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Types of hypersensitivity diseases The type of immune response and immunologic mechanisms that causes tissue injury The nature and location of the antigen that is the target of this response. Types of hypersensitivity diseases Immediate H.S (Type I) caused by IgE Type II H.S caused by antibodies other than IgE can cause tissue injury and interfering with normal cellular functions. Type III H.S caused by deposition of circulating Immune complexes in tissues Type IV or Delayed type hypersensitivity caused by T cells and Macrophages Disease caused by Immune responses *Activation of Th2 cells and production of IgE *Allergen Activation of Th2 B cell activation IgE binding of IgE to Fc receptor reexposure to Allergen release of mediators pathologic reactions General features (1) Immediate hypersensitivity با ورود آلرژن ،سلولهای B آن راشناسایی وپس از فعال شدن ،آنتی بادی IgEترشح میکنند . General features(2) There is a strong genetic predisposition for the development of immediate hypersensitivity *high level of IgE synthesis often run in families • Class –II MHC alleles • One locus for atopy is on chromosome 5,near the site of gene cluster encoding the IL-3,IL-4, • IL-5,IL-9,IL-13 and IL-4R General features افراد آتوپیك یا آلرژیك در مقابل عوامل آنتي ژنیك شایع محیطي ،پروتئین هاي موجود در گرده گیاهان)(pollen ،مواد غذایي ،فضوالت حیواني ،سم حشرات یا برخي داروها از طریق Th2پاسخ میدهند آلرژنها پروتئینهاي ریز مولكول با حاللیت باال ایمني ذاتي را فعال نمي كنند فراواني در محیط وبرخورد مكرر گلیكوزیالسیون باال َAllergens Type I is dependent on the activation of Th2 cells The clinical and pathologic manifestations of Type I:increased vascular permeability,vasodilation,smooth muscle contraction,local inflammation Mast cell activation Eosinophil and Basophil اين سلولها داراي گيرنده هاي high affinityبراي IgEبنام FCRمي باشند گرانولهايي سيتوپالسمي كه حاوي آنزيم ها و ساير مدياتورهاي فارماكولوژيك Mast cell activation Rapid release of granule contents(degranulation)such as Histamine,tryptase,chymase,proteoglyca ns(heparin and chondroitin sulfate) Synthesis and secretion of lipid mediators(prostaglandines ,Leukotrienes) Synthesis and secretion of cytokines(IL3,4,5,6,TNF-) Mediators actions Histamine= bronchoconstrictor,vascular leak,intestinal hypermotility PGD2=vasodilator and bronchoconstrictor , neut. Chemotaxis LTC4=bronchoconstriction,inflammation PAF=bronchoconstriction ,vasodilator, inflammation Clinical and pathologic features Hay fever(allergic rhinitis) Increased peristalsis Bronchial asthma Anaphylaxis Wheal and Flare reaction Therapy Inhibiting mast cell degranulation Antagonizing the effects of mediators Reducing inflammation Desensitization Anti IgE as a therapy Drugs Cromolyn sodium Theophyllin blocks phosphodiesterase epinephrin Prick test Prick test