Midterm Quizzes

Maturing dendritic cells that migrate to a lymph node from peripheral tissues end up mainly in: A) T cell zones B) The medullary sinus C) High endothelial venules D) Efferent arterioles E) Follicles

Answer: A Migrating dendritic cells express the chemokine receptor CCR7 and move into the T cell zones, where SLC (CCL21) and ELC (MIP-3b), the chemokines that bind CCR7, are expressed. In this location, the dendritic cells they are most likely to interact with are naive T cells that also migrate to the same area.

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) CD28 B) Tumor necrosis factor C) Inducible nitric oxide synthase (iNOS) D) Interleukin-12 E) E-selectin

Answer: A (CH. 2) 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-a (TNF-a), 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.

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) Circulating anti-tetanus toxin antibodies B) Intraepithelial lymphocytes presents in skin C) Circulating neutrophils migrating to the site of the wound D) Epithelial barrier function of the skin of her foot E) Soluble cytokines that induce a local inflammatory response

Answer: A (CH. 2) 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 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. Intraepithelial 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.

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 (NK 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) Failure to form viral peptide-class I MHC complexes B) Lack of cells whose activation is normally inhibited by self class I major histocompatibility complex (MHC) C) Lack of cells that are activated by IL-15 D) Impaired interferon (IFN)-γ production during early phases of viral infection E) Impaired granzyme B-dependent killing of virally infected target cells

Answer: A (CH. 2) 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-g as part of the early innate response to viral infection.

A child who suffers from a persistent viral infection is found to have a deficiency in lymphocyte production and very few T and B cells. Other bone marrow-derived cells are produced in normal numbers, and 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 the most likely explanation for why this therapeutic approach would fail? A) Donor T cell viral antigen recognition is restricted by MHC molecules not expressed in the patient. B) Viral infections are cleared by antibodies, not T cells. C) T cells recognize peptides, not viral particles. D) The patient's own immune system would destroy the transfused T cells before they could respond to the viral infection. E) In responding to the previous infection, the donor would have used up all his T cells specific for that virus.

Answer: A (CH. 3) T cells are "self MHC restricted," meaning they specifically recognize infected cells that display microbial peptides displayed by self MHC molecules. There may be no MHC molecules shared by donor and patient, and therefore the transfused T cells would not recognize virus-infected cells in the patient. Because the patient has very few B cells and T cells, his immune system is unlikely to be able to recognize and destroy (i.e., "reject") the transfused T cells. T cells do not recognize structures on intact viral particles but rather peptides derived from viral proteins bound to MHC molecules. Prior viral infection in the donor would be expected to generate memory T cells specific for the virus.

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)-g 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-γ. B) The therapeutic peptides could replace the damaged myelin and restore neuronal function. 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.

Answer: A (CH. 5) Altered peptide ligands are synthetic peptides in which the TCR contact residues have been changed, so that the peptide induces only partial responses by the responding T cell. These peptides still bind to the same MHC molecules as the original peptides, but they can cause T cell inactivation (anergy) or change in the cytokines the T cell produces. Altered peptide ligands do not interfere with processing of the natural proteins nor can they bind to TCRs without being presented by MHC molecules. There is no basis to say that peptides can down-regulate major MHC expression or replace damaged proteins in the myelin sheath.

All of the following are early T cell events that occur after antigen recognition by the TCR EXCEPT: A) 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 B) Formation of the immunologic synapse C) Clustering of the TCR and coreceptors leading to phosphorylation of ITAMs on CD3 by Lck D) Recruitment of signaling molecules, such as LAT, to glycolipid-enriched domains known as lipid rafts E) Binding of CD28 with costimulators on APCs in the cSMAC, resulting in signal transduction activation

Answer: A (CH. 5) On binding of the TCR complex with MHC-associated peptides on an antigen-presenting cell (APC), several T cell surface proteins and intracellular signaling molecules are rapidly mobilized to the site of contact, known as the immunologic synapse. Molecules that are recruited to the central supramolecular activation cluster, or center of the synapse, include the TCR complex (TCR, CD3, and z chains), CD4 or CD8 coreceptors, and costimulatory molecules (CD28). The clustering of signaling molecules results in the phosphorylation of ITAMs on CD3 by CD4- or CD8-associated Lck. Integrins remain at the peripheral zone of the synapse and stabilize the binding of the T cell to the APC. LAT is a transmembrane adaptor molecule recruited to the synapse whose cytoplasmic tail forms part of a scaffold of signaling molecules.

Which one of the following statements about T cells involved in an immune response is NOT true? A) 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. B) When an infection is eliminated, activated T cells die by apoptosis. C) The major effector function of helper T cells is to activate macrophages and other cells by releasing cytokines. D) Activated T cells contribute to the activation of antigen-presenting cells via CD40 ligand. E) Activated T cells receive survival signals from antigen during an infection.

Answer: A (CH. 5) Memory T cells are not actively proliferating and do not express high levels of IL-2 receptors. Instead, these cells are functionally quiescent and are not performing effector functions after a primary immune response. Effector T cells continue to survive in the periphery via proliferative signals from MHC-antigen binding to the TCR. Effector helper T cells can then activate macrophages and other lymphocytes via release of cytokines such as IFN-g, as well as through CD40 ligand on the cell surface. On elimination of the infection, the effector T cells die by apoptosis.

Which of the following statements about cell-mediated immunity (CMI) is 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) The principal form of CMI that protects against viral infections is mediated by B cells. D) Phagocytes are not essential in the effector phase of CMI responses to bacteria such as Listeria monocytogenes.

Answer: A (CH. 6 & 8) The original definition of cell-mediated immunity (CMI), which is still valid, is protection against infection that can be transferred by T cells but not by serum. Serum is a cell-free fraction of blood that includes antibodies, and therefore serum transfer can provide passive humoral immunity. CMI is required for protection against microbes that can reside within cells and therefore are inaccessible to antibodies. These organisms include microbes that are phagocytosed and viruses that replicate in the cytoplasm. Immunodeficiency states in which CMI is impaired (e.g., AIDS) result in infections by viruses and intracellular bacteria or fungi.

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

Answer: B (CH. 1) 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.

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 NOT a TLR ligand? A) Double-stranded RNA B) Transfer RNA C) Unmethylated CpG DNA D) Single-stranded RNA E) Peptidoglycan

Answer: B (CH. 2) 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. TLR9 binds CpG DNA. Transfer RNA is a normal component 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. TLR8 can recognize ssRNA viruses, such as Influenza. TLR8 is only functional in humans.

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 antigen-presenting cells (APCs), such as dendritic cells. If a virus infects epithelial cells in 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-dressing, whereby viral infection of the epithelial cell stimulates the expression of surface molecules that are typically found only on dendritic cells B) 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 C) Crossover, whereby part of the viral genome is exchanged with part of one chromosome of the host D) Crosstalk, whereby signals generated by the virus binding to class I MHC molecules intersect with T cell receptor signaling pathways E) Cross-reactivity, whereby the naive CD8+ T cell recognizes a self antigen that is structurally similar to a viral antigen presented by dendritic cells

Answer: B (CH. 3) Cross-presentation (or cross-priming) is the phenomenon by which a protein antigen made within one cell is processed and presented by the class I MHC pathway of a separate professional antigen-presenting cell (APC). Cross-presentation requires that the protein antigen from one cell be internalized from the extracellular milieu into the APC to gain access to the cytoplasm of the APC. Crossover and crosstalk are terms referring to genetic and signaling phenomena, which are not accurately described in the question.

Which type of antigen-presenting cell is most important for activating naive T cells? A) B lymphocyte B) Dendritic cells C) Endothelial Cells D) Macrophage E) Epithelial Cells

Answer: B (CH. 3) Dendritic cells are the key type of antigen-presenting cell (APC) for activation of naive T cells and initiation of T cell immune responses. Macrophages and B lymphocytes function as APCs for already differentiated effector T cells in cell-mediated and humoral immune responses, respectively. Epithelial cells usually do not function as APCs.

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) The nonresponders underwent determinant selection of another viral epitope. B) 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. C) The viral peptide is not an immunodominant epitope. D) Because of technical errors, the nonresponders had not received adequate doses of the vaccine. E) The nonresponders could not express class II MHC proteins.

Answer: B (CH. 3) The response to a viral protein (or peptide) requires T cell recognition of the peptide bound to an MHC molecule. Although the viral peptide in the vaccine may bind to many different MHC alleles, it likely will not bind to all. The nonresponders express an allelic variant of HLA-DR, which is a class II MHC molecule. Because the peptide evoked a response in 96% of the people in the trial, it can be considered a dominant epitope. Formally, this can be concluded only when the whole protein is the immunogen and the specificities of the responses for different epitopes are compared. Determinant selection is an older term that predates our knowledge of peptide-MHC binding, but it does not mean active selection for one versus another epitope. It is highly unlikely that the only people in the trial who were not adequately immunized for technical reasons happen to be the only ones homozygous for a particular MHC allele.

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 EBV-infected cells EXCEPT: A) β2-Microglobulin B) CTLA-4 C) TAP (transporter associated with antigen processing) D) HLA-A, -B or -C E) CD28

Answer: B (CH. 4) CD28 is not involved in antigen recognition by T cells, but is important for costimulation and activation of naive T cells. Cell-mediated immunity against intracellular organisms, such as viruses, is largely mediated by class I-restricted T cells, such as cytotoxic T lymphocytes (CTLs). The class I MHC molecules are HLA-A, HLA-B, and HLA-C. CTLs recognize complexes of viral peptides with class I MHC molecules. b2-Microglobulin is the nonpolymorphic, noncovalently associated polypeptide chain of MHC class I molecules. TAP is a critical protein involved in the processing and presentation of antigen by class I MHC. CTLA-4 is an inhibitory molecule that acts as an "off" switch for T cells when binding CD80/86 on APCs.

Most T lymphocytes have a dual specificity for which one of the following pairs of molecules? A) Both MHC class I and class II molecules B) A particular allelic form of a major histocompatibility complex (MHC) molecule and a peptide bound to the MHC molecule C) MHC molecules and CD4 or CD8 D) Both soluble peptides and peptide-MHC complexes E) Both peptide and glycolipid antigens

Answer: B (CH. 4) Most T cells are specific for polymorphic residues of a self major histocompatibility complex (MHC) molecule, which accounts for their MHC restriction, and for residues of a peptide antigen displayed by the MHC molecule, which accounts for antigen specificity. The receptor that recognizes peptide-MHC complexes is called the T cell receptor (TCR). Mature ab T cells (the predominant type) express either CD4 or CD8, but not both. As such, each ab T cell is restricted to bind either MHC class II or class I molecules, but not both. Although a small subset of T cells may recognize glycolipid antigens bound to class I MHC-like molecules called CD1, these T cells do not also recognize peptide antigens. Unlike the B cell receptor (immunoglobulins), the TCR can recognize only peptides displayed on MHC molecules, not soluble peptides alone. T cells express CD4 or CD8 and do not recognize CD4 or CD8 on other cells.

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 to viral envelope proteins and induce signals that inhibit viral replication. B) The antibodies bind extracellular viral particles and prevent them from infecting cells. C) The antibodies bind to viral antigens on the surface of infected cells and promote phagocytosis of the cells. D) The antibodies bind to extracellular viral particles and target Fc receptor-expressing cytolytic T lymphocytes to kill the viruses. E) The antibodies bind to viral antigens on the surface of infected cells and promote complement-mediated lysis of the cells.

Answer: B (CH. 6 & 8) Antiviral vaccines work by generating long-lived antibody-producing cells and memory B cells that can secrete high affinity neutralizing antibodies, which prevent viral particles from entering host cells. The antibodies may prevent primary infection as well as prevent reinfection of cells after virions are released from an infected cell. Some vaccine-induced antiviral antibodies may opsonize viral particles and promote their phagocytosis. Antibody-dependent complement activation may also promote phagocytes or lysis of extracellular enveloped viruses. However, opsonization and lysis of virally infected host cells may not always be protective since these mechanisms could promote spread of viruses from cell to cell. Cytolytic T lymphocytes do not have Fc receptors, and they cannot directly kill virions but only kill host cells expressing viral proteins. Membrane proteins of enveloped virions are not linked to signal transduction pathways.

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 gag mutation will enhance the ability of natural killer cells to recognize and kill HIV infected cells. B) The patient's CTL response to the virus provided selective pressure for the emergence of virus carrying the mutation. C) The CTLs specific for the original Gag peptide were incapable of killing HIV-infected cells. D) The CTL that recognized the original gag-encoded peptide will still be able to recognize the mutated Gag peptide. E) The gag mutations have more relevance to the viral evasion of the antibody response rather than the CTL response.

Answer: B (CH. 6 & 8) Cytolytic T lymphocytes (CTLs) are highly specific for short peptide epitopes of viral proteins bound to self-MHC molecules. Random mutations in the viral genome that alter these peptide sequences will lead to escape from CTL detection. Therefore, CTLs do provide a selective pressure for such mutations. Given these selective pressures, it is most likely that the mutations that are found in the virus that has survived in the patient are no longer recognized by the CTL. Because only one or two amino acid residues of a viral peptide will contact a particular TCR, point mutations that ablate T cell recognition are likely to occur. The emergence of escape variants with mutated peptides implies that the CTLs that recognized the original peptide were capable of killing the infected cells, but mutations arose before all infected cells were killed. Natural killer cells recognize alterations in self class I MHC expression but do not recognize specific viral peptide sequences. Although antibodies may be produced specific for distinct epitopes of the same proteins that elicit CTL responses, the information given about changes in a T cell epitope implicate the relevance of the CTL response.

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) P-selectin and tumor necrosis factor B) Perforin and granzyme B C) Perforin and Fas ligand D) Major basic protein and granzyme B E) C9 and interferon-γ

Answer: B (CH. 6 & 8) Perforin and granzyme B are the cytolytic T lymphocyte (CTL) granule constituents of most importance in killing of target cells. CTL granules are emptied by exocytosis into the intercellular space between the CTL and target cell. Here perforin polymerizes to form pore-like structures that insert into the target cell plasma membrane and/or in the membranes of endocytic vesicles in the target cell. Granzyme B is a proteolytic enzyme that cleaves substrates in the cytoplasm of the target cell, leading to a cascade of enzyme activation that ends in apoptosis. Granzyme B enters the target cell either through perforin pores or by receptor-mediated endocytosis. FasL is expressed on the surface of the CTL, not in granules. FasL binding to Fas on target cells may induce apoptosis of the target cells by a caspase-dependent pathway, but this is a minor mechanism of CTL killing relative to perforin- and granzyme B-dependent mechanisms. P-selectin is an endothelial adhesion molecule stored in cytoplasmic granules, and MBP is a cationic protein found in eosinophil granules. Although perforin is homologous to the complement protein C9, C9 is not present in CTL granules. CTLs do produce interferon-g, but they do not store this cytokine in granules.

Antibodies and T lymphocytes are the respective mediators of which two types of immunity? A) Passive and active B) Adult and neonatal C) Humoral and cell-mediated D) Specific and nonspecific E) Innate and adaptive

Answer: C (CH. 1) 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.

Which of the following is a unique property of the adaptive immune system? A) Responses that have the same kinetics and magnitude on repeated exposure to the same microbe B) Recognition of microbial structures by both cell-associated and soluble receptors C) Highly diverse repertoire of specificities for antigens D) Protection against viral infections

Answer: C (CH. 1) 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.

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) Passive immunity mediated by maternal antibodies limits the spread of infection. B) B and T lymphocytes recognize the virus and stimulate the innate immune response. C) The innate immune system responds rapidly to the viral infection and keeps the viral infection under control. D) The adaptive immune system responds rapidly to the virus and keeps the viral infection under control. E) The virus causes malignant transformation of respiratory mucosal epithelial cells, and the malignant cells are recognized by the adaptive immune system.

Answer: C (CH. 1) 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.

Which of the following comparisons of the innate and adaptive immune systems is FALSE? A) 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. B) Both the innate and adaptive immune systems can recognize nonmicrobial substances. C) The innate immune system is more likely to recognize normal self, and therefore cause autoimmunity, than is the adaptive immune system. D) The innate immune system does not have memory but the adaptive immune system does. E) The innate and adaptive immune systems share some of the same effector mechanisms.

Answer: C (CH. 2) 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.

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) CR2 B) Mannose receptor C) Mannose binding lectin D) C9 E) C1

Answer: C (CH. 2) 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.

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? A) IL-3 B) IL-2 C) Tumor necrosis factor-α D) IL-10 E) Transforming growth factor-β

Answer: C (CH. 2) 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)-a secretion by mononuclear phagocytes and other cell types. Most of the biologic effects of LPS are mediated through TNF-a. Transforming growth factor-b (TGF-b) 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.

Which of the following statements about the antigen-presenting function of macrophages is NOT correct? A) 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. B) 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. C) Macrophages express highly variable, high-affinity receptors for many different antigens, and these receptors facilitate the internalization of the antigens for processing and presentation. D) Macrophages present antigen to T cells in lymphoid organs and many nonlymphoid organs. E) Macrophages are particularly important at presenting peptides derived from particulate or opsonized antigens that are internalized by phagocytosis.

Answer: C (CH. 3) The description of high-affinity and highly variable receptors for antigen applies to B cells, which can present antigen to helper T cells, but does not apply to macrophages. Macrophages express receptors for the Fc region of Ig molecules, and these receptors do facilitate internalization of antibody-opsonized antigens. These Fc receptors are not highly variable and do not recognize the antigen. Macrophages are also highly competent at internalizing intact microbes and other large particulate antigens through phagocytosis. Macrophage class II MHC expression and microbicidal activity are enhanced by signals from the T cells to which they present antigen, including cytokines and CD40 ligand. Macrophages are abundant in spleen, lymph nodes, and most nonlymphoid tissues. They may perform antigen-presenting functions in all these locations.

The T cell receptor (TCR) complex differs from an immunoglobulin molecule in which one of the following ways? A) 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. B) Only the TCR can bind soluble antigen directly. C) On average, a TCR binds antigen with much lower affinity than does an Ig molecule. D) The TCR can serve as a lymphocyte antigen receptor, but an Ig molecule cannot. 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.

Answer: C (CH. 4) TCRs bind antigen with much lower affinity than immunoglobulins (the dissociation constant for the TCR is 10-5 to 10-7 versus 10-7 to 10-11 for secreted Ig). Both T cell receptors (TCRs) and membrane Ig serve as lymphocyte antigen receptors on T cells and B cells, respectively. TCRs do not bind soluble antigens, but rather cell surface-associated peptide-MHC molecule complexes. Only immunoglobulins undergo constant region changes, called heavy chain isotype switching. Both TCRs and Ig have short cytoplasmic tails and rely on associated signaling molecules (CD3 and z for TCR, Iga and Igb for membrane Ig).

The T cell receptor (TCR) complex contains all of the following except: A) A highly variable antigen αβ heterodimer receptor B) Invariable ζ chains noncovalently linked to the TCR αβ heterodimer C) CD28 D) Three homologous CD3 chains, each noncovalently linked to the TCR αβ heterodimer

Answer: C (CH. 4) The T cell receptor (TCR) complex contains a highly variable antigen receptor, usually composed of a heterodimer of α and β chains, called the TCR, which is responsible for antigen recognition, as well as invariant signaling proteins, CD3δ, CD3ε, and CD3λ, and the ζ protein. These signaling molecules are all noncovalently associated with the TCR. Coreceptors for T cells include CD4 and CD8; these are invariant proteins and are not part of the TCR complex itself. CD28 is involved in T cell costimulation, but it is not a member of the TCR complex.

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 integrins on the T cell with adhesion ligands on the APC B) Binding of B7-2 on the APC with CD28 on the T cell C) Binding of CD40L on the T cell with CD40 on the APC D) Binding of peptide-MHC complexes on the APC to the TCR on the T cell E) Binding of CD4 on the T cell to nonpolymorphic regions of class II MHC molecules on the APC

Answer: C (CH. 5) CD40L is not expressed on naive T cells and is only up-regulated subsequent to activation by an antigen-presenting cell (APC). In the naive helper T cell, the TCR binds to the MHC-peptide complex whereas the CD4 coreceptor engages a conserved region on the MHC II molecule. Integrins on the T cell interact with adhesion ligands on the APC. This region of binding between the T cell and the APC is known as the immunologic synapse and also includes costimulatory interactions, such as CD28 on the T cell binding to B7 on the APC.

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 by the presence of "danger" signals, such as lipopolysaccharide, as well as cytokines, such as interferon (IFN)-γ. 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) Activated helper T cells can induce expression of B7-1 and B7-2 on APCs via CD40L binding to CD40. E) B7-1 and B7-2 bind to CD28 on T cells and provide "second signals" for naive T cell activation.

Answer: C (CH. 5) The temporal patterns of B7-1 and B7-2 expression differ. B7-2 is expressed constitutively at low levels and induced early after activation of antigen-presenting cells (APCs), whereas B7-1 is not expressed constitutively and is induced hours or days later. The expression of B7-1 and B7-2 on APCs is induced by "danger signals" of infection. These signals are mediated by binding of lipopolysaccharide (LPS), unmethylated CpG DNA, and other ligands of Toll-like receptors. Signals mediated through cytokines, such as interferon (IFN)-g, as well as through CD40 ligand, can also up-regulate B7-1 and B7-2 expression on APCs. Both B7-1 and B7-2 bind to CD28 on naive T cells, thus providing the second signal needed for activation of T cells.

Which of the following mechanisms is used by TH1 cells to protect against microbes: A) Expression of CD40, which binds to CD40L on macrophages and activates them B) Secretion of IL-10, which promotes B cell production of opsonizing antibodies C) Secretion of interferon (IFN)-γ, which activates microbicidal functions of macrophages D) Release of granzyme B, which stimulates apoptosis of bacteria

Answer: C (CH. 6 & 8) Granzyme B, a product of CD8+ cytolytic T lymphocytes, promotes death of infected host cells, but not of extracellular microbes. The principal function of TH1 cells is to enhance phagocyte defense against intracellular infections. Interferon (IFN)-g and CD40 ligand, produced by TH1 cells, enhance killing of microbes ingested by macrophages, in part by stimulating the production of inducible nitric oxide synthase and phagocyte oxidase. IFN-g, produced by TH1 cells, is an isotype switch factor, promoting the production of IgG subtypes that bind to Fc receptors on phagocytes and fix complement. Therefore, these opsonizing IgG subtypes facilitate the phagocytosis of the microbes to which they bind. TH1 cells also secrete tumor necrosis factor and lymphotoxin, two cytokines that can activate neutrophil killing of internalized microbes.

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) TH2 cells are more likely to bind to E-selectin and P-selectin on endothelial cells than are TH1 cells. C) TH1 cells produce interferon (IFN)-γ but not IL-4, and TH2 cells produce IL-4 but not IFN-γ. D) The chemokine receptors CXCR3 and CCR5 are more highly expressed on TH2 cells than on TH1 cells. E) TH1 cells are class I major histocompatibility complex (MHC) restricted, and TH2 cells are class II MHC restricted.

Answer: C (CH. 6 & 8) The signature cytokines of TH1 and TH2 cells are interferon-g and interleukin (IL)-4, respectively. IL-5 and IL-13 are also very specific for TH2 cells. IL-1 is not typically produced by helper T cells of either subset. IL-2 is produced by naive T cells and TH1 cells. Both TH1 and TH2 cells are CD4+ helper T cells, and therefore are both restricted to recognizing peptide antigens bound to class II MHC molecules. The trafficking patterns of TH1 and TH2 cells differ, and this is related to differences in the expression of adhesion molecules and chemokine receptors. TH1 cells express abundant functional ligands for E-selectin and P-selectin and the chemokine receptors CXCR3 and CCR5, which bind to various chemokines found at sites of active innate immune responses. TH2 cells bind poorly to endothelial selectins and express less CXCR3 and CCR5.

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) Failure to produce neutrophils B) No ability to activate naive class I-restricted T cells C) Impaired ability to produce antibodies and activate macrophages D) No ability to produce IgM antibodies E) Complete absence of cytotoxic T lymphocyte (CTL) responses to viral infections

Answer: C (CH.4) Knockout mice lacking CD4 do not contain mature class II-restricted T cells because the CD4 coreceptor plays an essential role in the maturation of T cells in the thymus. Most CD4+ class II-restricted T cells are cytokine-producing helper cells that function in host defense against intracellular microbes. These helper T cells are critical for activating B cells to produce antibodies, and for activating macrophages to efficiently kill phagocytosed microbes. Knockout mice lacking CD4 therefore do not have any helper T cells. IgM antibody production is generally not dependent on help from CD4+ T cells. Because CD8 is still expressed, naive class I-restricted T cells are still present and able to respond to intracellular infections, although this ability may be impaired by lack of T cell help. Neutrophil production by the bone marrow should be relatively normal.

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) Cultural diversity B) Self-tolerance C) Specialization D) Specificity E) Amnesia

Answer: D (CH. 1) 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.

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) Non-reactivity to self B) Specificity C) Diversity D) Memory E) Specialization

Answer: D (CH. 1) 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.

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 and cytotoxic T lymphocytes D) Antigen-presenting cells E) B lymphocytes

Answer: D (CH. 1) T cell-mediated immune responses are initiated when naive T cells are activated. Antigen-presenting 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.

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) Phosphatidylinositol dimannoside B) Lipopolyysaccharide (LPS) C) Lipoarabinomannan D) Peptidoglycan E) Double-stranded RNA

Answer: D (CH. 2) 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.

Antigen-presenting cells (APCs) perform which of the following functions in adaptive immune responses? A) Initiate T cell responses by specifically recognizing and responding to foreign protein antigens B) Display polysaccharide antigens on their cell surfaces for surveillance by B lymphocytes C) Secrete peptides derived from protein antigens for binding to T cell antigen receptors D) Display MHC-associated peptides on their cell surfaces for surveillance by T lymphocytes E) Display major histocompatibility complex (MHC)-associated peptides on their cell surfaces for surveillance by B lymphocytes

Answer: D (CH. 3) Antigen-presenting cells (APCs) degrade proteins derived from either the extracellular environment or the cytoplasm. They form complexes of peptide fragments of these proteins with major histocompatability complex (MHC) molecules and display these complexes on their cell surfaces, where T cells can "see" them. Neither processing nor MHC association of protein or polysaccharide antigens by B cells is required for recognition. APCs do not distinguish between self and foreign proteins and will display peptides derived from a sampling of all cytoplasmic and extracellular proteins. APCs do not secrete peptide antigens, and T cell antigen receptors do not bind free peptides.

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 α chain, 2 in the β chain B) Hypervariable regions: 2 in the α chain, 2 in the β chain C) One peptide-binding groove formed by the α chain and the β2-microglobulin chain D) Complementarity-determining regions: 3 in the α chain, 3 in the β chain E) Congenic regions: 1 in the α chain, 1 in the β chain

Answer: D (CH. 4) Each a and b chain of the T cell receptor (TCR) contains both a constant and a variable domain. The variable domain contains short stretches of amino acids where the variability between different TCRs is concentrated, and these form the hypervariable or complementarity-determining regions (CDRs). Three CDRs in the a chain are juxtaposed to three similar regions in the b chain to form the part of the TCR that specifically recognizes peptide-MHC complexes. The variable regions of Ig molecules may undergo hypermutation during humoral immune responses, but this does not happen in TCRs. Congenic does not refer to a part of a protein, but rather to an inbred strain of animal. Peptide-binding grooves are part of MHC molecules, not TCRs.

Which of the following is only contained in heavy chains and NOT in light chains? A) Leader (L) B) Joining (J) C) Constant (C) D) Diversity (D) E) Variable (V)

Answer: D (CH. 4) The Ig light-chain locus lacks diversity (D) gene segments. Therefore a V region exon recombines directly with a J segment. Both the BCR and TCR gene loci contain Leader (L) segments, which are small stretches of nucleotides that encode a peptide that guides the proteins through the endoplasmic reticulum. The peptide is cleaved from the mature proteins.

Which one of the following cell types would be most potent at activating naive T cells? A) Follicular dendritic cells B) Kupffer cells C) B cells D) Langerhans cells E) Neutrophils

Answer: D (CH. 5) Antigen-presenting cells (APCs) are responsible for presenting peptide-MHC complexes and costimulatory molecules to naive T cells; this leads to activation of the T cells. The most potent APCs are the dendritic cells, because they constitutively express high levels of costimulatory molecules. Langerhans cells are dendritic cells found in epidermis. Other APCs include macrophages and B cells. Kupffer cells are a type of macrophage found in the liver. Neither neutrophils nor follicular dendritic cells (FDCs) are involved in antigen presentation to T cells. FDCs are unrelated to dendritic cells and are found within the germinal centers of lymph nodes.

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 ligand is required for maturation of CD4+ T cells in the thymus. B) CD40 ligand on T cells binds to B7-1 and B7-2 on APCs, and this enhances the function of the APCs. C) CD40 ligand is required for CTL killing of CD40-expressing infected cells. 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-dependent isotype switching is required to produce antibody isotypes that activate T cells.

Answer: D (CH. 5) CD40 ligand, a membrane-bound protein in the tumor necrosis factor (TNF) family of proteins, is expressed after T cell activation. When it binds to its receptor CD40, a TNF-receptor family member expressed on macrophages, and other antigen-presenting cells, signals are transmitted that enhance costimulator and cytokine expression (as well as other functions of macrophages). This serves to amplify the T cell response and enhance the killing of microbes ingested by macrophages. Antibodies are not required to activate T cells. CD40 does not transduce pro-apoptotic signals. CD40 ligand is not involved in T cell maturation and does not bind to B7-1 or B7-2.

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.

Answer: D (CH. 5) IL-2 is involved in the proliferation of both CD4+ and CD8+ T cells. Activation of the naive T cell results in signals transduced via the TCR (signal 1) and CD28 (signal 2). This signaling results in the activation of transcription factors, such as Fos, Jun, and NFAT, which increase transcription of the IL-2 gene. IL-2 is then secreted and acts as both a paracrine and autocrine growth factor for T cells by binding to the IL-2 receptor (one component of which is CD25). In addition to its growth factor activity, IL-2 also "primes" T cells for apoptotic death, and this role for IL-2 is important in homeostasis of the immune system.

Which one of the following statements about MHC-TCR interactions is NOT true? A) Only 1% or less of the MHC molecules on any antigen-presenting cell (APC) display a peptide recognized by a particular T cell. B) A subthreshold number of MHC-TCR interactions can lead to T cell inactivation. C) Antigen receptors on T cells bind to MHC molecules for only brief periods of time. D) The affinity of most TCRs for peptide-MHC complexes is similar to the affinity of antibodies for their antigens. E) T cells usually require multiple engagements with an APC before a threshold of activation is reached.

Answer: D (CH. 5) In general, the TCR binds to peptide-MHC complexes with lower affinity than antigen-antibody interactions. This relatively low-affinity interaction occurs briefly; thus, a T cell may need multiple engagements with the antigen-presenting cell (APC) before a threshold of activation occurs. If this threshold is not reached, the T cell may enter into an inactive state known as anergy. On any given APC, less than 1% of the MHC molecules display the same peptide.

Up to half of the IgG found in the serum of a normal individual is produced by which of the following cells? A) B cells in germinal centers of lymph nodes B) B lymphocytes in the gastrointestinal tract C) Activated B cells in spleen D) Long-lived plasma cells in the bone marrow E) Naive B cells in lymph nodes

Answer: D (CH. 6 & 8) During a humoral immune response, naive B cells differentiate into antibody-producing cells, and some of these migrate to the bone marrow, where they can reside and produce antibodies for years. Many of these cells are called plasma cells, based on their histologic appearance. Naive B cells do not secrete antibodies. Although activated B cells in spleen or lymph node germinal centers produce large amounts of antibody during an active humoral immune response, they do not account for most of the serum IgG normally. Intestinal B cells secrete large amount of IgA, which is transported into the lumen.

Which of the following events initiates activation of the alternative complement pathway? A) Complement receptor 1 (CR1) binding of C3b B) Factor I cleavage of C3 C) C1q binding to a microbial surface D) Spontaneous cleavage of C3 to C3b E) Mannose-binding lectin (MBL) binding to a microbial surface

Answer: D (CH. 6 & 8) The alternative pathway is initiated when C3b, generated by spontaneous cleavage of C3 in the fluid phase, covalently binds to a cell surface. C1q is required for initiation of the classical pathway. It does not bind directly to cell surfaces but rather to the constant regions of two Ig molecules, which may be bound to cell surface antigens. Mannose-binding lectin (MBL) binds to mannose on microbial surfaces to initiate the lectin pathway. Factor D is a constitutively active serum protease that cleaves factor B after it binds C3b in the alternative pathway. Factor I is a protease that cleaves C3b and C4b and regulates both alternative and classical pathways. CR1 on phagocytes binds C3b-opsonized microbes.

Which of the following anatomic regions is normally protected from pathogens only by humoral immune responses and not by cell-mediated immune responses? A) Central nervous system B) Skin C) Intestinal epithelium D) Intestinal lumen E) Spleen

Answer: D (CH. 6 & 8) The lumen of mucosal lined tissues, such as the intestinal and bronchial lumen, are protected by IgA, which is actively secreted at these sites. T cells do not normally migrate into these lumen and are usually involved in immune responses to organisms that breach the surface linings of these structures. The epithelial linings of mucosal tissues and the skin do contain lymphocytes that protect against invading pathogens. Both antibodies and T cells are involved in responses to infections within most other tissues.

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) Active cell-mediated immunity C) Passive cell-mediated immunity D) Innate Immunity E) Passive humoral immunity

Answer: E (CH. 1) 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.

The two major functional classes of effector T lymphocytes are: A) Memory T cells and effector T cells B) Natural killer cells and cytotoxic T lymphocytes C) Cytotoxic T lymphocytes and target cells D) Helper cells and antigen-presenting cells E) Helper T lymphocytes and cytotoxic T lymphocytes

Answer: E (CH. 1) 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.

Which of the following statements is consistent with the process of clonal selection? A) Lymphocytes do not express antigen receptors on their cell surfaces until after exposure to antigen. B) Many different antigen receptors with different specificities are expressed on each lymphocyte. C) The diversity of the lymphocyte repertoire for antigens is very small before exposure to antigen but increases significantly after antigen exposure. D) The specificity of a lymphocyte antigen receptor changes to accommodate the structure of an antigen that binds to it. 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.

Answer: E (CH. 1) 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.

All of the following molecules are opsonins that facilitate efficient phagocytosis of microbes by neutrophils and macrophages EXCEPT: A) IgG B) C3b C) C-reactive protein D) Mannose-binding lectin E) C5a

Answer: E (CH. 2) 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. C-reactive protein and mannose-binding lectin also can coat microbes and be recognized by phagocyte receptors; thus they serve as opsonins.

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) Membrane attack complex E) Reactive oxygen intermediates

Answer: E (CH. 2) 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 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.

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) 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. B) Virus-infected mucosal epithelial cells migrate to draining lymphoid tissues, where they present viral peptide antigens to naive CD8+ T cells. C) Viral infection of the mucosal epithelial cells stimulates them to express E-selectin, which promotes CD8+ T cell adhesion. D) In response to interferon-γ 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. E) 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.

Answer: E (CH. 3) Differentiated CD8+ cytolytic T lymphocytes (CTLs) can recognize class I-associated viral peptides on epithelial cells, as well as most other cell types, and become activated to kill those cells. Interferon-g may be secreted during the innate immune response to a virus, and this cytokine can up-regulate both class I and class II MHC expression of various cell types, but CD8+ T cells do not recognize class II-associated peptides. Antibodies may form a bridge between Fc receptor-bearing natural killer cells and infected cells expressing viral antigens on their surface, but this phenomenon does not apply to CD8+ CTLs. Mucosal epithelial cells do not migrate to draining lymph nodes in response to viral infection, nor do they express E-selectin, which is an endothelium-specific adhesion molecule.

A helper T cell response to a protein antigen requires the participation of antigen-presenting cells that express which of the following types of molecules? A) CD4 and costimulators B) Class II MHC and CD8 C) Class II MHC and CD4 D) Class I MHC and CD4 E) Class I MHC and CD8

Answer: E (CH. 3) Helper T cells are almost always CD4+. The activation of naive CD4+ T cells requires T cell receptor recognition of class II MHC-peptide complexes and the binding of costimulators, both on the antigen-presenting cell (APC) surface. CD4+ helper T cells bind to class II MHC molecules on the APC, not to class I MHC molecules. CD4 or CD8 expression on the APC surface is of no known relevance to T cell activation.

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) Small in size B) Present in an acidic vesicular compartment of the APC C) Internalized into the cell from the extracellular space D) Encoded by a viral gene E) Present in the cytosol of the APC

Answer: E (CH. 3) Regardless of the source of the protein, its presence in the cytosol makes it accessible to the tagging and proteolytic processing mechanisms that initiate the class I MHC antigen presentation pathway. Microbial proteins and self proteins have equal access to this pathway if they are present in the cytosol. Presence in acidic vesicles is the comparable major criterion for inclusion in the class II MHC pathway; such proteins are usually, but not always, internalized from the extracellular space. The size of an intact protein is not relevant to which processing and presentation pathway it will enter.

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) CD3γ B) CD3ε C) CD4 D) ζ E) TCRα

Answer: E (CH. 4) Although the T cell receptor (TCR) a and b chains are responsible for antigen recognition, they are not directly involved in signaling. Rather, the ab heterodimer is noncovalently associated with signaling molecules CD3γ, CD3δ, CD3ε, and ζ, all of which have ITAMs in their cytoplasmic tails. Although CD4 is not part of the TCR complex, it does play a critical role in initiating signaling during TCR recognition of antigen by binding Lck to its cytoplasmic tail and bringing this tyrosine kinase near the ITAMs of CD3 and ζ.

Which of the following is NOT a property shared by both CD4 and CD8? A) Is a member of the Ig superfamily B) Binds to nonpolymorphic regions of MHC molecules C) Functions as a coreceptor for αβ TCRs D) Functions as a coreceptor for αβ TCRs E) Neither are expressed until after positive selection

Answer: E (CH. 4) Both CD4 and CD8 are transmembrane glycoprotein members of the Ig superfamily, both serve as MHC-binding coreceptors for the T cell receptor, and both participate in early signal transduction events via cytoplasmic tail binding of the Src family tyrosine kinase Lck. T cells express both CD4 and CD8 in the thymus before they undergo positive selection. Upon recognition of MHC-I or MHC-II, T cells will down regulate either CD4 or CD8 respectively.

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) Maturation of MHC class I-restricted T cells B) Recognition of peptide antigen bound to class I MHC molecules C) Signaling via Lck tyrosine kinase to initiate T cell activation D) Strengthening the binding of T cells to antigen-presenting cells, albeit with low affinity E) Infection of T cells by human immunodeficiency virus (HIV)

Answer: E (CH. 4) CD4, but not CD8, serves as a receptor for the human immunodeficiency virus (HIV). CD8 is a coreceptor that binds to class I MHC molecules. It is expressed on T cells whose T cell receptors (TCRs) recognize complexes of peptide and class I MHC molecules. CD8 plays a critical role in the maturation of class I MHC-restricted T cells in the thymus because this process requires the maturing T cells to recognize class I MHC on thymic antigen-presenting cells (APCs). Both CD8 and CD4 associate with the Src family tyrosine kinase, called Lck, and thus they participate in the early signal transduction events that occur after T cell recognition of peptide-MHC complexes on APCs. The affinities of CD8 and CD4 for MHC molecules are very low, but they are still thought to play some role in mediating adhesion between T cells and APCs.

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 ab+ CD4+. In vitro lymphocyte-proliferative responses to PHA and anti-CD3 were absent, and the pattern of tyrosine-phosphorylated cytoplasmic proteins after anti-CD3 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) RAG-1 B) Pre-Tα C) CD3 D) TCRα E) Zap-70

Answer: E (CH. 5) The patient shows signaling defects in TCR-mediated T cell activation, as well as defects in CD8+ T cell maturation. Zap-70 is a tyrosine kinase required for TCR-mediated T cell activation. Mutations in Zap-70 result in impaired TCR signaling, with abnormal tyrosine phosphorylation of downstream signaling molecules, and also a defect in CD8+ T cell maturation. It is not known why CD8+ maturation is selectively impaired in Zap-70 deficiency. VDJ recombination, and therefore RAG-1 function, must still be intact because TCR-expressing CD4+ T cells do mature. CD3, pre-Ta, and TCRa are also required for maturation of CD4+ T cells, and therefore these molecules must all be expressed by this patient.

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) Serum complement proteins in the transfer directly promoted bacterial cell lysis and phagocytosis. B) The recipient animal's immune response to the foreign serum further activated host immune system function, allowing greater response to the bacillus infection. C) Inflammatory cytokines in the transferred serum increased the strength and efficacy of innate immune system activity. D) 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. E) Diphtheria-specific antibodies in the transferred serum neutralized bacillus toxins and promoted bacterial elimination by innate effector cells.

Answer: E (CH. 6 & 8) The serum from infected animals contains diphtheria-specific antibodies. Some of these antibodies can bind to and neutralize diphtheria toxin, reducing symptoms of infection, whereas others interact with the bacilli themselves, inducing bacterial death by phagocytosis and complement fixation. Antibodies have a half-life of several weeks in the circulation, and therefore promote short-term disease resistance and immunity. No B cell or T cell would have been transferred with the serum, which is a cell-free fraction of blood. It is unlikely that there are inflammatory cytokines in the serum donor, because it had already recovered from infection, and cytokines alone would not impart resistance to infection. Serum transfer should not provide any complement components not already present in the recipient. Although it is possible that the foreign serum elicited an immune response to allelic differences in the transferred serum proteins, this should not impart specific resistance to diphtheria.