Gell and Coombs Hypersensitivity Reactions
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Direct answer
Gell and Coombs classified hypersensitivity into four types according to the immune mechanism and the time taken for the reaction to appear. Type I is IgE-mediated and immediate, type II is antibody directed against cell-surface antigens, type III is immune-complex mediated, and type IV is delayed and driven by T cells. Each type has classic clinical examples that examiners ask students to match.
What you must remember
- Type I: IgE binds mast cells and basophils, which release histamine and leukotrienes within minutes; examples are anaphylaxis, urticaria and allergic asthma.
- Type II: antibody against a cell-surface or matrix antigen, causing cell killing through complement or antibody-dependent cell cytotoxicity; examples are ABO transfusion reaction and Graves disease.
- Type III: immune complexes deposit in vessels and tissues, and neutrophils and complement cause injury; examples are serum sickness and post-streptococcal glomerulonephritis.
- Type IV: a delayed reaction peaking at 48 to 72 hours, mediated by T cells; examples are contact dermatitis and the tuberculin test.
- Coombs test: the direct test detects antibody or complement coating red cells, as in autoimmune haemolytic anaemia; the indirect test detects free antibody in serum.
- Anti-GBM disease: a type II example, with linear immunofluorescence along the glomerular basement membrane.
- Serum sickness: a type III reaction appearing days to weeks after exposure, with fever, rash and joint pains.
Matching mechanism and timing
The four types are best remembered by the mediator and the timing, since those two features define most examples in examinations and in clinical practice. The table sets them side by side for quick comparison, in the same order as the original classification.
| Type | Main mediator | Timing | Classic example |
|---|---|---|---|
| I | IgE on mast cells and basophils | Minutes | Anaphylaxis to a drug or food |
| II | Antibody against a cell-surface antigen | Hours to days | ABO incompatible transfusion |
| III | Immune complexes and complement | Days to weeks | Serum sickness |
| IV | Sensitised T cells and macrophages | 48 to 72 hours | Mantoux reaction |
A reaction that appears within minutes points to IgE-mediated type I hypersensitivity, while one that appears after several days points to immune complexes or a slower T-cell response that takes time to build. Examiners often give the timing as the key clue in a case stem, so reading the time course first and the mechanism second avoids most errors when matching a case to its type.
Clues that get misread
Most matching errors come from treating every immune-mediated injury as an IgE reaction.
- Trap: labelling every transfusion reaction as type I Correct: ABO incompatibility is a type II reaction because antibody binds red cell antigens, whereas anaphylaxis to plasma protein is type I.
- Trap: expecting serum sickness to appear within minutes Correct: type III reactions need time for immune complexes to form, so they appear days to weeks after exposure.
- Trap: calling the Mantoux reaction type III Correct: the tuberculin test is a delayed type IV reaction, with induration peaking at 48 to 72 hours.
- Trap: classifying Graves disease as a type IV reaction because it is autoimmune Correct: Graves disease is type II, because stimulating antibodies bind the TSH receptor.
Frequently asked questions
Which hypersensitivity type causes the Mantoux reaction?
The Mantoux reaction is a type IV hypersensitivity, mediated by sensitised T cells and macrophages. Induration typically peaks at 48 to 72 hours after the intradermal injection. It reflects prior exposure to tuberculosis antigens rather than active disease alone.
Why is Graves disease classed as a type II hypersensitivity reaction?
Graves disease is a type II reaction because thyroid-stimulating antibodies bind the TSH receptor and stimulate the thyroid. The antibody targets a cell-surface receptor rather than forming immune complexes. Its stimulatory action distinguishes it from the cell-destructive type II reactions.
How do the direct and indirect Coombs tests differ?
The direct Coombs test detects antibody or complement already coating a patient's red cells, as in autoimmune haemolytic anaemia. The indirect Coombs test detects free antibody in the serum and is used for cross-matching and antenatal screening. Both tests rely on an antiglobulin reagent.
What is the timing of a type III hypersensitivity reaction?
Type III reactions develop days to weeks after antigen exposure, once immune complexes have formed and deposited in tissues. Serum sickness is the classic example, with fever, rash and joint pains. This delay is why type III reactions are not confused with immediate anaphylaxis.