receptors on NK cells express ITAM motifs in their cytoplasmic tails. b. Some inhibitory receptors on NK cells recognize HLA-A or HLA-C. c. Some inhibitory receptors on NK cells are members of the integrin family. d.

Some inhibitory receptors on NK cells are members of the Toll-like receptor family. e.

Inhibitory receptors on NK cells are not expressed on the same NK cells that express activating receptors.

ANS: B Natural killing (NK) inhibitory receptors recognize class I MHC molecules that are normally and constitutively expressed, including various alleles of HLA-A and HLA-C. The cytoplasmic tails of NK inhibitory receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), but not immunoreceptor tyrosine-based activation motifs (ITAMs). Some inhibitory receptors on NK cells are members of the Ig superfamily, but

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

not the integrin or TLR families. NK cells usually express both activating and inhibitory receptors, and activation is regulated by a balance between signals generated from both types of receptors. The inhibitory receptors on NK cells bind to self class I MHC molecules, which are expressed on most normal cells. When activating and inhibitory receptors are simultaneously engaged, the inhibitory receptor signals dominate and the NK cell is not activated.

24. Complement activation in the innate immune system can be initiated in the absence of antibody. Which of the following molecular components of the complement system is involved in initiation of antibody-independent complement activation? a. C1 b. C9 c. Mannose binding lectin d. CR2 e. Mannose receptor ANS: C Mannose-binding lectin (MBL) is a soluble serum component that is structurally similar to C1 of the classical complement pathway. MBL binds to mannan residues on microbial surfaces and triggers proteolytic cleavage and activation of downstream components of the complement system. C9 is not involved in initiation of complement activation but is part of the common final membrane attack complex (MAC) pathway. CR2 is a cell surface receptor for complement fragments. A mannose receptor is a cell surface receptor on phagocytes that binds mannan residues and promotes phagocytosis of microbes.

25. Which of the following is an example of how the innate immune response stimulates or modifies adaptive immunity? a.

Tumor necrosis factor (TNF) secreted by helper T cells enhances adhesion molecules on endothelial cells and promotes recruitment of inflammatory cells. b.

Interferon (IFN)- produced by T helper cells is a potent activator of macrophages, allowing killing of phagocytosed microbes. c.

B7-1 expression on antigen-presenting cells is up-regulated in response to signaling through Toll-like receptors, thus enabling costimulation of T cells. d.

Infected cells coated by IgG3 are recognized by Fc receptors on natural killer cells, allowing efficient killing of the infected cells. e.

Double-stranded RNA of replicating viruses potently stimulates IFN- expression by fibroblasts, inducing an “antiviral state” in neighboring, uninfected cells.

ANS: C Innate immune responses are important stimulators of adaptive immunity. Increased expression of B7-1 and B7-2 on antigen-presenting cells after microbial activation of Toll-like receptors (innate immunity) is critical in providing costimulatory signals for T cell activation (adaptive immunity) via binding to CD28 receptors on T cells. T helper cell–mediated endothelial or macrophage activation is an example of adaptive immunity using the effector mechanisms of innate immunity. Neither IgG3 opsonization facilitating natural killer cytolytic activity nor double-stranded RNA stimulating interferon- secretion involve innate immunity enhancing adaptive immunity.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 3: Antigen Capture and Presentation to Lymphocytes: What Lymphocytes See 1. When antigens enter through the skin, in what organs are they concentrated? What cell

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type(s) plays an important role in this process of antigen capture? a. Antigens that enter through the skin are captured by dendritic cells that live in the epidermis and dermis, and the dendritic cells transport the antigens to the skin-draining lymph nodes, where the antigens are displayed to lymphocytes.

What are MHC molecules? What are human MHC molecules called? How were MHC molecules discovered, and what is their function? a. Major histocompatibility complex (MHC) molecules are cell surface proteins that bind antigenic peptides and display them for recognition by T cells. Human MHC proteins are called HLA molecules. They were initially discovered as products of polymorphic genes that mediate transplant rejection. Their physiologic function is peptide antigen presentation to T cells.

What are the differences between the antigens that are displayed by class I and class II MHC molecules? a. Proteins that are produced in or enter the cytosol and processed by the proteasome are presented by class I MHC molecules. Proteins internalized into vesicles by endocytosis and processed by lysosomal proteases are presented by class II MHC molecules.

Describe the sequence of events by which class I and class II MHC molecules acquire antigens for display. a. Protein antigens in the cytosol are cleaved into peptides by proteasomes, and the peptides are transported into the endoplasmic reticulum by the TAP pump. Once inside the ER, these peptides bind to newly produced MHC class I molecules. The peptide-class I MHC complex is then transported to and displayed on the cell surface. MHC class II a and b chains are produced in the endoplasmic reticulum, where they assemble with each other and with an invariant chain that occludes the antigen binding cleft. The MHC class II-invariant chain complex is transported to a late endosomal/lysosomal compartment, where the invariant chain is degraded, leaving a peptide called CLIP in the cleft. Proteins internalized by the endocytic pathway are degraded in late endosomes and lysosomes into peptides. Specific peptides displace CLIP and bind tightly to the cleft of the MHC class II molecule, which is then transported to the cell surface.

Which subsets of T cells recognize antigens presented by class I and class II MHC molecules? What molecules on T cells contribute to their specificity for either class I or class II MHC-associated peptide antigens? a. CD4+ helper T cells recognize peptide antigens bound to class II MHC molecules, and CD8+ cytotoxic T lymphocytes recognize MHC class I-peptide complexes.

The CD4 coreceptor of helper T cells can bind to MHC class II molecules, and the CD8 coreceptor of cytotoxic T cells binds to MHC class I molecules.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 4: Antigen Recognition in the Adaptive Immune System: Structure of Lymphocyte Antigen Receptors and Development of Immune Repertoires 1. What are the functionally distinct domains (regions) of antibody and TCR molecules?

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What features of the amino acid sequences in these regions are important for their functions? a. Antibody and T cell receptor (TCR) proteins have variable domains that are involved in antigen recognition and constant domains that, in the case of antibodies, mediate effector functions. Variable domains have hypervariable regions (sequences that differ among different antibodies or TCRs) that form the binding sites for antigens.

What are the differences in the types of antigens recognized by antibodies and TCRs? a. Antibodies can recognize many types of molecules, including small chemicals, proteins, carbohydrates, lipids, and nucleic acids. In proteins, antibodies can recognize conformational or linear epitopes. TCRs can recognize only linear peptides bound to the clefts of MHC molecules.

What mechanisms contribute to the diversity of antibody and TCR molecules? Which of these mechanisms contributes the most to the diversity? a. The joining of segments of antibody and TCR genes in developing lymphocytes, known as V-D-J recombination, is responsible for the diversity of antibodies and TCRs. Variations in nucleotide sequences introduced using different V, D, and J segment combinations (combinatorial diversity) and during V-D-J joining (junctional diversity) contribute to diversity, with junctional alterations making the largest contribution.

What are some of the checkpoints during lymphocyte maturation that ensure survival of the useful cells? a. The first checkpoint in B and T cell maturation involves the selection of pre-B and pre-T cells that have productively rearranged the µ heavy-chain gene in the case of B lineage cells and the TCR b chain gene in the case of developing T cells.

The second checkpoint is after production of complete antigen receptors and ensures that only cells with the proper V-D-J rearrangement can mature. Positive selection is a process in which T cells that can recognize self MHC molecules weakly can survive and express the type of coreceptor that matches the type of MHC molecule recognized.

What is the phenomenon of negative selection, and what is its importance? a. Negative selection results in the deletion or editing of strongly self-reactive lymphocytes. This process eliminates many self-antigen-reactive lymphocytes, in the thymus for T cells and in the bone marrow for B cells.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 5: T Cell–Mediated Immunity: Activation of T Lymphocytes by Cell-Associated Antigens 1. What are the components of the TCR complex? Which of these components are

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responsible for antigen recognition and which for signal transduction? a. The T cell receptor (TCR) complex is made up of the TCR a and b chains, which are responsible for antigen recognition, and the CD3 complex and z homodimers, which are needed for signal transduction.

What are some of the molecules in addition to the TCR that T cells use to initiate their responses to antigens, and what are the functions of these molecules? a. Molecules other than the TCR used by T cells to respond to antigens include the CD4 and CD8 coreceptors, which bind to class II and class I MHC molecules, respectively; costimulatory receptors such as CD28, which bind to costimulators expressed on activated APCs; and adhesion molecules such as the integrin LFA-1, which mediate T-cell adhesion to APCs and control the migration of the T cells.

What is costimulation? What is the physiologic significance of costimulation? What are some of the ligand-receptor pairs involved in costimulation? a. Costimulation refers to signals delivered to a lymphocyte that are needed for lymphocyte activation but are independent of antigen receptor signaling.

Costimulatory signals are commonly referred to as a "second signal" and provide lymphocytes with the information that the antigen they are recognizing may be of microbial origin. B7-1 and B7-2 are the major costimulators on antigenpresenting cells, which bind to CD28 on T cells.

Summarize the links among antigen recognition, the major biochemical signaling pathways in T cells, and the production of transcription factors. a. Antigen recognition results in coreceptors in T cells bringing the Lck tyrosine kinase in proximity to CD3 and z chain ITAMs. Phosphorylation of the ITAMs results in the recruitment and activation of ZAP-70 tyrosine kinase, which in turn starts many different signaling pathways by activating different downstream enzymes. Some of these pathways include activation of phospholipase Cg, resulting in calcium signaling and the subsequent activation of the NFAT transcription factor; activation of PKCF, resulting in the activation of the NF-κB transcription factor; and activation of MAP kinases, leading to the production of the AP-1 transcription factor.

What is the principal growth factor for T cells? Why do antigen-specific T cells expand more than other (bystander) T cells on exposure to an antigen? a. The major growth factor for T cells is interleukin-2 (IL-2). It is produced by T cells in response to antigen receptor signals and costimulation. T cells that have recognized antigens express increased levels of receptors for IL-2 and thus preferentially respond to the growth factor during immune responses to the antigens.

What are the mechanisms by which CD4+ effector T cells activate other leukocytes? a. CD4+ helper T cells activate other cells (B lymphocytes, macrophages) by the surface molecule CD40-ligand engaging CD40 on the other cells and by the actions of secreted cytokines.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

7. What are the major properties of memory T lymphocytes?

a. Memory cells survive after the antigen is cleared and respond more rapidly and effectively to antigen exposure than do naive cells.

8. Why do naive T cells migrate preferentially to lymphoid organs and differentiated effector T cells (which have been activated by antigen) migrate preferentially to tissues that are sites of infection? a. Naive T cells express the adhesion molecule L-selectin and the chemokine receptor CCR7, which mediate homing to lymph nodes. Differentiated effector cells lose expression of these molecules and instead express adhesion molecules that bind to molecules on endothelium exposed to inflammatory cytokines. The effector cells also express receptors for chemokines produced at sites of inflammation, thus preferentially migrating to these sites.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 6: Effector Mechanisms of T Cell–Mediated Immunity: Functions of T Cells in Host Defense 1. What are the types of T lymphocyte-mediated immune reactions that eliminate microbes

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that are sequestered in the vesicles of phagocytes and microbes that live in the cytoplasm of infected host cells? a. Intracellular microbes that reside in phagosomes are eliminated by helper T cells, especially those of the Th1 subset that activate phagocytes to destroy ingested microbes. Microbes that reside in the cytosol may be eliminated by CD8+ T cellmediated killing of the infected cells, thus eliminating the reservoir of infection.

What are the major subsets of CD4+ effector T cells, how do they differ, and what are their roles in defense against different types of infectious pathogens? a. Th1 cells secrete the cytokine IFN-g, which activates macrophages to kill phagocytosed microbes. Th2 cells secrete IL-4 and IL-13, which stimulate intestinal mucus production and gut peristalsis, and IL-5, which activates eosinophils. IL-4 and IL-13 secreted by Tfh cells induces B cell IgE production, and IgE bound to eosinophils and mast cells contributes to immunity against helminths. Th2 cells are involved in defense against helminths. Th17 cells secrete IL-17, which recruits neutrophils and are involved in defense against extracellular fungi and bacteria.

What are the mechanisms by which T cells activate macrophages, and what are the responses of macrophages that result in the killing of ingested microbes? a. Activated Th1 cells secrete cytokines such as interferon-g that activate macrophages. These helper T cells also express CD40 ligand, which can activate macrophages by engaging CD40. Activated macrophages then induce NADPH oxidase activity to generate reactive oxygen species and nitric oxide synthase to make nitric oxide. These free radicals can destroy ingested microbes. Activated macrophages also produce increased amounts of lysosomal enzymes, which help to destroy microbes, and other molecules that promote inflammation and call more leukocytes into the reaction.

How do CD8+ CTLs kill cells infected with viruses? a. CD8+ T cells that recognize antigen on an infected tissue cell release granule that have perforin and granzymes, which enter the infected cells recognized by the T lymphocytes and induce apoptosis of these infected cells.

What are some of the mechanisms by which intracellular microbes resist the effector mechanisms of cell-mediated immunity? a. Some intracellular microbes evade immunity by preventing phagolysosomal fusion. Other intracellular microbes express molecules that can inactivate host complement responses. Many viruses inhibit antigen presentation, and some may inactivate effector T cells.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 7: Humoral Immune Responses: Activation of B Lymphocytes And Production Of Antibodies 1. A 4-year-old-girl sees her physician because of a severe necrotizing, oropharyngeal herpes simplex viral (HSV) infection. She has a past medical history of cytomegalovirus (CMV) pneumonitis and cutaneous HSV infection. Phenotypic analysis of her blood cell shows an absence of CD56+ and CD16+ cells. There are normal numbers of CD4+ and CD8+ cells in the blood, and serum antibody titers are normal. The patient’s CD8+ T cells were able to kill virally infected target cells in vitro. Which of the following is NOT characteristic of this girl’s immunodeficiency disease? a. Lack of cells whose activation is normally inhibited by self class I major histocompatibility complex (MHC) b. Impaired granzyme B–dependent killing of virally infected target cells c. Lack of cells that are activated by IL-15 d. Impaired interferon (IFN)-γ production during early phases of viral infection e. Failure to form viral peptide-class I MHC complexes 2. Which of the following is an example of how the innate immune response stimulates or modifies adaptive immunity? a. Tumor necrosis factor (TNF) secreted by helper T cells enhances adhesion molecules on endothelial cells and promotes recruitment of inflammatory cells. b. Interferon (IFN)-γ produced by T helper cells is a potent activator of macrophages, allowing killing of phagocytosed microbes. c. B7-1 expression on antigen-presenting cells is up-regulated in response to signaling through Toll-like receptors, thus enabling costimulation of T cells. d. Infected cells coated by IgG3 are recognized by Fc receptors on natural killer cells, allowing efficient killing of the infected cells. e. Double-stranded RNA of replicating viruses potently stimulates IFN-β expression by fibroblasts, inducing an “antiviral state” in neighboring, uninfected cells.

3. 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 4. 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

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

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cells are produced in normal numbers, and 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 clear his infection. Which one of the following is a reasonable explanation for why this therapeutic approach would fail? a. Viral infections are cleared by antibodies, not 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.

Many vaccines now in development will include highly purified, recombinant, or synthetic peptide antigens. These vaccine antigens are expected to stimulate highly specific immune responses, but they are less immunogenic than vaccines containing intact killed or live microbes. Adjuvants are substances added to such vaccines to enhance their ability to elicit T cell immune responses. Which of the following statements about adjuvants is NOT correct? a. Adjuvants induce local inflammation, thereby increasing the number of antigen- presenting cells (APCs) at the site of immunization. b. Adjuvants stimulate the expression of costimulators on local APCs. c. Adjuvants enhance local production of cytokines that promote T cell activation. d. Adjuvants prolong the expression of peptide-MHC complexes on the surface of APCs. e. Adjuvants bind to T cell antigen receptors and promote their proliferation.

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 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 Which type of antigen-presenting cell is most important for activating naive T cells? a. Macrophage b. Dendritic cell c. Endothelial cell d. B lymphocyte e. Epithelial cell Which of the following statements about the antigen-presenting function of macrophages is NOT correct? a. Macrophages are particularly important at presenting peptides derived from particulate or opsonized antigens that are internalized by phagocytosis. b. Macrophages become activated by the helper T cells to which they present microbial peptides, and as a result of this activation they become efficient at killing the microbes.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

c. Resting macrophages express low levels of class II MHC molecules, but higher class II MHC expression is induced on activation by the T cells to which they present antigen. d. Macrophages express highly variable, high-affinity receptors for many different antigens, and these receptors facilitate the internalization of the antigens for processing and presentation. e. Macrophages present antigen to T cells in lymphoid organs and many nonlymphoid organs.

9. Which one of the following statements about dendritic cells is true? a. Immature dendritic cells are ubiquitously present in skin and mucosal tissues. b. Dendritic cell maturation occurs after migration to lymph nodes in response to signals derived from activated T cells c. Class II MHC and T cell costimulators are highly expressed on immature dendritic cells and are down-regulated during maturation. d. Dendritic cells that enter lymph nodes through draining lymphatics migrate to the B cell–rich follicles in response to chemokines.

10. Maturing dendritic cells that migrate to a lymph node from peripheral tissues end up mainly in: a. Follicles b. High endothelial venules c. The medullary sinus d. T cell zones e. Efferent arterioles 11. A young adult is exposed to a virus that infects and replicates in mucosal epithelial cells of the upper respiratory tract. One component of the protective immune response to this viral infection is mediated by CD8+ cytolytic T lymphocytes (CTLs), which recognize and kill virus-infected cells. The CTLs can recognize and kill the infected cells because: a. In response to interferon-ã secreted during the innate immune response to the virus, the mucosal epithelial cells express class II MHC, with bound viral peptides, on their cell surfaces. b. Mucosal epithelial cells, like all nucleated cells, express class I MHC molecules and are able to process cytoplasmic viral proteins and display complexes of class I MHC and bound viral peptides on their cell surfaces. c. Antibodies specific for viral antigens bind to these antigens on infected cell surfaces and engage Ig Fc receptors on the CTL, thereby targeting the CTL to the infected cells. d. Virus-infected mucosal epithelial cells migrate to draining lymphoid tissues, where they present viral peptide antigens to naive CD8+ T cells. e. Viral infection of the mucosal epithelial cells stimulates them to express Eselectin, which promotes CD8+ T cell adhesion.

12. Naive CD8+ T cells require signals in addition to T cell receptor recognition of peptide- MHC to become activated and differentiate into cytolytic T cells. These signals are called costimulatory signals and are provided by professional antigenpresenting cells (APCs), such as dendritic cells. If a virus infects epithelial cells in

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

the respiratory tract but does not infect professional APCs, what process ensures that naive T cells specific for viral antigens will become activated? a. Cross-reactivity, whereby the naive CD8+ T cell recognizes a self antigen that is structurally similar to a viral antigen presented by dendritic cells b. Crossover, whereby part of the viral genome is exchanged with part of one chromosome of the host c. Crosstalk, whereby signals generated by the virus binding to class I MHC molecules intersect with T cell receptor signaling pathways d. Cross-presentation, whereby infected epithelial cells are captured by dendritic cells, and the viral proteins originally synthesized in the epithelial cells are processed and presented in association with class I MHC molecules on the dendritic cell e. Cross-dressing, whereby viral infection of the epithelial cell stimulates the expression of surface molecules that are typically found only on dendritic cells 13. Which of the following is the main criterion that determines whether a protein is processed and presented via the class I MHC pathway in an antigen-presenting cell (APC)? a. Encoded by a viral gene b. Present in an acidic vesicular compartment of the APC c. Present in the cytosol of the APC d. Internalized into the cell from the extracellular space e. Small in size 14. Which one of the following molecules does NOT play an important role in the class II MHC pathway of antigen presentation? a. B2-Microglobulin b. Cathepsin c. Invariant chain d. HLA-DM e. Calnexin 15. In the class I MHC pathway of antigen presentation, peptides generated in the cytosol are translocated into the endoplasmic reticulum in which of the following ways? a. By ATP-dependent transport via the transporter associated with antigenprocessing (TAP) 1/2 pump b. By passive diffusion c. By receptor-mediated endocytosis d. Through membrane pores e. Via the proteasome 16. In the class I MHC pathway of antigen presentation, cytoplasmic proteins are tagged for proteolytic degradation by covalent linkage with which of the following molecules? a. Calreticulin b. Nuclear factor (NF)-êB c. Tapasin d. Ubiquitin

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

e. Calnexin 17. Which one of the following statements about T cell tolerance to self proteins is accurate? a. Self proteins are not presented by the class I pathway because only microbial proteins, and not self proteins, are ubiquinated in the cytosol. b. Peptides derived from self proteins are not presented by the class I or class II pathways because MHC molecules are expressed only in response to infections. c. Self proteins are not presented by the class II pathway because endosomal acidic proteases digest microbial proteins but not eukaryotic proteins. d. Self peptide/self MHC complexes are formed and displayed by antigenpresenting cells in both class I and class II MHC pathways, but T cells that recognize these complexes usually are not present or are functionally inactive. e. Peptides derived from self proteins are not displayed by MHC molecules because they usually are displaced by the more abundant microbial peptides.

18. In a clinical trial of a new antiviral vaccine composed of a recombinant viral peptide and adjuvant, 4% of the healthy recipients did not show evidence of response to the immunization. Further investigation revealed that all the nonresponders expressed the same, single allelic variant of HLA-DR but all the responders were heterozygous for HLA-DR alleles. Which of the following is the most likely explanation for this finding? a. Response to the vaccine requires T cell recognition of complexes of the viral peptide with HLA-DR, but the peptide cannot bind to the allelic variant of HLA-DR found in the nonresponders. b. The nonresponders could not express class II MHC proteins. c. The viral peptide is not an immunodominant epitope. d. The nonresponders underwent determinant selection of another viral epitope. e. Because of technical errors, the nonresponders had not received adequate doses of the vaccine.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter. 8: Effector mechanisms of humoral immunity: Elimination of extracellular microbes and toxins 1. Most T lymphocytes have a dual specificity for which one of the following pairs of molecules? a. A particular allelic form of a major histocompatibility complex (MHC) molecule and a peptide bound to the MHC molecule b. Both MHC class I and class II molecules c. Both peptide and glycolipid antigens d. Both soluble peptides and peptide-MHC complexes e. MHC molecules and CD4 or CD8 2. The T cell receptor (TCR) complex contains: a. A highly variable antigen coreceptor b. CD28 c. Three homologous CD3 chains, each covalently linked to the TCR áâ heterodimer d. Invariable æ chains noncovalently linked to the TCR áâ heterodimer Igâ 3. A 4-year-old boy suffers from an immunodeficiency disease characterized by impaired T cell activation. The disease is caused by genetic deficiency of a membrane protein whose cytoplasmic tail is involved in intracellular signaling in response to T cell receptor (TCR) recognition of antigen. Which one of the following proteins does NOT fit this description? a. TCRa b. CD3g c. Æ d. CD4 e. CD3e 4. A healthy 45-year-old child-care worker becomes infected with a virus and develops a sore throat, cough, and fever. Infected cells in the bronchial mucosa of this patient process virus-encoded proteins through an intracellular pathway and display peptides derived from the protein on the cell surface bound to class I MHC molecules. CD8+ T cells migrate to the mucosa and recognize these peptide-MHC complexes. Which of the following components of the TCR actually bind to the viral peptide-MHC complex? a. Hypermutated regions: 1 in the á chain, 2 in the â chain b. Complementarity-determining regions: 3 in the á chain, 3 in the â chain c. Hypervariable regions: 2 in the á chain, 2 in the â chain d. Congenic regions: 1 in the á chain, 1 in the â chain e. One peptide-binding groove formed by the á chain and the â2-microglobulin chain 5. The T cell receptor (TCR) complex differs from an immunoglobulin molecule in which one of the following ways? a. On average, a TCR binds antigen with much lower affinity than does an Ig molecule. b. The TCR can serve as a lymphocyte antigen receptor, but an Ig molecule cannot. c. Only the TCR can bind soluble antigen directly. d. The TCRs expressed by one clone of T cells can undergo changes in constant region structure after cellular activation, whereas Ig molecules expressed by one clone of B cells do not.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

e. The TCR polypeptide chains have short cytoplasmic tails and rely on associated proteins for signaling functions, whereas membrane Ig receptors are competent signaling molecules on their own.

6. CD1-restricted T cells differ from other T cells restricted to class I or class II MHC molecules in which one of the following ways? a. CD-1 restricted T cells cannot rapidly secrete cytokines. b. CD-1 restricted T cells recognize non-peptide antigens, such as lipids. c. CD-1 restricted T cells bind both cell-associated and soluble antigens. d. CD-1 restricted T cells express both CD4 and CD8 coreceptors. e. CD-1 restricted T cells are actually natural killer (NK) cells.

7. ãä T cells may be important for recognition of common antigens at epithelial boundaries between the host and the external environment. The ãä T cells differ from the áâ T cells in which one of the following ways? a. ãä T cells recognize only nonprotein antigens. b. ãä T cells are not MHC-restricted and do not recognize MHC-associated antigens. c. The ãä TCR complex contains CD3ã or CD3ä but not CD3å. d. Most mature ãä T cells express either CD4 or CD8 but not both. e. ãä T cells lack key biologic activities, including the ability to lyse target cells.

8. CD8 is a protein that functions as a coreceptor for a subset of T cells and plays a significant role in all of the following EXCEPT: a. Recognition of peptide antigen bound to class I MHC molecules b. Maturation of MHC class I–restricted T cells c. Infection of T cells by human immunodeficiency virus (HIV) d. Signaling via Lck tyrosine kinase to initiate T cell activation e. Strengthening the binding of T cells to antigen-presenting cells, albeit with low affinity 9. After 2 years of hard work, a graduate student finally succeeds in creating a gene knockout mouse lacking CD4. The student is particularly careful to keep this mouse line in a microbe-free animal facility because these mice are expected to show: a. No ability to produce IgM antibodies b. Impaired ability to produce antibodies and activate macrophages c. No ability to activate naive class I–restricted T cells d. Complete absence of cytotoxic T lymphocyte (CTL) responses to viral infections e. Failure to produce neutrophils 10. which of the following not a property shared. By cd4 y cd8 a. Binds to nonpolymorphic regions of MHC molecules b. Cytoplasmic tail associates with the Src family kinase Lck c. Is a member of the Ig superfamily d. Functions as a coreceptor for áâ TCRs e. Is expressed on the majority of mature blood T cells 11. A 15-year-old girl develops malaise, headache, and low-grade fever, followed by pharyngitis and cervical lymph node enlargement as a result of infectious mononucleosis caused by Epstein-Barr virus (EBV). Her acute symptoms resolve within 2 weeks, and the fatigue improves within 3 months. All of the following are required for CD8+ cytotoxic T lymphocyte (CTL) recognition and killing of EBVinfected cells EXCEPT: a. â2-Microglobulin

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

b. HLA-A, -B or -C c. CD28 d. LFA-1 (leukocyte function-associated antigen-1) 12. A 15-year-old girl develops malaise, headache, and low-grade fever, followed by pharyngitis and cervical lymph node enlargement as a result of infectious mononucleosis caused by Epstein-Barr virus (EBV). Her acute symptoms resolve within 2 weeks, and the fatigue improves within 3 months. Following the primary infection described in this patient, the patient’s subsequent exposure to Epstein-Barr virus (EBV) will trigger clonal expansion of EBV-specific T cells expressing which one of the following surface molecules? a. CD62Lhigh b. CD44low c. CD45RAhigh d. CD45ROhigh e. CD21high 13. Both CD28 and CTLA-4 are receptors on T cells that are critical for regulating T cell activation. In which one of the following ways does CD28 differ from CTLA4? a. Only CD28 binds the costimulatory ligands B7-1 and B7-2 expressed on professional antigen-presenting cells. b. CD28 counteracts positive, pro-proliferative T cell signals delivered by CTLA-4. c. CD28 is constitutively expressed on naive T cells, whereas CTLA-4 is expressed on activated T cells. d. CD28 binds its ligand with 10-fold greater affinity than does CTLA-4. e. CD28 is important for delivering “signal 1” for T cell activation, whereas CTLA- 4 is important for delivering “signal 2.”

14. LFA-1 is an integrin that promotes T cell activation by which one of the following mechanisms? a. Binds to the á3 domain of class I MHC molecules, mediating high avidity between T cells and antigen-presenting cells (APCs) b. Binds to B7-1 or B7-2 on the surface of APCs, mediating “signal 2” c. Binds to GlyCAM-1 on high endothelial venules of lymph nodes, mediating rolling of T cells on endothelium d. Binds to ICAM-1 on the surface of a variety of cells, mediating firm adhesion between T cells and APCs or endothelial cells e. Binds to VCAM-1 on the surface of cytokine-activated endothelial cells, mediating homing of T cells to peripheral sites of inflammation 15. Selectins differ from integrins in which one of the following ways? a. Selectins are expressed only on endothelial cells and integrins are expressed only on leukocytes. b. Selectins are important mediators of leukocyte adhesion to endothelium, but integrins are not. c. Selectins bind carbohydrate ligands, but integrins do not. d. Selectins mediate rolling of leukocytes on endothelium, but integrins do not. e. Selectins are a family of homologous molecules, but integrins are not.

16. A 2-year-old boy suffers from recurrent bacterial infection of his ears, sinuses, lungs, and skin; laboratory studies indicate absence of sialylated Lewis X on his leukocytes. He is diagnosed with leukocyte adhesion deficiency type 2 (LAD-2).

Which type of adhesive interaction required for leukocyte migration is defective in

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

this boy? a. E-selectin ligand binding to E-selectin b. CD4 binding to class II MHC c. VLA-4 binding to VCAM-1 d. Ig Fc receptor binding to Ig-coated cells e. LFA-1 binding to ICAM-1 17. CD44 expressed on the surface of T cells is critical for the binding of activated T cells to endothelium at sites of inflammation, and for the retention of T cells in extravascular tissues at sites of infection. CD44 does this by binding to which one of the following molecules? a. VCAM-1 b. Hyaluronate c. ICAM-1 d. Fibronectin e. E-selectin 18. Neonates, elderly persons, and otherwise immunocompromised patients are particularly susceptible to infections with Listeria monocytogenes. These patients typically have fever and chills, often progressing to hypotension and septic shock.

In healthy individuals, however, such intracellular microbes are usually effectively phagocytosed and killed by macrophages, which become activated via: a. CD40L-CD40 interactions between activated T helper cells and macrophages b. CD28-B7 interactions between activated T cells and macrophages c. Fas ligand–Fas interactions between activated cytotoxic T lymphocytes and macrophages d. TCR-MHC class II interactions between activated T helper cells and macrophages e. LFA-1–ICAM-1 interactions between activated T cells and macrophages 19. The strength of integrin-dependent binding of T cells to antigen-presenting cells (APCs) may be rapidly increased by which one of the following mechanisms? a. Integrin clustering and increased integrin affinity are induced by chemokines and antigen recognition. b. Integrins stored in cytoplasmic organelles are mobilized to the T cell surface in response to TCR-mediated signals. c. Integrin gene transcription is enhanced by chemokine-generated signals. d. The affinity of integrin ligands on APCs is increased in response to chemokines. e. Integrin ligands stored in cytoplasmic granules in the APCs are mobilized to the cell surface in response to CD40-CD40 ligand interaction.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

CHAPTER 9: Immunological Tolerance and Autoimmunity: Self–Nonself Discrimination in the Immune System and Its Failure 1. All of the following protein-protein interactions are involved in activation of naive helper T cells by antigen-presenting cells (APCs) EXCEPT: a. Binding of peptide-MHC complexes on the APC to the TCR on the T cell b. Binding of CD4 on the T cell to nonpolymorphic regions of class II MHC molecules on the APC c. Binding of integrins on the T cell with adhesion ligands on the APC d. Binding of B7-2 on the APC with CD28 on the T cell e. Binding of CD40L on the T cell with CD40 on the APC 2. Which one of the following statements about MHC-TCR interactions is NOT true? a. Antigen receptors on T cells bind to MHC molecules for only brief periods of time. b. The affinity of most TCRs for peptide-MHC complexes is similar to the affinity of antibodies for their antigens. c. Only 1% or less of the MHC molecules on any antigen-presenting cell (APC) display a peptide recognized by a particular T cell. d. T cells usually require multiple engagements with an APC before a threshold of activation is reached. e. A subthreshold number of MHC-TCR interactions can lead to T cell inactivation.

3. Which one of the following cell types would be most potent at activating naive T cells? a. Kupffer cell b. B cells c. Follicular dendritic cells d. Neutrophils e. Langerhanscells 4. Which one of the following descriptions of cytokine interleukin-2 is NOT true? a. Expression of its gene requires multiple transcription factors, such as Fos, Jun, and NFAT. b. It acts as an autocrine growth factor for T cells. c. It binds to CD25 on the cell membrane of T cells. d. It is only involved in the proliferation of helper T cells and not CTLs. e. It promotes susceptibility of T cells to apoptosis.

5. Which one of the following statements about T cells involved in an immune response is NOT true? a. Activated T cells receive survival signals from antigen during an infection. b. Activated T cells contribute to the activation of antigen-presenting cells via CD40 ligand. c. Memory T cells generated during a primary immune response express high levels of interleukin-2 receptors and actively proliferate long after the primary response is completed. d. The major effector function of helper T cells is to activate macrophages and other cells by releasing cytokines. e. When an infection is eliminated, activated T cells die by apoptosis.

6. Which one of the following statements about the molecules B7-1 and B7-2 is NOT true? a. B7-1 and B7-2 expression on antigen-presenting cells (APCs) is upregulated

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

by the presence of “danger” signals, such as lipopolysaccharide, as well as cytokines, such as interferon (IFN)-ã b. B7-1 and B7-2 are expressed at low levels on some resting APCs. c. Induction of B7-1 usually occurs before the induction of B7-2 in an immune response. d. B7-1 and B7-2 bind to CD28 on T cells and provide “second signals” for naive T cell activation. e. Activated helper T cells can induce expression of B7-1 and B7-2 on APCs via CD40L binding to CD40.

7. In patients with hyper IgM syndrome, there is a genetically based deficiency in expression of CD40 ligand. In addition to defects in antibody isotype switching, these patients have defects in T cell–mediated immune responses and become infected with intracellular parasites. Which one of the following normal functions of CD40 ligand is important in T cell–mediated immunity? a. CD40-dependent isotype switching is required to produce antibody isotypes that activate T cells. b. CD40 ligand is required for CTL killing of CD40-expressing infected cells. c. CD40 ligand is required for maturation of CD4+ T cells in the thymus. d. CD40 ligand on activated T cells binds to CD40 on antigen-presenting cells (APCs), and this enhances the expression of B7-1, B7-2, and cytokines by the APCs. e. CD40 ligand on T cells binds to B7-1 and B7-2 on APCs, and this enhances the function of the APCs. 8. All of the following molecules act as transcription factors in T cell activation signaling EXCEPT: a. NF-êB b. Jun c. Fos d. NFAT e. Ras 9. Which one of the following statements about the molecule Lck is NOT true? a. It is a member of the Src family of kinases. b. It binds to the cytoplasmic tails of T cell coreceptors CD4 or CD8. 3. c. It phosphorylates ITAM motifs on the CD3 complex. d. It phosphorylates tyrosine residues on Zap-70 and activates it. e. It phosphorylates PIP2 to PIP3 and leads to the activation of Itk. 10. A 7-month-old boy, the only child of second-degree cousins, saw a pediatrician for immunologic evaluation after developing Pneumocystis carinii pneumonia. Serum IgG, IgM, and IgA levels were normal. Blood cell count showed 10,600 leukocytes/mm3 and 80% lymphocytes; 90% of the lymphocytes were TCR áâ+ CD4+. In vitro lymphocyte- proliferative responses to PHA and anti-CD3 were absent, and the pattern of tyrosine- phosphorylated cytoplasmic proteins after antiCD3 treatment of the T cells was distinctly abnormal. This boy most likely carries homozygous mutations in the gene encoding which one of the following proteins? a. Zap-70 b. RAG-1 c. CD3 d. Pre-Tá e. TCRá 11. Which one of the following signaling molecules, if mutated, would affect B cell

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

maturation and function primarily without affecting T cell function? a. Btk b. Itk c. Tec d. PI-3 kinase e. Zap-70 12. All of the following are early T cell events that occur after antigen recognition by the TCR EXCEPT: a. Formation of the immunologic synapse b. Recruitment of signaling molecules, such as LAT, to glycolipid-enriched domains known as lipid rafts c. Enhanced adhesion between T cells and antigen-presenting cells (APCs) via T cell integrin LFA-1 and its ligand on the APC, ICAM-1, at the central zone of the immunologic synapse d. Clustering of the TCR and coreceptors leading to phosphorylation of ITAMs on CD3 by Lck e. Binding of CD28 with costimulators on APCs in the cSMAC, resulting in signal transduction activation 13. An experiment is performed in which a point mutation is introduced randomly into the Zap-70 gene for a particular strain of mice. The mutant mice display a defect in T cell development. However, precursor T cells isolated from the thymus of these mice show normal expression levels of Zap-70 of the correct molecular weight. On further in vitro analysis, the mutant Zap-70 is found to bind to ITAM motifs in the cytoplasmic tail of the æ chain, but only when the æ chain is phosphorylated. No phosphorylated LAT is detected, however. Given these data, in which of the following protein domains is the mutation most likely to be present? a. Pleckstrin homology (PH) domain b. Proline-rich (PR) domain c. SH1 domain d. SH2 domain e. SH3 domain 14. Which one of the following accurately depicts the correct order of events in a TCR signal transduction pathway? a. TCR→ Lck→ Zap-70→ LAT→ Grb-2→ SOS→ Ras→ Erk→ Fos b. TCR→ Lck→ Zap- 70→ LAT→ SOS→ Grb-2→ Ras→ Erk→ Fos c. TCR→ Lck→ ITK→ LAT→ Grb-2→ SOS→ Ras→ Erk→ Fos d. TCR→ Lck→ Zap-70→ LAT→ SOS→ Grb-2→ Ras→ Erk→ Jun e. TCR→Lck→Zap-70→LAT→PLCã→DAG→calciumrelease 15. Damage to neurons in patients with multiple sclerosis (MS) may be caused by autoreactive T cells that recognize peptides derived from myelin proteins presented by self MHC molecules. These autoreactive T cells secrete interferon (IFN)-ã and promote inflammation, which damages the myelin sheath surrounding neurons. The exact immunodominant epitopes recognized by autoreactive T cells in MS patents have been identified. One potential method of therapy for patients with MS is to administer therapeutic peptides that differ from the immunodominant epitopes by one or two amino acids. Which one of the following statements best describes the basis for this therapeutic approach? a. The therapeutic peptides, called “altered peptide ligands,” could inactivate T cells specific for myelin proteins, or drive them to differentiate into T cells that do not produce IFN-ã.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

b. The therapeutic peptides, called “altered peptide ligands,” could interfere with processing of the natural myelin proteins by the patient’s antigenpresenting cells. c. The therapeutic peptides could bind to the TCRs of myelin-specific T cells but not to the self MHC molecules, thereby blocking T cell activation. d. The therapeutic peptides could down-regulate MHC expression. e. The therapeutic peptides could replace the damaged myelin and restore neuronal function.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 10: Immune Responses Against Tumors and Transplants: Immunity to Noninfectious Transformed and Foreign Cells 1. Which of the following statements about cell-mediated immunity (CMI) is NOT true? a. Deficiencies in CMI result in susceptibility to infections by viruses and intracellular bacteria. b. CMI can be adoptively transferred by injecting serum from one individual to another. c. Delayed-type hypersensitivity (DTH) is not a protective response against intracellular bacteria such as Mycobacterium tuberculosis. d. The principal form of CMI that protects against viral infections is mediated

by CD8+ cytolytic T lymphocytes. e. Phagocytes are essential in the effector phase of CMI responses to bacteria such as Listeria monocytogenes.

2. The induction phase of a cell-mediated immune response includes which of the following events? a. CD4+ T cell secretion of interferon-ã leading to macrophage activation b. CD8+ T cell lysis of a virally infected cell c. Clonal expansion of CD8+ T cells within a lymph node d. Migration of CD4+ effector T cells from blood vessels into a tissue site of infection e. Migration of a naive CD4+ T cell from the thymic medulla into the circulation 3. Which of the following comparisons between TH1 and TH2 cells is true? a. TH1 cells produce interleukin (IL)-1 but not IL-2, and TH2 cells produce IL-2 but not IL-1. b. TH1 cells are class I major histocompatibility complex (MHC) restricted, and TH2 cells are class II MHC restricted. c. The chemokine receptors CXCR3 and CCR5 are more highly expressed on TH2 cells than on TH1 cells. d. TH2 cells are more likely to bind to E-selectin and P-selectin on endothelial cells than are TH1 cells. e. TH1 cells produce interferon (IFN)-ã but not IL-4, and TH2 cells produce IL-4 but not IFN-ã.

4. Differentiation of TH2 cells from naive precursor cells is dependent on which of the following? a. Toll-like receptor (TLR) ligands b. T-bet c. Interleukin-12 d. GATA-3 e. Interferon-á 5. The mechanisms by which TH1 cells protect against microbes include all of the following EXCEPT: a. Secretion of interferon (IFN)-ã, which activates microbicidal functions of macrophages b. Expression of CD40 ligand, which binds to CD40 on macrophages and

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

activates them c. Secretion of IFN-ã, which promotes B cell production of opsonizing antibodies d. Secretion of lymphotoxin and tumor necrosis factor, which enhance neutrophil killing of ingested microbes e. Release of granzyme B, which stimulates apoptosis of bacteria 6. Activated macrophages perform all of the following functions EXCEPT: a. Inhibition of fibroblast proliferation and angiogenesis within damaged tissues b. Production of lysosomal enzymes and reactive oxygen species that kill phagocytosed microbes c. Presentation of antigen to helper T cells d. Secretion of inflammatory cytokines such as tumor necrosis factor and interleukin-1 e. Production of nitric oxide, which helps kill microorganisms 7. Which of the following molecules is NOT important in the interaction between a cytolytic T lymphocyte and a target cell? a. B7-1 b. ICAM-1 c. LFA-1 d. T cell receptor e. Class I MHC 8. Which pair of molecules is a component of cytolytic T lymphocyte (CTL) granules and is important in the mechanism of CTL killing of target cells? a. Perforin and Fas ligand b. P-selectin and tumor necrosis factor c. Major basic protein and granzyme B d. C9 and interferon-ã e. Perforin and granzyme B 9. Which of the following mechanisms does NOT contribute to the generation of a cytolytic T lymphocyte (CTL) response to a viral infection? a. Dendritic cells phagocytose infected cells or viral particles and present them to naive CD8+ T cells via the class I MHC pathway. b. Dendritic cells are infected with the virus and present viral peptides to naive CD8+ T cells via the class I MHC pathway. c. CTLs are directly activated by CD40L expressed on activated helper T cells through CD40. d. Helper T cells secrete cytokines, such as interleukin-2, that promote the proliferation and differentiation of CD8+ T cells. e. Helper T cells activate infected antigen-presenting cells (APCs) via the CD40 ligand-CD40 pathway, and the activated APCs present viral peptides to naive CD8+ T cells via the class I MHC pathway.

10. A 23-year-old man who was recently infected by the HIV virus volunteered for investigative studies of his immune response to the virus. Investigators identified cytolytic T lymphocytes (CTLs) in the patient’s blood that recognized a particular peptide derived from a protein encoded by the HIV gag gene. Six months later, viral isolates from the patient showed point mutations in the gag gene sequence encoding that peptide. Which of the following statements about the HIV gag mutations is most likely to be correct? a. The patient’s CTL response to the virus provided selective pressure for the

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

emergence of virus carrying the mutation. b. The CTL that recognized the original gag-encoded peptide will still be able to recognize the mutated Gag peptide. c. The CTLs specific for the original Gag peptide were incapable of killing HIV- infected cells. d. The gag mutation will enhance the ability of natural killer cells to recognize and kill HIV infected cells. e. The gag mutations have more relevance to the viral evasion of the antibody response rather than the CTL response.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 11: Hypersensitivity: Disorders Caused by Immune Responses 1. Which one of the following statements about primary and secondary antibody responses is NOT true? a. Antibodies in primary responses generally have lower affinity for antigen than those produced in secondary responses. b. Secondary responses reach peak levels more quickly than primary responses. c. Primary responses require higher concentrations of antigen for initiation than secondary responses. d. Primary responses occur to all types of antigens, but secondary responses mostly occur only to protein antigens. e. Primary responses are characterized by IgG antibodies, whereas secondary responses are dominated by IgM antibodies.

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

3. All of the following assays are used to detect antibody production EXCEPT: a. BrdU (bromodeoxyuridine) assay b. Enzyme-linked immunosorbent assay (ELISA c. ELISPOT assay d. Hemolytic plaque assay e. Radioimmunoassay (RIA) 4. A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. Which of the following abnormalities would NOT be likely in this patient? a. The IgG antibodies that are present are of lower affinity for antigen than of those of a healthy individual. b. Lymph nodes are without well-developed follicles containing germinal centers. c. Macrophage killing of intracellular microbes is impaired. d. There is limited diversity in the repertoire of IgM antibodies produced. e. There is no evidence of somatic mutation of IgM variable regions.

5. A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. Which of the following genes most likely contains a mutation in this patient? a. AID (activation-induced deaminase)

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

6.

7.

8.

9.

b. CD40 c. CD40L d. CD28 e. CTLA-4 A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. If this patient did have a sister affected with the same condition, which of the following genes would most likely contain a mutation? a. AID (activation-induced deaminase) b. CD40 c. CD40L d. CD28 e. CTLA-4 The B cell receptor (BCR) complex and the signaling cascades to which it is linked share many similarities with the T cell receptor (TCR) complex and its linked signaling cascades. Which of the following comparisons between BCR and TCR signaling is NOT true? a. There are ITAMs in the cytoplasmic tails of CD3 in the TCR complex and in the cytoplasmic tails of Ig and Ig in the BCR complex. b. The cytoplasmic tails of membrane Ig and TCR antigen receptors are very short and lack intrinsic signaling functionality. c. Early signaling events induced by antigen binding to both BCR and TCR involve both Src family and Zap-70 family protein tyrosine kinases. d. Phospholipase C–mediated generation of IP3 and DAG occurs downstream of both BCR and TCR signaling. e. CD4/CD8 coreceptors in T cells and the CR2 coreceptor in B cells both enhance responses to antigen by a PI3 kinase–dependent mechanism.

The initial cellular events that are induced by antigen-mediated cross-linking of the B cell receptor (BCR) complex include all of the following EXCEPT: a. Increased percentage of time spent in mitosis, resulting in rapid proliferation b. Increased expression of B7, resulting in enhanced APC function c. Increased expression of bcl-2, resulting in improved survival d. Increased expression of CCR7, promoting migration into lymph node follicles e. Increased expression of the interleukin-2 receptor, resulting in enhanced proliferation and response to T cell signals Which one of the following statements accurately describes antigen recognition events in a lymph node during a helper T cell–dependent antibody response to a protein antigen? a. Naive B cells and naive T cells simultaneously recognize the intact protein antigen. b. Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with major histocompatibility complex (MHC) molecules to naive helper T cells. c. Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with MHC molecules to differentiated helper T cells. d. Naive T cells recognize peptides bound to MHC molecules presented by

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

dendritic cells, and naive B cells recognize the intact protein antigen bound to the surface of follicular dendritic cells.

10. Which one of the following B cell responses is NOT stimulated by CD40 ligand? a. Association of TRAFs with the cytoplasmic tails of CD40 molecules b. Activation of NF- B c. Enhanced expression of B7-1 and B7-2 d. Enhanced Ig isotype switch recombinase activity e. Enhanced production of membrane Ig f. Which of the following mechanisms contributes to the change from B cell production of membrane Ig to secreted Ig? V(D)J recombinase-mediated deletion of the exon encoding the transmembrane domain g. Alternative processing of primary RNA transcripts to remove the transmembrane domain and include a secretory tail piece h. Increased vesicular exocytosis of intracellular stores of the secretory form of Ig i. Switch recombinase-mediated recombination of the heavy chain locus to juxtapose the V(D)J segment with the exon encoding a secretory tail piece j. Up-regulation of ectoenzymes that proteolytically cleave membrane Ig heavy chains just proximal to the membrane 11. Which of the following statements about Ig isotype switching is NOT true? a. Interleukin-4 promotes switching to the IgE isotype by increasing germline transcription of the C exon. b. Isotype switching involves recombination of a V(D)J complex with downstream C region genes and the deletion of intervening DNA including other C region genes. c. Activation-induced deaminase (AID) is required for switch recombination. d. The enzymes that mediate isotype switching recognize conserved heptamer and nonamer DNA sequences adjacent to the constant region exons. e. The same recombined V(D)J gene complex is used to encode the antigenbinding region of the antibodies produced by a B cell before and after isotype switching.

12. Which one of the following molecules is important for the production of IgE antibodies? a. CD28 b. CD40 c. IFNd. IL-2 e. TGF13. Which of the following events does NOT occur within germinal centers? a. Somatic mutation of Ig V genes b. Generation of memory B cells c. B cell proliferation d. Affinity maturation e. Ig gene V(D)J recombination 14. Which of the following descriptions about affinity maturation is correct? a. Depends on somatic mutation of V genes b. Depends on negative selection of B cells that can bind antigen in the germinal center c. Depends on antigen processing and presentation by dendritic cells within the germinal center

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

d. Depends on the autoimmune regulator (AIRE) gene e. Depends on somatic recombination of Ig V genes 15. Which of the following antigenic structures might activate B cell antibody production without the aid of T cells? a. Lysozyme b. Benzene c. Glucose-6-phosphate d. ABO blood group antigen e. Rh factor antigen 16. Antibody feedback is mediated by which of the following molecules? a. Ig Fc RIIB b. Ig Fc c. Ig Fc RI d. CR1 e. IgM

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 12: Congenital and Acquired Immunodeficiencies: Diseases Caused by Defective Immunity 1. In 1890, Emil von Behring and Shibasaburo Kitasato demonstrated the efficacy of serum transfer at conferring infection resistance—a process now known as “passive immunity.” The researchers isolated serum from animals that had recovered from infection with the diphtheria bacilli and subsequently injected the serum into other healthy animals. This procedure conferred specific resistance against the pathologic effects of diphtheria infection in the recipient animals. Which of the following immune phenomena were primarily responsible for these effects? a. Pathogen-specific B and T cells from the original infected animals triggered a robust immune response after re-exposure to diphtheria antigens in the recipient animal. b. Inflammatory cytokines in the transferred serum increased the strength and efficacy of innate immune system activity. c. Diphtheria-specific antibodies in the transferred serum neutralized bacillus toxins and promoted bacterial elimination by innate effector cells. d. Serum complement proteins in the transfer directly promoted bacterial cell lysis and phagocytosis. e. The recipient animal’s immune response to the foreign serum further activated host immune system function, allowing greater response to the bacillus infection.

2. Which of the following anatomic regions is normally protected from pathogens only by humoral immune responses and not by cell-mediated immune responses? a. Skin b. Intestinallumen c. Intestinalepithelium d. Central nervous system e. Spleen 3. Up to half of the IgG found in the serum of a normal individual is produced by which of the following cells? a. Naive B cells in lymph nodes b. Activated B cells in the spleen c. B cells in germinal centers of lymph nodes d. B lymphocytes in the gastrointestinal tract e. Long-lived plasma cells in the bone marrow

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

4. Treatment of antibodies with the enzyme papain under conditions of limited proteolysis results in hinge-region cleavage, yielding monovalent antigen-binding Fab fragments that lack a constant region. Which effector function of antibodies would Fab fragments be able to perform? a. Complement pathway activation b. Antibody-dependent cell-mediated cytotoxicity c. Opsonization d. Antigen cross-linking and precipitation e. Microbeneutralization 5. Most effective vaccines that are currently in widespread use are specific for pathogenic viruses, and the immunity induced by the vaccines is mediated largely by antibodies. Which of the following statements accurately describes the major mechanism by which these vaccine-dependent antibody responses function? a. The antibodies bind extracellular viral particles and prevent them from infecting cells. b. The antibodies bind to viral antigens on the surface of infected cells and promote phagocytosis of the cells. c. The antibodies bind to viral antigens on the surface of infected cells and promote complement-mediated lysis of the cells. d. The antibodies bind to extracellular viral particles and target Fc receptorexpressing cytolytic T lymphocytes to kill the viruses. e. The antibodies bind to viral envelope proteins and induce signals that inhibit viral replication.

6. Which of the following binds to and is readily phagocytosed by mononuclear phagocytes and neutrophils? a. Antigen-IgM complexes b. Bound complement protein C3b c. FreeserumIgG d. IgE bound to a helminthic parasite e. Mannose-binding lectin (MBL) 7. An 8-month-old boy infant with a 3-month history of recurrent upper and lower respiratory tract infections is admitted to the hospital. The physicians consider the possibility of a hereditary immune disorder and run several tests, eventually determining that the patient has undetectable levels of serum IgA. The infant is treated with strong antibiotics and recovers. Which of the following is NOT a medical problem likely to occur in this patient as he gets older? a. Anaphylactic reactions to blood transfusions b. Chronicgastrointestinalinfections c. Lactose and wheat gluten intolerance d. Inflammatory skin disease e. Recurrent nasal sinus congestion 8. Which of the following statements about Ig Fc receptors is NOT true? a. Some Fc receptors or Fc receptor–associated signaling chains contain ITAMs in their cytoplasmic tails. b. Some Fc receptors are linked to signal transduction pathways that cause granule exocytosis. c. There are Fc receptors specific for all common Ig isotypes.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

d.

Some Fc receptors with ITIMs in their cytoplasmic tails transduce inhibitory signals. e. Fc receptor signaling may enhance generation of reactive oxygen intermediates in phagocytes.

9. Which of the following events initiates activation of the alternative complement pathway? a. C1q binding to a microbial surface b. Mannose-binding lectin (MBL) binding to a microbial surface c. Complement receptor 1 (CR1) binding of C3b d. Factor I cleavage of C3 e. Spontaneous cleavage of C3 to C3b 10. Which of the following is NOT a property of the classical pathway C3 convertase? a. Composed of proteolytic fragments of C4 and C2 b. Has protease activity specific for C3 to form C3b c. Inhibited by decay acceleration factor (DAF) d. Stabilized by C4 binding protein (C4bp) e. Same substrate specificity as the alternative pathway C3 convertase 11. Which of the following statements about C3 is NOT correct? a. C3 contains an internal thioester bond that participates in covalent linkage to cell surfaces. b. C3 is the most abundant complement protein in the serum. c. A proteolytic fragment of C3 is part of both the C3 and C5 convertases. d. Activated C3 is a serine protease that cleaves C4. e. C3 in the plasma is spontaneously cleaved into C3b.

12. A 17-year-old boy is taken to the emergency department because of severe abdominal and lumbar pain. Physical examination reveals splenomegaly, and laboratory studies reveal hemoglobinemia and thrombocytopenia. A urine sample is remarkable for gross hemoglobinuria. The patient reports a history of bloody urine on multiple occasions in the past. Flow cytometric analysis of the patient’s red blood cells (RBC) will most likely indicate reduced or absent expression of which pair of molecules that is normally present on RBC membranes? a. Complement receptor 1 (CR1) and CR2 b. C1 inhibitor (C1 INH) and membrane cofactor protein (MCP, CD46) c. Decay accelerating factor (DAF, CD55) and CD59 d. C4 binding protein (C4bp) and factor H e. Complement receptor 3(CR3) and complement receptor 4(CR4) 13. A 15-year-old girl is brought to a pediatric clinic with severe abdominal pain, nausea, and vomiting. She does not have a fever, peritoneal signs, or an elevated white blood cell count. The symptoms resolve in 48 hours. She has a history of multiple transient episodes of facial edema without pruritus. Laboratory examination is most likely to reveal which of the following abnormalities in this patient? a. C4 deficiency b. Reduced levels of C1 inhibitor (C1 INH) c. Absence of C3 d. Presence of C3 nephritic factor e. Deficiency of factor I

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

14. All of the following are accurate statements about neonatal immunity EXCEPT: a. Transfer of maternal IgG across the placenta is mediated by an Fc receptor structurally similar to class I MHC. b. IgA is absorbed in the gut from breast milk and re-secreted by the infant into the bronchial mucosa. c. IgA secretion into breast milk involves transport through breast epithelial cells, and is dependent on the poly-Ig receptor. d. Transport of IgG across the neonatal intestinal epithelium is mediated by an Fc receptor structurally similar to class I MHC. e. Loss of maternal antibodies is partly responsible for increased frequency of infections in infants at about 6 months of age.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

CHAPTER 9: Additional Questions

19. 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. 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.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

7. Which one of the following statements regarding positive and negative selection of T cells is NOT true? a. Thymic epithelial cells present self-peptide-MHC to developing T cells undergoing the selection process. b. T cells that do not recognize self-peptide-MHC die by neglect. c. T cells that bind too strongly to self-peptide-MHC die by Fas ligand-mediated apoptosis. d. During positive selection, developing T cells express higher levels of anti- apoptotic proteins such as bcl-2.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

e. A breakdown in negative selection may result in the development of some autoimmune diseases.

10. Many tumors are found to overexpress bcl-2, which favors survival of the transformed

cells. Which of the following best describes the function of bcl-2? a. b. c. d. e.

Direct inhibition of caspase-8 Direct inhibition of caspase-9 Up-regulates expression of DNA repair enzymes Reduces the leakiness of the mitochondrial membrane Inhibits the activity of granzymes released from cytotoxic T lymphocytes

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

16. Which of the following statements about B cell tolerance is NOT true?

a. Negative signaling induced by monovalent antigens is a mechanism of central B cell tolerance. b. Exclusion of B cells from follicles is a mechanism of peripheral B cell tolerance. c. Functional anergy is a mechanism of peripheral B cell tolerance. d. Receptor editing is a mechanism of central B cell tolerance. e. Down-regulation of antigen receptor expression is a mechanism of central B cell tolerance.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

CHAPTER 11: Additional Questions

3. Which type of hypersensitivity disease is caused by deposition of antigen-antibody

complexes in blood vessel walls? a. b. c. d. e.

Type I Type II Type III Type IV Type V

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

10. An 8-year-old boy from the intermountain region of the United States is brought to the

pediatrician with fever, rash, and pain in his knees and ankles. Pericarditis is evident on auscultation, and echocardiography confirms mitral valve regurgitation. Three weeks before this episode, the patient had experienced a sore throat but had not received medical attention. High titers of antistreptococcal antibodies are present in the serum. This child’s disease is a result of which one of the following phenomena? a. b. c. d. e.

Clonal anergy Peripheral tolerance Epitope spreading Central tolerance Molecular mimicry

12. Which one of the following statements concerning autoimmune disease is true? a. Autoimmunity manifests as organ-specific, not systemic, disease. b. Infectious microorganisms are frequently present in autoimmune lesions. c. Effector mechanisms in autoimmunity include circulating autoantibodies, immune complexes, and autoreactive T lymphocytes. d. Among the genes associated with autoimmunity, associations are particularly prevalent with class I MHC genes. e. Many autoimmune diseases show higher incidence in males than in females.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Which of the following examples can be considered an illustration of vaccination?

Inoculating an individual with cowpox in order to protect that individual against smallpox

Which of the following options is not a mechanism by which an antibody can protect against a pathogen?

Co- stimulation of t cells

Which of the following is an appropriate definition for immunological memory? the persistence of pathogen-specific antibodies and lymphocytes after the original infection has been eliminated so that reinfection can be prevented

In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis.

This leads to bone marrow failure, which disrupts the production of hematopoietic cell

The immunologist’s ‘dirty little secret’ involves the addition of microbial constituents in order to stimulate a strong immune response against the desired protein antigen of interest. Which of the following is not a receptor or receptor family that can recognize microbial products in order to achieve a potent immune response?  t-cell antigen receptor (tCr) Which of the following processes is not a mechanism of maintaining immunologic tolerance?

Clonal expansion Which of the following events do not occur during inflammation?

Constriction of blood vessels Which cell type forms an important link between the innate immune response and the adaptive immune response? dendritic cell This study source was downloaded by 100000872359968 from CourseHero.com on 10-07-2023 15:51:11 GMT -05:00

lineages. All of the following cell types would be affected by this EXCEPT: Endothelial cells The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: Mucus production Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon reinfection with the same pathogen, are the basis of: Vaccines Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: The presence of adenosine residues in viral RNA When macrophages in a tissue encounter bacterium, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

cells of the blood vessel wall to: Increase their permeability, allowing fluid and proteins to leak into the tissue Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can

perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: The naive B cell expresses a membrane-bound form of the antibody as a receptor and secretes that same antibody when it differentiates into a plasma cell.

Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate.

This is because the effector functions of T cells are restricted to: Interactions with other cells, such as virus-infected cells or other immune cells The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptidebinding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: Intracellular pathogens, such as viruses and some protozoa The clonal selection theory was first proposed in the 1950s, decades before the molecular

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details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that: Circulating antibodies are generated by many different antibody-secreting cells, each of which

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

expresses a single type of antibody on its surface as a receptor.

The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: Some antigen receptors might recognize the individuals on cells or antigens

An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: The defective immune response

Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses.

Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: It concentrates antigens in centralized locations for rare lymphocytes to encounter Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: From the blood by crossing the high endothelial venules This study source was downloaded by 100000872359968 from CourseHero.com on 10-07-2023 15:51:11 GMT -05:00

occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.

The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses.

The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes.

The best evidence supporting the concept of immunological memory is: The increased rapidity and magnitude of the secondary response to the same antigen Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2–4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: Upregulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection.

The majority of vaccines work by eliciting pathogen- specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: They neutralize the virus or toxin, preventing it from attaching to and entering our cells.

When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by:  Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody- based) immune responses. The defect in antibody responses in SCID patients is due to: The important role of T follicular helper cells in generating protective antibody responses Inherited immunodeficiency diseases result

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from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens, a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: The essential immune mechanism required for resistance to each category of pathogen One surprising aspect of the immune system is that individuals make responses to human tissues from a

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: The extensive polymorphism of MHC genes in the human population Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses.

lupus erythematosus usually present with low C3 and C4 levels in blood due to the activation of the classical complement pathway. In contrast, diseases such as dense deposit disease or C3 glomerulonephritis generally have low C3 due to activation of the alternative complement pathway. What would be the expected levels of C2 and C4 in a patient suffering from dense deposit disease or C3 glomerulonephritis?

Normal

The widely used β-lactam antibiotics are mainly active against Gram-positive bacteria. These inhibit the transpeptidation step in synthesis of peptidoglycan, a major component of the bacterial cell wall that is critical for the survival of the microorganism. Which of the following is an antimicrobial enzyme that functions to disrupt the same bacterial structure that β-lactams ultimately target?

Lysozyme Choose the option that correctly describes ficolins.

Fibrinogen-like domain, affinity for carbohydrates such as fucose and Nacetylglucosamine (GlcNAc), synthetized in the liver and lungs Diseases such as cryoglobulinemia and systemic This study source was downloaded by 100000872359968 from CourseHero.com on 10-07-2023 15:51:11 GMT -05:00

Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections, except: Virus-infected cell Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection. Examples of damage caused by the host immune response are: Endotoxin – Immune complexes Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: Secretion of antimicrobial peptides by epithelial cells Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.

Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure Q2.7 shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth.

Which statement could account

for the data in these graphs?

Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme resistant.

The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human Paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is: Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.

Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response.

This is because: Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.

The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious

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outcome is largely avoided by: The rapid hydrolysis of active C3b in solution, rendering it inactive.

Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

pathogens rather than host cells because: They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes.

immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: The C3 convertase of the alternative pathway contains C3b and can generate more of itself.

The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses?

Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure.

Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients was found to have defects in complement

Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis?

A

The alternative pathway of complement activation has an important role in innate This study source was downloaded by 100000872359968 from CourseHero.com on 10-07-2023 15:51:11 GMT -05:00

activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained. Based on these data, the identity of the green neutrophil mediator in Figure Q2.19 is likely to be: Factor P (properdin) One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a ‘GPI-linkage.’

Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because: DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces.

Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to: Ensure that pathogens are

readily detected by the adaptive immune system before they replicate to high levels in the host

an inflammatory response? vascular permeability

The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: The limited susceptibility to infections of patients with deficiencies in terminal complement components

Which of the following is a G-protein-coupled receptor?  fMLF receptor

Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because: Uncontrolled complement activation leads to the depletion of serum complement proteins.

The importance of complement activation as an innate immune defense against infections is illustrated by: The evolution of complement avoidance strategies by many pathogens Which of the following does not occur during This study source was downloaded by 100000872359968 from CourseHero.com on 10-07-2023 15:51:11 GMT -05:00

Decreased

Which of the following is not true?

The inflammasome is a large oligomer composed of the sensor NLRP3, the adaptor ASC, and caspase 8.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface.

However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: The complement receptor Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating ‘classical’ monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to: Amplify the local innate immune response by entering tissues that are infected Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to: Prevent fusion of phagosomes with lysosomes

An infection in the skin, such as a pimple, often produces pus. The major component of pus is: Dead and dying neutrophils When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because: It couples to a heterotrimeric G protein that has a and bg subunits with independent activities.

Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the:

Macrophages express multiple types of receptors on their surface that stimulate This study source was downloaded by 100000872359968 from CourseHero.com on 10-07-2023 15:51:11 GMT -05:00

Chemokines that induce directed migration of blood monocytes The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: The production of antimicrobial peptides As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi.

Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients’ cells.

Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure Q3.11?

C (The nucleic acid sensing TLRs reside in the membranes of endosomes, not the plasma membrane. These TLRs are transported to the endosomes from the endoplasmic reticulum after their synthesis. They are specialized to recognize nucleic acids of viruses that have been internalized by endocytosis or by the phagocytosis of dying host cells in the process of replicating viral genomes. In order for these TLRs to be delivered to the endosome from the endoplasmic reticulum they must interact

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

with a protein known as UNC93B1. Patients with mutations in UNC93B1 have been identified and show susceptibility to herpesvirus infections.)

A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation.

This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT:  Induced phosphorylation preventing protein degradation Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid- sensing TLRs is characterized by production of: The antiviral cytokine, type I interferon Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous

studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K+ efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study (Figure Q3.16) was performed: Figure Q3.16 The explanation for these results is: The live S. aureus bacteria activate a TLR and NLRP3.

Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1.

The reason for many different sensors in this innate response system is that: Each NODlike receptor recognizes different PAMPs and is activated by different pathogens.

In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses.

They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to: Stimulate dendritic cells to up-regulate co- stimulatory molecules and migrate to the regional lymph node

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Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is: The activation of an extracellular proteolytic cascade involving cleavage of selfproteins To identify genes encoding the receptors for the cytokines IL-2, IL-4, and IL-7, an siRNA screen is performed using purified T lymphocytes. To identify siRNAs that knock- down cytokine receptor expression, the T cells have been transfected with a construct that produces green fluorescent protein (GFP) when any one of these three cytokines is used to stimulate the cells.

When the screen is completed, several different siRNAs have been identified that substantially reduce the T cells ability to respond to these cytokines as shown in Figure Q3.22. A correct statement regarding these data is: siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not.

Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

receptor subunit in this superfamily binds a specific JAK kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by:  The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit’s cytoplasmic tail Immunodeficiency diseases occur when individuals have defects in leukocyte adhesion to inflamed endothelial cells, thereby impeding the extravasation of phagocytes into infected tissues.

When neutrophils from one class of these patients were isolated and tested using in vitroassays for neutrophil-endothelial cell interactions and extravasation, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is: An integrin Chemokines such as CXCL8 have a key role in the rapid recruitment of neutrophils to the site in the tissue containing the focus of an infection. In this response, CXCL8 has two different functions. In addition to inducing integrin activation on the neutrophil, CXCL8 also functions to: Induce directional migration of the neutrophil in the tissue

Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPSinduced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS-induced septic shock is: TNF-receptor-deficient mice In healthy adults, neutrophils represent approximately half of their white blood cells.

During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: Release of neutrophils into the blood from the bone marrow Two strains of mice were infected with 5 ´ 104 PFU of Influenza A virus, and the survival data shown in Figure Q3.31 were obtained. Figure Q3.31 Next, both strains were infected again with Influenza A, and levels of type I interferons (IFN-a and IFN-b) were measured and found to be similar between the two strains. Likewise, cells from both strains expressed similar levels of the IFN-a/b receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza A infection?

Mx-1

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Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by: Cytokines made by other innate cells, such as macrophages or dendritic cells Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus- infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: Inhibitory receptors that recognize MHC class I proteins NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual: Each express only a subset of all possible NK receptors

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

NK cells can be activated following recognition of a virus-infected cell, if that cell has downregulated expression of MHC class I proteins on its surface. However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing: Molecules on the target cell upregulated by cellular or metabolic stress

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Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 3: The Induced Responses of Innate Immunity - Additional Questions Pattern recognition by cells of the innate immune system 3-1 After entering tissues, many microbes are recognized, ingested, and killed by

phagocytes 3.1

Multiple choice: Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells.

Yet the blood also contains a high number of circulating ‘classical’ monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to: A. Phagocytose and kill pathogens in the blood B. Line the endothelial surfaces of the blood vessels with phagocytic cells C. Enter lymph nodes and patrol for infecting microbes in these organs D. Amplify the local innate immune response by entering tissues that are infected E. Differentiate into dendritic cells during an inflammatory response

3.2

True/False: Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells.

3.3

Multiple choice: Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to: A. Prevent induction of nitric oxide production in the phagosome B. Prevent the acidification of phagosomes C. Prevent the expression of antimicrobial peptides in the phagosome D. Prevent fusion of phagosomes with lysosomes E. Kill the macrophage before it kills them

3.4

Multiple choice: Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction.

Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: A. The mannose receptor B. The class A scavenger receptor C. The lipid receptor D. The macrophage C-type lectin receptor E. The complement receptor Page 85 of 22

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3-2 G-protein-coupled receptors on phagocytes link microbe recognition with increased

efficiency of intracellular killing 3.5 Short answer: The NBT (Nitro Blue Tetrazolium) test is used to diagnose the genetic disorder Chronic Granulomatous Disease (CGD). To perform this test, peripheral blood cells from the patient are stimulated with bacterial extracts, and then incubated with the NBT compound. Normal neutrophils turn blue in this test due to cleavage of the compound, while patient neutrophils remain uncolored, as shown in Figure Q3.5.

Figure Q3.5 Name a neutrophil receptor that is likely to be stimulated by the bacterial extract in this assay, and describe how this receptor regulates the activity of the enzyme that cleaves NBT. 3.6

Multiple choice: An infection in the skin, such as a pimple, often produces pus. The major component of pus is: A. Toxic oxygen molecules released by macrophages B. Toxic nitrogen molecules released by macrophages C. NETs released by neutrophils D. Dead epithelial cells killed by lysozyme E. Dead and dying neutrophils

3.7

Multiple choice: When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because: A. It couples to a heterotrimeric G protein that has α and βy subunits with Page 86 of 22

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B. C. D. E.

independent activities.

It couples directly to two different guanine nucleotide exchange factors (GEFs).

It binds to Rac, Rho, and cdc42 directly.

It promotes fusion of phagosomes with lysosomes, initiating multiple signals.

It induces assembly of multiple enzymes from individual cytosolic components.

3-3 Microbial recognition and tissue damage initiate an inflammatory response 3.8

True/False: The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as ‘sterile inflammation.’ When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.

3.9

Multiple choice: Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the: A. Cytokines that induce increased vascular permeability B. Chemokines that induce directed migration of blood monocytes C. Cytokines that induce increased expression of adhesion molecules D. TNF produced by tissue-resident sensor cells E. Bradykinin produced that causes pain

3-4

Toll-like receptors represent an ancient pathogen-recognition system

3.10

Multiple choice: The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: A. The synthesis of prostaglandins and leukotrienes B. The inflammatory response in Drosophila hemolymph vessels C. The production of antimicrobial peptides D. The recruitment of phagocytic cells to the site of infection E. The activation of Drosophila complement

3-5 Mammalian Toll-like receptors are activated by many different pathogen-associated

molecular patterns 3.11

Multiple choice: As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi. Patients with a specific

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susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients’ cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure Q3.11?

Figure Q3.11 3-6 TLR-4 recognizes bacterial lipopolysaccharide in association with the host

accessory proteins MD-2 and CD14 3.12 True/False: All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.

3-7 TLRs activate NF1B, AP-1, and IRF transcription factors to induce the expression of

inflammatory cytokines and type I interferons 3.13

Multiple choice: A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT: A. Induced ubiquitination leading to protein degradation B. Induced ubiquitination inducing protein–protein interactions C. Induced phosphorylation leading to nuclear translocation D. Induced phosphorylation leading to kinase activation E. Induced phosphorylation preventing protein degradation

3.14

Multiple choice: Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acidsensing TLRs is characterized by production of: A. The antiviral cytokine, type I interferon B. TNF-α, which induces increased vascular permeability C. Antimicrobial peptides by macrophages D. Chemokines that recruit neutrophils E. The inflammatory complement fragments, C3a and C5a

3-8 The NOD-like receptors are intracellular sensors of bacterial infection and cellular

damage 3.15

Short answer: NOD1 and NOD2 are cytoplasmic sensors of bacterial products such as muramyl dipeptide (MDP), a constituent in the peptidoglycans of most bacteria. These sensors are highly expressed in epithelial cells that line the body surfaces that pathogens must cross to establish an infection. Interestingly, a subset of patients with an inflammatory bowel disease called ‘Crohn’s disease’ have inactivating mutations in Page 88 of 22

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NOD2. Why might this deficiency in NOD2 lead to chronic inflammation in the gut?

3-9 NLRP proteins react to infection or cellular damage through an inflammasome to

induce cell death and inflammation Multiple choice: Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K+ efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study (Figure Q3.16) was 3.16

performed: Figure Q3.16 The explanation for these results is: A. NLRP3 is not activated by K+ efflux from the cells.

B. The S. aureus toxin does not kill the Langerhans cells.

C. The live S. aureus bacteria activate a TLR and NLRP3.

D. The S. aureus membrane prep does not contain a TLR ligand.

E. TLR activation by S. aureus membranes induces interferon production.

3.17

Multiple choice: Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that: A. Each NOD-like receptor is expressed in a different set of phagocytic cells, depending on its tissue location.

B. Each NOD-like receptor resides in a different intracellular compartment.

C. Each NOD-like receptor performs a different step in the multi-step cascade leading to inflammasome activation.

D. Each NOD-like receptor binds to a different adapter protein and triggers a different form of the inflammasome.

E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.

3-10 The RIG-I-like receptors detect cytoplasmic viral RNAs and activate MAVS to induce type

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3-11 Cytosolic DNA sensors signal through STING to induce production of type I

interferons 3.18

Short answer: RIG-I like receptors (RLRs) such as RIG-I, MDA-5, and STING are cytoplasmic nucleic acid sensors. Give two examples of how such innate sensors distinguish between the RNA/DNA of the host from that of an infecting pathogen.

3-12 Activation of innate sensors in macrophages and dendritic cells triggers changes in gene

expression that have far reaching effects on the immune response 3.19

Multiple choice: In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to: A. B. C. D. E.

Mimic the process of normal virus entry by binding to the host receptor and inducing receptor-mediated endocytosis Induce vascular permeability to promote the accumulation of fluid and serum proteins at the vaccine injection site Induce the production of chemotactic proteins that recruit neutrophils and then monocytes to the site of vaccine injection Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node Promote the activation of the complement cascade to induce complement deposition on the viral subunit proteins

3-13 Toll signaling in Drosophila is downstream of a distinct set of pathogen-recognition

molecules 3.20

Multiple choice: Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is: A. The activation of an extracellular proteolytic cascade involving cleavage of selfproteins B. The deposition of Toll signaling proteins onto the microbial surface C. The release of soluble fragments of Toll that induce inflammation D. The assembly of a membrane attack complex in the microbial membrane following Toll activation E. The presence of receptors for Toll cleavage products on phagocytic cells to promote pathogen ingestion

3-14 TLR and NOD genes have undergone extensive diversification in both invertebrates and

some primitive chordates Page 90 of 22

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3.21

True/False: In the sea urchin, a massive diversification of innate recognition receptors has occurred, resulting in the presence of over 200 TLR genes, over 200 NOD-like receptor genes, and over 200 scavenger receptor genes in the genome of these organisms. These receptors are unlikely to contribute to an enhanced innate immune response in sea urchins, because nearly all of these genes are pseuodgenes.

Induced innate responses to infection 3-15 Cytokines and their receptors fall into distinct families of structurally related

proteins 3.22

Multiple choice: To identify genes encoding the receptors for the cytokines IL-2, IL-4, and IL-7, an siRNA screen is performed using purified T lymphocytes. To identify siRNAs that knock-down cytokine receptor expression, the T cells have been transfected with a construct that produces green fluorescent protein (GFP) when any one of these three cytokines is used to stimulate the cells. When the screen is completed, several different siRNAs have been identified that substantially reduce the T cells ability to respond to these cytokines as shown in Figure Q3.22.

Figure Q3.22 A correct statement regarding these data is: A. siRNA-1 and siRNA-3 target subunits of the IL-2 receptor but siRNA-2 does not.

B. siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not.

C. siRNA-3 targets a subunit of the IL-7 receptor, but the other two siRNAs do not.

D. siRNA-2 and siRNA-3 do not target a subunit of the IL-2 receptor.

E. siRNA-2 targets a subunit shared by all receptors in the hematopoietin receptor superfamily.

3-16 Cytokine receptors of the hematopoietin family are associated with the JAK family of

tyrosine kinases, which activate STAT transcription factors 3.23

Multiple choice: Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each receptor subunit in this superfamily binds a specific JAK Page 91 of 22

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kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by: A. The specificity of each JAK kinase for only phosphorylating one or two out of the seven possible STAT members B. The specificity of each cytokine receptor complex to only activate one of the four Jak kinase members, which then homodimerizes C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit’s cytoplasmic tail D. The expression of only one STAT member in each type of immune cell, depending on which cytokine receptors are expressed E. The inhibition of all but one STAT protein by the inhibitor SOCS proteins expressed in each cell type 3-17 Chemokines released by macrophages and dendritic cells recruit effector cells to sites of

infection True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.

3-18 Cell-adhesion molecules control interactions between leukocytes and endothelial cells during an inflammatory response 3.24

3.25

Multiple choice: Immunodeficiency diseases occur when individuals have defects in leukocyte adhesion to inflamed endothelial cells, thereby impeding the extravasation of phagocytes into infected tissues. When neutrophils from one class of these patients were isolated and tested using in vitro assays for neutrophil-endothelial cell interactions and extravasation, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is: A. ICAM-1 or ICAM-2 B. P-selectin C. E-selectin D. An integrin E. Sulfated sialyl-LewisX

3-19 Neutrophils make up the first wave of cells that cross the blood vessel wall to enter an

inflamed tissue 3.26

Multiple choice: Chemokines such as CXCL8 have a key role in the rapid recruitment of neutrophils to the site in the tissue containing the focus of an infection. In this response, CXCL8 has two different functions. In addition to inducing integrin activation on the neutrophil, CXCL8 also functions to: A. Induce directional migration of the neutrophil in the tissue B. Induce increased expression of P-selectin and E-selectin on the endothelium Page 92 of 22

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

C. D. E. 3.27

Induce increased expression of integrins on the neutrophil surface Induce blood vessel dilation and fluid leakage into the infected tissue Induce increased phagocytic activity by the neutrophil

True/False: The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.

3-20 TNF-α is an important cytokine that triggers local containment of infection but

induces shock when released systemically 3.28

Multiple choice: Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPSinduced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPSinduced septic shock is: A. TNF-receptor-deficient mice B. TLR-2-deficient mice.

C. LFA-1-deficient mice D. Neutrophil-deficient mice E. Complement receptor-deficient mice

3-21 Cytokines made by macrophages and dendritic cells induce a systemic reaction known

as the acute-phase response 3.29 True/False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.

3.30

Multiple choice: In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: A. Recruitment of neutrophils from tissues into the blood B. Proliferation of neutrophils at the site of infection C. Proliferation of neutrophils in the blood D. Differentiation of blood monocytes into neutrophils E. Release of neutrophils into the blood from the bone marrow

3-22 Interferons induced by viral infection make several contributions to host defense

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3.31

Multiple choice: Two strains of mice were infected with 5 104 PFU of Influenza A virus, and the survival data shown in Figure Q3.31 were obtained.

Figure Q3.31 Next, both strains were infected again with Influenza A, and levels of type I interferons (IFN-α and IFN-β) were measured and found to be similar between the two strains.

Likewise, cells from both strains expressed similar levels of the IFN-α/β receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza A infection?

A. MHC class I B. Mx-1 C. TLR4 D. Complement C3 E. ICAM-1 3-23 Several types of innate lymphoid cells provide protection in early infection 3.32

Multiple choice: Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by: A. Microbial PAMPs that stimulate pattern recognition receptors on ILCs B. TNF-α, which is produced during the inflammatory response C. Acute phase response proteins produced in the liver during an infection D. Cytokines made by other innate cells, such as macrophages or dendritic cells E. Antimicrobial peptides made by epithelial cells in response to infection

3-24 NK cells are activated by type I interferon and macrophage derived cytokines 3.33

Short answer: Individuals with natural killer (NK) cell deficiencies have susceptibilities to infections with herpesviruses and other DNA viruses, as well as with intracellular bacteria such as the mycobacteria that cause tuberculosis. Mycobacterium tuberculosis is a pathogen that infects macrophages and replicates in their phagocytic vesicles.

Which effector function of NK cells is likely most important in promoting immunity to M. tuberculosis?

3-25 NK cells express activating and inhibitory receptors to distinguish between healthy and Page 94 of 22

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infected cells 3.34

Multiple choice: Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: A. Activating receptors that recognize MHC class I proteins B. A mechanism to secrete antiviral peptides C. Inhibitory receptors that recognize viral capsid proteins D. Activating receptors that recognize viral capsid proteins E. Inhibitory receptors that recognize MHC class I proteins

3-26 NK-cell receptors belong to several structural families, the KIRs, KLRs, and NCRs 3.35

True/False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.

3.36

Multiple choice: NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual: A. Always express a majority of activating versus inhibitory receptors B. Are more potent effectors of cytotoxicity than of cytokine-production C. Each express only a subset of all possible NK receptors D. Are not considered members of the innate lymphoid cell lineage E. Undergo massive proliferation in response to infection, similar to T lymphocytes

3-27 NK cells express activating receptors that recognize ligands induced on infected cells or

tumor cells 3.37

Multiple choice: NK cells can be activated following recognition of a virus-infected cell, if that cell has down-regulated expression of MHC class I proteins on its surface.

However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing: A. Molecules on the target cell up-regulated by cellular or metabolic stress B. Cytokines secreted by the virus-infected or tumor cell C. MHC class I-like decoy molecules encoded by the virus D. Mutated self-proteins expressed by the tumor cell E. Double-stranded DNA in the cytoplasm of the infected or tumor cell Page 95 of 22

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3.38

Synthesis question: Influenza virus infects and replicates in airway epithelial cells. This virus has a segmented single-stranded RNA genome. Experiments to determine which innate immune sensors were recognizing the virus and inducing production of type I IFNs (IFN-α and IFN-β) were performed. For these studies, mice were infected with Influenza A virus by the intranasal route, which leads to a potent infection in the lungs.

Two days post-infection, Type I IFNs were measured in the lung; Figure Q3.38A shows

the results.

Figure Q3.38A a) Name two innate sensor categories that are likely involved in recognizing influenza

virus. b) A common symptom of virus infections is fever. Which innate receptor sensing

pathway is most likely responsible for this response, and how is it induced?

Several cell culture lines of epithelial cells, called “Cell Line A, B, or C,” are incubated with 104 infectious particles of influenza virus, and viral titers in the culture media are measured 2 days later. Looking at the results of this experiment, it is apparent that the three lines do not all show the same response to the virus. To investigate these differences, mixing experiments are performed, where cells from two different cell lines are mixed together at a 1:1 ratio before the Influenza infection. c) Based on the results shown in Figure Q3.38B, propose an explanation for these data.

Figure Q3.38B Page 96 of 22

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3.39

Synthesis Question: Streptococcus pyogenes is a Group A Streptococcal (GAS) bacterium that causes a variety of diseases, depending on the tissue that is infected. Most frequently, this bacterium causes strep throat and localized infections in the skin.

However, on occasion, the bacteria spread to the blood, and can a cause life-threatening infection that has a mortality rate of ~25%. Studies in mouse models have shown that the recruitment of neutrophils to the site of infection is essential in the efficient elimination of a Group A strep infection. To determine the innate immune pathways involved in protection against GAS, mice lacking the adapter protein MyD88 were tested for their response to GAS compared with wild-type (C57BL/6) control mice. For these studies, mice were infected with 104 PFU of GAS subcutaneously (under the skin). The results

are shown in Figure Q3.39A. Figure Q3.39A To assess the magnitude of the increased susceptibility of MyD88 -/- mice to GAS, mice were tested with increasing doses of bacteria, and the LD50 (dose required to generate a lethal infection in 50% of the mice) was calculated. The conclusion of this analysis was an LD50 of 2 106 PFU for the wild-type mice, and <1 104 for the MyD88-/- mice. In addition, when mice were infected with 5 107 PFU of GAS subcutaneously, as shown in Figure 3.39B panel A, all the mice eventually succumbed to the infection, but the average survival time of the wild-type mice was significantly longer than for the MyD88-/- mice.

In addition, measurements of bacterial counts in the blood within the first day postinfection (panel B) confirmed the poor innate immune response of the MyD88 -/- mice.

Figure Q3.39B However, when various knockouts of individual TLRs were tested, none of them showed increased susceptibility to GAS of a magnitude similar to the MyD88 -/- mice; similarly, double knockouts of several TLRs in various combinations also failed to recapitulate the severe defect in innate immune response observed in the absence of MyD88.

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a) Propose an explanation for the importance of MyD88 in the innate immune response

to GAS. b) If TLRs are not required for the innate immune response to GAS, what other sensor of

bacterial components is a good candidate to induce the transcription of pro-inflammatory cytokine genes?

To investigate the innate immune response to GAS further, macrophages were isolated from mice, and cultured together with live GAS bacteria. In addition to macrophages from wild-type mice, macrophages were also isolated from MyD88-/-, RIP2-/-, TAK1-/and ASC-/- mice. After 18 hours of incubation, the supernatants from these cultures were test for IL-1β and TNF-α concentrations. The results are shown in Figure Q3.39C. (HINT: MyD88 is required for TLR and IL-1R signaling; RIP2 for NOD receptor signaling; TAK1 for TLR and NOD receptor signaling; ASC for NLRP3 signaling to

activate Caspase-1) Figure Q3.39C c) Based on these data, what can you conclude about the function of MyD88 in the

innate response to GAS? d) On the graphs in Figure Q3.39D, draw the expected results for IL-1β and TNF-α

mRNA levels in these macrophages. The results from wild-type macrophages are shown for reference.

Figure Q3.39D ANSWERS Page 98 of 22

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3.1 : D.

Circulating ‘classical’ monocytes are recruited to enter tissues by the local release of cytokines and chemokines resulting from an infection. Once entering the tissues, the cells differentiate into activated inflammatory monocytes or macrophages, where they can function to phagocytose and destroy pathogens, as well as to produce additional cytokines and chemokines to amplify the local immune response.

3.2 : True.

Dendritic cells are considered to be the bridge between innate and adaptive immunity. They are tissue resident cells that rapidly respond to infections, due to their expression of many PRRs. However, unlike macrophages and neutrophils, the latter of which are recruited to infected tissues, dendritic cells do not function in large-scale pathogen destruction. Instead, they phagocytose pathogens and degrade them to generate peptides for presentation and activation of T cells.

3.3 : D.

Once a microbe is phagocytosed by a macrophage, it is sequestered in an intracellular vesicle known as a phagosome. The phagosome then fuses with one or more lysosomes, to form the phagolysosome. The phagolysosome is the compartment which has the capacity to expose the ingested pathogen to acidification, antimicrobial peptides, and reactive oxygen species. These events do not occur in the phagosome prior to its fusion to lysosomes. Mycobacteria have evolved mechanisms to prevent phagosome–lysosome fusion as an immune evasion strategy.

3.4 : E.

The complement receptor expressed on phagocytes binds to complement-coated pathogens. A pathogen becomes opsonized with complement proteins when it is first recognized by an initiating member of the complement pathway, such as MBL, other collectins or ficolins, or by antibody. Another example of a receptor on phagocytes that stimulates phagocytosis but does not directly recognize the pathogen surface is one of the Fc receptors.

3.5 : CGD is a disease that results from a genetic deficiency in the NADPH oxidase. Normal

phagocytes express this enzyme and its activity produces toxic oxygen derivatives that kill ingested microorganisms. The most common form of CGD is X linked, and is due to a defect in the gp91 subunit of the enzyme. Neutrophils are stimulated to produce toxic oxygen molecules in a process known as the respiratory burst. This process is stimulated by bacterial components binding to the fMLF receptor on phagocytes, or by a complement-tagged microbe binding to the C5a receptor on phagocytes. Stimulation of these receptors activates the small GTPase Rac, which promotes the movement of the cytosolic components of the NADPH oxidase to assemble with the membrane-bound subunits to produce the active enzyme.

3.6 : E.

Neutrophils are recruited in large numbers to sites of infection. These cells are short-lived (<1 day) and die shortly after a round of phagocytosis when they have used up their primary and secondary granules. Infections of extracellular encapsulated bacteria, such as streptococci and staphylococci, recruit large numbers of neutrophils, and are known as pus-forming bacteria.

When these neutrophils die, they form the pus often seen in wounds and abscesses caused by these Page 99 of 22

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infections.

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3.7 : A.

Signaling by the fMLF receptor induces cell motility, metabolism, gene expression, and cell division through activation of several Rac and Rho family small GTPase proteins. To accomplish this, the fMLF receptor, a member of the G-protein-coupled receptor family, activates a heterotrimeric G protein consisting of Gα, Gβ, and Gy subunits. After receptor stimulation, the heterotrimeric G protein undergoes a conformational change, leading to the exchange of GDP for GTP by the Gα subunit. This causes dissociation of the trimer into two components, Gα and Gβy, each of which has separate activities. The α subunit of the activated G protein indirectly activates Rac and Rho, while the βγ subunit indirectly activates the small GTPase Cdc42.

Activation of these small GTPases is dependent on the activation of guanine nucleotide exchange factors (GEFs), one for each specific GTPase.

3.8 : True.

The inflammatory response is effective at promoting immunity and eradicating infections, but at the same time causes damage to the host. The influx of fluid and cells into tissues can cause damage, and the production of antimicrobial compounds, such as toxic oxygen and nitrogen species, also causes collateral damage. Inflammatory responses also induce tissue repair, a process that when chronic can also lead to tissue damage.

3.9 : B.

Most of the inflammatory mediators produced by tissue-resident macrophages in response to infection act on vascular endothelial cells to cause blood vessel dilation, leakiness of endothelial junctions allowing fluid and proteins to leak out of the blood, and induce increased expression of adhesion molecules on endothelial cells. In contrast, the chemokines that are produced act on the white blood cells adhering to the endothelium. These chemokines induce the blood cells, such as monocytes, to migrate across the endothelium into the tissue and then direct the cells toward the site of infection in the tissue.

3.10 : C.

In response to activation of Toll by Gram-positive bacteria and some fungi, transcription factors related to mammalian NF1B are activated. This pathway leads to the expression of host defense proteins, including several antimicrobial peptides.

3.11 : C.

The nucleic acid sensing TLRs reside in the membranes of endosomes, not the plasma membrane. These TLRs are transported to the endosomes from the endoplasmic reticulum after their synthesis. They are specialized to recognize nucleic acids of viruses that have been internalized by endocytosis or by the phagocytosis of dying host cells in the process of replicating viral genomes. In order for these TLRs to be delivered to the endosome from the endoplasmic reticulum they must interact with a protein known as UNC93B1. Patients with mutations in UNC93B1 have been identified and show susceptibility to herpesvirus infections.

3.12 : False.

Some TLRs have been shown to make direct contact with microbial ligands based on X-ray crystal structures. However, this has not been confirmed for all TLRs. The Drosophila receptor Toll does not recognize microbial products directly, but instead, recognizes a cleaved product of a self-protein, Spätzle. This leaves open the possibility that some mammalian TLRs may Page 101 of 22

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function similarly to Drosophila Toll. Furthermore, TLR4 requires an accessory protein, MD-2 for binding to LPS. 3.13 : E. TLR signaling pathways lead to the activation of NF1B and of IRF family transcription factors.

Each pathway has multiple steps, beginning with the adapter proteins MyD88, MAL, TRAM, and TRIF in various combinations. These steps include both K48-linked and K63-linked ubiquitination, resulting in protein degradation or protein–protein interactions, respectively. Also included are steps of protein phosphorylation, leading to nuclear localization of the IRF factors, and leading to kinase activation for TAK1. None of these steps include a process whereby protein phosphorylation stabilizes protein turnover by preventing degradation.

3.14 : A.

The nucleic acid sensing TLRs, such as TLR-3 and TLR-7, induce the activation of IRF transcription factors, leading to the secretion of antiviral type I interferons. Each of these two endosomal receptors uses a distinct signaling pathway, starting with the binding of distinct adapter proteins to induce IRF factor phosphorylation. However, consistent with their importance in innate responses to virus infections, these TLRs both induce transcription of type I interferon genes when they are stimulated.

3.15 : NOD2 is highly expressed in the Paneth cells of the gut, where it regulates the expression

of potent antimicrobial peptides such as the defensins. Since NOD2 recognizes bacterial components that are found in most strains of bacteria, not just pathogenic microbes, it is likely that NOD2-induced antimicrobial peptide production is occurring constitutively in response to the gut microbiota. This constitutive production of antimicrobial peptides at the intestinal epithelium is an important component of maintaining the natural barrier function of the gut epithelium. In the absence of this, barrier function is weakened, leading to an increased prevalence of microbes crossing the epithelial barrier and inducing an inflammatory response by stimulating the other innate sensors. This chronic inflammation is the hallmark of Crohn’s disease.

3.16 : C.

IL-1 secretion by dendritic cells requires two signals. One signal is needed to induce the transcription of the IL-1 mRNA by the cells. This signal is often provided by stimulation of a TLR expressed on the dendritic cells. In this example, the S. aureus membrane prep or the live S. aureus bacteria would provide the ligand for TLR stimulation. The second signal needed for IL-1 secretion is the activation of the inflammasome, leading to caspase-1-mediated cleavage of the pro-IL-1 protein. This second signal is provided by the S. aureus toxin or by the live bacteria, which would be producing the toxin. Without both of these signals, no IL-1 is secreted by the dendritic cells.

3.17 : E.

Each of the NOD-like receptors is activated by distinct signals or PAMPs that arise from different pathogenic infections. For example, NLRP3 is activated by ROS, ATP, and crystalline substances such as alum, NLRP1 by MDP and B. anthracis lethal factor, NAIP2 and NAIP5 by proteins injected into host cells by bacterial secretion systems, whereas AIM2 is activated by cytosolic double-stranded DNA typically found in virus-infected cells.

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3.18 :

1.

Unique structure: RIG-I recognizes single-stranded RNA that lacks the 5′-cap structure found on mammalian mRNA. A second example is MDA-5, which recognizes doublestranded RNA, a form of RNA not generally found in healthy host cells. A third example is STING, which recognizes cyclic dinucleotides made by bacteria, but not by host cells.

2.

Localization: Innate DNA sensors recognize double-stranded DNA found in the cytosol; in contrast, host DNA is generally localized to the nucleus. An example is cGAS, which binds to cytosolic DNA and stimulates the production of cyclic GMP-AMP (cGAMP) that, in turn, activates STING.

3.19 : D.

Adjuvants are substances that are mixed with protein antigens to promote their ‘immunogenicity’ in generating adaptive immune responses. Historically, it was found that adjuvants containing microbial components were the most effective. These compounds stimulate tissue macrophages and dendritic cells to express co-stimulatory molecules. They also stimulate tissue dendritic cells to migrate out of the tissue into the lymph, and traffic to the regional lymph node. These features are essential in generating an adaptive immune response, which is initiated in a lymph node, not in the tissue site. Current efforts to develop new adjuvants for use in subunit vaccines have taken advantage of our knowledge of PAMPs, and which ones are effective at stimulating innate sensors (PRRs) in dendritic cells.

3.20 : A.

Like the complement cascade in mammals, Toll signaling is initiated by pathogen recognition receptors that activate the first step of a proteolytic cascade following recognition of microbial products. This extracellular proteolytic cascade ultimately ends with the cleavage of the Drosophila protein Spätzle. Cleavage of Spätzle changes its conformation, enabling it to bind to Toll and induce Toll dimerization, thereby initiating Toll signaling.

3.21 : False.

While some of these genes are pseudogenes, the majority encode functional proteins. It is likely that these genes have undergone rapid evolution, indicating a rapid change in receptor specificities, perhaps in response to microbial evolution and/or immune evasion. The properties of the LRR domains are consistent with the idea that these receptors represent a highly diversified pathogen recognition system.

3.22 : B.

The receptors for IL-2, IL-4, and IL-7 each contain unique subunits as well as a common (shared) subunit. Based on these data, the correct conclusion would be that siRNA-1 targets a subunit unique to the IL-2 receptor, siRNA-3 targets a subunit unique to the IL-7 receptor, and siRNA-2 targets the shared subunit used by all three of these cytokine receptors.

3.23 : C.

Following cytokine binding, the subunits of the cytokine receptor are induced to dimerize, bringing the associated JAK kinases (one on each subunit, in general) together. These kinases then phosphorylate each other, leading to kinase activation. The activated kinases then phosphorylate tyrosine residues on the cytoplasmic tail of one subunit, usually the subunit that Page 103 of

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is unique to each cytokine. This phosphorylated sequence on the receptor subunit tail is recognized by a specific STAT protein, which binds to the phosphorylated receptor. This brings the STAT protein into proximity with the activated JAK kinase, leading to STAT protein phosphorylation, dimerization, and migration into the nucleus.

3.24 : False.

Chemokines encompass a large family of molecules that are structurally related. The different chemokines are made by distinct cell types and also act as chemoattractants for different cell types. The differences generally result from differential expression of specific chemokine receptors on different cell types. For instance the receptor for CXCL8 is expressed on neutrophils, but not on monocytes; thus, CXCL8 is a chemoattractant for neutrophils but not monocytes.

3.25 : D.

One class of patients with leukocyte adhesion deficiencies result from genetic defects in expression of integrins on their white blood cells. These cells, including the neutrophils, will undergo normal rolling along the endothelial blood vessel wall, as these interactions are mediated by selectins binding to selectin ligands. However, cells with defects in their integrin expression will be unable to arrest on activated (inflamed) endothelium, and therefore will be unable to migrate across the endothelial layer.

3.26 : A.

Chemokines such as CXCL8 are produced by tissue macrophages that first encounter the infecting pathogen. This chemokine binds to extracellular matrix in the tissue, forming a concentration gradient emanating from the focus of infection. Neutrophils that have entered the tissue will migrate along this chemokine gradient in the direction of higher chemokine concentrations, resulting in their efficient recruitment to the focus of the infection.

3.27 : True.

Both the endothelium and the neutrophils respond to cytokines and chemokines made in the tissue in response to infection. For the endothelium, the changes include vascular dilation and up-regulation of P-selectin, E-selectin, and ICAM molecules. For the neutrophil, the chemokines bound to proteoglycans on the surface of the endothelial cells induce a conformational change in the integrins on the surface of the neutrophil, converting them into high affinity binding partners for the ICAMs on the activated endothelium.

3.28 : A.

Septic shock is caused by a massive release of TNF-α into the bloodstream, which causes systemic vasodilation leading to a loss of blood pressure, and increased vascular permeability, which leads to a loss of plasma volume. TNF-α also causes blood clotting in small vessels throughout the body, leading to compromised blood perfusion of many organs and thus to organ failure. Mice with defects in TNF-α receptors or in which the ADAM17 gene (encoding TACE, the TNF-α-converting enzyme) has been inactivated in myeloid cells, are resistant to septic shock. TACE is needed to release TNF-α from the cell membrane of myeloid cells, generating soluble TNF-α that enters the bloodstream.

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3.29 : False.

The acute phase is induced by inflammatory cytokines (TNF-α, IL-1β, IL-6) produced by the host in response to infection. These cytokines act on hepatocytes to produce a variety of proteins, including C-reactive protein, MBL, surfactant proteins, and fibrinogen. Many of these proteins bind pathogens, but not host cells, and contribute to pathogen clearance by promoting phagocytosis and complement activation.

3.30 : E.

Cytokines produced by macrophages in response to a bacterial infection induce leukocytosis, referring to an increase in the numbers of neutrophils circulating in the blood. These neutrophils come from two sources. First, increased numbers of neutrophils are released from the bone marrow, their normal site of maturation. Second, neutrophils are released from sites in blood vessels, where they are loosely attached to endothelial cells.

3.31 : B. Mx proteins are induced by type I interferons, and are important in protection against Influenza A infection. These proteins are small GTPases found in the nucleus of cells and are thought to function by inhibiting viral RNA transcription. Somewhat surprisingly, most laboratory strains of inbred mice have inactivated both Mx genes, whereas these genes are intact in mice isolated from the wild. In the survival data shown above, strain A is any common inbred lab strain of mice, and strain B is a transgenic line derived from strain A in which a functional Mx-1 gene has been introduced.

3.32 : D.

ILCs function as effector cells that amplify signals produced by innate sensor cells. They are stimulated by cytokines produced by cells such as macrophages and dendritic cells when the macrophages or dendritic cells have been activated by innate sensors of microbial infection or tissue damage.

3.33 : In addition to cytolytic activity, NK cells secrete large amounts of IFN-y when they are

activated. Secretion of IFN-y is likely the most important effector mechanism by which NK cells help protect against intracellular bacterial infections such as M. tuberculosis. IFN-y directly activates macrophages to enhance their ability to kill pathogens, including intracellular pathogens replicating in the macrophage. IFN-y also influences the adaptive immune response by promoting the differentiation of pro-inflammatory TH1 CD4 T cells, which are critical in controlling intracellular bacterial infections. NK cells also produce cytokines and chemokines, such as TNF-α, GM-CSF, CCL3, CCL4, and CCL5 that function to recruit and activate macrophages.

3.34 : E.

NK cells express both activating and inhibitory receptors, and it is believed that their decision to kill a target cell depends on the relative balance of these two types of signals. When the activating signals are dominant over the inhibitory signals, the NK cell will kill that target cell.

Normal host cells constitutively express high levels of MHC class I molecules, and therefore are poor targets for NK cells. However, when a virus infection causes down-regulation of MHC class I proteins on the infected cells, the engagement of inhibitory receptors for MHC class I proteins is lost, tipping the balance in favor of the activating signals. This leads to NK cell Page 105 of

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killing of the virus-infected target cell.

3.35 : True.

KIRs and KLRs are two different families of NK cell receptors. Each has members that send activating signals to the NK cell and members that send inhibitory signals. The activating receptors associate with a signaling adapter protein, called DAP12, that contains amino acid sequence motifs known as ITAMs. When phosphorylated, ITAM sequences recruit tyrosine kinases to promote NK cell activation. In contrast, inhibitory receptors generally have longer cytoplasmic tails than the activating receptors. Rather than associating with an adapter protein such as DAP12, these receptors have amino acid motifs known as ITIMs in their cytoplasmic tails. ITIM motifs recruit inhibitory phosphatases when the receptor is stimulated, and therefore, down-regulate signaling in the NK cell.

3.36 : C.

NK receptors belong to several different families, including the killer cell immunoglobulin-like receptor family (KIRs), the killer cell lectin-like receptors (KLRs), and in mice, the Ly49 receptors. Within each family, individual receptors can be activating or inhibitory, and are highly polymorphic between different strains of mice. An important feature of the NK-cell population is that any given NK cell expresses only a subset of the receptors in its potential repertoire, and so not all NK cells in the individual are identical.

3.37 : A.

One important receptor on NK cells is NKG2D, which forms a homodimer on the NK cell surface. This activating receptor binds to ligands that are MHC class I-like molecules induced by various types of cellular stress. For example, the ligands for NKG2D are expressed in response to cellular or metabolic stress, and so are up-regulated on cells infected with intracellular bacteria and most viruses, as well as on incipient tumor cells that have become malignantly transformed. Thus, recognition by NKG2D acts as a generalized ‘danger’ signal to the immune system.

3.38 :

a)

b)

TLRs and Rig-I-like receptors (RLRs). Based on the data in the figure, TLRs are contributing to IFN-α/β production in the lung following Influenza A infection. This is likely due to TLR-7 recognition of viral RNA in the endocytic compartments of dendritic cells. This response is due to dendritic cell ingestion of viral particles, and degradation of the viruses to release the viral RNA in this intracellular compartment. However, TLR-7 (or another TLR) stimulation cannot account for the entire Type I interferon response, as elimination of all TLRs only reduces the IFN-α/β production by about one-half. This indicates that a second receptor family is involved. The most likely candidate is the Rig-Ilike receptor (RLR) family, possibly Rig-I itself. Rig-I recognizes single-stranded RNA that lacks the 5′ cap found on host mRNA, and stimulates type I IFN production.

Detection of uncapped 5′-triphosphates on RNA by RIG-I changes the conformation of the CARD domain on RIG-I so that it interacts with the amino terminal CARD domain of MAVS. This interaction leads to MAVS aggregation and the recruitment of TRAFS, leading in turn to the formation of a ubiquitin K63-linked scaffold. This scaffold recruits TBK1 and IKK complexes, leading to activation of IRFs and NF1B, respectively. The IRFs induce transcription of type I interferons and NF1B induces expression of Page 106 of 22

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c)

proinflammatory cytokines. Proinflammatory cytokines then induce fever by inducing the synthesis of prostaglandin E2 by the enzyme cyclooxygenase-2, the expression of which is induced by these cytokines. Prostaglandin E2 then acts on the hypothalamus, resulting in an increase in both heat production from the catabolism of brown fat and heat retention from vasoconstriction, which decreases the loss of excess heat through the skin.

Line B is making a robust type I interferon response to the virus infection. This response leads to the production of multiple interferon responsive genes (ISGs) in the cells, thereby inhibiting virus replication. Line A is defective in producing type I interferons in response to influenza virus infection. Therefore, when infected with 104 PFU of virus, the virus replicates to produce ~107 PFU/ml in the culture supernatant. The evidence that Line A is defective in producing type I IFNs, not in responding to the IFNs, is that a mixed culture of cell lines A + B is also resistant to the virus. If cell line A was unable to produce intracellular antiviral ISGs, the virus would replicate in ~1/2 of the cells in the mixed culture, and viral titers would only be reduced by ~2-fold. Cell line C is an example of this. Cell line C cannot respond to type I IFNs by inducing antiviral ISGs. When cultured alone, influenza replicates to high titers in these cells. When co-cultured with cell line B, the virus still replicates efficiently in the cells from line C, leading to only a modest (~2- fold) reduction in viral titers (B + C).

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3.39 :

a)

b)

c)

d)

There are two possible answers. First, it is possible that MyD88 is functioning as an adapter for IL-1R signaling, rather than as an adapter for TLR signaling in this system.

This would indicate a critical role for IL-1 in the protective innate immune response to GAS. A second possibility is that multiple different TLRs are able to respond to components of GAS. In this case, knockouts of single receptors or even two receptors might not be sufficient to eliminate the overall TLR signaling leading to transcription of proinflammatory cytokine genes.

As noted above, neutrophil recruitment is critical in protecting against lower doses of GAS; furthermore, invasion of the bacteria into the blood causes septic shock. These data indicate that the innate response to GAS involves the production of proinflammatory cytokines, such as IL-1β and TNF-α. An alternative pathway for the transcription of these genes is the sensing of bacterial products by the NOD receptors, a subfamily of NLRs. NOD receptors recognize fragments of bacterial cell walls, a binding event that induces their dimerization, followed by recruitment of RIP2 and E3 ubiquitin ligases. This leads to the formation of a ubiquitin scaffold and the recruitment of TAK1 and the IKK complex, resulting in NF1B activation. This pathway leads to transcription of pro-inflammatory cytokine genes.

These data indicate that MyD88 is not needed for the production of proinflammatory cytokines by macrophages in response to GAS bacteria. Therefore, it is likely that MyD88 is functioning as an adapter for IL-1R signaling in this pathway, rather than as an adapter for TLR signaling. IL-1R signaling is not required for macrophages to produce inflammatory cytokines.

Graph as shown in Figure A3.39D. In ASC-/- macrophages, IL-1β mRNA is induced, but the inflammasome is not activated. Therefore, the pro-IL-1β protein would be synthesized, but no mature IL-1β would be secreted. TNF-α is unchanged, as no

processing is required for TNF-α secretion.

Figure A3.39D

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Additional Questions 1) H1N1 Influenza A is an example of a(n): a) Hyperendemic b) Outbreak c) Pandemic (Correct Answer) d) Epidemic e) Endemic 2) COVID-19 binds to receptor. B cells and cytotoxic T cells to fight against the infection. a) ACE2, make antibodies and mark the virus for destruction, identify and destroy infected cells. (Correct Answer) b) CD155, make antibodies and mark the virus for destruction, identify and destroy infected cells. c) LDLR, identify and destroy infected cells, make antibodies and mark the virus for destruction. d) SRB2, make antibodies and mark the virus for destruction, identify and destroy infected cells. e) DC-SIGN, identify and destroy infected cells, make antibodies and mark the virus for destruction.

3) Adaptive Immunity, also knowns as immunity and has a(n) response and is as somatic recombination a) Natural, immediate, not classified b) Natural, immediate, classified c) Acquired, immediate, classified d) Acquired, slow, classified (Correct Answer) e) Acquired, slow, not classified 4) Mucosa-associated lymphoid tissue (is): a) Important for defense against infection at mucosal layers b) Promotes proliferation of infected cells c) Organizes responses to antigens that enter mucosal tissues d) A and C (Correct Answer) e) None of the above 5) is the elimination phagocytized microbe in macrophages, infected, reservoirs of infection a) Apoptosis b) Autoimmunity c) Cell-mediated immunity

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

d) Dysbiosis e) Humoral Immunity 6) is the nomenclature for cell membrane proteins expressed by cells of the immune system a) Major Histocompatibility Complex Type I and Type II b) Binomial nomenclature c) Cluster of Differentiation d) Neuraminidase and Hemagglutinin e) Immunoglobulin 7) is the process of coating a microbe with molecules that are recognized by receptor proteins a) Opsonization b) Antigen capturing c) Phagocytosis d) Clonal selection e) Pyroptosis 8) Which of the following are false about Dendritic cells a) Considered professional antigen-presenting cells b) Produced in the bone marrow c) Migrate to the liver where they present antigens to T cells circulating the bloodstream d) Capture antigen and load the antigen to MHC class I and II molecules e) Able to costimulate T cell activation 1. A defect in the T Cell Receptor complex prevents activation of T lymphocytes. Which component(s) is(are) most likely affected?

1. Ig𝞪 2. TCR 3. CD3 4. 𝛇-chain 5. C and D 2. What protein(s) is(are) responsible for signaling transduction in B cell lymphocytes?

1. Ig𝞪 2. CD3 3. Ig𝝱 4. A and C 5. A and B

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

3. Any B cell can produce only one of the two light chains, 𝝀 or □. If there is a massive proliferation of MOSTLY 𝝀-producing B cells, then this is an indication of: 1. Septic Shock 2. Allergic reaction 3. Malignant tumor 4. Infection 5. A and D 4. In the class I MHC pathway, the enzymatic cleavage of antigen peptides is defective.

Which one is most likely TRUE? 1. Class II MHC pathway is adopted 2. Class I MHC molecule is not expressed on the surface of the cell 3. CLIP molecule won't bind to the cleft of the MHC molecule 4. A and B 5. B and C 5. The Spanish flu, a.k.a. the 1918 flu pandemic, was one of the deadliest pandemics in human history. The pandemic was caused by the influenza A virus subtype H1N1. What do H and N stand for?

1. H: Hemoglobin, N: N-terminus 2. H: Hemagglutinin, N: N-terminus 3. H: Hemoglobin, N: Neuraminidases 4. H: Hemagglutinin, N: Neuraminidases 5. H: Histones, N: N-terminus 6. Which of the following information about the fluid mosaic model is NOT true?

1. It is composed of many different proteins and structures 2. In high temperatures, it allows for more fluidity in the membrane 3. Cholesterol is an essential component of the cell membrane because it maintains the fluidity of the membrane.

4. It is mosaic because it has a wide variety of materials 5. It is selectively permeable meaning it allows certain materials to enter the cell or restrains them.

7. Which of the following about CD4+ is incorrect?

1. CD4* count increases in HIV-infected adults 2. CD stands for cluster of differentiation 3. It has diverse specificities for peptide-class II MHC complexes 4. It kills cells infected with intracellular microbes, tumor cells 5. Its antigen receptor is alpha-beta heterodimers 8. Which of the following tissues is named incorrectly matching to each organ?

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

1. Liver: Kupffer cells 2. Bladder: Urocyst cells 3. Brain: Microglial cells 4. Lung: Alveolar macrophage 5. Spleen: Sinusoidal macrophages 9. Which of the following is the correct order of people who received the Nobel prizes for immunological research?

1. Landsteiner, Tonegawa, Porter & Edelman, Doherty & Zinkernagel, Hoffman & Steinman 2. Porter & Edelman, Tonegawa, Doherty & Zinkernagel, Hoffman & Steinman, Landsteiner 3. Porter & Edelman, Landsteiner, Doherty & Zinkernagel, Tonegawa, Hoffman & Steinman 4. Landsteiner, Porter & Edelman, Tonegawa, Doherty & Zinkernagel, Hoffman & Steinman 5. Porter & Edelman, Landsteiner, Tonegawa, Doherty & Zinkernagel, Hoffman & Steinman 10. Which of the following is correct for the features of peptide binding to MHC molecules?

1. Binds peptides only 2. The addition of peptide stabilizes MHC molecules 3. Displays only one peptide at a time with broad specificity 4. A & B only 5. A, B, & C 11. Why was Jenner an important figure in the history of immunology?

1. Discovered how inoculation works 2. Discovered the vaccination through a young boy to the disease 3. Made postulates to understand the relationship between a particular microorganism and disease 4. Found “antoxixin antibody” 5. None of the above 12. Which of the following is the correct choice for innate and adaptive immunity and B and T lymphocytes?

1. Innate immunity is immediate response and adaptive immunity is long time response B lymphocyte function as part of adaptive immune system and T lymphocyte function as part of immediate immune system 2. Innate immunity is long time response and adaptive immunity is immediate response B lymphocyte function as part of adaptive immune system and T lymphocyte function as part of immediate immune system

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

3. Innate immunity is long time response and adaptive immunity is immediate response B lymphocyte function as part of immediate immune system and T lymphocyte function as part of adaptive immune system 4. Innate immunity is immediate response and adaptive immunity is long time response B lymphocyte function as part of immediate immune system and T lymphocyte function as part of adaptive immune system 5. None of the above 12. There are two T cell receptors by function, but there is also T cell receptor(s) by structure, what is/are they called?

1. CD4 & CD8 2. TCR α 𝛽 & TCR gd 3. Alpha Beta 4. CD3 5. All of the above 13. Out of all the active enzymes that lead to protein synthesis, which one is different/unique because of its protein type and tell me what is the type?

1. PKC-kinase 2. ERK, JNK-kinase and phosphatase 3. Calcineurin-kinase 4. ERK, JNK-phosphatase only 5. Calcineurin-phosphatase 14. Which one of the following is NOT a mechanism to generate diversity in naive B cells?

1. P nucleotide addition 2. Exonuclease training 3. Multiple gene segments 4. Combinatorial diversity of H/L chain 5. Nontemplated N nucleotide addition 15. In what chain can we get autoreactive receptors and what is done to resolve the body’s antibodies from binding to self-antigens?

1. In both heavy and light chains; receptor editing 2. Heavy chain; apoptosis of self-antigens 3. Light chain; receptor editing 4. Heavy chain; inactivate antibody response 5. Light chain; apoptosis of self-antigen

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

16. Which is NOT an Epithelial barrier?

A. Skin B. Gastrointestinal tract C. Defensins D. Neutrophils E. Respiratory tract 17. Which is NOT a Cytokine?

A. IL-6 B. TNF-α C. CD4 D. IL-12 E. IFN 18. is a form of cell signaling where the cell induces behavior changes in close by cells by producing a signal.

A. Paracrine signaling B. Autocrine signaling C. Juxtacrine signaling D. Endocrine signaling E. Intracrine signaling 19. Who vaccinated James Phipps from smallpox by using Sarah Nelms cowpox lesions?

A. Robert Koch B. Louis Pasteur C. Lady Mary Wortley Montagu D. Elie Metchnikoff E. Edward Jenner

1. ( chapter 3) Which of the following features is NOT optimal for the protectiveness of

the immune system? a. Normal cellular expression of MHC Class I and II b. Specificity of CD8 and CD4 coreceptors for Class I and II c. Normal cellular expression of regulatory T cells d. Mutation that leads to dysfunction of TAP molecules e. Function of CD8+ cells as cytosolic T lymphocytes (CTLs) and of CD4+ as helper T cells

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

2. ( chapter 3, 4) Which of the following is INCORRECT about antigen recognition?

a. Antigen receptor of T cells can distinguish between intracellular and extracellular microbes b. Antigen receptors are specific c. B lymphocytes use membrane-bound antibodies for antigen recognition d. Antigens that are presented to B lymphocytes are in its unprocessed form e. The structure that is responsible for antigen recognition is the 3 complementarity-determining regions 3. (chapter 3) Which of the following structures can pass through the plasma membrane?

I. 𝜶 chain of Class I MHC II. β chain of Class I MHC III. 𝜶 chain of Class II MHC IV. β chain of Class II MHC

a. b. c. d. e.

III ONLY I and II ONLY I and III ONLY I, III, IV ONLY I, II, III, IV

4. (chapter 4) What happens when both of the N-terminal ends of an immunoglobulin is

chopped out? a. All of the disulfide bridges will be gone b. Antigen-elicited response can still occur c. Antigen-elicited response can not occur anymore d. The hinge will be broken e. It will have no effect on the cell or its response

5. : Which of the following statements are CORRECT about the types of B and T

lymphocytes?

B lymphocytes are mediators of humoral immunity while, T lymphocytes are mediators of cell mediated immunity II. B lymphocytes recognize peptide fragments of protein antigens present on surface of Major Histocompatibility complex (MHC) III. T lymphocytes consists of three main types: Helper T, Neutrophil T, and Regulatory T IV. T lymphocytes are generated and mature in the bone marrow while, B lymphocytes in the thymus organ A. I, III I.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

B. I ONLY C. III, IV D. II, III, IV E. II ONLY 6. (Chapter 1&2): Which of the following statements of active and passive immunity

are INCORRECT? A. Both active and passive immunity provide and develop resistance to later infection in an individual.

B. Active immunity is induced in an individual by an infection or vaccination.

C. Passive immunity is given to an individual through the transfer of antibodies and lymphocytes from an actively immune individual.

D. An individual with active immunity becomes immune to the microbe as a result of primary immune response.

E. A pregnant mother gives her child passive immunity through her placenta before birth and also through breast milk after birth.

7. ( Chapter 4) Which type of antibody plays a major role and is the MOST effective way

of activating complement?

A. IgG1 B. IgG2 C. IgG3 D. IgM E. IgA 8. (Chapter 3) Peptides must be transported to what organelle in order to form peptide-MHC complexes?

A. Mitochondria B. Plasma membrane C. Lysosome D. Golgi apparatus E. Endoplasmic reticulum

9. (COVID19 Article from Nature: “Profile of a Killer Virus” from 5/21) SARS-CoV-2

has proven to be much more contagious than previous pathogens in the coronavirus family. David Cyranoski, a writer for Nature, has noted how SARS-CoV-2 “evolved an array of adaptations that make it much more lethal than the other coronaviruses humanity has met so far.” Why is that so?

A. SARS-CoV-2 has a genomic “proofreading” mechanism, which prevents the virus from accumulating mutations that could weaken it.

B. SARS-CoV-2 can frequently recombine with other coronaviruses, swapping chunks of its RNA to create more formidable versions of itself.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

C. The spike proteins of SARS-CoV-2 bind efficiently to human ACE2 proteins, making it uniquely equipped for forcing entry into cells.

D. A and C E. A, B, and C 10. ( Chapter 2) Immediate innate immune response first involves neutrophil and monocyte

migration from the blood into extravascular tissue. These leukocytes have membrane-bound receptors called integrins that allow firm adhesion to the endothelium, thereby anchoring themselves to the luminal surface and facilitating their passage through the epithelia to the site of infection. Which of the following are integrins that are involved in this extravasation process?

I. LFA-1 II. VLA-4 III. CD3 IV. CTLA-4 A. I ONLY B. III ONLY C. I and II D. I, II, and III E. II and IV 11. (Chapter 3) Intracellular antigens of the endogenous pathway are polyubiquitinated and

destined for degradation via proteasomes. Which of the following is false regarding these essential protein complexes?

A. A typical proteasome is composed of three subcomponents: a 20S Core Particle and two 19S Regulatory Particles.

B. The Core Particle is capped at each end by a 19S Regulatory Particle.

C. Immunoproteasomes are efficient at cleaving cytosolic proteins into the necessary peptide sizes needed for class I MHC binding.

D. Because the 20S CP of an immunoproteasome is composed of different subunits than a constitutive proteasome, the same antigen peptide can be cut into different fragments.

E. Because the 19 RP of an immunoproteasome is composed of different subunits than a constitutive proteasome, the same antigen peptide can be cut into different fragments. (THIS IS FALSE) 12. (Chapter 5) T cell activation requires stimulation of a multitude of positive and negative

costimulatory receptors to regulate proliferation and differentiation of the T lymphocyte. Which of the following shows an incorrect pairing between T cell receptor and its costimulatory ligand?

A. CD28 … binds to … B7-1 and/or B7-2 B. ICOS … binds to … CD275

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

C. PD-1 … binds to … B7-H1 and/or B7-DC D. CTLA4 … binds to … PD-L1 and/or PD-L2 (THIS IS INCORRECT) E. All of the above pairings are correct 13. What are the four major categories of pathogens?

A. Viruses, bacteria, and parasites B. Bacteria, fungi, and parasites C. Viruses, prokaryotes, eukaryotes D. Viruses, bacteria, fungi, parasites 14. What is a mechanism of evasion of innate immunity?

A. Resistance to phagocytosis B. Acceptance of antimicrobial peptides C. Compliance to complement activation D. Compliance to reactive oxygen intermediates in phagocytes 15. The first immunoglobulin heavy chain class to be expressed on the surface of a newly

produced B-cell is A. IgA B. IgD C. IgE D. IgG E. IgM 16. Which of the following infectious diseases was prevented by the first successful

vaccination?

A. Polio B. Tuberculosis C. Smallpox D. Tetanus E. Rubella 1.

A. B. C. D. E.

Which organ/tissue does not belong among the Peripheral Lymphoid System?

Spleen Lymph Node Kidney Mucosal system Cutaneous system

What are the first stages of a new infection that take place in the immune system?

A. Adaptive immune system responds rapidly, infection is under control B. Innate immune system responds rapidly, infection is under control 2.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

C. Passive immunity mediates from existing antibodies to limit infectivity D. Virus causes B cells to activate Phagocytes to attack and destroy the antigen E. B and T lymphocytes recognize the virus and stimulate proper response sequence to eliminate the virus 3.

A. B. C. D. E.

4.

A. B. C. D. E.

Which two types of immunity require antibodies and T lymphocytes?

Passive and Active Specific and Nonspecific Humoral and Cell-Mediated Adult and Neonatal Innate and Adaptive

Which cell type is required for all humoral immune responses?

B Lymphocytes Dendritic cells Natural Killer (NK) cells Helper T cells Cytolytic T lymphocytes

1.

Where is tumor necrosis factor alpha (TNF) secreted?

A. From virally infected cells B. From bacterial infected cells C. From macrophages D. From dendritic cells E. From epithelial cells 2.

Where would you most likely find a TLR that recognizes viral RNA? A. In the nucleus B. On the cell surface C. In the endosome/lysosome membrane D. In the cytoplasm E. In the mitochondria

3.

Which of the following does NOT apply to innate immune mechanisms?

A. It involves pathogen recognition receptors (PRRs) B. It consists of pre-existing mechanisms that are broadly specific C. It involves the anatomical barriers of the skin and mucosal surfaces D. It occurs in minutes to hours

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

E. It is highly specific and is more rapid and effective with each subsequent exposure 4.

In a lymph node, which cells utilize fibroblastic reticular cell networks: A. Neutrophils B. Dendritic cells C. T cells D. B cells E. Both B and C are correct

Which of the following is not true about class II MHC molecules?

A. It is a member of the Ig superfamily and possesses Ig domains B. Is heterodimeric, containing a 22 kDa α chain and a 28 kDa β chain C. Only the α chain passes through the plasma membrane D. α1 and β1 domains form a peptide-binding cleft E. MHC class II present to CD4+ T cells Dendritic cell maturation occurs in A. Epithelial tissue of the skin B. Lymphatic vessels C. The blood D. Spleen E. Lymph nodes Which of the following types of cells do NOT express class II MHC A. Dendritic cells B. Mononuclear phagocytes C. Thymic epithelial cells D. B Lymphocytes E. All nucleated cells express class II MHC Which of the following is true about proteolysis and binding of peptides in class I MHC ?

A. TAP is an complex composed of stacked rings of proteolytic enzymes that degrades unfolded proteins into peptides.

B. Peptides that bind originate from the extracellular matrix C. MHC molecules are located in the cytosol while the peptides produced by proteasomal digestion are synthesized in the ER D. Tapasin links newly synthesized class I MHC molecules to TAP molecules in the ER membrane E. Proteins are degrades into 2-3 peptide fragments before associating to TAP molecules

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

1. Which hypervariable region has the greatest variability and contributes most to antigen binding?

1. CDR1 2. CDR2 3. CDR3 4. Fc 5. Cα2 2. How many antigen-binding sites does each IgA antibody molecule have?

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

What model was used to generate hybridomas? a. Shark b. Drosophila c. Mouse d. Zebrafish e. Guinea pig 4. a. b. c. d. e.

Which cells are fused together to create a hybridoma?

T cells + myeloma B cells + myeloma T cells + granuloma B cells + granuloma Fab + Fc

1. A property of the immune system is known as Immunological tolerance, which statement best explains this property? a. naive or memory lymphocytes are activated by antigens they undergo proliferation, generating many thousands of cells all with the same antigen receptors and specificity b. Immune responses are specialized and different responses are designed to defend best against different types of microbes c. Immune system is able to react against an enormous number of microbes and other foreign antigens but it normally does not react against the hosts own potentially antigenic substances also called self antigens d. Immune system remembers every encounter with antigen

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

e. Immune system does attack its own host cells but because of evolution host cells are able to withstand it 2. The frequency of memory cells with age a. Increase up to 5% compared to newborn b. Decrease up to 5% compared to newborn c. Decrease up to 50% compared to newborn d. Increase up to 50% compared to newborn e. Increase up to 99% compared to newborn 3. What is not a property of a class 1 MHC a. Possesses Ig domains b. Larger 45 kDa glycoprotein α chain c. α1 andα2 domain α-helix and β-pleated sheet form walls and floor of peptide binding site, respectively d. A peptide-binding cleft is formed by the pairing of the α1 and β1 domains e. Alpha 1 and 2 chains 4. Which of these roles of the Immune system are False? a. The immune system defends against infections is a major role and without it susceptibility to infections increases greatly b. The immune system is able to adapt to any antigens, those with stronger immune systems have no need for vaccinations c. The immune system controls tissue regeneration and can repair damaged tissues d. The Immune system can induce pathologic inflammation and these can be identified as allergic or autoimmune diseases e. The immune system does play a role in tumor suppression 5. Which non-specific defense cells are specialized in attacking cancer and virus infected cells? a. Natural killer cells b. Macrophages c. Plasma cells d. Helper T-lymphocytes e. Basophils 6. Which of these toll-like receptors are specific for an endotoxin made by gram-negative bacteria? a. TLR-1 b. TLR-2 c. TLR-3 d. TLR-4 e. TLR-8

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

7. Without , there is no immune response. a. Antibodies b. Antigens c. Plasma cells d. T lymphocytes e. B lymphocytes 8. Activation of naive T lymphocytes is best achieved by which antigen presenting cell? a. Macrophages b. Neutrophils c. Dendritic Cells d. Mast cells e. B cells 9. What is the role of phagocytes in the process of adaptive immunity? a. Mediators of adaptive immune response b. Proteins made by immune system cells used to block or eliminate potentially harmful molecules c. White blood cells d. Ingest and destroy microbes e. Increase likelihood of cell death 10. Which of the following are considered to be effector cells in a cell-mediated immune response?

I. Dendritic Cells II. Macrophages III. B Lymphocytes IV. T Lymphocytes V. Granulocytes a. I and II b. II, IV, V c. II, III, V d. I, IV, V e. I, III, V 11. Which of the following is NOT true regarding humoral immunity? a. Mediated by antibodies produced by B lymphocytes b. Antibodies defend against microbes by neutralizing toxins c. Mediated by antibodies produced by T lymphocytes d. Deals with extracellular microbes e. All of the above are true 12. What is the meaning of the abbreviation ”CD” in the field of immunology? a. Cluster of Differentiation b. Cluster of Dendrites c. Cells of Differentiation

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

d. Core of Denaturation e. Center of Determination 13. If there is a mutation in the gene that is responsible for production of TLR, which is likely to happen? a. b. c. d. e.

Production of antiviral cytokines, type I interferon, will increase.

The individual will become immune to virus and bacterial infections.

There will be no delay in inflammatory response.

Alternative macrophage activation will occur.

Intracellular bacteria are eliminated by phagocytes.

14. Which of these statements is not true regarding T cell receptors? a. Antigen receptors of T cells cannot distinguish between intracellular and extracellular microbes b. Some T cells have receptors for small molecules and metal ions. c. T cell activation requires recognition of MHC-associated peptide antigen by the TCR and simultaneous recognition of the MHC molecule by the coreceptor. d. Each TCR, and hence each clone of CD4 + or CD8 + T cells, recognizes one peptide displayed by one of the many MHC molecules in every individual. e. NK-T cells do not express TCRs 15. How do vaccines confer long-lasting protection? a. b. c. d. e.

Immunologic memory Immunological tolerance Innate recognition Active immunity clonal expansion

16. Operation warp speed is an aggressive program to deliver COVID-19 vaccines to Americans this year. Of the five vaccines selected, which one platform has ever been used in an approved shot? a. b. c. d. e.

Pfizer Merck AZ J&J Moderna

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 1 1. What are the two types of adaptive immunity, and what types of microbes do these

adaptive immune responses combat? a. Humoral immunity (extracellular microbes) and cell-mediated immunity (intracellular) via T lymphocytes b. Both primarily combat extracellular microbes. c. Humoral Immunity: i. Also called antibody – mediated immunity ii. Antibodies are produced by plasma B cells with the help of helper T cells.

1. Antibodies kill the target iii. Combats pathogens that are circulating freely or occur outside the infected cells.

1. Example: viruses and bacteria d. Cell – Mediated Immunity: i. Mediated by T – lymphocytes ii. Occurs inside the infected cells. iii. Antigen of a pathogen is expressed on APCs. iv. Cytokines secreted by helper T cells help the T lymphocytes to bind to the infected cells through MHC. 1. Leads to differentiation of T lymphocytes into cytotoxic T cells. v. Infected cells die of lysis vi. Destroy intracellular pathogens and infected host cells to prevent further expansion of the disease.

2. What are the principal classes of lymphocytes, and how do they differ in function? a. Lymphocytes aka white blood cells i. Main cells of body’s defense mechanism b. B-cells- express surface immunoglobulin, which are antigen receptors.

Humoral immunity: can differentiate into plasma cells that secrete antibodies or memory cells that improve immune responses. i. Neutralization of microbe, phagocytosis, complement activation. ii. Recognize soluble or cell surface antigens. c. T-lymphocytes express helper T or cytotoxic T cells. After activation, they

express MHC, which present protein antigens from ingested microbes. i. Helper- CD4 1. Activation of macrophages, inflammation, activation of B lymphocytes 2. Identify antigens on APCs. 3. Secrete cytokines.

4. Initiate immune responses. ii. Cytotoxic-CD8 1. Killing of infected cell 2. Identify antigens on the surface of the infected cells and destroy them via lysis. iii. Regulatory

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas 1. Suppression of immune response

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

d. NK Cells i. Elimination of infected/ malignant cells ii. Recognize certain surface proteins characteristic to: 1. Viruses 2. Bacteria 3. Cancers iii. Control viral infections by secreting interferons.

1. Interferons – signaling proteins which are displayed by those cells

which are infected by viruses.

3. What are the important differences among naive, effector, and memory T and B lymphocytes? a. Naive cells -> mature T or B cells that are not activated by a microbe antigen yet. i. Pass through circulation in lymph nodes or wait in the tissue. ii. All lymphocytes which exit the main lymphoid organs are naïve iii. Mobilized through the peripheral lymphoid organs in order to encounter and eliminate foreign antibodies. b. Effector cells -> are activated by a pathogen and elicit an antimicrobial defense to protect or eliminate pathogens. (Most die, but some can live on.) i. Functional lymphocytes that have encountered an antigen. ii. Example: cytotoxic T lymphocyte iii. Effector T – lymphocytes: 1. Travel to peripheral locations of infection and eliminate disease causing microorganisms. iv. Effector B – Lymphocytes: 1. Stay in the lymphoid organs and bone marrow.

2. Secrete antibodies that pass into the circulation and eradicate the pathogens. c. B cells - secrete antibodies that bind to antigens, or initiate the complement system. d. T cells - recognize, ingest, and destroy microbes, display their peptides to B cells activating their humoral response. e. Memory B cells--> live even after the immune response dies down. They change isotopes of antibody immunoglobulin to improve affinity and specialize for antigens. Improve reaction to second exposure. i. Crucial for launching the secondary immune response if the same pathogen attacks the body later in life.

4. Where are T and B lymphocytes located in lymph nodes, and how is their anatomic separation maintained? a. Lymph Node: i. Made of the outer cortex and inner medullar zone.

1. Cortex contains primary and secondary follicles. b. B lymphocytes in follicles in peripheral lymphoid organs i. Secondary Follicles

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

c. T lymphocytes in T cell zone of cortex of lymph nodes i. Parafollicular cortex (aka paracortical areas) d. Kept there by cytokines called chemokines, which are secreted by stromal cells in

the follicle and the parafollicular cortex. i. Chemokines – proteins which act as attractants and are secreted by the endothelial cells of the lymph nodes. e. Lymphocytes are transported to the lymph nodes or organs through specialized organs aka HEV’s (high endothelial venules). i. Directed towards different areas of the lymph nodes via chemokines.

5. How do naive and effector T lymphocytes differ in their patterns of migration? a. Naive T lymphocytes flow through the peripheral organs and recirculate until activated by an antigen. b. Effector T lymphocytes are activated in the lymph node but go to the marginal or peripheral site of infection where the antigen may be located.

Chapter 2 1. How does the specificity of innate immunity differ from that of adaptive immunity?

a. Innate immunity is directed against common molecular patterns shared by different microbes and the products of damaged cells and is mediated by cell surface receptors and secreted proteins of limited diversity. i. Recognizes and eliminates dead cells and microbes. b. Adaptive immunity uses an extremely diverse set of antigen receptors to recognize a wide range of microbial and nonmicrobial antigens.

2. What are examples of microbial substances recognized by the innate immune system, and what are the receptors for these substances? a. Lipopolysaccharide recognized by toll-like receptor-4 (TLR-4) b. Flagellin recognized by TLR-5. c. Microbial DNA recognized by TLR-9. d. Viral RNAs recognized by TLR-3, -7, and –8. e. Bacterial peptidoglycans recognized by NOD-like receptors. f. Mannans recognized by mannose receptor and mannose binding protein.

3. What is the inflammasome, and how is it stimulated? a. The inflammasome is a multiprotein complex found in the cytoplasm of phagocytes, dendritic cells, and other cell types. It proteolytically cleaves a precursor of the cytokine interleukin-b (IL-1b), generating an active proinflammatory form of IL-1b that is released from the cell. The inflammasome has a NOD family molecule called NLRP3 and the proteolytic enzyme caspase 1.

NLRP3 responds to many different stimuli that show cell infection or injury, leading to activation of caspase-1, which then cleaves the IL-1b precursor. Stimuli that activate the inflammasome include various microbial products, crystals such as sodium urate, reduced potassium concentration, and reactive oxygen species.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

4. What are the mechanisms by which the epithelium of the skin prevents the entry of

microbes? a. The skin supplies an impermeable epithelial barrier by virtue of a surface layer of keratin and by tight junctions between keratinocytes. These epithelial cells secrete antimicrobial peptide antibiotics, and the skin also has protective intraepithelial lymphocytes. b. The continuous epithelia also protect the gastrointestinal tract, genitourinary tract, respiratory tract, and skin. c. Contents of the epithelia: i. Tight adhering cells 1. Provide mechanical support ii. Mucosal Epithelial cells 1. Produce keratins which prevents microbes from infecting the epithelial cells iii. Peptide antibiotics 1. Produce by epithelial cells (defensins and cathelicidins) iv. Intraepithelial T lymphocytes 1. Act against infectious pathogens that breach epithelia 5. How do phagocytes ingest and kill microbes? a. Phagocytes have a range of receptors that recognize microbial carbohydrates and Fc receptors that recognize microbes coated (opsonized) by antibodies. i. Microbes that bind to these receptors are internalized into phagosomes, which fuse with lysosomes, where the microbes are destroyed by reactive oxygen and nitrogen species and lysosomal enzymes. b. The mechanism of phagocytosis begins with the adherence of the phagocytes to the microbes. (Note - in the case of bacteria, phagocytes adhere with the help of opsonin's) 6. What is the role of MHC molecules in the recognition of infected cells by NK cells, and what is the physiologic significance of this recognition? a. NK cells recognize pathogen infected cells and later respond by killing the infected cells via the secretion of IFN-gamma (macrophage activating cytokine). b. NK cells express inhibitory receptors that recognize MHC class I molecules on host cells and can then inhibit NK cell activation. In virally infected cells, MHC class I molecules are downregulated and therefore fail to engage inhibitory receptors, and at the same time, ligands for activating NK cell receptors are expressed. As a result, NK cells are activated to kill these infected cells.

7. What are the roles of the cytokines TNF, IL-12, and type I interferons in defense against infections? a. TNF stimulates inflammation in part by helping to recruit neutrophils and monocytes to sites of infection. IL-12 made by macrophages and dendritic cells

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

contributes to NK cell and T cell activation. Type I interferons inhibit viral replication (inducing an antiviral state). i. TNF are mainly involved in employing monocytes in blood neutrophils to the site of infection. ii. TNF possess systemic effects comprising fever by reacting on the hypothalamus. iii. Thrombus formation is promoted by TNF at high concentrations which reduces blood pressure. iv. Severe clinical and pathologic manifestation of septic shock is caused by high levels of TNF. v. IL-12 Really activates NK cells, which in turn activates macrophages. vi. Type –I interferons are produced by dendritic cells upon infection by the virus. This cytokine inhibits viral replication and prevents infection spread.

8. How do innate immune responses enhance adaptive immunity? a. Innate immune responses induce the expression of costimulators on dendritic cells that can provide second signals for T cell activation. Innate immune cells also make cytokines that promote the adaptive immune response. Complement activation as part of the innate immune response can lead to the generation of complement fragments that enhance B lymphocyte activation.

Chapter 3 1. When antigens enter through the skin, in what organs are they concentrated? What cell

type(s) plays an important role in this process of antigen capture? a. Antigens that enter through the skin are captured by dendritic cells that live in the epidermis and dermis, and the dendritic cells transport the antigens to the skin-draining lymph nodes, where the antigens are displayed to lymphocytes.

2. What are MHC molecules? What are human MHC molecules called? How were MHC molecules discovered, and what is their function? a. Major histocompatibility complex (MHC) molecules are cell surface proteins that bind antigenic peptides and display them for recognition by T cells. Human MHC proteins are called HLA molecules. They were initially discovered as products of polymorphic genes that mediate transplant rejection. Their physiologic function is peptide antigen presentation to T cells.

3. What are the differences between the antigens that are displayed by class I and class II MHC molecules? a. Proteins that are produced in or enter the cytosol and processed by the proteasome are presented by class I MHC molecules. Proteins internalized into vesicles by endocytosis and processed by lysosomal proteases are presented by class II MHC molecules.

4. Describe the sequence of events by which class I and class II MHC molecules acquire antigens for display.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

a. Protein antigens in the cytosol are cleaved into peptides by proteasomes, and the peptides are transported into the endoplasmic reticulum by the TAP pump. Once inside the ER, these peptides bind to newly produced MHC class I molecules. The peptide-class I MHC complex is then transported to and displayed on the cell surface. MHC class II a and b chains are produced in the endoplasmic reticulum, where they assemble with each other and with an invariant chain that occludes the antigen binding cleft. The MHC class II-invariant chain complex is transported to a late endosomal/lysosomal compartment, where the invariant chain is degraded, leaving a peptide called CLIP in the cleft. Proteins internalized by the endocytic pathway are degraded in late endosomes and lysosomes into peptides. Specific peptides displace CLIP and bind tightly to the cleft of the MHC class II molecule, which is then transported to the cell surface.

5. Which subsets of T cells recognize antigens presented by class I and class II MHC molecules? What molecules on T cells contribute to their specificity for either class I or class II MHC-associated peptide antigens? a. CD4+ helper T cells recognize peptide antigens bound to class II MHC molecules, and CD8+ cytotoxic T lymphocytes recognize MHC class I-peptide complexes.

The CD4 coreceptor of helper T cells can bind to MHC class II molecules, and the CD8 coreceptor of cytotoxic T cells binds to MHC class I molecules.

Chapter 4 1. What are the functionally distinct domains (regions) of antibody and TCR molecules?

What features of the amino acid sequences in these regions are important for their functions? a. Antibody and T cell receptor (TCR) proteins have variable domains that are involved in antigen recognition and constant domains that, in the case of antibodies, mediate effector functions. Variable domains have hypervariable regions (sequences that differ among different antibodies or TCRs) that form the binding sites for antigens.

2. What are the differences in the types of antigens recognized by antibodies and TCRs? a. Antibodies can recognize many types of molecules, including small chemicals, proteins, carbohydrates, lipids, and nucleic acids. In proteins, antibodies can recognize conformational or linear epitopes. TCRs can recognize only linear peptides bound to the clefts of MHC molecules.

3. What mechanisms contribute to the diversity of antibody and TCR molecules? Which of these mechanisms contributes the most to the diversity? a. The joining of segments of antibody and TCR genes in developing lymphocytes, known as V-D-J recombination, is responsible for the diversity of antibodies and TCRs. Variations in nucleotide sequences introduced using different V, D, and J segment combinations (combinatorial diversity) and during V-D-J joining

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

(junctional diversity) contribute to diversity, with junctional alterations making the largest contribution.

4. What are some of the checkpoints during lymphocyte maturation that ensure survival of the useful cells? a. The first checkpoint in B and T cell maturation involves the selection of pre-B and pre-T cells that have productively rearranged the µ heavy-chain gene in the case of B lineage cells and the TCR b chain gene in the case of developing T cells.

The second checkpoint is after production of complete antigen receptors and ensures that only cells with the proper V-D-J rearrangement can mature. Positive selection is a process in which T cells that can recognize self MHC molecules weakly can survive and express the type of coreceptor that matches the type of MHC molecule recognized.

5. What is the phenomenon of negative selection, and what is its importance? a. Negative selection results in the deletion or editing of strongly self-reactive lymphocytes. This process eliminates many self-antigen-reactive lymphocytes, in the thymus for T cells and in the bone marrow for B cells.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

Chapter 5: Additional Questions 1. What are the components of the TCR complex? Which of these components are

2.

3.

4.

5.

6.

7.

responsible for antigen recognition and which for signal transduction? a. The T cell receptor (TCR) complex is made up of the TCR a and b chains, which are responsible for antigen recognition, and the CD3 complex and z homodimers, which are needed for signal transduction.

What are some of the molecules in addition to the TCR that T cells use to initiate their responses to antigens, and what are the functions of these molecules? a. Molecules other than the TCR used by T cells to respond to antigens include the CD4 and CD8 coreceptors, which bind to class II and class I MHC molecules, respectively; costimulatory receptors such as CD28, which bind to costimulators expressed on activated APCs; and adhesion molecules such as the integrin LFA-1, which mediate T-cell adhesion to APCs and control the migration of the T cells.

What is costimulation? What is the physiologic significance of costimulation? What are some of the ligand-receptor pairs involved in costimulation? a. Costimulation refers to signals delivered to a lymphocyte that are needed for lymphocyte activation but are independent of antigen receptor signaling.

Costimulatory signals are commonly referred to as a "second signal" and provide lymphocytes with the information that the antigen they are recognizing may be of microbial origin. B7-1 and B7-2 are the major costimulators on antigenpresenting cells, which bind to CD28 on T cells.

Summarize the links among antigen recognition, the major biochemical signaling pathways in T cells, and the production of transcription factors. a. Antigen recognition results in coreceptors in T cells bringing the Lck tyrosine kinase in proximity to CD3 and z chain ITAMs. Phosphorylation of the ITAMs results in the recruitment and activation of ZAP-70 tyrosine kinase, which in turn starts many different signaling pathways by activating different downstream enzymes. Some of these pathways include activation of phospholipase Cg, resulting in calcium signaling and the subsequent activation of the NFAT transcription factor; activation of PKCF, resulting in the activation of the NF-κB transcription factor; and activation of MAP kinases, leading to the production of the AP-1 transcription factor.

What is the principal growth factor for T cells? Why do antigen-specific T cells expand more than other (bystander) T cells on exposure to an antigen? a. The major growth factor for T cells is interleukin-2 (IL-2). It is produced by T cells in response to antigen receptor signals and costimulation. T cells that have recognized antigens express increased levels of receptors for IL-2 and thus preferentially respond to the growth factor during immune responses to the antigens.

What are the mechanisms by which CD4+ effector T cells activate other leukocytes? a. CD4+ helper T cells activate other cells (B lymphocytes, macrophages) by the surface molecule CD40-ligand engaging CD40 on the other cells and by the actions of secreted cytokines.

What are the major properties of memory T lymphocytes?

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

a. Memory cells survive after the antigen is cleared and respond more rapidly and effectively to antigen exposure than do naive cells.

8. Why do naive T cells migrate preferentially to lymphoid organs and differentiated effector T cells (which have been activated by antigen) migrate preferentially to tissues that are sites of infection? a. Naive T cells express the adhesion molecule L-selectin and the chemokine receptor CCR7, which mediate homing to lymph nodes. Differentiated effector cells lose expression of these molecules and instead express adhesion molecules that bind to molecules on endothelium exposed to inflammatory cytokines. The effector cells also express receptors for chemokines produced at sites of inflammation, thus preferentially migrating to these sites.

Chapter 6 Additional Questions 1. What are the types of T lymphocyte-mediated immune reactions that eliminate microbes

that are sequestered in the vesicles of phagocytes and microbes that live in the cytoplasm of infected host cells? a. Intracellular microbes that reside in phagosomes are eliminated by helper T cells, especially those of the Th1 subset that activate phagocytes to destroy ingested microbes. Microbes that reside in the cytosol may be eliminated by CD8+ T cellmediated killing of the infected cells, thus eliminating the reservoir of infection.

2. What are the major subsets of CD4+ effector T cells, how do they differ, and what are their roles in defense against different types of infectious pathogens? a. Th1 cells secrete the cytokine IFN-g, which activates macrophages to kill phagocytosed microbes. Th2 cells secrete IL-4 and IL-13, which stimulate intestinal mucus production and gut peristalsis, and IL-5, which activates eosinophils. IL-4 and IL-13 secreted by Tfh cells induces B cell IgE production, and IgE bound to eosinophils and mast cells contributes to immunity against helminths. Th2 cells are involved in defense against helminths. Th17 cells secrete IL-17, which recruits neutrophils and are involved in defense against extracellular fungi and bacteria.

3. What are the mechanisms by which T cells activate macrophages, and what are the responses of macrophages that result in the killing of ingested microbes? a. Activated Th1 cells secrete cytokines such as interferon-g that activate macrophages. These helper T cells also express CD40 ligand, which can activate macrophages by engaging CD40. Activated macrophages then induce NADPH oxidase activity to generate reactive oxygen species and nitric oxide synthase to make nitric oxide. These free radicals can destroy ingested microbes. Activated macrophages also produce increased amounts of lysosomal enzymes, which help to destroy microbes, and other molecules that promote inflammation and call more leukocytes into the reaction.

4. How do CD8+ CTLs kill cells infected with viruses? a. CD8+ T cells that recognize antigen on an infected tissue cell release granule that have perforin and granzymes, which enter the infected cells recognized by the T lymphocytes and induce apoptosis of these infected cells.

Basic Immunology: Functions and Disorders of the Immune System 7th Edition by Abbas

5. What are some of the mechanisms by which intracellular microbes resist the effector

mechanisms of cell-mediated immunity? a. Some intracellular microbes evade immunity by preventing phagolysosome fusion. Other intracellular microbes express molecules that can inactivate host complement responses. Many viruses inhibit antigen presentation, and some may inactivate effector T cells.