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HYPERSENSITIVITY REACTIONS Innocous materials can cause hypersensitivity in certain individuals unwanted inflammation damaged cells and tissues ANTIBODY MEDIATED HYPERSENSITIVITY REACTIONS HYPERSENSITIVITY REACTIONS TYPE I ALLERGY TYPE II TYPE III Soluble antigen Cell surface or matrix antigen Soluble antigen IgE Mast cell Hay fever Asthma Systemic anaphylaxis IgG FcγR+ cells NK, macrophage Certain drug allergies (penicillin) IgG – immune complex FcγR+ cells Complement Serum sickness TYPE I HYPERSENSITIVITY REACTION ALLERGY IgE MAST CELL RESPONSE TO SURFACE FcRεI CROSSLINKING a g b I I TT AA MM PLA2 foszfa tidil-kolin LYSO-PC arachidonsav Fc eRI I T A M MAPkináz I T A M Lyn II TT AA MM Syk endoplazmás retikulum 2 Ca + 5-lipoxigenáz PIP2 PI-PLCg DAG IP3 foszfolipid ciklooxigenáz Ca 2+ PGD2 citokin gének transzkripciója LTC4 NFAT AP-1 NF-k B PAF szekretoros granulum 2+ PKC Ca Ca 2+ proteinek (miozinkönnyűlánc) foszforilációja Ca 2+ szekréció PGD2 EARLY MEDIATORS LTC4 LTD4 LTE4 LATE MEDIATORS mediátorok citokinek IL-3, IL-4, IL-5, IL-6 TNFa Biogenic amins – histamin Enzymes – triptase, chymase, carboxypeptidase ALLERGENS USUALLY ENTER THE BODY VIA MUCOSAL SURFACES AND THEY ARE PRESENT AT A LOW DOSE DC B cell Th2 Th2 antigen presentation T cell priming and polarization allergic response soluble proteins on te surface of small particles (pollen, dust mite „drops”) small molecular weight trans-mucosal entry, enzymatic activity low dose (ragweed: 1µg/year) The enzymatic activity of some allergens enables penetration of epithelial barriers Der p1 A légutak intakt epitéliuma A Der p1 hasítja az okkludint A Der p1 –t felveszik a DC-k, Th2-priming A Der p1-specifikus IgE a hízósejtekhez kötődik (LTB4, PGE2) Copyright ©2005 American Society for Clinical Investigation IMMUNE RESPONSES MEDIATED BY Th2 CELLS DC Bas Th0 IL-4 ALLERGEN Th2 C D 4 0 mucosal membranes B IL-13 CD40L C D 4 0 M H CII B IgE Mechanism of the initiation of Th2 response Immunology and Cell Biology (2008) 86, 637–638 GENETIC/ENVIRONMENTAL PREDISPOSITION TO ALLERGY Genetic factors chromosome 11q FcεRβ chain gene chromosome 11q IL-3-5 IL-9, IL-13 GMCSF HLAII DRB1*015 Inproper immunregulation Th1/Th2 inbalance regulation of IgE synthesis high eosinophil counts allergy Environmental factors lack of tolerance Treatment Types of IgE-derived allergic response SYNDROME ALLERGENS ROUTE OF ENTRY systemic anaphylaxis drugs anti-serum peanuts intravenous Per os acute urticaria bug bite allergy test subcutan local increase in blood flow and vascular permeability allergic rhynitis pollen dust mite drops inhaled irritation and edema of nasal mucosa airway inflammation asthma animal fur pollen dust mite drops inhaled bronchial constriction, increased mucus production food allergy nut, peanuts, fish, shellfish milk, eggs Per os vomiting, diarrhea pruritis (itching) urticaria (hives) anaphylaxia (rare) RESPONSE edema, increased vascular permeability tracheal occlusion circulatory collapse, death