Immunology Exam 1 (4)

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

A. A particular allelic form of a major histocompatibility complex (MHC) molecule and a peptide bound to the MHC molecule 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 αβ T cells (the predominant type) express either CD4 or CD8, but not both. As such, each αβ 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.

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 antigen-processing (TAP) 1/2 pump B. By passive diffusion C. By receptor-mediated endocytosis D. Through membrane pores E. Via the proteasome

A. By ATP-dependent transport via the transporter associated with antigen-processing (TAP) 1/2 pump The TAP1/TAP2 heterodimer is an ATP-dependent pump that delivers peptides generated by the proteasome into the endoplasmic reticulum.

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

A. CD40L-CD40 interactions between activated T helper cells and macrophages Activated CD4+ T cells express CD40 ligand (CD40L), which binds to CD40 on B lymphocytes, macrophages, dendritic cells, and endothelial cells thereby activating these cells. Only activated macrophages can effectively phagocytose and kill intracellular microbes such as Listeria. CD28-B7 and TCR-MHC class II interactions provide signals 2 and 1, respectively, in the activation of T cells by antigen-presenting cells (not the activation of macrophages by T cells). Engagement of Fas by Fas ligand (FasL) on T cells results in apoptosis and provides one of the mechanisms by which CTLs kill their targets. LFA-1-ICAM-1 mediates cell adhesion interactions important in T cell activation and homing.

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. 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

A. Class II MHC and costimulators 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.

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 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

A. E-selectin ligand binding to E-selectin Leukocyte adhesion deficiency type 2 (LAD-2) is a rare genetic disorder characterized by severely impaired neutrophil rolling and adhesion to activated endothelium. The cause is a defect in the synthesis of sialylated Lewis X, the carbohydrate ligand on neutrophils and other leukocytes that is required for binding to E-selectin and P-selectin on cytokine-activated endothelium. In a clinically similar disorder called LAD-1, there is absent or deficient expression of the CD11CD18 family of integrins (of which LFA-1 is a member). Adhesion interactions mediated by CD4, Fc receptor, and VLA-4 are normal in patients with LAD-2.

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

A. Helper T lymphocytes and cytotoxic T lymphocytes 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 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

A. Highly diverse repertoire of specificities for antigens 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.

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. E. The principal function of mature dendritic cells is antigen capture.

A. Immature dendritic cells are ubiquitously present in skin and mucosal tissues. Tissues that are barriers between the external environment and the inside of the body, such as skin and mucosa, are rich in resting dendritic cells. In this location, the dendritic cells are well positioned to internalize samples of the environment and respond to innate immune system signals, which will drive their maturation into competent antigen-presenting cells. Dendritic cell maturation occurs during migration from infected tissues via lymphatics to the T cell zones of draining lymph nodes. Maturation must occur before, and is required for, activation of T cells, not vice versa. Class II MHC molecule up-regulation occurs during dendritic cell maturation and is one of the changes that make mature dendritic cells better able to present antigen to CD4+ T.

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.

A. Integrin clustering and increased integrin affinity are induced by chemokines and antigen recognition. T cell integrin affinity is enhanced by "inside-out signaling" in response to antigen binding to the T cell receptor (TCR) and chemokine binding to chemokine receptors. In addition, antigen and chemokines can induce clustering of integrins in the region of the T cell membrane in contact with the antigen-presenting cell (APC). These changes cause stronger T cell binding to APCs displaying the peptide-MHC complex that the T cell recognizes, thus ensuring prolonged T cell/APC contact and T cell activation. Integrins are not stored in cytoplasmic granules, and transcriptional activity cannot account for rapid changes in integrin-mediated binding. Integrin ligands (such as ICAM-1) do not undergo changes in affinity, nor are they stored in cytoplasmic granules.

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. 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.

A. On average, a TCR binds antigen with much lower affinity than does an Ig molecule. 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 ζ for TCR, Igα and Igβ for membrane Ig).

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

A. Peptidoglycan 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.

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.

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. 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 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

A. Specificity 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.

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. TCRα B. CD3γ C. ζ D. CD4 E. CD3ε

A. TCRα Although the T cell receptor (TCR) α and β chains are responsible for antigen recognition, they are not directly involved in signaling. Rather, the αβ 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 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.

A. The innate immune system is more likely to recognize normal self, and therefore cause autoimmunity, than is the adaptive immune system. 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.

Which one of the following molecules does NOT play an important role in the class II MHC pathway of antigen presentation? A. β2-Microglobulin B. Cathepsin C. Invariant chain D. HLA-DM E. Calnexin

A. β2-Microglobulin β2-Microglobulin is one of the polypeptide chains of a class I MHC molecule and is required for assembly of the peptide-class I MHC complex. All the other molecules listed are involved in the class II MHC of antigen presentation. Cathepsins are acid proteases that degrade proteins in acidic vesicles in the class II MHC pathway. The invariant chain directs appropriate sorting of new class II MHC molecules from the Golgi to endosomes, and it protects the class II MHC peptide binding groove from occupancy by peptides until the class II MHC molecules are delivered to the endosome. Calnexin is an endoplasmic reticulum chaperone involved in the assembly of both class I and class II molecules.

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. C. Neutrophils proliferate at inflammatory sites, but macrophages are terminally differentiated and cannot proliferate. D. Neutrophils, but not macrophages, express the high-affinity FcγRI 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.

B. Both neutrophils and macrophages are phagocytic and can kill internalized microbes. Neutrophils and macrophages can both actively phagocytose and kill microbes, and both express opsonin receptors, such as FcγRI 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.

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

B. C5a 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.

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.

B. CD-1 restricted T cells recognize non-peptide antigens, such as lipids. A small population of T cells express T cell receptors that recognize lipids bound to class I MHC-like molecules called CD1 molecules. These lipid antigen-specific T cells include CD4+CD8+, or CD4−CD8− αβ T cells. Many of these T cells also express markers found on natural killer (NK) cells and are therefore called NK T cells, although they are not actually NK cells. CD1-restricted T cells are still capable of rapidly producing cytokines such as IL-4 and IFN-γ, but their physiologic function is unknown.

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

B. Complementarity-determining regions: 3 in the α chain, 3 in the β chain Each α and β 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 α chain are juxtaposed to three similar regions in the β 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 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

B. Dendritic cell 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.

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 D. Myeloperoxidase E. Lysozyme

B. Granzyme 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.

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

B. Hyaluronate CD44 is a glycoprotein expressed on a variety of cells, particularly on recently activated and memory T cells. CD44 binds to hyaluronate, which allows for the retention of T cells in extravascular tissues at sites of infection and for the binding of activated and memory T cells to endothelium at sites of inflammation.

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

B. Impaired ability to produce antibodies and activate macrophages 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 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-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. 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 E-selectin, which promotes CD8+ T cell adhesion.

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. 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-γ 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 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

B. Passive humoral immunity 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.

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.

B. Some inhibitory receptors on NK cells recognize HLA-A or HLA-C. 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 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.

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.

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

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. Transforming growth factor-β B. Tumor necrosis factor-α C. Interleukin (IL)-2 D. IL-10 E. IL-3

B. Tumor necrosis factor-α 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)-α secretion by mononuclear phagocytes and other cell types. Most of the biologic effects of LPS are mediated through TNF-α. Transforming growth factor-β (TGF-β) 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.

γδ T cells may be important for recognition of common antigens at epithelial boundaries between the host and the external environment. The γδ T cells differ from the αβ T cells in which one of the following ways? A. γδ T cells recognize only nonprotein antigens. B. γδ T cells are not MHC-restricted and do not recognize MHC-associated antigens. C. The γδ TCR complex contains CD3γ or CD3δ but not CD3ε. D. Most mature γδ T cells express either CD4 or CD8 but not both. E. γδ T cells lack key biologic activities, including the ability to lyse target cells.

B. γδ T cells are not MHC-restricted and do not recognize MHC-associated antigens. T cells expressing the γδ TCR are a lineage distinct from the much more numerous αβ-expressing T lymphocytes. The γδ T cells do not recognize MHC-associated peptide antigens and are not MHC restricted. Some γδ T cells recognize protein or nonprotein antigens that do not require processing or particular types of antigen-presenting cells for their presentation. The γδ heterodimer associates with the same CD3 and ζ proteins as do αβ receptors. Most γδ cells do not express CD4 or CD8. The γδ cells are capable of several biologic activities, including secretion of cytokines and lysis of target cells.

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 co-stimulation 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.

C. B7-1 expression on antigen-presenting cells is up-regulated in response to signaling through Toll-like receptors, thus enabling co-stimulation of T cells. 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-β secretion involve innate immunity enhancing adaptive immunity.

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. HLA-A, -B or -C C. CD28 D. LFA-1 (leukocyte function-associated antigen-1) E. TAP (transporter associated with antigen processing)

C. CD28 CD28 is not involved in antigen recognition by T cells, but rather, in costimulation. 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. β2-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. LFA-1 is an important integrin mediating adhesion of the CD8+ T cells to virus-infected target cells.

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 CTLA-4? 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."

C. CD28 is constitutively expressed on naive T cells, whereas CTLA-4 is expressed on activated T cells. CD28 is constitutively expressed on more than 90% of CD4+ T cells and 50% of CD8+ T cells, whereas CTLA-4 is expressed only on activated T cells. Both B7-1 and B7-2, expressed on professional antigen-presenting cells (APCs), bind to both CD28 and CTLA-4 receptors on T cells. Binding of B7 molecules on APCs to CD28 delivers "positive" signals to the T cells that stimulate production of growth factors, promote T cell proliferation and differentiation, and induce expression of anti-apoptotic proteins. CTLA-4, however, functions to inhibit T cell activation by counteracting signals delivered by CD28. CTLA-4 also binds B7-1 with 10-fold greater affinity than CD28 binds B7-1; this difference may play an important role in the temporal sequence of T cell activation.

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

C. Defense against microbial infections The immune system has evolved in the setting of selective pressures imposed by microbial infections. Although immune responses to cancer may occur, the concept that "immunosurveillance" against cancer is a principal function of the immune system is controversial. Repair of injured tissues may be a secondary consequence of the immune responses and inflammation. Although the immune system has regulatory features that are needed to prevent excessive inflammation, prevention of inflammatory diseases is not a primary function. The immune system can protect against microbial toxins, but it generally does not offer protection against toxins of nonbiologic origin.

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

C. Display MHC-associated peptides on their cell surfaces for surveillance by T lymphocytes 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.

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

C. Effector phase 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.

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

C. Infection of T cells by human immunodeficiency virus (HIV) 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.

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.

C. Innate immunity is better suited for eliminating virulent, resistant microbes than is adaptive immunity. 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.

The required number of complexes of a microbial peptide and a particular class II MHC allele on the surface of an antigen-presenting cell to initiate a T cell response specific for the viral peptide is: A. At least equal to the number of complexes of self peptides with class II MHC on the cell surface B. Greater than 103 C. Less than or equal to 0.1% of the total number of class II MHC molecules on the cell surface D. Greater than 106 E. Zero

C. Less than or equal to 0.1% of the total number of class II MHC molecules on the cell surface As few as 100 complexes of a particular peptide and a particular class II MHC molecule are needed to activate naive T cells specific for that complex and thereby initiate a detectable T cell response. This represents less than 0.1% of the total class II MHC molecules on a typical antigen-presenting cell surface.

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.

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

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

C. Mannose binding lectin 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.

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

C. Present in the cytosol of the APC 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.

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.

C. Selectins bind carbohydrate ligands, but integrins do not. Selectins specifically bind carbohydrate groups on cell surface glycoproteins, whereas integrins do not bind carbohydrate groups on Ig superfamily molecules. L-selectin and several integrins are both expressed on some lymphocytes. Both selectins and integrins are important mediators of leukocyte adhesion to endothelium. Both selectins and integrins (especially VLA-4) can mediate rolling interactions; selectins are more specialized in this regard. There are three members of the selectin family (E-, P-, and L-) and more than 30 different members of the integrin family.

Which of the following infectious diseases was prevented by the first successful vaccination? A. Polio B. Tuberculosis C. Smallpox D. Tetanus E. Rubella

C. Smallpox 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.

The estimated number of distinct structures that can be recognized by the mammalian adaptive immune system is A. 1-10 B. 10^2-10^3 C. 10^3-10^5 D. 10^7-10^9 E. ∞

D. 10^7-10^9 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.

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

D. Antigen-presenting cells 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.

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

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

LFA-1 is an integrin that promotes T cell activation by which one of the following mechanisms? A. Binds to the α3 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

D. Binds to ICAM-1 on the surface of a variety of cells, mediating firm adhesion between T cells and APCs or endothelial cells LFA-1 is an integrin expressed on the surface of leukocytes, which binds ICAM-1 to mediate specific, firm adhesion between T cells and antigen-presenting cells, as well as leukocytes and endothelial cells. As such, it plays an important role in the activation of T lymphocytes and in their migration to sites of infection and inflammation. In contrast, CD8 binds the α3 domain of class I MHC molecules, CD28 and CTLA-4 bind B7 proteins, L-selectin is the receptor for GlyCAM-1, and VLA-4 is the receptor for VCAM-1.

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

D. CD45ROhigh After primary infection, subsequent exposure to Epstein-Barr virus (EBV) (i.e., secondary infection) will trigger clonal expansion of EBV-specific memory T cells. Memory T cells express CD45RO. CD45RA is expressed on naive human T cells. CD62L, or L-selectin, is a peripheral lymph node homing receptor that is expressed at high levels on naive T lymphocytes but not on activated or memory T lymphocytes. CD44 is an adhesion molecule that is expressed at low levels on naive T lymphocytes and at high levels on activated and memory T lymphocytes. CD21 is actually the EBV receptor, but it is expressed on B cells (and follicular dendritic cells). It normally functions as a coreceptor to deliver activating signals in B cells.

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-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

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 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. Cross-dressing is not a term used in immunology.

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 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.

D. Donor T cell viral antigen recognition is restricted by MHC molecules not expressed in the patient. 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.

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

D. Humoral and cell-mediated 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 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

D. Increased number of lymphocytes with identical specificities, all derived from a single lymphocyte stimulated by a single antigen 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.

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 αβ heterodimer D. Invariable ζ chains noncovalently linked to the TCR αβ heterodimer E. Igβ

D. Invariable ζ chains noncovalently linked to the TCR αβ heterodimer 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. Igβ is a component of the B lymphocyte antigen receptor complex.

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. 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.

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. 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.

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

D. Mannose receptor 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.

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

D. Memory 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.

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. NFκB and AP-1 E. Lck and Jun

D. NFκB and AP-1 The predominant signaling pathway used by Toll-like receptors (TLRs) results in the activation of the NF-κB transcription factor. Ligand binding to the TLR at the cell surface leads to recruitment of several cytoplasmic signaling molecules through specific domain-domain interactions, resulting in degradation of IκB and subsequent activation of NFκB. 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 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.

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

D. Reactive oxygen intermediates 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.

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 antigen-presenting 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.

D. Self peptide/self MHC complexes are formed and displayed by antigen-presenting 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. T cell tolerance is a result of deletion or inactivation of self-reactive T cells. The various steps in both the class I and the class II MHC antigen-presenting pathways do not discriminate between self and microbial proteins. Although expression of MHC molecules is up-regulated as a result of the innate immune responses to infections, there is some degree of constitutive expression of class II MHC on professional antigen-presenting cells, and class I MHC is constitutively expressed on most cells in the body. Only a small fraction of the surface MHC molecules of an infected cell will express peptides derived from microbial peptides.

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

D. T cell zones Migrating dendritic cells express the chemokine receptor CCR7 and move into the T cell zones, where SLC and ELC, 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.

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)-κB C. Tapasin D. Ubiquitin E. Calnexin

D. Ubiquitin In the class I pathway, proteins are tagged for proteasomal degradation by covalent addition of several copies of the polypeptide ubiquitin. Ubiquitin-dependent proteasomal degradation is also important in many other cellular processes besides antigen presentation. For example, NF-κB is a transcription factor whose activation is dependent on ubiquitination and proteasomal degradation of an inhibitor (called IκB). Calreticulin, tapasin, and calnexin regulate the assembly of class I MHC proteins within the endoplasmic reticulum.

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

D. Unmethylated CpG DNA 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.

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.

E. Adjuvants bind to T cell antigen receptors and promote their proliferation. Adjuvants are not necessarily T cell antigens. Some adjuvants may be T cell antigens, but their adjuvant activity is unrelated to their ability to be recognized, in peptide form, by T cells. Adjuvants are surrogates of the innate immune response to a microbe, required along with antigen component of a vaccine for naive T cell activation. Adjuvants stimulate local inflammation, influx of antigen-presenting cells (APCs), and activation of APCs to secrete cytokines and express costimulatory molecules, and they prolong peptide-MHC expression on the APC membrane.

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

E. CD28 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-α (TNF-α), 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. 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

E. Circulating anti-tetanus toxin antibodies 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. 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

E. Failure to form viral peptide-class I MHC complexes 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-γ as part of the early innate response to viral infection.

Which of the following is NOT a property shared by both CD4 and 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 αβ TCRs E. Is expressed on the majority of mature blood T cells

E. Is expressed on the majority of mature blood T cells CD4 is expressed on the majority (~65%) of mature blood T cells, whereas CD8 is expressed on a minority (~35%). 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.

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.

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. 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.