1. Immune responses that are inadequately controlled, inappropriately targeted to host tissues, or triggered by commensal microorganisms or usually harmless environmental antigens. HYPERSENSITIVITY REACTIONS

2. Type I. „immediate” Type II.Type III.Type IV. „late” Antibody mediatedT cell mediated AN OVERVIEW OF HYPERSENSITIVITY REACTIONS

3. Types of antibody mediated hypersensitivity reactions Fc  RIα)

4. TYPE I HYPERSENSITIVITY REACTION ALLERGY Immune responses to nonmicrobial environmental antigens that involve TH2 cells, immunoglobulin E, mast cells, and eosinophils

6. Common allergic symptoms

7. Sequence of events in immediate hypersensitivity reactions Cellular and Molecular Immunology, 7th ed., 2012 Elsevier T FH

8. Sensitization to an inhaled allergen

9. Properties of inhaled allergens

10. Reed and Kita JACI 2004 Proteolytic activity of allergens

11. (LT, PGE) Pollen grains liberate bioactive lipids

12. Copyright ©2005 American Society for Clinical Investigation Hydrated pollen grains genetate ROS

13. High-affinity IgE receptor (FcεRI)

14. Comparison of the diversity of allergen-specific antigen receptors on a B cell and a mast cell

15. Biochemical events of mast cell activation

17. The physical effects of IgE-mediated mast-cell degranulation vary with the tissue exposed to allergen

18. Allergic reactions consist of an immediate reaction followed after some hours by a late-phase reaction

19. The acute response in allergic asthma leads to T H 2-mediated chronic inflammation of the airways

20. Defense against many helminthic infections is mediated by IgE antibodies and activation of eosinophils

21. Activated eosinophils release toxins, cytokines and other inflammatory mediators

22. Normal larynxLaryngeal oedema Systemic anaphylaxis

23. Systemic anaphylaxis is caused by allergens that reach the blood stream

24. chromosome 11q FcεRβ chain gene chromosome 11q IL-3-5 IL-9, IL-13 GMCSF HLAII DRB1*015 allergy Inproper immunregulation Th1/Th2 inbalance regulation of IgE synthesis high eosinophil counts Environmental factors lack of tolerance Genetic/environmental predisposition to allergy Genetic factors

25. Genes associated with the susceptibility to asthma

26. Hygiene Hypothesis early childhood infections inhibit the tendency to develop allgergic disease

27. Hygiene Hypothesis - Infection history makes a difference

29. The wheal and flare reaction in the skin Cellular and Molecular Immunology, 7th ed., 2012 Elsevier

30. ImmunoCAP Specific IgE Blood Test Anti-IgE Serum IgE Allergen Solid phase

31. 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

32. Mediators and treatment of asthma Cellular and Molecular Immunology, 7th ed., 2012 Elsevier

33. Monoclonal Anti-IgE Anti-IgE therapy represents a novel immunomodulatory approach that targets an early point in the allergic inflammatory cascade. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody

34. Anti-IgE has multiple effects in allergic diseases Holgate ST, et al. Nat Rev Immunol. 2008;8:218-230. Plasma Cell B Cell lgE Antibodies Binds to free lgE, decreasing cell-bound lgE lgE class- switching Release of lgE Anti-lgE FcεRI Mast Cell (and basophil, eosinophil, dendritic cell) Decreases expression of high-affinity receptors Release of soluble mediators Decreases mediator release Allergic Inflammation Decreases allergic inflammation Prevents exacerbation of asthma and reduces symptoms