Four types (ABCD): Anaphylactic and Atopic (type I), AntiBody-mediated (type II), Immune Complex (type III), Delayed (cell-mediated, type IV). Types I, II, and III are all antibody-mediated.
- Type I hypersensitivity
- Anaphylactic and atopic—two phases:
- Immediate (minutes): antigen crosslinks preformed IgE on presensitized mast cells → immediate degranulation → release of histamine (a vasoactive amine) and tryptase (a marker of mast cell activation).
- Late (hours): chemokines (attract inflammatory cells, eg, eosinophils) and cytokines (eg, leukotrienes) from mast cells → inflammation and tissue damage.
- First (type) and Fast (anaphylaxis).
- Test: skin test or blood test (ELISA) for allergen-specific IgE.
- Example: Anaphylaxis (eg, food, drug, or bee sting allergies)
- Anaphylactic and atopic—two phases:
- Type II hypersensitivity
- Antibodies bind to cell-surface antigens → cellular destruction, inflammation, or cellular dysfunction.
- Cellular destruction—cell is opsonized (coated) by antibodies, leading to either:
- Phagocytosis and/or activation of complement system.
- NK cell killing (antibody-dependent cellular cytotoxicity).
- Examples:
- Autoimmune-hemolytic anemia
- Immune thrombocytopenia
- Transfusion reactions, hyperacute rejection
- Hemolytic disease of the newborn
- Inflammation—binding of antibodies to cell surfaces → activation of complement system and Fc receptor-mediated inflammation.
- Examples:
- Goodpasture syndrome
- Rheumatic fever
- Hyperacute transplant rejection
- Examples:
- Cellular dysfunction—antibodies bind to cell surface receptors → abnormal blockade or activation of downstream process.
- Examples:
- Myasthenia gravis
- Graves disease
- Pemphigus vulgaris
- Examples:
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- Coombs test:
- Direct Coombs test—detects antibodies attached directly to the RBC surface.
- Indirect Coombs test—detects presence of unbound antibodies in the serum
- Coombs test:
- Type III hypersensitivity
- Immune complex—antigen-antibody (mostly IgG) complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes.
- Can be associated with vasculitis and systemic manifestations.
- In type III reaction, imagine an immune complex as 3 things stuck together: antigen-antibody-complement.
- Examples:
- SLE
- Polyarteritis nodosa
- Poststreptococcal glomerulonephritis
- Henoch-Schonlein purpura
- Stevens-Johnson syndrome
- Serum sickness—the prototype immune complex disease. Antibodies to foreign proteins are produced and 1–2 weeks later, antibody-antigen complexes form and deposit in tissues → complement activation → inflammation and tissue damage.
- Fever, urticaria, arthralgia, proteinuria, lymphadenopathy occur 1–2 weeks after antigen exposure. Serum sickness-like reactions are associated with some drugs which may act as haptens (eg, penicillin & other beta lactams, sulfonamides) and infections (eg, hepatitis B).
- Arthus reaction—a local subacute immune complex-mediated hypersensitivity reaction. Intradermal injection of antigen into a presensitized (has circulating IgG) individual leads to immune complex formation in the skin. Characterized by edema, necrosis, and activation of complement.
- Type IV hypersensitivity
- Two mechanisms, each involving T cells:
- Direct cell cytotoxicity: CD8+ cytotoxic T cells kill targeted cells.
- Inflammatory reaction: effector CD4+ T cells recognize antigen and release inflammation-inducing cytokines (shown in illustration).
- Response does not involve antibodies (vs types I, II, and III).
- Examples: contact dermatitis (eg, poison ivy, nickel allergy), Guillain-Barré syndrome, multiple sclerosis and graft-versus-host disease.
- Tests (purpose): PPD (tuberculosis infection); patch test (cause of contact dermatitis); Candida extract (T cell immune function).
- 4T’s: T cells, Transplant rejections, TB skin tests, Touching (contact dermatitis).
- Fourth (type) and last (delayed).
- Two mechanisms, each involving T cells: