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13 Cards in this Set
- Front
- Back
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Delayed Type Hypersensitivity
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TH1 interaction with macrophage response
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Describe the development, function and cytokines produced by CD4+ TH2 cells
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Presence of IL-4 (from mast cells and pre-existing TH2 cells) favors development of naïve T cells into TH2 cells
IL-4 activates STAT6 which induces expression of transcription factor: GATA-3 Chart on Slide 7 Produces: IL4 (main cytokine), 5, 13, 10 IL-4 (+ IL-13) promotes B cell isotype switching to IgE (important in immunity to helminths; allergy) IL-4 promotes B cell isotype switching to IgG4 (neutralizing antibody) IL-5 potently activates eosinophils (major basic protein in eosinophil granules harms and helps expel helminthic parasites = worms) IL-13 stimulates mucous secretion (helps expel parasites) IL-4, IL-10 and IL-13 promote “alternative” macrophage activation (after inflammation comes healing) |
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Cytokines
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Pro-inflammatory: TNFa, IL1, IL6, IL12 (classical activation of macrophages)
Anti-inflammatory: TGFb, IL10 (alternative activation of macrophages via TH2) IL-23 (one of the classical activation inflammatory cytokines) very similar to IL-12 in function |
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Define the term “alternative” macrophage activation and describe the role of CD4+ TH2 cytokines in wound healing
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During infection/inflammation macrophage is activated (M1) by microbial products (PRRs*) and IFN-g from TH1 cells. M1 produces IL-12, IL-1, TNF-a, NO* ROS* (and others)
During healing macrophage is “alternatively” activated (M2) by IL-4, IL-13 and IL-10 (from TH2 cells) produces TGF-b, IL-10, growth factors TGF-b is anti-inflammatory but fibrogenic, can cause scarring IL-13 from TH2 cells also contributes to fibrosis/scarring |
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Explain the role of cytokines produced by CD4+ TH1 and TH2 cells in immunoglobulin heavy chain isotype (class) switching
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Slide 17 picture
Besides the CD40:CD40L interaction, cytokines are required for isotype switching Switching to IgA is stimulated by TFG-b and other factors produced at mucosal sites Switching to IgG1 and IgG3 (opsonizing antibodies) is stimulated by IFN-g, a signature TH1 cell cytokine Switching to IgE (responses to helminths/allergens) is stimulated by IL-4 (+ IL-13), signature TH2 cell cytokines Switching to IgG4 (neutralizing antibody) is stimulated by IL-4, a signature TH2 cell cytokine |
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Define the processes of opsonization and neutralization
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A neutralizing antibody binds to an antigen (i.e. toxin) or an infectious agent (i.e. virus) and inhibits its ability to produce a biologic effect
TH2 responses produce neutralizing antibodies (like IgG4) TH2 also produce IgE Fab region binds microbe (i.e. virus) and prevents it from attaching/infecting new cell or bind toxin and prevents it from binding to host cell and exerting toxic effect (Fc region not important) An opsonin is a molecule (IgG1 or IgG3; or C3b) that when attached to the surface of a microbe binds to a molecule (FcgR1for IgG1 or IgG3 ; or CR1 for C3b) on phagocytes (neutrophils, macrophages) and increases efficiency of phagocytosis. (produced by TH1 response, Fc region is most important) |
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Describe the function and types of Fc receptors
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Opsonization: Fc receptors (FcgRI) on phagocytes bind IgG1 or IgG3 on microbe, assists phagocytosis
Mast cells/basophils degranulate when IgE bound to their Fc receptors (FceR1) is cross-linked by antigen (helminth or allergen) IgM, IgG1, IgG3 activate classical complement pathway, can cause complement mediated: lysis, phagocytosis (C3b binds to CR1 on phagocytes), and inflammation (C5a, C3a) |
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FcgRI (aka CD64)
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on macrophages or neutrophils:
IgG1 or IgG3 binds microbe Antibody-mediated phagocytosis (by spleen phagocytes) is very important in defense against encapsulated bacteria. Splenectomy predisposes patients to disseminated infections with encapsulated bacteria (which are poorly bound by complement)! |
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FcgRIIB (aka CD32; has an ITIM*): - Slide 28
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B cell feedback inhibition by IgG
Possible benefit in diseases caused by autoantibody: intravenous immunoglobulins bind antigens, engage this receptor, suppress autoantibody production |
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Describe the process of antibody-dependent cellular cytotoxicity (ADCC)
FcgRIIIA (aka CD16): |
NK cells express FcgRIIIA which allows them to bind/kill IgG-coated target cells
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List and compare the specific effector functions of IgM, IgG1, IgG3, IgG4 and IgE
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IgG1/3 = opsonizing
IgG4 = neutralizing IgM = naive/complement |
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Explain the role of IgE in protection against helminth infections and in Type I Hypersensitivity
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IgE binds with very high affinity to FceRI, expressed on mast cells, basophils and eosinophils
Within minutes, Cross-linking of IgE activates mast cell because of ITAMs* on FceRIs Activation results in release of granules (histamine) and lipid mediators Mediators released from activated mast cells are toxic to helminthic parasites (worms) |
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IgE’s Role In Type I Hypersensitivity
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TH2/IgE responses occur more often in people who are “atopic” (genetically predisposed to allergy)
On first exposure to allergen: TH2 cells and IgE are produced (individual becomes sensitized) Type I Hypersensitivity (allergic response) occurs immediately* upon repeat exposure to antigen |
