1. Hypersensitivity Department of Microbiology

2. Important terms Hypersensitivity reactions are exaggerated antigen-specific immune responses which is harmful to the host. Allergen ： The antigens that give rise to immediate hypersensitivity Atopy ： The genetic predisposition to synthesize inappropriate levels of IgE specific for external allergens Types of hypersensitivity: As per Coomb and Gel Classification hypersensitivity is of four types (Type I, Type II, Type III and Type IV)

3. Type I Hypersensitivity – Mediated by IgE antibodies. – Also known as “immediate hypersensitivity "or “Allergic response”. – Antigens that induce type I hypersensitivity are also termed as “Allergens”.

4. Type I Hypersensitivity – The IgE antibodies produced against Allergens remain bound to Mast cells. – Upon exposure to specific Allergens IgE antibodies induce degranulation of Mast cells. – This leads to release of inflammatory mediators like Histamine, Serotonin, Prostaglandins etc. – Some common Allergens are Pollen, Dust etc. – Example: P-K reaction

5. Type I Hypersensitivity

9. Histamine:Dilate blood vesselIncrease vascular permeability 2. Leukotrienes:Bronchial smooth muscles contract Asthmas 3. Prostaglandin:High concentration of PGEInhibit the secretion of histamine low concentration of PGEpromote the release of histamine 4. Platelet activating factor (PAF) : Agglutinate and activate platelets to release histamine 5. Eosinophil chemotactic factor （ ECF-A ） : 6. Bradykinin :Vasodilator function

11. Type II Hypersensitivity Type II Hypersensitivity is mediated by antibodies that are produced against the antigenic determinants present on cell surface. As the antigenic determinants are present on cell surface, thus type II reaction is manifested in the form of massive cell destruction. The target cells are lysed by: activation of Complement cascade by the antibody molecules bound on the cell surface. antibody dependent cell mediated cytotoxicity (ADCC). Transfusion reactions and Hemolytic Disease of the Newborn are examples of type II reaction.

12. 2. Mechanism of Type II hypersentivity 1. Surface antigen on target cells Target cells: Normal tissue cell, changed or modified self tissue cells 2. Antibody, complement and modified self-cell Antigen : Blood group antigen, Common antigen, Self-antigen modified by physical factors or infection Drug antigen, Antigen-antibody complex Activate complementLyse target cells Opsonic phogacytosisDestroy target cells ADCC M  、 NK 、 T Stimulating or blocking effect Promote /surpress the target cell funcion

13. Antigen or hapten on cell Antibody (IgG, IgM) Activate complement Lyse target cell Opsonic phagocytosis NK, phagocyteStimulate / block Destroy target cellADCC Target cell injury Change the function ofTarget cell Mechanism of Type II hypersensitivity

14. 3. Common disease of type II hypersensitivity 1)Transfusion reaction hemolysis : mismatch of ABO blood group, severely destroy RBC nonhemolysis : repeat transfusion of allogenic HLA drug anaphylactic shock ： penicillin 2) Hemolytic disease of newborn Mother Rh - : first baby Rh + (Ab), second baby Rh +, fetal RBC destroyed 3) Autoimmune hemolytic anemia and type II drug reaction i. Foreign antigen or hapten Penicillin RBC hemolytic anemia Quinin Platlet thrombocytopenic purpura Pyramidone Granulocyte agranulocytosis ii. Self-antigen Drug conversion from a hapten to a full antigen induce self antibody autoimmune hemolytic anemia

15. Auto-Immune Hemolytic Anaemia

16. Type II Hypersensitivity Antibody Dependent Cell Mediated Cytotoxicity Animation: Antibodies react with epitopes on the host cell membrane and NK cells bind to the Fc of the antibodies. The NK cells then lyse the cell with pore-forming perforins and cytotoxic granzymes

17. 17 Type II Hypersensitivity Antibody-Mediated Cell Disfunction Example: Myasthenia Gravis

18. Type III Hypersensitivity – Mediated by immune complexes (Antigen-Antibody complex). – During normal immune response only moderate quantity of immune complexes are formed and they are removed efficiently from circulation by phagocytosis. – In case of production of large quantities of immune complexes, phagocytes fail to remove all the immune complexes from circulation. – Thus, Ag-Ab complexes are deposited in various tissues. They lead to activation of complement components. Activation of complement may leads to destruction of bystander cells.

19. Type III Hypersensitivity – Moreover, under the influence of chemotactic complement components polymorphonuclear cells are recruited at the site. – These cells, in their attempt to engulf immune complexes, releases lysozymal enzymes in the tissue and thus cause tissue destruction. – Arthus reaction is an example of localized type III hypersensitivity. – Serum Sickness is an example of Systemic type III hypersensitivity. – Blue Eye: Dogs infected or vaccinated with live canine adenovirus I develops anterior uveitis. This lead to corneal oedema and opacity. The blue eye is considered to be an immune complexes mediated condition.

20. Immunreaktionen der Haut20 Type III Hypersensitivity “Immune complex disease” Soluble Ag / IgG or IgM – high titers of each required Immune processes involved: – classical complement pathway – phagocytic cells

21. Soluble antigen BodyAntibody Immune complex Small molecular soluble Immune complex intermediate molecular soluble Immune complex Large molecular insoluble Immune complex Deposit on the basement of capillaries Combine and activate complement system C3a,C5a,C3b Infiltration of neutrophils Phagocytose complex Release the enzymes in lysosome Tissue injury Eliminate by phogacytosis Platelets Thrombus Aggregation of platlets Blood Clotting Mechanisms Release of vasoactive amine Increase vascular permeability BleedingEdema Basophils and mast cells Release of vasoactive amine Increase vascular permeability Edema Local or systemic immune complex diseases

22. 3. common disease of type III hypersensitivity 1. Local immune complex disease Arthus reaction ： Experimental local reaction, Necrotic vasculitis vasculitis, Ulcer Human local reaction: insulin-dependent diabetes mellitus (IDDM) 2. Acute systemic immune complex disease serum sickness Anti-serum Ab+Ag systemic tissue injury,fever, arthritis, skin rash Pinicillin 、 Sulfanilamide Acute immune complex glomerulonephritis : Streptococcus infection 3. Chronic immune complex disease SLE Rheumatoid arthritis ： RF+IgG Deposit on synovial membrane

23. Type IV hypersensitivity reaction – Because of delay in onset of response, type IV hypersensitive reaction is also known as Delayed Type Hypersensitivity (DTH). – It approx takes 24 to 48 hours from the time of antigenic stimulation. – Unlike Type I, II, and III response (antibody mediated), Type IV reaction is mediated by Cellular immune components.

24. Type IV hypersensitivity reaction – The effector cells of Type IV hypersensitivity response are CD4+ (T h ), CD8+ cells and activated macrophages. Some common examples of type IV hypersensitivity reaction: – Tuberculin test (used for diagnosis of Tuberculosis), – Johnin test (used for diagnosis of Johnes disease), – Mallein test (used for diagnosis of Glanders), – Brucellin test (used for diagnosis of Brucellosis).

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