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

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

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

Classification: Gell & Coombs(1963) Kher

Type II Reactions : Cytolytic, Cytotoxic & Cell Stimulatory Involve reaction between IgG (rarely IgM) & Ag determinant on the surface of cells. 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 Agonist effect -Cell stimulatory effect seen (LATS in Graves’ disease). Antagonist effect – Myasthenia gravis Kher

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. 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.

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

Coombs (Antiglobulin)Tests Incomplete Ab Direct Coombs Test Detects antibodies on erythrocytes + ↔ Y Patient’s RBCs Coombs Reagent (Antiglobulin)

Coombs (Antiglobulin)Tests Indirect Coombs Test Detects anti-erythrocyte antibodies in serum Y Patient’s Serum Target RBCs + ↔ Step 1 + ↔ Y Coombs Reagent (Antiglobulin) Step 2

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. Occurs when slightly high antigen-antibody ratio is present.

Immune Complex Mediated Hypersensitivity Kher

Type III Reaction: Immune Complex Disease 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 – Farmer’s lung & other hypersensitivity pneumonitis following inhaled Ag like Actinomycetes. Kher

Arthus reaction Arthus reaction Wheal & flare reaction Type-III Type-I Kher

Type III Reaction: Immune Complex Disease 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. Kher

Serum Sickness (contd) Plasma concentration of C falls due to massive activation and fixation to Ag+Ab complexes. Disease self limited. Single dose of Antiserum can serve both as sensitizing & shocking dose. 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. Kher

Serum sickness Kher

Type IV Reactions: Delayed Hypersensitivity Two types – Tuberculin (Infection) type Contact dermatitis type Tuberculin type – ID inoculation of PPD in sensitized indivisual leads to induration & inflammation in 48-72 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. Kher

Type IV (Cell-Mediated) Reactions Involve reactions by TD memory cells. First contact sensitizes person. 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. 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)

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

Granuloma in a leprosy patient Kher

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

Contact dermatitis reaction Kher

Allergic Contact Dermatitis Response to Poison Ivy Hapten Kher

Diagnostic tests Type IV 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. Kher

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