Hypersensitivity reactions
On this page
Hypersensitivity reactions are abnormal immune-mediated responses that cause tissue damage. They may target exogenous antigens (environmental) or self-antigens (autoimmunity).
They are classified by Gell and Coombs into four types* (I–IV).
Summary table: hypersensitivity reactions
*Some people use a Coombs & Gell 5 type classification. Type V reactions are a subtype of Type 2 reactions where autoimmune reactions involve the antibodies reacting with cell surface receptors e.g. Graves and Myasthenia Gravis.
Onset: Minutes (early) to hours (late).
Clinical examples:
Type II – Cytotoxic (antibody-mediated)
Onset: Hours to days.
Clinical examples:
Type III – Immune complex-mediated
Mechanism:
Predilection sites: Small blood vessels, kidneys, joints.
Onset: Hours to days.
Clinical examples:
Type IV – Delayed-type (T-cell-mediated)
Onset: 48–72 hours.
Clinical examples:
They are classified by Gell and Coombs into four types* (I–IV).
Summary table: hypersensitivity reactions
| Type | Description | Mediators | Examples |
|---|---|---|---|
| Type 1 | Allergy (immediate) | IgE | Anaphylaxis Atopy Asthma |
| Type 2 | Cytotoxic / Antibody dependent | IgG IgM Compliment MAC | Autoimmune haemolytic aenamia Goodpastures syndrome Thrombocytopenia Graves disease* Myasthenia gravis* |
| Type 3 | Immune complex mediated | IgG IgM Compliment Neutrophils | SLE Rheumatoid arthritis Post streptococcal glomerulonephritis |
| Type 4 | Delayed hypersensitivity reactions | T-cells | Contact Dermatitis Mantoux test Multiple Sclerosis |
*Some people use a Coombs & Gell 5 type classification. Type V reactions are a subtype of Type 2 reactions where autoimmune reactions involve the antibodies reacting with cell surface receptors e.g. Graves and Myasthenia Gravis.
Type I – Immediate (IgE-mediated)
Mechanism:
- Sensitisation phase involving initial antigen exposure which activates B cells to overproduce IgE. IgE binds Fc receptors on mast cells and basophils, coating them.
- Subsequent exposure results in allergen antigens cross-linking with surface IgE leading to degranulation of mast cells/basophils which release histamine, leukotrienes and prostaglandins.
- Late-phase response see's eosinophils recruited causing ongoing inflammation hours after exposure.
Onset: Minutes (early) to hours (late).
Clinical examples:
- Allergic rhinitis
- Allergic conjunctivitis
- Asthma (allergic type)
- Urticaria
- Angioedema
- Systemic anaphylaxis
- Penicillin allergy
Type II – Cytotoxic (antibody-mediated)
Mechanism:
- IgG or IgM antibodies bind cell surface antigens (foreign or self).
- Cell destruction occurs via complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis
Onset: Hours to days.
Clinical examples:
- Incompatible blood transfusions
- Haemolytic disease of the newborn
- Autoimmune haemolytic anaemia (AIHA)
- Goodpasture’s syndrome
- Rheumatic heart disease
- Bullous pemphigoid
- Myasthenia gravis
- Graves’ disease
Type III – Immune complex-mediated
Mechanism:
- IgG (or IgM) antibodies bind soluble antigens and form immune complexes.
- Normally cleared by complement opsonization and phagocytosis in the spleen.
- Excess antigen or impaired clearance leads to immune complex deposition in tissues triggering complement activation and neutrophil recruitment which results in inflammation and tissue damage.
Predilection sites: Small blood vessels, kidneys, joints.
Onset: Hours to days.
Clinical examples:
- Systemic lupus erythematosus (SLE)
- Post-streptococcal glomerulonephritis
- Serum sickness
- Arthus reaction
- Extrinsic allergic alveolitis
- Rheumatoid arthritis
- Reactive arthritis
Type IV – Delayed-type (T-cell-mediated)
Mechanism:
- On first exposure antigen activates T helper (Th1) cells leading to clonal expansion (1–2 weeks).
- On subsequent exposure sensitised T cells release cytokines, recruit and activate macrophages leading to tissue injury.
- CD8+ T cells also directly kill target cells.
Onset: 48–72 hours.
Clinical examples:
- Contact dermatitis (e.g., poison ivy, nickel)
- Tuberculin skin test (Mantoux)
- Hashimoto’s thyroiditis
- Chronic transplant rejection
- Granulomatous inflammation (sarcoidosis, Crohn’s disease)
- Primary biliary cholangitis
- Type 1 diabetes
Mnemonic to Remember Types
ACID:
ACID:
- A = Anaphylaxis / Allergic (Type I)
- C = Cytotoxic (Type II)
- I = Immune complex (Type III)
- D = Delayed (Type IV)