Hypersensitivity types

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), tryptase (marker of mast cell activation), and leukotrienes.

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• Late (hours): chemokines (attract inflammatory cells, eg, eosinophils) and other mediators 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)
• Allergic asthma

Type II hypersensitivity

Antibodies bind to cell-surface antigens or extracellular matrix → cellular destruction, inflammation, and cellular dysfunction.

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Direct Coombs test

—detects antibodies attached directly to the RBC surface.

Indirect Coombs test

—detects presence of unbound antibodies in the serum.

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).

Inflammation

—binding of antibodies to cell surfaces → activation of complement system and Fc receptor-mediated inflammation.

Cellular dysfunction

—antibodies bind to cell-surface receptors → abnormal blockade or activation of downstream process.

Examples:

• Autoimmune hemolytic anemia (including drug-induced form)
• Immune thrombocytopenia
• Transfusion reactions
• Hemolytic disease of the newborn
• Goodpasture syndrome
• Rheumatic fever
• Hyperacute transplant rejection
• Myasthenia gravis
• Graves disease
• Pemphigus vulgaris

Topics Covered:

• Overview of Hypersensitivity Types
• Type I Hypersensitivity: Immediate Phase
• Type I: Late Phase, Diagnosis & Examples
• Type II Hypersensitivity: Introduction & Coombs Test
• Type II: Mechanisms of Destruction & Inflammation
• Type II: Cellular Dysfunction & Clinical Examples