Hypersensitivity reactions.pptx

PRESENTATION ON HYPERSENSITIVITY REACTION

1. ADITYA BANGALORE INSTITUTE OF PHARMACY. DEPARTMENT OF PHARMACOLOGY Advanced Pharmacology-II Seminar on: Hypersensitivity Reactions Submitted to: Dr. N VENKATESAN Presented by: RAJESH YADAV M. Pharm (2019-2021)

2. Introduction Hypersensitivity is defined as an exaggerated or inappropriate state of normal immune response with onset of adverse effects on the body. The lesions of hypersensitivity are a form of antigen-antibody reaction. These lesions are termed as hypersensitivity reactions or immunologic tissue injury. These are grouped into: Immediate type: Reaction occurs immediately (within seconds to minutes) on administration of antigen. Immune response is mediated by humoral antibodies (B cell mediated). It includes type I, II & III. Delayed type: The reaction is slower in onset & develops within 24-48 hours & the effect is prolonged. It is mediated by cellular response ( T cell mediated) & includes type IV reaction.

3. Type I: Anaphylactic (Atopic) Reaction State of rapidly developing or anaphylactic type of immune response to an antigen to which the individual is previously sensitized, within 15-30 minutes of exposure to Ag. Etiology: mediated by humoral Abs of IgE type 1) Genetic Basis 2) Environmental pollutants 3) Concomitant factors Pathogenesis It includes participation by B lymphocytes, plasma cells, mast cells & basophils, neutrophils & eosinophils Mechanism i ) sensitization during 1st contact with antigen, B lymphocytes activation & differentiation to form IgE secreting plasma cells IgE antibodies bind to Fc receptors present on surface of mast cells & basophils ii) during 2 nd contact, IgE antibodies are so firmly bound that it sets in cell damage-membrane lysis, influx of Na & water and degranulation of mast cells-basophils

4. The released chemicals & enzymes have proinflammatory properties- histamine, serotonin, vasoactive intestinal peptide, chemotactic factors of anaphylaxis for neutrophils & eosinophils, leukotrienes B4 & D4, prostaglandins & platelet activating factor The effects include: i ) increased vascular permeability ii) smooth muscle contraction iii) early vasoconstriction followed by vasodilatation iv) shock v) increased gastric secretion vi) increased nasal & lachrymal secretions vii) increased migration of eosinophils & neutrophils at the site of local injury as well as their rise in blood

5. Examples Systemic anaphylaxis i ) Administration of antisera e.g. anti-tetanus serum ii) Administration of drugs e.g. penicillin iii) Sting by wasp or bee Clinical features include itching, erythema, contration of respiratory bronchioles, diarrhoea, pulmonary oedema, pulmonary haemorrhage, shock & death Local anaphylaxis i ) Hay fever due to pollen sensitization of conjunctiva & nasal passages ii) Bronchial asthma due to allergy to inhaled allergens like house dust iii) Food allergy to ingested allergens like fish, cows milk, eggs.etc iv) Cutaneous anaphylaxis due to contact of antigen with skin characterized by urticaria, wheal & flare v) Angioedema characterized by laryngeal oedema, oedema of eyelids, lips, tongue & trunk

6. Type II: Antibody-mediated (cytotoxic) reaction Reaction by humoral antibodies that attack cell surface antigens on specific cells & tissues & cause lysis of target cells. It appears within 15-30 minutes after exposure to antigen. Etiology & Pathogenesis Type II reactions have participation by complement system, tissue macrophages, platelets, natural killer cells, neutrophils & eosinophils while main antibodies are IgG & IgM. It is tissue-specific and reaction occurs after antibodies bind to tissue specific antigens. Mechanism i ) Antigen on surface of target cell (foreign cell) attracts & binds Fab portion of the antibody (IgG or IgM) forming Ag-Ab complex ii) Unattached Fc fragment of antibodies forms a link between antigen & complement iii) Ag-Ab binding with Fc forming a link causes activation of classical pathway of serum complement which generates activated complement component, C3b, by splitting C4 & C2 by C1 iv) Activated C3b bound to the target cell acts as an opsonin and attracts phagocytes to the site of cell injury and initiates phagocytosis v) Ag-Ab complex also activates complement system and exposes membrane attack complex(MAC) (C5b-C9) that attacks and destroys the target cell

7. Examples: Cytotoxic antibodies to blood cells i ) Autoimmune haemolytic anaemia, red cell injury brought by autoantibodies (direct Coombs’ test) ii) Transfusion reactions due to incompatible blood transfusion iii) Erythroblastosis foetalis in which foetal red cells destroyed by maternal isoantibodies iv) Immune thrombocytopenic purpura (ITP), destruction of platelets by autoantibodies v) Leucopenia with agranulocytosis, leucocyte destruction by autoantibodies vi) Drug-induced cytotoxic antibodies, formed in response to administration of certain drugs like penicillin, methyl dopa, rifampicin, etc. The drugs or metabolites act as haptens binding to surface of blood cells, which are destructed by antibodies. Cytotoxic antibodies to tissue components i ) In Grave’s disease (primary hyperthyroidism), thyroid autoantibody is formed which reacts with TSH receptor to cause hyperfunction and proliferation. ii) Myasthenia gravis, antibody to Ach receptors of skeletal muscle is formed which blocks the neuromuscular transmission at the motor-end plate, causing muscle weaknes iii) In male sterility, antisperm antibody is formed which reacts with spermatozoa iv) Type I DM, islet cell autoantibodies are formed which react against islet cell tissue v) Hyperacute rejection reaction

8. Type III: Immune Complex Mediated (Arthus) Reaction It occurs from deposition of antigen-antibody complexes on tissues, followed by activation of complement system & inflammatory reaction, resulting in cell injury 6 hours after exposure to antigen Etiology & Pathogenesis It is not tissue specific and occurs when antigen-antibody complexes fail to get removed by the body’s immune system. 1) Persistence of low-grade microbial infection 2) Extrinsic environmental antigen 3) Autoimmune process Type III has participation by IgG & IgM Abs, neutrophils, mast cells & complement Mechanism: i ) Immune complexes formed by interaction of soluble Ab and soluble or insoluble Ag ii) Immune complexes which fail to get removed from body fluid get deposited into tissues iii) Fc component of Ab links with complement & activates classical pathway of complement resulting in formation of C3a, C5a, and membrane attack complex iv) C3a stimulates release of histamine from mast cells and its resultant effects of increased vascular permeability and oedema

9. v) C5a releases proinflammatory mediators & chemotactic agents for neutrophils vi) Accumulated neutrophils and macrophages in the tissue release cytokines and result in tissue destruction Examples: i ) Immune complex glomerulonephritis in which Ag may be glomerular basement membrane ii) SLE in which there is nuclear Ag iii) Rheumatoid arthritis in which there is nuclear Ag iv) Farmer’s lung in which actinomycetes-contaminated hay acts as Ag v) Polyarteritis nodosa & Wegner’s granulomatosis with antineutrophil cytoplasmic Ag vi) Henoch- Schonlein purpura in which respiratory viruses acts as Ag vii) Drug-induced vasculitis in which drug acts as antigen. Type IV: Delayed Hypersensitivity (T cell mediated) reaction It is a tissue injury by T cell mediated immune response without formation of Abs but it’s a slow & prolonged response. Reaction occurs about 24 hrs. after exposure to Ag, may last upto 14 days

10. Etiology & Pathogenesis It involves role of mast cells & basophils, macrophages and CD8+ T cells Mechanism i ) Ag is recognized by CD8+ T cells and is processed by Ag presenting cells ii) Ag presenting cells migrate to lymph node where Ag is presented to helper T cells (CD4+ T cells) iii) Helper T cells release cytokines that stimulate T cell proliferation & activate macrophages iv) Activated T cells and macrophages release proinflammatory mediators and cause cell destruction Examples 1) Reaction against mycobacterial infection e.g. Tuberculin reaction in tuberculosis 2) Reaction against virally infected cells 3) Reaction against malignant cells in the body 4) Reaction against organ transplantation e.g. Transplant rejection

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