Hypersensitivity Types I and II
On this page
Direct answer
Type I hypersensitivity is an immediate IgE-mediated reaction in which allergen cross-linking on mast cells releases histamine within minutes, causing urticaria, bronchospasm or anaphylaxis. Type II hypersensitivity is an antibody reaction in which IgG or IgM binds a cell-surface antigen, leading to complement lysis, phagocytosis or antibody-dependent killing. Transfusion reactions and autoimmune haemolytic anaemia are classic examples of type II injury.
What you must remember
- Type I mechanism: IgE sensitises mast cells through FcεRI, and cross-linking by re-exposure to the allergen triggers release of histamine, tryptase and leukotrienes.
- Early and late phases: the early phase occurs within minutes, while a late phase several hours later involves eosinophils and Th2 cells.
- Anaphylaxis treatment: intramuscular adrenaline is the first-line drug, with fluids, antihistamines and corticosteroids as adjuncts.
- Atopy: a genetic tendency to make IgE against common environmental allergens, linked to asthma, allergic rhinitis and atopic dermatitis.
- Type II mechanism: IgG or IgM binds a cell-surface antigen, and the target cell is destroyed by complement, opsonisation or antibody-dependent cell-mediated cytotoxicity.
- Type II examples: ABO transfusion reactions, autoimmune haemolytic anaemia, pemphigus vulgaris and Goodpasture syndrome.
- Receptor-directed antibodies: Graves disease stimulates the TSH receptor, whereas myasthenia gravis blocks the acetylcholine receptor, both classic type II patterns.
- Coombs tests: the direct test detects antibody or complement on the patient's own red cells, and the indirect test detects free antibody in serum.
How IgE-mediated anaphylaxis unfolds
The reaction in type I hypersensitivity happens in two timed stages, and the first sensitisation is silent. The steps below follow the sequence from first exposure to clinical outcome.
- Sensitisation: an allergen is taken up by antigen presenting cells, Th2 cells help B cells switch to IgE, and the IgE binds FcεRI on mast cells and basophils.
- Re-exposure: the same allergen returns and binds at least two adjacent IgE molecules, cross-linking the receptors on the mast cell surface.
- Degranulation: cross-linking triggers mast cells to release preformed histamine, tryptase and heparin within minutes.
- Mediator synthesis: leukotrienes and prostaglandin D2 are generated from membrane lipids, sustaining vasodilation and bronchoconstriction.
- Late phase: several hours later, eosinophils, neutrophils and Th2 cells infiltrate the tissue, producing persistent inflammation and airway hyper-responsiveness.
- Clinical outcome: the effects range from urticaria and rhinitis to bronchospasm, hypotension and laryngeal oedema in anaphylaxis.
Viva angles that separate type I from type II
Both types are antibody-mediated, so examiners separate them by timing, antibody class and target. The three traps below catch most wrong answers on this subject.
- Trap: labelling every antibody reaction as type I Correct: type I needs IgE on mast cells and acts within minutes, whereas type II needs IgG or IgM bound to a cell-surface antigen.
- Trap: using the skin prick test to diagnose ABO reactions Correct: ABO reactions are diagnosed by blood grouping and crossmatching, while prick tests detect IgE sensitisation to allergens.
- Trap: reading a positive direct Coombs test as proof of a transfusion mismatch Correct: the direct test shows antibody or complement on the patient's own red cells, which also occurs in autoimmune haemolysis and haemolytic disease of the newborn.
Frequently asked questions
Which drug is the first-line treatment for anaphylaxis?
Intramuscular adrenaline is the first-line treatment for anaphylaxis, because it reverses bronchospasm, laryngeal oedema and hypotension. Antihistamines and corticosteroids are adjuncts and do not replace adrenaline during the acute phase.
Which tests detect IgE sensitisation in atopic patients?
Skin prick testing and serum specific IgE assays detect IgE sensitisation in atopic patients. Total serum IgE is also measured, although it is raised in many conditions and cannot on its own confirm sensitisation to a particular allergen.
What is the difference between the direct and indirect Coombs tests?
The direct Coombs test detects antibody or complement already bound to a patient's red cells, as in autoimmune haemolytic anaemia. The indirect Coombs test detects free antibody in the patient's serum, and it is used for antibody screening and crossmatching before transfusion.
Why does an ABO mismatch cause an immediate transfusion reaction?
ABO mismatch causes an immediate reaction because naturally occurring IgM anti-A or anti-B antibodies fix complement and lyse donor red cells within the circulation. This intravascular haemolysis can cause fever, haemoglobinuria and renal failure, so the transfusion must be stopped at once.