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

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

Types of antibody mediated hypersensitivity reactions Fc  RIα)

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 Cellular and Molecular Immunology, 7th ed., 2012 Elsevier T FH

Sensitization to an inhaled allergen

Properties of inhaled allergens

Reed and Kita JACI 2004 Proteolytic activity of allergens

(LT, PGE) Pollen grains liberate bioactive lipids

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

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 T H 2-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

Normal larynxLaryngeal oedema Systemic anaphylaxis

Systemic anaphylaxis is caused by allergens that reach the blood stream

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

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 Holgate ST, et al. Nat Rev Immunol. 2008;8: 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