Transcript 36_Allergy
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 Properties of inhaled allergens Proteolytic activity of allergens Reed and Kita JACI 2004 Pollen grains liberate bioactive lipids (LT, PGE) Hydrated pollen grains genetate ROS Copyright ©2005 American Society for Clinical Investigation High-affinity IgE receptor (FcεRI) 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 Genes associated with the susceptibility to asthma 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 Mediators and treatment of asthma Cellular and Molecular Immunology, 7th ed., 2012 Elsevier 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 Anti-IgE has multiple effects in allergic diseases Anti-lgE Binds to free lgE, decreasing cell-bound lgE B Cell Decreases expression of high-affinity receptors Decreases mediator release • Decreases allergic inflammation • Prevents exacerbation of asthma and reduces symptoms lgE classswitching Release of lgE FcεRI Plasma Cell lgE Antibodies Mast Cell (and basophil, Release of eosinophil, dendritic cell) soluble mediators Holgate ST, et al. Nat Rev Immunol. 2008;8:218-230. Allergic Inflammation