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Kher1 Hypersensitivity A damage to the host, mediated by pre-existing immunity to self or foreign antigen. Dr. Sudheer Kher.

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Presentation on theme: "Kher1 Hypersensitivity A damage to the host, mediated by pre-existing immunity to self or foreign antigen. Dr. Sudheer Kher."— Presentation transcript:

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2 Kher1 Hypersensitivity A damage to the host, mediated by pre-existing immunity to self or foreign antigen. Dr. Sudheer Kher

3 Kher2 Musts for Hypersensitivity Contact with allergen Contact with allergen Sensitizing/priming dose Sensitizing/priming dose Induction of AMI/CMI Induction of AMI/CMI Shocking dose Shocking dose

4 Kher3 Classification : Hypersensitivity reactions Immediate hypersensitivity Immediate hypersensitivity –Anaphylaxis –Atopy –Antibody mediated cell damage –Arthus phenomenon/reaction –Serum sickness Delayed hypersensitivity Delayed hypersensitivity –Infection (Tuberculin) type –Contact dermatitis type Type I Type II Type III Type IV

5 Kher 4 Classification: Gell & Coombs(1963)

6 Kher5 Type II Reactions : Cytolytic, Cytotoxic & Cell Stimulatory Involve reaction between IgG (rarely IgM) & Ag determinant on the surface of cells. Involve reaction between IgG (rarely IgM) & Ag determinant on the surface of cells. Leads to cytolytic or cytotoxic effect. Leads to cytolytic or cytotoxic effect. –Autoimmune anemias –Hemolytic disease of the new born –Drug induced hemolytic anemias –Drug induced thrombocytopenic purpura –Drug induced agranulocytosis Rarely normal cell function may be disrupted Rarely normal cell function may be disrupted –Agonist effect -Cell stimulatory effect seen (LATS in Graves disease). –Antagonist effect – Myasthenia gravis

7 Type II (Cytotoxic) Reactions –Involve activation of complement by IgG or IgM binding to an antigenic cell. –Antigenic cell is lysed. –Transfusion reactions: ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream. ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream. Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells. Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells. –Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.

8 Diagnostic tests for type II Detection of circulating/fixed antibody against tissues involved. Coombs test. Detection of circulating/fixed antibody against tissues involved. Coombs test. Presence of antibody and complement in the lesion (biopsy) by immunofluorescence. Presence of antibody and complement in the lesion (biopsy) by immunofluorescence. The staining pattern is normally smooth and linear, such as that seen in Goodpastures nephritis (renal and lung basement membrane) and pemphigus (skin intercellular protein, desmosome). The staining pattern is normally smooth and linear, such as that seen in Goodpastures nephritis (renal and lung basement membrane) and pemphigus (skin intercellular protein, desmosome). Kher7

9 Coombs (Antiglobulin)Tests Incomplete Ab Direct Coombs Test – Detects antibodies on erythrocytes + Patients RBCs Coombs Reagent (Antiglobulin)

10 Coombs (Antiglobulin)Tests Indirect Coombs Test Indirect Coombs Test –Detects anti-erythrocyte antibodies in serum Patients Serum Target RBCs + Step 1 + Coombs Reagent (Antiglobulin) Step 2

11 Type III (Immune Complex) Reactions –Involve reactions against soluble antigens circulating in serum. –Usually involve IgG, IgM antibodies. –Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage. Glomerulonephritis: Inflammatory kidney damage. Glomerulonephritis: Inflammatory kidney damage. –Occurs when slightly high antigen- antibody ratio is present.

12 Kher11 Immune Complex Mediated Hypersensitivity

13 Kher12 Type III Reaction: Immune Complex Disease Arthus Reaction – Localized manifestation of generalized hypersensitivity Arthus Reaction – Localized manifestation of generalized hypersensitivity –Ag+Ab precipitates cause C activation and release of inflammatory molecules. Leads to vascular permeability & neutrophil infiltrate. Leucocyte-platelet thrombi formed which reduce blood supply leading to necrosis. –Clinical example – Farmers lung & other hypersensitivity pneumonitis following inhaled Ag like Actinomycetes.

14 Kher13 Arthus reaction Type-III Wheal & flare reaction Type-I

15 Kher14 Type III Reaction: Immune Complex Disease Serum Sickness – Systemic form of Type III reaction. Serum Sickness – Systemic form of Type III reaction. –Takes place following serum therapy –e.g. ADS, ATS, AGGS, Hyperimmune globulin, Anti Snake venum. –Clinically Fever, lymphadenopathy, splenomegaly, arthritis, glomerulonephritis, endocarditis, vasculitis, urticarial rashes, abdominal pain, nausea, vomiting. –Pathogenesis – Formation of immune complexes, its deposition on the endothelial lining of BVs all over the body, leads to inflammation.

16 Kher15 Serum Sickness (contd) Plasma concentration of C falls due to massive activation and fixation to Ag+Ab complexes. Plasma concentration of C falls due to massive activation and fixation to Ag+Ab complexes. Disease self limited. Disease self limited. Single dose of Antiserum can serve both as sensitizing & shocking dose. Single dose of Antiserum can serve both as sensitizing & shocking dose. Can also be seen after administration of penicillin or other antibiotics. Can also be seen after administration of penicillin or other antibiotics. Immune complexes occur in many bacterial, viral, parasitic infections e.g. poststreptococcal glomerulonephritis, Hepatitis B & Malaria. Also seen in disseminated malignancies & autoimmunity. Immune complexes occur in many bacterial, viral, parasitic infections e.g. poststreptococcal glomerulonephritis, Hepatitis B & Malaria. Also seen in disseminated malignancies & autoimmunity.

17 Kher16 Serum sickness

18 Kher17 Type IV Reactions: Delayed Hypersensitivity Two types – Two types – –Tuberculin (Infection) type –Contact dermatitis type Tuberculin type – Tuberculin type – –ID inoculation of PPD in sensitized indivisual leads to induration & inflammation in hrs. This is not same as skin test done for Type I hypersensitivity. –Used for diagnosis / exclusion of diagnosis of many bacterial / fungal / parasitic / viral and autoimmune diseases.

19 Type IV (Cell-Mediated) Reactions –Involve reactions by T D memory cells. First contact sensitizes person. First contact sensitizes person. Subsequent contacts elicit a reaction. Subsequent contacts elicit a reaction. –Reactions are delayed by one or more days (delayed type hypersensitivity). Delay is due to migration of macrophages and T cells to site of foreign antigens. Delay is due to migration of macrophages and T cells to site of foreign antigens. –Reactions are frequently displayed on the skin: itching, redness, swelling, pain. –Tuberculosis skin test –Poison ivy –Metals –Latex in gloves and condoms (3% of health care workers)

20 Kher19 Type IV Reactions: Delayed Hypersensitivity One aspect of CMI One aspect of CMI Provoked by specific Ag, involves lymphocytes & Macrophages. Provoked by specific Ag, involves lymphocytes & Macrophages. Not induced by circulating Ab but by sensitized lymphocytes. Not induced by circulating Ab but by sensitized lymphocytes. Sensitized lymphocytes release lymphokines which have biological effects on leucocytes, macrophages & tissue cells. Sensitized lymphocytes release lymphokines which have biological effects on leucocytes, macrophages & tissue cells. Transfer possible thru lymphocytes / transfer factor. Transfer possible thru lymphocytes / transfer factor.

21 Kher20 Granuloma in a leprosy patient

22 Kher21 Contact dermatitis Ag possibly enters thru sebaceous glands Ag possibly enters thru sebaceous glands Lesions vary from macules & papules to vesicles which subsequently breakdown leaving weeping surface typical of acute eczematous dermatitis. Lesions vary from macules & papules to vesicles which subsequently breakdown leaving weeping surface typical of acute eczematous dermatitis. Detected by patch test Detected by patch test

23 Kher22 Contact dermatitis reaction

24 Kher23 Allergic Contact Dermatitis Response to Poison Ivy Hapten

25 Diagnostic tests Type IV Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux test) and patch test (for contact dermatitis). Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux test) and patch test (for contact dermatitis). In vitro tests for delayed hypersensitivity include mitogenic response, lympho- cytotoxicity and IL-2 production. In vitro tests for delayed hypersensitivity include mitogenic response, lympho- cytotoxicity and IL-2 production. Kher24

26 Treatment of type II, III, IV Antiinflammatory drugs Antiinflammatory drugs Corticosteroids & other immunosuppressives Corticosteroids & other immunosuppressives Kher25


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