typeihypersensitivitypptpresentationmode-130430132219-phpapp02 (2).ppt
- 1. Type I Hypersensitivity reaction Dr.Pavulraj.S M.V.Sc., scholar, Division of Pathology Indian Veterinary
- 2. Introduction • Hypersensitivity - excessive, undesirable reactions produced by the normal immune system • Hypersensitivity reactions require a pre- sensitized (immune) state of the host • 1906 – Von Pirquet coined term: hypersensitivity
- 3. • Gell-Coombs Classified the reactions into four types based on the mechanisms involved and time taken for the reaction Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV
- 4. 3 involve antibody- • Type I (immediate): mediated by IgE (Mast Cells) • Type II: mediated by IgG or IgM • Type III (immune complex disease): IgG & complement One involves antigen specific cells • Type IV: Delayed type hypersensitivity, cell mediated immune memory response. Type I Hypersensitivity
- 6. TYPE I Hypersensitivity • Type I hypersensitivity – immediate or anaphylactic hypersensitivity • Immediate hypersensitivity is mediated by IgE • The primary cellular component in this hypersensitivity is the mast cell or basophil • The reaction is amplified by neutrophils and eosinophils
- 7. • 1902 - Charles Richet and Paul Portier discovered anaphylaxis • The symptoms resulting from allergic responses are known as anaphylaxis • Includes: Hay fever, asthma, eczema, bee stings, food allergies • Exposure may be by ingestion, inhalation, injection or direct contact
- 8. Allergens • Allergens are nonparasite antigens that can stimulate a type I hypersensitivity response. • Allergens bind to IgE and trigger degranulation of chemical mediators
- 9. Characteristics of allergens • Small 15-40,000 MW proteins • Protein components – Often enzymes • Low dose of allergen • Mucosal exposure • Most allergens promote a Th2 immune
- 11. Atopy • Atopy is the term for the genetic trait to have a predisposition for localized anaphylaxis • Atopic individuals have higher levels of IgE and eosinophils
- 12. Mechanisms of allergic response Sensitization • Repeated exposure to allergens initiates immune response that generates IgE isotype • Th2 cells required to provide the IL-4 required to get isotype switching to IgE
- 13. Mechanisms of allergic response Sensitization • The IgE can attach to Mast cells by Fc receptor, which increases the life span of the IgE • Half-life of IgE in serum is days whereas attached to FcεR it is increased to months
- 14. Mechanisms of allergic response Fc ε receptors (FcεR) • FcεR1 - high affinity IgE receptor found on mast cells/basophils/activated eosinophils • Allergen binding to IgE attached to FcεR1 triggers release of granules from the mast cell
- 15. Mechanisms of allergic response Effector Stage of Hypersensitivity • Secondary exposure to allergen • Mast cells are primed with IgE on surface • Allergen binds IgE and cross-links to activate signal with tyrosine phosphorylation, Ca++ influx, degranulation and release of mediators
- 19. Mediators of Type I Hypersensitivity Immediate effects Histamine Constriction of smooth muscles. Bronchiole constriction = wheezing. Constriction of intestine = cramps-diarrhea. Vasodilation with increased fluid into tissues Causing increased swelling or fluid in mucosa. Activates enzymes for tissue breakdown. • Leukotrienes • Prostaglandins
- 20. Primary Mediators Pre-formed mediators in granules • Histamine • Cytokines TNF-α, IL-1, IL-6. • Chemoattractants for Neutrophils and Eosinophils • Enzymes – Tryptase, Chymase, Cathepsin – Changes in connective tissue matrix, tissue breakdown
- 21. Secondary mediators Mediators formed after activation • Leukotrienes • Prostaglandins • Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF
- 22. Continuation of sensitization cycle • Mast cells control the immediate response • Eosinophils and neutrophils drive late or chronic response. • More IgE production further driven by activated Mast cells, basophils, eosinophils
- 23. Localized anaphylaxis • Target organ responds to direct contact with allergen • Digestive tract contact results in vomiting, cramping, diarrhea • Skin sensitivity usually reddened inflamed area resulting in itching • Airway sensitivity results in sneezing and rhinitis or wheezing and asthma
- 24. Systemic anaphylaxis • Systemic vasodilation and smooth muscle contraction leading to severe bronchiole constriction, edema, and shock • Similar to systemic inflammation
- 25. Other types of anaphylaxis
- 26. Diagnostic tests for immediate hypersensitivity Skin (prick and intradermal) tests • Measurement of total IgE and specific IgE antibodies against the suspected allergens • Total IgE and specific IgE antibodies are measured by a enzyme immunoassay (ELISA) • Increased IgE levels are indicative of an atopic condition • A genetic predisposition for atopic diseases
- 30. REFERENCES • Brostoff, J., Scadding, G. K., Male, D., & Roitt, I. M. (1991). Introduction to Immune Responses. In J.Brostoff, G. K. Scadding, D. Male, & I. M. Roitt (Eds.), Clinical Immunology ( New York: Gower Medical Publishing) • Gell, P. G. H. & Coombs, R. R. A. (1963). The classification of allergic reactions underlying disease. In R.R.A.Coombs & P. G. H. Gell (Eds.), Clinical Aspects of Immunology ( Blackwell Science) • Shamberger, R. (2008). Types of Food Allergy Testing. Townsend Letter, January, 71-72 • Kuby immunology, Sixth edition • Yamasaki, S. & Saito, T. (2005). Regulation of mast cell activation through FcepsilonRI. Chem.Immunol.Allergy, 87, 22-31.