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Hypersensitivity Reactions Injurious, patologic immune reactions causing tissue injury and disease Excessive or aberrant immune response to: Foreign antigens (non-self) - non-infectious (environmental) - infectious Self (autologous) antigens failure of self-tolerance (autoimmunity, autoimmune diseases) Types of Hypersensitivity Reactions Type I Type II Antibody mediated Type III Type IV T cell mediated Type I (Immediate hypersensitivity) (Allergy) Atopy – inherited propensity of an individual to produce high levels of IgE to various environmental antigens Alergen – an antigen that induces immediate hypersensitivity in atopic people Charles Richet 1913 Nobel Prize of Medicine and Physiology "in recognition of his work on anaphylaxis" Common allergens Common allergens Food allergens (“the big eight”) The sequence of events The sequence of events Type I hypersensitivity Biochemical events in mast cell activation High level IgE production is determined by: • Genetic factors (MHC II, cytokines, cytokine receptors...) • Nature of allergen (mass, glycosylation, charge, stability) • Environmental factors (exposure to microbes, polution, smoking...) Clinical manifestasions • • • • • • • Alergic conjuctivitis Alergic rhinitis (hay fever) Alergic (bronchial) asthma Hives (Urticaria) Atopic dermatitis Food allergy Anaphylaxis (systemic) Testing for type I hypersensitivityin vivo Skin tests Prick testing Intradermal testing Provokativni testovi Bronchoprovocative tests (metacholin chloride or alergen) DBPCFC (Double-Blind Placebo-Controlled Food Challenge) Prick testing 15 min. Swelling and redness Swelling 2mm › negative control – positive ≥ 5mm – clinically relevant 5-10 mm weak sensitivity 10-15 mm moderate sensitivity › 15 mm strong sensitivity Testing for type I hypersensitivityin vitro Total IgE nephelometry ... Alergen specific IgE RAST (RadioAllergoSorbent Test) EIA (PHADIA ImmunoCap ...) Therapy • Inhibition of mast cell degranulation (cromolyn) • Blocking of mast cell mediator effects (antihistamines) • Reduction of inflammation (corticosteroids) • Bronchial smooth muscle relaxation (phosphodiesterase inhibitors) • “Desensitization” – repeated administration of allergen • Epinephrine - anaphylaxis