Hypersensitivity Reactions
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Direct answer
Hypersensitivity reactions are exaggerated or inappropriate immune responses that damage the host's own tissues. The Gell and Coombs classification divides them into four types: type I, immediate IgE-mediated mast cell degranulation; type II, cytotoxic IgG or IgM with complement; type III, deposition of circulating immune complexes; and type IV, delayed T-cell-mediated reactions. A fifth, stimulatory type — antibody acting as an agonist, as in Graves disease — is often added.
What you must remember
- Type I (immediate, minutes): allergen cross-links IgE bound to mast cell Fc receptors, releasing histamine, leukotrienes and prostaglandins; examples are anaphylaxis, allergic asthma, allergic rhinitis, urticaria and eczema; intramuscular adrenaline is first-line for anaphylaxis.
- Type II (cytotoxic, hours): IgG or IgM against a fixed tissue antigen activates complement, causing lysis, opsonisation or antibody-dependent cellular cytotoxicity; examples are autoimmune haemolytic anaemia, ABO transfusion reactions, haemolytic disease of the newborn, Goodpasture syndrome and pemphigus.
- Type III (immune complex, hours to days): circulating antigen-antibody complexes deposit in vessel walls and glomeruli, activating complement and attracting neutrophils; examples are serum sickness, the Arthus reaction, lupus nephritis, post-streptococcal glomerulonephritis and farmer's lung.
- Type IV (delayed, 48 to 72 hours): antigen presented to sensitised T cells releases cytokines and activates macrophages; examples are contact dermatitis from nickel, the tuberculin (Mantoux) test, granulomatous reactions of tuberculosis and sarcoidosis, graft rejection and type 1 diabetes.
- Type V (stimulatory, an addition by Roitt): autoantibody stimulates a receptor — anti-TSH receptor antibody in Graves disease — sometimes taught as a subtype of type II.
- Timing is the quickest discriminator in the exam: minutes for type I, hours for II and III, two to three days for IV.
Common confusion
Type II and type III both involve IgG and complement and are constantly interchanged. In type II the antibody binds an antigen that is part of the target tissue, so damage is organ-confined; in type III the complexes form in circulation and deposit wherever flow favours — glomeruli, joints, skin and vessels — producing systemic patterns. Another favourite contrast is type I versus type IV: immediate, antibody-mediated and transferable by serum versus delayed, cell-mediated and transferable by T lymphocytes.
Exam-focused takeaway
For theory, reproduce the Gell and Coombs table as bullets — mechanism, mediator, timing and two to three diseases for each type. Viva examiners ask which types involve complement (II and III) and which cells drive type IV. MCQs are dominated by disease-to-type matching — farmer's lung, contact dermatitis, Goodpasture, Graves — plus the 48-to-72-hour reading window of the tuberculin test.
Frequently asked questions
Which antibody and cells mediate type I hypersensitivity?
IgE bound to mast cells; cross-linking by allergen releases histamine and leukotrienes, producing anaphylaxis or allergic disease within minutes.
How do types II and III hypersensitivity differ?
Type II antibodies attack fixed tissue antigens directly; type III involves deposition of circulating immune complexes, causing multi-organ patterns such as serum sickness and lupus nephritis.
What is the Arthus reaction?
A local type III reaction — immune-complex vasculitis in the skin appearing hours after repeated antigen exposure, classically at injection sites.
Why is type IV called delayed hypersensitivity?
Because the reaction peaks at 48 to 72 hours, the time needed to recruit sensitised T cells and macrophages rather than preformed antibody.
Which hypersensitivity type is the tuberculin test?
Type IV — intradermal purified protein derivative produces induration read at 48 to 72 hours, reflecting cell-mediated immunity.