Immunology 23 - Immunology 23-Allergy and Allergic...

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Immunology 23-Allergy and Allergic Reactions Atopy Susceptibility to allergic disease (type 1 and/or TH2 associated) Eczema, allergies, hay fever, asthma Genetic susceptibility (inheritable) Rates are increasing (environmental component too) Is NOT allergy itself; atopy ≠ allergy Eczema as a child= prone to later on develop food allergy and asthma Genetic Factors Many attempts to isolate the genes responsible; many associated polymorphisms, few causes (not just one gene so its hard to find a cause) Almost always has a close link to your HLA haplotype Asthma susceptibility genes: genes triggering the immune response or directing CD4 T cell differentiation; genes regulating TH2 cell differentiation and effector afunction; genes expressed in epithelial cells; genes identified by positional cloning Environmental Factors Hygiene hypothesis (associated with growing up in really clean environment) Atopy linked to: decreased in children with more siblings, attended day care, farm children (dirty environment); increased in Western (developed countries), with higher income, as countries improve hygiene (water decontamination, pasteurization) Increased hygiene= increased rates of allergy/asthma Hygiene Hypothesis Mechanisms Lack of TH1 stimulation promotes TH2 response?; not exposed to viruses early in life therefore decreased TH1 Helminthic infections (TH2) are protective in atopy Experimental support: -Animal models of disease -Small clinical trials stimulating immune system with parasites or antigens -Anecdotal evidence **exposure to parasites= biggest differences/protective exposure between developing/developed worlds Immune disregulation through development; some risk factors linked to early life; immune development in association with commensals? Mechanism of TH2 induction: Enzymatic antigens (papain, Der P1) Route—skin and mucosa Dose-low dose Types of Hypersensitivity Gell and Coombs—1960’s Type I Type II Type III Type IV Immune reactant IgE IgG IgG TH1 Cells TH2 Cells CTL Antigen Soluble antigen Cell or matrix Cell surfac Soluble antigen Soluble antigen Soluble antigen Cell associat
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associate d antigen e recept or ed antigen Effector mechanism Mast cell activatio n Comple ment FcR+ cells (phagocy tes, NK cells) Antibo dy alters signali ng Complem ent, phagocyt es (immune complexe s activate complem ent) Macroph age activatio n IgE producti on, eosinoph il activatio n, mastocyt osis cytotoxi city Example of hypersensit ivity reaction Allergic rhinitis, allergic asthma, atopic eczema, systemic anaphyl axis, some drug allergies Some drug allergies (penicilli n) Chroni c urticar ia (antib ody agains t FcER1 alpha chain) Serum sickness, arthus reaction Allergic contact dermatiti s, tuberculi n reaction Chronic asthma, chronic allergic rhinitis Graft rejectio n, allergic contact dermatit is to poison ivey Type I Hypersensitivity Immediate hypersensitivity
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Immunology 23 - Immunology 23-Allergy and Allergic...

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