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Basic Immunology Functions And Disorders of the Immune System 4th Edition by Abul K. Abbas Test Bank
Abbas: Basic Immunology, 4th Edition
Chapter 02: Innate Immunity
Test Bank
MULTIPLE CHOICE
ANS: C
Innate immunity is the first line of defense against infections, yet many pathogenic microbes have evolved strategies to resist innate immunity. Adaptive immunity, being more potent and specialized, plays a critical role in defending against these virulent microbes. Innate immunity is the phylogenetically oldest mechanism of microbial defense, and it is present in all multicellular organisms, including plants and insects. Studies have shown that hampering effector mechanisms of innate immunity renders hosts much more susceptible to infection, even with a functional adaptive immune system. It is also true that, like the adaptive response, the innate immune response consists of recognition, activation, and effector phases. Although it provides the initial, rapid response against microbes, innate immunity can influence adaptive immune responses to tailor them against particular microbes.
ANS: E
Secreted antibodies against protein antigens are effectors of humoral immunity, a component of the adaptive immune system. All other mechanisms listed are part of the innate immune system. Intact epithelial surfaces prevent microbial entry, and epithelial cells express anti-microbial factors, such as defensins. Neutrophils are effector cells that function in early phagocytosis and killing of microbes. Cytokines that mediate inflammation (e.g., tumor necrosis factor, interleukin-1, chemokines) are components of innate immunity. Intraepithe-lial T lymphocytes present in the epidermis and mucosal epithelia express a limited diversity of antigen receptors; as such, they are considered effector cells of innate immunity and function in host defense by secreting cytokines, activating phagocytes, and killing infected cells.
ANS: A
Innate immune system receptors are encoded by germline genes that have evolved to recognize microbial structures or molecules produced by stressed self, and therefore there is little chance of innate immune responses to normal self. Because the specificities of adaptive immune system receptors (Ig or T cell receptor molecules) are randomly generated by somatic recombination and junctional-diversity mechanisms, there is a greater chance that the adaptive immune system receptors may recognize normal self molecules, leading to autoimmunity. Mechanisms of tolerance minimize this possibility, but these mechanisms can fail. The adaptive immune system receptors can recognize nonmicrobial structures. Although most innate immune system receptors recognize microbial structures, some Toll-like receptors and activating receptors of natural killer cells do recognize nonmicrobial self proteins expressed by stressed, damaged, or infected cells. Memory is a unique property of the adaptive and not the innate immune system.
ANS: D
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.
ANS: A
Gram-positive bacteria contain cell walls rich in peptidoglycan. When shed by bacteria such as Streptococcus pneumoniae, peptidoglycan serves as a ligand that binds Toll-like receptor 2 (TLR2), stimulating an innate immune response. The other choices listed are also ligands that stimulate TLRs, but they are not present in gram-positive bacteria. Double-stranded RNA is found in replicating viruses, lipopolysaccharide (LPS) is a component of the outer cell wall of gram-negative bacteria, and both lipoarabinomannan and phosphatidylinositol dimannoside are present in mycobacteria.
ANS: D
The predominant signaling pathway used by Toll-like receptors (TLRs) results in the activation of the NF-kB 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 IkB and subsequent activation of NFkB. 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.
ANS: E
CD28, the activating receptor for B7-1 and B7-2 costimulatory molecules, is constitutively expressed on the surface of many T cells and is not induced by Toll-like receptor (TLR) signaling. TLR signaling does induce expression of B7-1 and B7-2 on antigen-presenting cells. Other genes expressed in response to TLR signaling encode proteins important in many different components of innate immune responses. These include inflammatory cytokines such as tumor necrosis factor-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.
ANS: D
The macrophage mannose receptor binds to terminal mannose and fucose residues on bacterial glycoproteins and glycolipids. Mammalian cells do not typically contain these residues. CD36 binds many different ligands, including microbial and self molecules. Fc receptors, complement receptors, and ICAM-1 are receptors for mammalian complement fragments, Ig, and LFA-1, respectively.
ANS: B
Neutrophils and macrophages can both actively phagocytose and kill microbes, and both express opsonin receptors, such as FcgRI 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.
ANS: B
This patient is suffering from septic shock, characterized by the clinical triad of disseminated intravascular coagulation (DIC), hypoglycemia, and cardiovascular failure. This condition is most often initiated by endotoxin, also known as lipopolysaccharide (LPS), a component of the outer cell walls of gram-negative bacteria. LPS is a potent stimulus for tumor necrosis factor (TNF)-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.
ANS: B
Granzyme B, a proteolytic enzyme component of cytolytic T lymphocyte (CTL) and natural killer (NK) cell granules, is involved in initiating caspase-dependent CTL killing of target cells. Granzyme B is not involved in phagocyte killing of ingested microbes. Inducible nitric oxide synthase (iNOS) generates NO in macrophages, and NO is toxic to microbes. Phagocyte oxidase and myeloperoxidase are involved in generating free radical species that kill ingested microbes in phagocytes. Lysozyme is a proteolytic enzyme in neutrophil granules that contributes to microbial killing.
ANS: B
C5a is a peptide released after cleavage of C5 protein during the complement cascade. It stimulates the influx of neutrophils to the site of infection, thus acting as a chemoattractant, not as an opsonin. C3b (covalently bound to microbes on which complement activation has taken place) and IgG bound to antigen, are particularly potent opsonins, because phagocytes have receptors for both C3b and the Fc region of IgG. C-reactive protein and mannose-binding lectin also can coat microbes and be recognized by phagocyte receptors; thus they serve as opsonins.
ANS: D
Chronic granulomatous disease (CGD) is a rare, inherited immunodeficiency disease associated with a defective intracellular respiratory burst in phagocytes. It consists of a group of heterogeneous disorders of oxidative metabolism in which the pathways 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.
ANS: E
The presence of normal numbers of CD8+ T cells and the ability of these cells to kill virally infected target cells indicates that the class I major histocompatibility complex (MHC) pathway of viral peptide antigen presentation is intact. The patients 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 Bdependent mechanisms (similar to cytolytic T lymphocyte killing), and produce interferon-g as part of the early innate response to viral infection.
ANS: B
Natural killing (NK) inhibitory receptors recognize class I MHC molecules that are normally and constitutively expressed, including various alleles of HLA-A and HLA-C. The cytoplasmic tails of NK inhibitory receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), but not immunoreceptor tyrosine-based activation motifs (ITAMs). Some inhibitory receptors on NK cells are members of the Ig superfamily, but 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.
ANS: C
Mannose-binding lectin (MBL) is a soluble serum component that is structurally similar to C1 of the classical complement pathway. MBL binds to mannan residues on microbial surfaces and triggers proteolytic cleavage and activation of downstream components of the complement system. C9 is not involved in initiation of complement activation but is part of the common final membrane attack complex (MAC) pathway. CR2 is a cell surface receptor for complement fragments. A mannose receptor is a cell surface receptor on phagocytes that binds mannan residues and promotes phagocytosis of microbes.
ANS: C
Innate immune responses are important stimulators of adaptive immunity. Increased expression of B7-1 and B7-2 on antigen-presenting cells after microbial activation of Toll-like receptors (innate immunity) is critical in providing costimulatory signals for T cell activation (adaptive immunity) via binding to CD28 receptors on T cells. T helper cellmediated 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-b secretion involve innate immunity enhancing adaptive immunity.
Abbas: Basic Immunology, 4th Edition
Chapter 04: Antigen Recognition in the Adaptive Immune System
Test Bank
MULTIPLE CHOICE
ANS: A
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.
ANS: D
The T cell receptor (TCR) complex contains a highly variable antigen receptor, usually composed of a heterodimer of a and b chains, called the TCR, which is responsible for antigen recognition, as well as invariant signaling proteins, CD3d, CD3e, and CD3l, and the z 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. Igb is a component of the B lymphocyte antigen receptor complex.
ANS: A
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 CD3g, CD3d, CD3e, and z, 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 z.
ANS: B
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.
ANS: A
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 surfaceassociated 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).
ANS: B
A small population of T cells express T cell receptors that recognize lipids bound to class I MHClike molecules called CD1 molecules. These lipid antigen-specific T cells include CD4+CD8+, or CD4-CD8- ab 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-g, but their physiologic function is unknown.
ANS: B
T cells expressing the gd TCR are a lineage distinct from the much more numerous ab-expressing T lymphocytes. The gd T cells do not recognize MHC-associated peptide antigens and are not MHC restricted. Some gd T cells recognize protein or nonprotein antigens that do not require processing or particular types of antigen-presenting cells for their presentation. The gd heterodimer associates with the same CD3 and z proteins as do ab receptors. Most gd cells do not express CD4 or CD8. The gd cells are capable of several biologic activities, including secretion of cytokines and lysis of target cells.
ANS: C
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 MHCrestricted 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.
ANS: B
Knockout mice lacking CD4 do not contain mature class IIrestricted T cells because the CD4 coreceptor plays an essential role in the maturation of T cells in the thymus. Most CD4+ class IIrestricted 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 Irestricted 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.
ANS: E
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.
ANS: C
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 Irestricted 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. LFA-1 is an important integrin mediating adhesion of the CD8+ T cells to virus-infected target cells.
ANS: D
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.
ANS: C
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.
ANS: D
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 a3 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.
ANS: C
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.
ANS: A
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.
ANS: B
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.
ANS: A
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-1ICAM-1 mediates cell adhesion interactions important in T cell activation and homing.
ANS: A
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.
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