Allergy : An Overview

1. Allergy: An Overview Salwa Hassan Teama

2. Contents • Allergy • Hypersensitivity • Allergy: IgE Mediated: Type I • Immunopathogenesis • Performed Mediators • Food Hypersensitivity • Laboratory Tests • Prevention • Treatment

3. Allergy • Type of hypersensitivity reactions of the immune system. Allergy may involve more the one type of reaction. • An allergy is a immune reaction to something that does not affect most other people. Substances that often cause reactions are: • Pollen • Dust mites • Mold spores • Pet dander • Food • Insect stings • Medicines • …….

4. Allergy Risk factor • Host factors; heredity, gender, race, and age. • Environmentalfactor;infectious diseases during early childhood, environmental pollution, allergen levels and dietary changes.

5. Hypersensitivity • Hypersensitivity (hypersensitivity reaction)refers to undesirable immune reactions produced by the normal immune system. • Hypersensitivity reactionsrequire a pre-sensitized (immune) state of the host. • Hypersensitivity reactions:four types; based on the mechanisms involved and time taken for the reaction, a particular clinical condition (disease) may involve more than one type of reaction.

6. Classification of Immunologic Reactions (Gel and Coombs)

7. Hypersensitivity Reactions

8. Allergy Ig E mediated (Type I hypersensitivity) Allergy Non Ig E mediated

9. IgE Mediated: Type I • Overreaction to an allergen that is contact through skin, inhaled through lung, swallowed or injected. • Triggered by harmless substances such as; pollen, dust, animal danders, food, … can also occur as a result of drug or bee stings or stings from other insects(an allergen). • An allergen;an antigen that causes allergy. Either inhaled, ingested, .. Can be complete protein antigens (Pollen and animal dander) or low molecular weight proteins.

10. Atopy • Atopyis the genetic predisposition to make IgE antibodies in response to allergen exposure. • Etiologyis unknown but there is strong evidence for a complex of genes with a variable degree of expression encoding protein factors. • Allergic rhinitis, allergic athma, atopic dermatitisare the most common manifestation of atopy. Allergic gastroenteropathy is rara. These manifestation may coexist in the same patients at different times. Atopy can be asymptomatic.

11. Genes Identified to date in Atopy

12. Common allergens associated with type I hypersenstivity • Foods • Nuts • Seafood • Eggs • Peas, beans • Milk • Insect products • Bee venom • Wasp venom • Ant venom • Cockroach calyx • Dust mites • Mold spores • Animal hair and dander • Proteins • Foreign serum • Vaccines • Plant pollens • Rye grass • Ragweed • Timothy grass • Birch trees • Drugs • Penicillin • Sulfonamides • Local anethetics • Salicylates

13. Mechanism • While first-time exposure may only produce a mild reaction, repeated exposures may lead to more serious reactions. Once a person is sensitized (has had a previous sensitivity reaction), even a very limited exposure to a very small amount of allergen can trigger a severe reaction. • Most occur within seconds or minutes after exposure to the allergen, but some can occur after several hours, particularly if the allergen causes a reaction after it is partially digested. In very rare cases, reactions develop after 24 hours.

14. Immunopathogenesis • Both mast cells and basophilsare involved in immunopathogenesis of IgE mediated diseases. Mast cells and basophils have a high affinity IgE cell membrane receptors for IgE. • Immediate hypersensitivity reactions are mediated by IgE, but T and B cells play important roles in the development of these antibodies

17. Mast Cell • Mast cell are abundant in the mucosa of the respiratory, gastrointestinal tracts and in the skin, where atopic reaction localize. • Mast cell release mediator cause the pathophysiology of the immediate and late phases of atopic diseases.

18. Mast Cell Activation

19. Mast cell Hours Minutes Classic Allergic Reaction Flushing Hypotension Increased mucus production Pruritus Smooth muscle contraction Vascular leakage Late –phase Reaction Eosinophil infiltration Neutrophil infiltration Fibrin deposition Mononuclear infiltration Tissue destruction

20. Performed Mediators/ Primary Mediators Histamine:is one well-known mediator. This mediator acts on histamine 1 (H1) and histamine 2 (H2) receptors to cause: contraction of smooth muscles of the airway and GI tract, increased vascular permeability and vasodilation, nasal mucus production, airway mucus production, pruritus, cutaneous vasodilation, and gastric acid secretion. Serotonin: increased vascular permeability and contraction of smooth Muscles. Tryptase: is a major protease released by mast cells; its exact role is uncertain, but it can cleave C3 and C3a. Tryptase is found in all human mast cells but in few other cells and thus is a good marker of mast cell activation. Proteoglycans:include heparin and chondroitin sulfate. Chemotactic factors ………………….

21. Performed Mediators/ Secondary Mediators • Platelet activating factor • Leukotriens • Prostaglandinin • Bardykainin • Cytokines • IL1 ,TNF • IL2,IL3,IL4,IL5,L6

23. Important Clinical Aspects of Immediate Hypersensitivity

24. Food Hypersensitivity Source: http://www.allergycentre.com.my/index.html

25. Food Hypersensitivity Source: http://www.allergycentre.com.my/index.html

26. Immunopathologic Response Classification System Proposed by Sell et al., 1996 Immunopathologic responses into the following 7 categories: • Inactivation/activation antibody reactions • Cytotoxic or cytolytic antibody reactions • Immune-complex reactions • Allergic reactions • T-cell cytotoxic reactions • Delayed hypersensitivity reactions • Granulomatous reactions This system accounts for the fact that multiple components of the immune system can be involved in various types of hypersensitivity reactions. For example, T cells play an important role in the pathophysiology of allergic reactions . In addition, the term immediate hypersensitivity is somewhat of a misnomer because it does not account for the late-phase reaction or for the chronic allergic inflammation that often occurs with these types of reaction. References & more: http://emedicine.medscape.com/article/136217-overview#a0104 References: Sell S, Rich RR, Fleisher TA, et al, eds. Clinical Immunology: Principles and Practice. ed. St. Louis, Mo: Mosby-Year Book; 1996:449-77

27. Allergic Hypersensitivity: Non IgE Mediated • Hypersensitivity pneumonitis involves inhalation of an antigen. This leads to an exaggerated immune response (hypersensitivity). Type III hypersensitivity and type IV hypersensitivity occur in hypersensitivity pneumonitis. • Allergic contact dermatitis. • …

28. Comparison of Allergy with other Responses

29. Laboratory Diagnosis IgE-Mediated Allergies

30. Skin Tests • The cutaneous test • (prick test, puncture test epicutaneous test) • Routine diagnosis in diseases (atopic or anaphylactic). • A single drop of concentrated aqueous allergen extract placed on the skin which is then pricked lightly with a needle point at the center of the drop. After 20 minutes the reaction is graded and recorded

31. Laboratory Tests • IgE levels may be elevated in patients who are atopic, but the level does not necessarily correlate with clinical symptoms. • The tryptase level can be elevated, which is indicative of mast cell degranulation. False-negative results can occur. • An elevated eosinophil count may be observed in patients with atopic disease. • RAST/CAP RAST/CAP FEIA (fluorenzymeimmunoassay): measures antigen-specific IgE.

32. Nasal smear/ Spirometry • Nasal smear • Elevated eosinophil levels can be consistent with allergic rhinitis. • Spirometry or pulmonary function tests • offer an objective means of assessingasthma. Peak-flow meters can also be used for this and can be used by patients at home to monitor their status

33. Standardized diagnostic allergens are not available for drugs

34. Prevention • Avoid triggerssuch as foods and medications,…… that have caused an allergic reaction, even a mild one. This includes detailed questioning about ingredients when eating away from home. Ingredient labels should also be carefully examined. • A medical ID tagshould be worn by people who know that they have serious allergic reaction. • If any history of a serious allergic reactions, carry emergency medications(such as diphenihydramine and injectable epinephrine. • Do not use your injectable epinephrine on anyone else. They may have a condition (such as a heart problem) that could be affected by this drug.

35. Treatment

36. References &Further Reading Allergic diseases: in Medical Immunology .eds ( TristramG.Parslow, Daniel P. A Stites, Abba I.Terr.and John B. Imboden), 814 pages tenth edition.McGraw-Hill/Appleton & Lange; 10 edition 2001) (March 23, ISBN-13: 978-0838563007 ISBN-10: 0838563007 Anaphylaxis and Urticaria: in Medical Immunology .eds ( TristramG.Parslow, Daniel P. A Stites, Abba I.Terr.and John B. Imboden), 814 pages tenth edition.McGraw-Hill/Appleton & Lange; 10 edition 2001) (March 23, ISBN-13: 978-0838563007 ISBN-10: 0838563007 Adkinson NF Jr. Middleton’s Allergy: Principles and Practice. 6th ed. Philadelphia, Pa: Mosby; 2003. Rakel RE. Textbook of Family Medicine. 7th ed. Philadelphia, Pa: WB Saunders; 2007.  Miriam K Anand, Michael A Kaliner, et al., Advances in Immunology. N Engl. J.Med,. vol. 344, No.1. January4, 2001. Available from. http://emedicine.medscape.com/article/136217-overview#a0104 Sell S, Rich RR, Fleisher TA, et al, eds. Clinical Immunology: Principles and Practice. ed. St. Louis, Mo: Mosby-Year Book; 1996:449-77

37. Image Citation • SariSabban. Allergy Pathway. 1September 2011The http://en.wikipedia.org/wiki/File:The_Allergy_Pathway.jpg • Wolfgang Ihloff. Allergy skin.30.1.2008. testing. http://en.wikipedia.org/wiki/File:Allergy_skin_testing.JPG • Mast cell. Http://en.wikipedia.org/wiki/File:Mast_cells.jpg Wenliang Zhang. • Universtyof Geogorgia. Immunology. The immune system.. http://wenliang.myweb.uga.edu/mystudy/immunology/ScienceOfImmunology/Hypersensitivitydiseases.html • Dr. M. Yadav. Food Hypersensitivity. http://www.allergycentre.com.my/index.html

38. THANK YOU