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167 Cards in this Set
- Front
- Back
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What are PAMPs?
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Pathogen-associated Molecular Patterns
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Examples of PAMPs?
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LPS (lipopoly saccharide); Flagellin
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Where do dendritic cells come from?
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Mature from monocyte precursors
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In what region of lymph nodes are B cells found?
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Follicles
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In what region of lymph nodes are T cells found?
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Paracortex
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What are M cells?
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Multifenestrated cells; present in lining of small intesting -- form membrane overlying lymphoid compartments within a Peyer's patch; transport antigens from lumen of gut to APCs
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What are the components of the innate immunity system?
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Physical barriers, complement system, phagocytes, natural killer cells
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What are the three major physical barriers in the innate immune system?
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Skin, GI tract, respiratory tract
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Where do macrophages come from?
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Monocyte precursors that migrate into tissues
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What is the process by which leukocytes are recruited to the site of an infection?
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Macrophages secrete TNF and IL1 etc., causing endothelial cells to produce other proteins that make rolling leukocytes stick
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What is the role of cytokines in innate immunity?
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Mediate the early inflammatory reactions to microbes and promote elimination of microbes
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Are cytokines used in innate or adaptive response?
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BOTH
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What is the role of cytokines in adaptive response?
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Stimulate proliferation and differentiation of antigen-stimulated lymphocytes and activate specialized effector cells
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What is chronic granulomatous disease?
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Phagocytes lack the oxidases necessary to kill ingested gram + bacteria
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What cytokines are involved in innate immunity?
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IL-12 and IFN-γ
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What is ADCC?
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Antibody dependent cytotoxicity; how natural killer cells and eosinophils are signaled to lyse cells; involves recognition of Fc regions of bound antibodies by NK or eosinophils
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What class of immunoglobin signals NK cells?
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IgG
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What class of immunoglobin signals eosinophils?
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IgE
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What do NK cells secrete as a signaling molecule? What cells respond to it?
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IFN-γ; activates macrophages
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What do NK cells respond to?
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IL-12
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What is the purpose of NK cells?
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Eliminate reservoirs of infection
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How do NK cells kill their targets?
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Release perforin
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How are normal cells spared from NK action?
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MHC class I inhibits NK cell action
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What are TLRs?
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Toll-like receptors;serve as pattern recognition receptors for cells of innate immune system
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What recognizes PAMPs?
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TLRs
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How does an innate immune response lead to an adaptive immune response?
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Macrophages and dendritic cells express costimulators and secrete cytokinds that together activate T lymphocytes (signals 2 and 3)
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What is the basic function of a helper T lymphocyte?
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Activate macrophages and B cells
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What is the basic function of a Cytolytic T lymphocyte?
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Kill infected cells and eliminate reservoirs of infection
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What is the basic function of a B lymphocyte?
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Secrete antibodies that block infections and promote elimination of extracellular microbes
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What are the three pathways of complement activation?
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Classical, Alternative, MBL
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What is the hallmark of the classical complement pathway?
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Triggered by antibodies that bind pathogens (ie part of adaptive response)
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What is the part of the complement system that promotes obsonization?
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C3b binding (also coated with C4d, iC3b, and C3dg)
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What is the function of the MAC complex formed by the late components of complement?
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Osmotic lysis of the microbe
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What initiates the classical complement cascade?
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C1 must bind two or more Fc portions of IgM or IgG that are bound to antigen
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What are the three responses that complement triggers?
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Lysis, Phagocytosis, and Inflammation
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What is the first common step of all three complement pathways?
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Production of C3b
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What component of complement stimulates inflammation?
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C5a (also C4a and C3a)
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How are immune complexes (opsonized antigen-antibody complexes) cleared from bloodstream?
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Erythrocytes bind the complexes and carry then to spleen or liver where the complexes are cleared by the resident phagocytic cells (eg Kupffer cells in liver)
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What is the effect of attaching C3d to microbial antigens in a nonimmune host?
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Amplifies T-dependent B cell response to that antigen
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What is the order of activation of the components of the classical complement pathway?
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C1, C4, C2, C3, C5, C6, C7, C8, C9
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How is the alternative complement pathway activated?
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C3b binding to various activating surfaces (note that C3b is constantly being produced as part of innate immune response)
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How is the lectin complement pathway activated?
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Activates C4 in absence of antibody, then follows classical pathway; triggered by binding mannose on pathogen surfaces
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What forms the MAC?
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Multiple C9 molecules
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What inhibits C1 activation?
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C1INH-
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What inhibits the convertases involved in complement?
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DAF and Factor1
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What inhibits the MAC
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CD59 and S protein
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What is angioneurotic edema?
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Hereditary failure in regulation of C1 activity by C1 INH-
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What is paroxysmal nocturnal hemoglobinuria?
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Absense of functional DAF on erythrocytes (normally inhibits formation of C3 convertases)
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What defects in complement lead to hemolytic anemia and strokes?
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Deficiency of CD59, which normally inhibits formation of the MAC
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What structural difference is there between IgM and IgG?
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IgM has one more heavy chain C region domain; has C-terminal transmembrane and cytoplasmic portions that anchor molecule in plasma membrane
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Where do the highly variable regions of antibody molecules map to?
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The parts of the antigen binding surface loops (CDR1, CDR2, CDR3) that make the most contacts with antigen
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What is CDR?
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"Complementarity determining regions" -- highly variable regions of antibody molecules that make the most contacts with antigen
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What proteins mediate recombination of antibody molecules?
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RAG1 and RAG2 ("recombinase activating gene")
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How many chromosomes are used to make antibody molecules?
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Only One!
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Genetic difference between heavy and light chain recombination?
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Light chain gnes do not have D segments; two separate light chain loci (only one for heavy chain)
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What is junctional diversity?
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Result of inexact RAG-mediated cutting -- leads to different DNA sequences
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About how many different antigen combining regions can be made?
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10E23!
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What is the process by which additional variability is introduced into IgV regions, and is associated with increased affinity for the antigen?
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Somatic Hypermutation
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Where is AID expressed?
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Only in B cells
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What is necessary for somatic hypermutation?
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AID protein (specific for B cells)
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What processes does AID mediate?
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somatic hypermutation and immunoglobulin heavy chain isotype switching
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What form of Ig is expressed ona Pre-B cell?
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cytoplasmic mu and pre-B receptor-associated mu
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What form of Ig is expressed on an immature B cell?
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Membrane IgM (mu and kappa or lambda light chain)
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What form of Ig is expressed on a Pro-B cell?
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none
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What form of Ig is expressed on a mature B cell (not activated)?
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Membrane IgM or IgM and IgD
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What provides second signal to B cells?
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CD4+ T cells
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Where does affinity maturation occur?
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Germinal centers of follicles
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What signals drive class switching of B cells?
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CD40-CD40L and cytokines
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[go through class switching and antigen recombination in book!]
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Are RAG proteins involved in class switching?
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No
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What is the effector function of IgM?
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Activation of classical complement pathway
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What is the effector function of IgG?
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Neutralization of microbes and toxins; opsonization to promote phagocytosis; activation of classical complement pathway; Feedback inhibition of B cell activation
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What is the effector function of IgE?
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Immunity against helminths (activation of eosinophils); Mast cell degranulation
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What is the effector function of IgA?
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Mucosal immunity (transport of IgA through epithelia)
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What part of antibody structure changes during isotype switching?
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C regions
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What part of antibody structure changes during affinity maturation?
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V regions
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Where do naïve T cells preferentially migrate to?
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Lymph nodes
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Where do newly activated T cells preferentially migrate to?
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Circulation
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Where do effector and memory T cells in blood preferentially move to?
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Peripheral tissues
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[look up terminal deoxyribonucleotide transferase]
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How does AID promote somatic hypermutation?
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Converts C nucleotides to uridine (U), causing mutation by base pair substitution
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What causes IgM and IgD to be co-expressed?
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No stop site is present between mu and delta regions
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What form of Ig is never secreted?
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IgD
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What triggers affinity maturation and class switching on B cells?
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CD40-CD40L interaction between B and T cells
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What cells can function as APCs?
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Macrophages, dendritic cells, B cells
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What are the MOST efficient APCs?
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Dendritic cells
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What is an example of an "MHC-like" molecule?
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CD1; presents lipid antigens to unique population of lymphocytes
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What cells recognice MHC class I molecules?
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CD8+ T cells (CTLs)
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What are the alleles for the MHC class I molecules?
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HLA-A, B, C
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Which MHC molecules are expressed on all nucleated cells?
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Class I
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what are the components of a MHC class I molecule?
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single polymorphic heavy (alpha) chain and non-MHC encoded, non-polymorphic light chain called beta-2-microglobulin
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What are the components of a MHC class II molecule?
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Alpha and beta chains, both polymorphic
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What cells express MHC class II?
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APCs and thymic epithelial cells
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What are the alleles for class II MHC?
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DP, DQ, DR
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What is another name for helper T cells?
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CD4+ T cells
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Peptides that end up in the cleft of MHC class I generally arise from:
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proteins that are synthesized in the cell (can also contain peptides from proteins that escaped phagosomes)
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Peptides that end up in the cleft of MHC class II generally arise from:
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proteins that are made externally to the cell then taken up by professional APCs
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What is the class II invariant chain protein?
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Protein that stabilizes a newly synthesized class II MHC molecule before it fuses with an endosome containing broken down peptides from ingested antigens
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What are TAPs?
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The special transporters that transport peptide fragments into the ER where they bind to newly synthesized class I MHC molecules
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How do DCs take up material that they will then present to T cells?
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Macropinocytosis
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What is DM protein? (involved with class II MHC proteins
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present in endosomes that fuse with vesicles containing just-synthesized MHC class II molecules; competes for binding with invariant chain, freeing up binding site for antigenic peptide
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What is the result of a TAP deficiency?
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Variant of SCID; No peptides present in ER for class I MHC to bind
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What is bare lymphocyte syndrome?
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Variant of SCID; failed expression of MHC class II molecules
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What is MHC restriction?
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Idea that T cells are specific to self MHC molecules
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How can you distinguish between T cells, B cells, and NK cells (in a lab)?
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Cell surface markers stained by monoclonal antibodies
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What are the two chains of the TCR?
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alpha and beta
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What gene segments are combined for the alpha chain of the TCR?
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V, J, and C
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What gene segments are combined for the beta chain of the TCR?
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V, D, J, and C
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What are the two chains of the BCR?
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heavy and light
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Major difference in binding between TCR and BCR?
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TCR binds to peptide+MHC, and requires simultaneous binding of CD4 or CD8 to MHC; (BCR binds to just peptide, no requirement for simultaneous binding)
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What is the alternate form of the TCR expressed by a minority of T cells?
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gamma/delta; often responds to lipid instead of peptide antigens
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What are Natural Killer T cells? What is their function?
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Cells that have the surface markers of both T cells and NK cells; Critical for protection against autoimmunity and cancer
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What are CD3 chains?
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Series of proteins found in association with TCRs; responsible for initiating signal transduction
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What is responsible for initiating signal transduction (activating the cell) after a T cell binds to MHC+peptide?
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CD3 chains and CD4
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What molecules play the role of co-stimulation (signal 2) for T cells being activated by APCs?
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CD28 is receptor, B7 is ligand (on activated APCs)
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What is necessary for T cell activation?
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MHC-TCR interaction PLUS B7-CD28 interaction
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What is the role of CD40/CD40L?
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Activated T cells upregulate expression of CD40L; When this interacts with CD40 on an APC, that APC becomes activated to express more B7
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What is CTLA4?
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Molecule on T cells that is expresed late in the activation process; Binds B7 more avidly than does CD28, thus preventing CD28 signaling and terminating the T cell response (makes cell anergic)
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What is the ITAM? (relates to T cell activation)
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Specific domain within CD3 proteins that is responsible for initiating signal pathways
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What is IL-2?
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Interleukin-2; produced by activated T cells; promotes proliferation of T cells
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How does TCR stimulation affect IL-2 interactions?
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Stimulation causes production of IL-2 as well as expression of alpha chain of receptor, which makes receptor high-affinity; signaling results in cellular proliferation
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What markers do immature T cells entering the thymus express?
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None; negative for CD3, CD4, and CD8
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How does homing of T cells occur?
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Naïve T cells express L-selectin, which targets them to lymph nodes; after activation, E and P selectins are expressed, which target the cells to the site of infection
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How do CTLs effect death of target cells?
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Release granules containing perforin and granzymes (initate apoptosis) into target cells when restimulated by MHC class I presenting the antigen to which they are primed
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What is anergy?
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The state in which a lymphocyte has lost the ability to be stimulated; produced by receiving signal 1 without signal 2
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What is the principal action of IL-4?
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B cell switching to IgE
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What is the principal action of IL-5?
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Activation of eosinophils
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What is the principal action of IFN-gamma?
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Activation of macrophages
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What is the principal action of TGF-beta?
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Inhibition of T cell activation
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If a naïve T cell is stimulated in the absence of TGF-beta but the presence of IFN-gamma and/or IL-12, what type of effector cells will develop?
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Th1
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If a naïve T cell is stimulated in the absence of TGF-beta but the presence of IL-4, what type of effector cells will develop?
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Th2
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If a naïve T cell is stimulated in the presence of TGF-beta and IL-6, what type of effector cells will develop?
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Th17
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If a naïve T cell is stimulated in the presence of TGF-beta and in the absence of IL-6, what type of effector cells will develop?
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Treg cells
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What is the dominant transcription factor for Th1 cells?
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T-bet
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What is the dominant transcription factor for Th2 cells?
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Gata-3
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What is the dominant transcription factor for Th17 cells?
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ROR-gamma
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What is the dominant transcription factor for Treg cells?
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FoxP3
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What do Th1 cells do?
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activate macrophages to kill engulfed bacteria
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What do Th2 cells do?
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stimulate B cells to make antibody and class switch
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What are the major cytokines produced by Th1 cells?
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IFN-gamma and IL-2
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What are the major cytokines produced by Th2 cells?
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IL-4 and IL-5
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Imbalance in what T cell effector group often leads to inflammatory diseases?
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Th1
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Imbalance in what T cell effector group often leads to allergic responses?
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Th2
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What is the major cytokine produced by Th17 cells?
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IL-6 and IL-17
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What seems to result from uncontrolled activity of Th17 cells?
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autoimmunity
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What do Th17 cells do?
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Stimulate neutrophil recruitment
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Note that CD4+ T cell subsets negatively regulate each other
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What type of T cells can be subdivided into several subgroups based on the cytokines they produce?
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CD4+ T cells
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What is the difference between long-lived plasma cells and memory cells?
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Memory cells can be any type of T or B cells; do NOT secrete anything. Plasma cells are B cells that continue to secrete small amounts of antibodies
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How is apoptosis stimulated in T cells?
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Engagement of Fas (CD95) receptor on activated T cells signals for apoptosis
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What is AIRE?
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Transcription factor involved in expression of self-antigens in thymus; genetic abnormalities result in auto-immune disease
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What is APECED?
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Autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia; caused by genetic abnormality in AIRE gene
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In a primary immunodeficiency, upper and lower resp infections indicate what kind of deficiency?
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B cell
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In a primary immunodeficiency, obligate intracellular organisms indicate what kind of deficiency?
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T cell
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In a primary immunodeficiency, unusual bacteria indicate what kind of deficiency?
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Neutrophils
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If your IgG is less than 100mg/dl and you have no IgA or IgM, what do you have?
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X-linked Agammaglobulinemia
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If you don't have tonsils because of a congenital abnormality, what do you have?
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X-linked Agammaglobulinemia
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Chronic Granulomatous Disease is a disorder of what?
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The INNATE immune system; can't make ROS to kill engulfed bad stuff in phagocytes
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What is a type I hypersensitivity?
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Allergies… IgE mediated; over stimulation of mast cells
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What is a type II hypersensitivity?
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Antibody mediated but not IgE; tissue damage and inflammation
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What is a type III hypersensitivity?
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immune complexes get deposited in blood vessels, cause inflammation
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What is a type IV hypersensitivity?
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T cell dependent
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What type of antibody dominates in a secondary response (as compared with a primary response)?
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IgG
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What are the advantages and disadvantages of live attenuated virus vaccines?
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Good immunogens that induce long-lied, appropriate immunity BUT are biochemically and genetically unstable and often not possible to produce; dangesrs of contamination or reversion to virulence
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What are the advantages and disadvantages of inactivated vaccines?
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Stable with little or no risk of virulence BUT not possible for all viruses and not as effective as live attenuated; does not create mucosal or cell immunity and often need reimmunization
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What are the advantages and disadvantages of using fragments or sub-unit vaccines?
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Safe BUT poor antigenicity and problems with vaccine delivery into body
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What cells are responsible for tumor immunity?
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T cells
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