Types of Hypersensitivity Reactions.pptx

Hypersensitivity as an immunological dysfunction is defined as exaggerated or inappropriate response of the immune system. Hypersensitivity can be classified into four types; namely, type I (Immediate), type II (antibody-mediated), type III (immune complex-mediated), and type IV (cell-mediated or delayed-type) hypersensitivity.
Type I hypersensitivity or allergy, the most common immune disorder, is mainly mediated by immunoglobulin (Ig)E and mast cells. It can cause anaphylaxis, food allergy, and asthma.
Type II hypersensitivity can lead to tissue damage by three main mechanisms: (1) direct cellular destruction (e.g., autoimmune hemolytic anemia and immune thrombocytopenia, (2) inflammation (e.g., Goodpasture's syndrome and acute rheumatic fever), and (3) disrupting cellular function (e.g., myasthenia gravis and Graves’ disease).
Type III hypersensitivity is caused by excess production of immune complexes or impaired clearance of them and includes serum sickness, systemic lupus erythematosus, and post-streptococcal glomerulonephritis.
Type IV hypersensitivity is mediated by T cells and macrophages, causing diseases like multiple sclerosis and rheumatoid arthritis.

1. Hypersensitivity Reactions Presented by: Isha Pandey M.Sc. (Medical Biotechnology) Pt. J.N.M. Medical college, Raipur (Chhattisgarh).

2. Contents Introduction Types Of Hypersensitivity Reactions Type-I Hypersensitivity Type-II Hypersensitivity Type-III Hypersensitivity Type-IV Hypersensitivity Mechanism

3. Introduction " Hypersensitivity " is a broad term used to describe an excessive and/or pathogenic immune response to either foreign or self antigens. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction.

4. Gell and Coombs Classification

5. IgE-Mediated (Type I) Hypersensitivity A type I hypersensitive reaction is induced by certain types of antigens referred to as allergens. In type I or immediate hypersensitivity the plasma cells respond by secreting IgE specific for allergens. This class of antibody binds with high affinity to Fc receptors on the surface of tissue mast cells and blood basophils, causing degranulation of these cells Mast cells and basophils coated by IgE are said to be sensitized. The pharmacologically active mediators released from the granules act on the surrounding tissues. The principal effects are vasodilation and smooth-muscle contraction.

6. Components of Type I Reactions Allergens : IgE responses only as a defense against parasitic infections. After an individual has been exposed to a parasite, serum IgE levels increase and remain high until the parasite is successfully cleared from the body. Basophils are granulocytes and account for 0.5%–1.0% of the circulating WBCs. Mast cells are found in connective tissues, specially near blood and lymphatic vessels, Some tissues, skin and mucous membrane, surfaces of the respiratory and gastrointestinal tracts. IgE -binding Fc receptors : IgE bind to a receptor specific for the Fc region of the heavy chain.

7. IgE Crosslinkage Initiates Degranulation When an allergen comes in contact with sensitized basophils and mast cells it causes crosslinkage between IgE antibodies bound to the Fc receptor on the surface of mast cell or basophil initiate the process of degranulation.

8. Degranulation Of Mast Cells

9. Pharmacologic Agents Mediate Type I Reactions Histamine Leukotrienes and Prostaglandins Heparin ECF NCF Proteases Platelet Activating Factor Bradykinin Cytokines : IL1, IL2, IL3, IL4, IL5, IL6, GMCSF.

10. Type I Reactions Can Be Systemic or Localized Systemic anaphylaxis : It is a shock-like and often fatal state whose onset occurs within minutes of a type I hypersensitive reaction. Localized anaphylaxis (Atopy) : This type of reaction is limited to a specific target tissue or organ, often involving epithelial surfaces at the site of allergen entry. It is often inherited from generation to generation and is called atopy. e.g. allergic rhinitis, asthma, atopic dermatitis.

11. Allergen Individual IgE IgE binds to the mast cell and basophil Secondary Crosslikage of Fc e RI Degranulate and release the biological mediators Preformed granule mediators New generated mediators Histamine Bradykinin Leukotrienes PAF Prostaglandin D2 Dilate capillaries,increase permeability, increase mucus secretion, contract smooth muscle Systemic anaphylaxis Skin Respiratory tract Degist tract Mechanism of type I hypersensitivity

12. Some drugs used to treat type I hypersensitivity Drug Action Antihistamines Block H1 and H2 receptors on target cells Cromolyn sodium Blocks Ca2+ influx into mast cells Theophylline Prolongs high cAMP levels in mast cells by inhibiting phosphodiesterase, which cleaves cAMP to 5-AMP Epinephrine Stimulates cAMP production Cortisone Reduces histamine levels by blocking conversion of histidine to histamine and stimulates mast-cell production of cAMP

13. Antibody-Mediated Cytotoxic (Type II) Hypersensitivity Type II hypersensitive reactions involve antibody-mediated destruction of cells. Antibody can activate the complement system, creating pores in the membrane of a foreign cell or it can mediate cell destruction by antibody dependent cell-mediated cytotoxicity (ADCC). In this process, cytotoxic cells with Fc receptors bind to the Fc region of antibodies on target cells and promote killing of the cells. e.g. transfusion reaction, Hemolytic Disease of the Newborn

14. Hemolytic disease of the newborn

15. Drug-Induced Hemolytic Anemia Is a Type II Response Certain antibiotics (e.g., penicillin, cephalosporin, and streptomycin) can adsorb nonspecifically to proteins on RBC membranes, forming a complex similar to a hapten-carrier complex. These drug-protein complexes induce formation of antibodies.

16. Immune Complex–Mediated (Type III) Hypersensitivity This type of hypersensitivity is mediated by antigen antibody complement complexes. Antigen antibody complexes can stimulate an acute inflammatory response that leads to complement activation. Formation of the immune complex Deposition of the immune complex Tissue injury by the immune complex

17. Development of a localized Arthus reaction (type III hypersensitive reaction)

18. antigen Body Antibody Immune complex Immune complex Combine and activate complement system C3a,C4a,C3b Infiltration of neutrophils Phagocytose complex Release the enzymes in lysosome Tissue injury Basophils and mast cells degranulation Increase vascular permeability Edema Mechanism of Type III hypersensitivity reactions

19. Type IV or Delayed-Type Hypersensitivity (DTH) When some subpopulations of activated TH cells encounter certain types of antigens, they secrete cytokines that induce a localized inflammatory reaction called delayed-type hypersensitivity (DTH). This type of reaction was first described in 1890 by Robert Koch, who observed that individuals infected with Mycobacterium tuberculosis developed a localized inflammatory response when injected intradermally with a filtrate derived from a mycobacterial culture.

20. The development of the DTH response begins with an initial sensitization phase of 1–2 weeks after primary contact with an antigen. During this period, TH cells are activated and clonally expanded by antigen presented together with the requisite class II MHC molecule on an appropriate antigen presenting cell.

21. Development of delayed-type hypersensitivity reaction

22. Antigen T cell (CD4 + ,CD8 + ) Secondary contact Induce CD4 + T cell CD8 + T cell Release Cytokines IL-2 TNF- b INF- g TF MCF MIF MAF Directly kill target cells Infiltration of monocyte Proliferation of T cell Exudation and edema Cytotoxicity Inflammation characterized by infiltration of monocyte, And tissue injury Mechanism of type IV hypersensitivity

23. Reference Kuby Immunology- Sixth Edition.

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