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HYPERSENSITIVITY REACTIONS Immune responses that are inadequately controlled, inappropriately targeted to host tissues, or triggered by commensal microorganisms or usually harmless environmental antigens. AN OVERVIEW OF HYPERSENSITIVITY REACTIONS Type I. Type II. „immediate” Type III. Type IV. „late” Antibody mediated T cell mediated Types of antibody mediated hypersensitivity reactions FcRIα) TYPE I HYPERSENSITIVITY REACTION ALLERGY Immune responses to nonmicrobial environmental antigens that involve TH2 cells, immunoglobulin E, mast cells, and eosinophils Common allergic symptoms Sequence of events in immediate hypersensitivity reactions TFH Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Sensitization to an inhaled allergen Comparison of the diversity of allergen-specific antigen receptors on a B cell and a mast cell Biochemical events of mast cell activation The physical effects of IgE-mediated mast-cell degranulation vary with the tissue exposed to allergen Allergic reactions consist of an immediate reaction followed after some hours by a late-phase reaction The acute response in allergic asthma leads to TH2-mediated chronic inflammation of the airways Defense against many helminthic infections is mediated by IgE antibodies and activation of eosinophils Activated eosinophils release toxins, cytokines and other inflammatory mediators Systemic anaphylaxis Normal larynx Laryngeal oedema Systemic anaphylaxis is caused by allergens that reach the blood stream 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 Hygiene Hypothesis early childhood infections inhibit the tendency to develop allgergic disease Hygiene Hypothesis - Infection history makes a difference The wheal and flare reaction in the skin Cellular and Molecular Immunology, 7th ed., 2012 Elsevier ImmunoCAP Specific IgE Blood Test Anti-IgE Serum IgE Allergen Solid phase Possible approaches to decrease allergic reactions Enhancement of T reg activity Inhibition of IgE production Hyposensitization – IgE vs. IgG Inhibition of IgE binding Inhibition of allergen binding Inhibition of signal transduction Inhibition of degranulation Blocking of mediators’ effects TYPE II HYPERSENSITIVITY IgG or IgM antibodies bound to antigens of particular cells or the extracellular matrix Mechanisms of type II hypersensitivity reactions Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Frustrated phagocytosis mediated by IgG antibodies Binding Opsonization Internalization C3b C3b C3b C3b Enzyme release C3b C3R FcR The target, which cannot be phagocytosed, is damaged C3b Absorbed antigen Opsonized surface Binding Frustrated (drug) Enzyme release phagocytosis Examples of type II hypersensitivity Development of drug sensitivity I. Development of drug sensitivity II. TYPE III HYPERSENSITIVITY Antibodies form immune complexes in the circulation, and the complexes are subsequently deposited in tissues, particularly in blood vessels, and cause injury Immune complex–mediated tissue injury Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Tissue damage caused by deposited immune complexes Frustrated phagocytosis Immune complexes activate the complement system, neutrophils, basophils and thrombocytes Examples of human immune complex–mediated diseases Symptoms caused by type III hypersensitivity reactions depend on the site of immunecomplex deposition Arthus-reaction • Localized Type III hypersensitivity • Local vasculitis develops as a result of immune complex deposition • Inhaled antigens (fungi, animal feces) may induce similar reaction in the lung (Farmer’s lung and piegeon-breeder’s lung) Localized deposition of immune complexes within a tissue causes a type III hypersensitivity reaction TYPE IV HYPERSENSITIVITY REACTION T lymphocytes injure tissues either by triggering inflammation or by directly killing target cells Type IV hypersensitivity reactions Mechanisms of T cell–mediated hypersensitivity reactions Cellular and Molecular Immunology, 7th ed., 2012 Elsevier Delayed-type hypersensitivity (DTH) (e.g. tuberculin skin test) TH1 from a previous immunization (memory) Tuberculin skin test Introduction of Ag Ag = antigen Purified protein derivate (PPD) DTH as a result of a contact-sensitizing agent* CONTACT DERMATITIS *a contact-sensitizing agent is usually a small molecule that penetrates the skin then binds to self-proteins, making them “look” foreign CONTACT DERMATITIS Physical contact with poison ivy transfers pentadecacatechol, which causes dermatitis CELIAC DISEASE Delayed-type hypersensitivity
