Hypersensitivity

Hypersensitivity Overview

  • Hypersensitivity refers to an exaggerated or inappropriate immune response harmful to the host.

  • Triggered by external stimuli (antigens).

  • Four types:

    • Type I (IgE-mediated)

    • Type II (IgG or IgM-mediated cytotoxic)

    • Type III (immune complex-mediated)

    • Type IV (cell-mediated)

Type I: Immediate Hypersensitivity

  • Mechanism: IgE-mediated immune response involving Th2 cells, mast cells, basophils, and eosinophils.

  • Pathogenesis:

    • First exposure: Allergen stimulates IgE production, which binds to mast cells and basophils.

    • Second exposure: Allergen cross-links IgE on mast cells, leading to degranulation and mediator release.

  • Immediate Phase:

    • Rapid response (minutes after exposure).

    • Release of preformed mediators like histamine causing edema, erythema, and itching.

  • Late Phase:

    • Occurs 6 hours post-exposure.

    • Involves newly synthesized mediators (e.g., leukotrienes) and influx of inflammatory cells.

Clinical Manifestations

  • Anaphylaxis: Severe, systemic reaction causing widespread edema, bronchoconstriction, and vascular shock.

  • Local Anaphylaxis: Local wheal and flare reactions, used for allergy testing.

Mediators

  • Histamine: Causes smooth muscle contraction, mucous secretion, and increased vascular permeability.

  • Eosinophil Chemotactic Factor (ECF-A): Attracts eosinophils to the site of inflammation.

  • Leukotrienes (SRS-A): Potent bronchoconstrictors not influenced by antihistamines.

  • Prostaglandins: Cause vasodilation and bronchoconstriction.

Type II: Cytotoxic Hypersensitivity

  • Mechanism: Involves IgG or IgM antibodies targeting cell surfaces or extracellular matrix.

  • Pathogenesis:

    • ADCC: Antibody-dependent cell-mediated cytotoxicity involving leukocytes.

    • Complement Activation: Leads to opsonization and phagocytosis of target cells.

  • Clinical Examples:

    • Hemolytic Anemias: Result from antibodies binding to erythrocyte antigens.

    • Drug Reactions: Drugs like penicillin can bind to cells, triggering antibody responses leading to cell lysis.

Type III: Immune Complex Hypersensitivity

  • Mechanism: Formation of antigen-antibody complexes causing inflammation.

  • Pathogenesis:

    • Localized Reaction (Arthus Reaction): Acute immune complex vasculitis.

    • Systemic Reaction (Serum Sickness): Wide dissemination of immune complexes leading to systemic vasculitis.

  • Clinical Manifestations:

    • Glomerulonephritis: Post-streptococcal infection leading to immune complex deposition in kidneys.

    • Rheumatoid Arthritis: Chronic inflammation with immune complex deposition in joints.

    • Systemic Lupus Erythematosus (SLE): Autoantibodies form immune complexes causing systemic damage.

Type IV: Cell-mediated (Delayed) Hypersensitivity

  • Mechanism: T-cell mediated immune response, does not involve antibodies.

  • Pathogenesis:

    • Contact Dermatitis: Result from haptens binding to skin proteins, eliciting a T-cell response upon re-exposure.

    • Delayed-Type Hypersensitivity (DTH): Response to intracellular pathogens like Mycobacterium tuberculosis.

  • Clinical Examples:

    • Tuberculin Reaction: Skin test for tuberculosis exposure.

    • Contact Dermatitis: Inflammatory response to substances like poison ivy.