1. Allergic Reactions & Diseases BTE 303 Romana Siddique 1

2. Hypersensitivity Hypersensitivity is an immune reaction to innocuous antigen that results in tissue injury and/or disease An antigen that causes allergy is an allergen There are four types of hypersensitivity reactions: Type I, Type II, Type III &Type IV 2

3. Types of hypersensitivity  Four types- 1.Type I: contact sensitivity/IgE mediated 2.Type II: Ab mediated response against self antigen 3.Type III: immune-complex mediated i.e. immune complex deposited on self kidney, skin, joints etc 4.Type IV: delayed type hypersensitivity Types I, II and III are antibody mediated and immediate Type IV is cell mediated and delayed 3

4. Type I: contact sensitivity/ Ig E mediated Immediate hypersensitivity an allergic reaction provoked by exposure to a specific type of antigen referred to as an allergenantigenallergen Allergen induces humoral Ab response i.e. able to produce Ab generating plasma cells and memory cells Plasma cells mostly secrete IgE antibody 4

5. Components of type I hypersensitivity Allergen recognized by specific APC IgE Ab produced by plasma cells Mast cells and basophils carrying receptors Fc for IgE become sensitized Second exposure of allergen cause mast cell degranulation 5

6. Atopy The predisposition to produce high quantities of Immunoglobulin (Ig)-E Immediate (Type I hypersensitivity) Mast cells, basophils, eosinophils, Th2 cells

7. Allergy Allergic Disease is mediated by IgE First described by Prausnitz & Kustner in 1921 Proposed the existence of “atopic reagin” in serum of allergic subjects 45 years later Ishizaka described a new class of immunoglobulin - IgE

8. Allergic Disease Seen in 30-35% of the population Perennial & seasonal allergic rhinitis Allergic (extrinsic asthma) Atopic and contact dermatitis Urticaria Food intolerance

9. Allergy Elevated IgE levels seen in allergy and parasitic infection Binds to mast cells and basophils Often specific for harmless environmental factors - allergens

10. characteristics of allergens Proteins often with carbohydrate side chains Low dose Low molecular weight Highly soluble Stable Binds to host MHC 10

11. 11

12. General mechanism of Type I hypersensitivity Exposure to an allergen activates APC cells to form IgE secreting plasma cells. The secreted IgE molecules bind to target allergen Second exposure to the allergen leads to crosslinking with IgE that bound to Fc receptor on mast cells and basophils, thereby sensitizing them to respond when the host is later re-exposed to the allergen Initiate mast cell degranulation Release mediators like histamine, prostaglandin, leukotrienes, cytokines (TNF) 12

13. Mast cell crosslinked Allergen bound IgE 13

14. The mediators cause 1.smooth-muscle contraction, 2. increased vascular permeability, 3.Vasodilation The mast cell degranulation is also initiated by anaphylatoxins like C3a, C4a, C5a 14

15. General mechanism of Type I hypersensitivity 15

16. General mechanism of Type I hypersensitivity 16

17. Mast cell degranulation 17

18. Mast cell activation (degranulation) has many effects Mast cells are most common near epithelial surfaces (e.g., skin, lungs, gut). Most IgE is on mast cells, not in the blood 18

19. Common disease of type I hypersensitivity 1.Systemic anaphylaxis Shock like often fatal Occurs within minutes A wide range of allergen can trigger a.Venom from bee b.Drugs-penicillin c.Seafood d.nuts 19

20. 2. Localized anaphylaxis Limited to specific target tissue a. Respiratory allergic diseases Allergic asthma ： acute response, chronic response Allergic rhinitis b. Gastrointestinal allergic diseases c. Skin allergic diseases 20

21. 21

22. Representative type I reaction ASthma Asthma is a condition in which the airways of the lungs become either narrowed or completely blocked, impeding normal breathing the airways may become obstructed by one of the following: 1.constriction of the muscles surrounding the airway; 2.inflammation and swelling of the airway; or 3.increased mucus production which clogs the airway. Asthmatic response 1.Early response 2.Late response 22

23. 23

24. Early phase of asthma: The early phase of asthma is characterized by: 1. marked constriction/tightened of bronchial airways (bronchospasm) /air way obstration 2. edema (an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body)of the airways 3. production of mucus 24

25. The bronchospasm 1. The bronchospasm that occurs may be the result of the increased release of certain inflammatory mediators such as histamine, prostaglandins and bradykinin that, in the early stages of asthmatic response, promote bronchoconstriction rather than inflammation. 25

26. 26

27. Late phase of asthma: The late phase of asthma is characterized by: The late phase of asthma can occur several hours after the initial onset of symptoms and manifests mainly as an inflammatory response. Production of excess mucus (Mucous is thick, Airways can be blocked by mucous plugs) Thickening of bronchial wall Fluid accumulation -Edema 27

28. Detection of type I reaction Assesed by skin testing Small amount of allergen introduced by intradermal injection or superficial scratching Mast cell degranulation occurs within 30 minutes Inexpensive and allow screening of large number of allergen 28

29. Skin test procedure for type I 29

30. Representatives disease Some examples: Allergic asthmaasthma Allergic conjunctivitisconjunctivitis Allergic rhinitis ("hay fever") Allergic rhinitis Anaphylaxis Angioedema Urticaria (hives) Urticaria Eosinophilia Penicillin allergy Penicillin Cephalosporin allergy Cephalosporin Food allergy 30