There are 5 Types of Hypersensitivity Reactions (Type 1 to 4) which are given below. Anaphylactic Type, Antibody Mediated Type, Immune Complex Mediated & Cell Mediated.
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Type I Hypersensitivity (Anaphylactic Type)
Reaction within minutes - may be systemic or localized Systemic form can be fatal within an hour from massive
laryngeal edema, pulmonary edema and hemorrhage Local form (atopy) often hereditary
Bee sting, cutaneous swelling (hives), hay fever, bronchial asthma, allergic gastroenteritis (food allergy)
Antigen binds to IgE on surface of sensitized mast cells and basophils, crosslinking IgE receptors resulting in degranulation with release of rapidly acting factors (via rapid increase in cAMP) and subsequent production and release of slow acting factors
Some factors can directly induce degranulation independent of IgE: C3a, C5a, codeine, morphine, mellitin (in bee venom), trauma, heat, cold, sunlight
- Primary (rapidly acting) factors:
- histamine: bronchial smooth muscle contraction, increased vascular permeability
- eosinophil and neutrophil chemotactic factors
- granule matrix derived factors: heparin, proteases Secondary (slow reacting substances of anaphylaxis):
- Leukotrienes C4, D4: most potent vasodilators known
- Prostaglandin D2: bronchospasm and vasodilation
- Leukotriene B4: chemotactic for neutrophils
- Platelet activating factor
Type II Hypersensitivity (Antibody Mediated Type)
AKA: Cytotoxic Type (although not always cytotoxic)
Antibodies directed against normal or modified cell surface or tissue components induce cell lysis
Complement Dependent Two mechanisms:
• Direct lysis by complement activation
• Lysis by opsonization (C3b) - often involves RBCs Eg: Transfusion reactions, erythroblastosis fetalis,
autoimmune hemolytic anemia or thrombocytopenia, certain drug reactions
Antibody Dependent Cell Mediated Cytotoxicity
Monocytes, neutrophils, eosinophils, or NK cells recognize cells by Fc portion of IgG bound to cell and kills cell without phagocytosis
Eg, Goodpasture’s syndrome Anti-Receptor Antibodies
Non-cytotoxic
Eg, myasthenia gravis from antibody to ACh receptor
Type III Hypersensitivity (Immune Complex Mediated)
Antigen-antibody complexes produce tissue damage by activation of serum mediators (primarily complement)
Systemic Form
Acute serum sickness is the prototype (described in 1905)
Antibodies are produced to a large dose of administered antigen (~5 days after administration). Ag-Ab complexes are deposited in the tissues, often inducing localized type I hypersensitivity reactions in glomeruli, joints, skin, heart, serosal surfaces, and small blood vessels where they can activate complement. An inflammatory reaction ensues (~10 days) with resulting fever, urticaria, arthralgias, lymphadenopathy, proteinuria
Inflammation in and around vessels causes an acute necrotizing vasculitis with fibrinoid deposition and acute inflammation (innocent bystander destruction)
Localized Form (Arthus Reaction)
Introduction of antigen to which patient has been sensitized Localized tissue necrosis resulting from acute immune
complex vasculitis, usually in the skin Lesion develops over 4-10 hrs; may ulcerate
Histology shows fibrinoid necrosis of vessels, platelet thromboses, edema, hemorrhage, and numerous neutrophils
Type IV (Cell Mediated)
Mediated by sensitized T-Cells Delayed-Type Hypersensitivity
Eg tuberculin reaction: reddening and induration begins 8-12 hrs after injection; peaks 24-72 hrs.
Histology: perivascular cuffing of mononuclear cells in deep and superficial dermis
Induration is caused by fibrin deposition in interstitium Reaction mediated by CD4+ T-Cells: memory T-Cells release
lymphokines to amplify response, specifically macrophage chemotactic and activating factors
T-Cell Mediated Cytotoxicity
CD8+ cytotoxic T-Cells kill cells via pore formation; recognize modified self- MHC Class I antigens