Exam 1: Practice Set 2 Flashcards
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.
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 bacterium 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.
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 Ag – 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 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- as part of the early innate response to viral infection.
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 activatingreceptors.
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 Ag – 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.
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 an example of how the innate immune response stimulates or modifies adaptive immunity?
A. Tumor necrosis factor (TNF) secreted by helper T cells enhances adhesion molecules on endothelial cells and promotes recruitment of inflammatory cells.
B. Interferon (IFN)-γ produced by T helper cells is a potent activator of macrophages, allowing killing of phagocytosed microbes.
C. B7-1 expression on antigen-presenting cells is up-regulated in response to signaling through Toll-like receptors, thus enabling costimulation of T cells.
D. Infected cells coated by IgG3 are recognized by Fc receptors on natural killer cells, allowing efficient killing of the infected cells.
E. Double-stranded RNA of replicating viruses potently stimulates IFN-γ 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 costimulation 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- secretion involve innate immunity enhancing adaptive immunity.
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.
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.
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.
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.
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.
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 α/β heterodimer
D. Invariable ζ chains noncovalently linked to the TCR α/β heterodimer
E. Igβ
D. Invariable ζ chains noncovalently linked to the TCR α/β 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.
