1. Hypersensitivity Reactions

2. 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)

3. Types of Hypersensitivity Reactions Type I Type II Type III Type IV Antibody mediated T cell mediated

4. 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

5. "in recognition of his work on anaphylaxis" Charles Richet 1913 Nobel Prize of Medicine and Physiology

6. Common allergens

8. Food allergens (“the big eight”)

9. The sequence of events

10. Type I hypersensitivity

11. Biochemical events in mast cell activation

13. 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...)

17. Clinical manifestasions Alergic conjuctivitis Alergic rhinitis (hay fever) Alergic (bronchial) asthma Hives (Urticaria) Atopic dermatitis Food allergy Anaphylaxis (systemic)

19. 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)

20. 15 min. Prick testing Swelling 2mm › negative control – positive ≥ 5mm – clinically relevant 5-10 mm weak sensitivity 10-15 mm moderate sensitivity › 15 mm strong sensitivity Swelling and redness

21. Testing for type I hypersensitivityin vitro Total IgE  nephelometry...

22. Alergen specific IgE  RAST (RadioAllergoSorbent Test)  EIA (PHADIA ImmunoCap...)

23. 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