Pathology chapters
Hypersensitivity reactions
The four types of hypersensitivity (harmful immune reactions): type I immediate (IgE, mast cells, anaphylaxis), type II antibody-mediated, type III immune-complex and type IV T-cell-mediated delayed reactions, with mechanisms, timings, examples and tests.
- Type I (immediate): allergen cross-links IgE on mast cells → histamine, leukotrienes within minutes; examples: anaphylaxis, allergic asthma, hay fever, urticaria, food allergy.
- Type II (antibody-mediated): IgG or IgM against antigens on cells or tissues → complement lysis, phagocytosis or changed receptor function; examples: transfusion reactions, haemolytic disease of the newborn, Goodpasture, and receptor diseases Graves (stimulating) and myasthenia gravis (blocking).
- Type III (immune complex): circulating antigen-antibody complexes deposit in vessels, joints and kidneys → complement, neutrophils, vasculitis; examples: SLE, serum sickness, Arthus reaction, post-streptococcal glomerulonephritis; Type IV (delayed, 48–72 h): T cells, no antibody; examples: tuberculin test, contact dermatitis, granulomas.
On this page
Overview
Hypersensitivity reactions are excessive or inappropriate immune responses that damage the host. They may be directed at harmless environmental antigens (allergy), at self antigens (autoimmunity) or at microbes. The Gell and Coombs classification has four types.
ACID: type I Anaphylactic, type II Cytotoxic (antibody-mediated), type III Immune complex, type IV Delayed (T-cell).
Summary
| Type | Mediator | Mechanism | Timing | Examples |
|---|---|---|---|---|
| I Immediate | IgE, mast cells | Allergen cross-links IgE on mast cells → release of histamine and other mediators | Minutes | Anaphylaxis, allergic asthma, hay fever, urticaria, food and drug allergy, atopic eczema |
| II Antibody-mediated | IgG, IgM against cell or tissue antigens | Complement lysis, phagocytosis (opsonisation), ADCC, or interference with receptors | Minutes to hours | ABO transfusion reaction, haemolytic disease of the newborn, autoimmune haemolytic anaemia, Goodpasture, Graves, myasthenia gravis, pemphigus, acute rheumatic fever |
| III Immune complex | Antigen–antibody complexes (IgG, IgM) | Complexes deposit in vessel walls, glomeruli and joints → complement → neutrophils → damage | Hours (local) to days (systemic) | SLE, serum sickness, Arthus reaction, post-streptococcal glomerulonephritis, polyarteritis nodosa (hepatitis B), reactive arthritis |
| IV Delayed (cell-mediated) | T cells (CD4 Th1 and CD8), macrophages | Sensitised T cells release cytokines (IFN-γ) or kill cells directly; no antibody | 48–72 hours | Tuberculin (Mantoux) test, contact dermatitis (nickel, poison ivy), granulomas (TB, leprosy), type 1 diabetes, multiple sclerosis, transplant rejection |
Type I: immediate hypersensitivity
Sequence:
- Sensitisation: first exposure → Th2 cells release IL-4 (IgE class switching) and IL-5 (eosinophils) → IgE binds Fc receptors on mast cells and basophils.
- Re-exposure: allergen cross-links the bound IgE → mast cells degranulate.
- Immediate phase (minutes): histamine and other preformed mediators → vasodilation, leaky vessels, smooth muscle spasm.
- Late phase (2–24 hours): newly made leukotrienes, prostaglandins and cytokines recruit eosinophils and neutrophils → ongoing inflammation (important in chronic asthma).
Atopy is an inherited tendency to make IgE responses (asthma, hay fever, eczema run in families).
Anaphylaxis is the systemic form: hypotension (shock), bronchospasm, laryngeal oedema, urticaria. Causes: drugs (penicillin), insect stings, foods (nuts), vaccines rarely. Treatment: intramuscular adrenaline first.
Tests: skin prick testing, specific IgE, raised total IgE and eosinophils.
Type II: antibody-mediated
Antibodies bind antigens that are fixed on cell surfaces or in the tissue matrix. Damage occurs by:
- Complement activation and lysis (transfusion reactions).
- Opsonisation and phagocytosis in the spleen (autoimmune haemolytic anaemia, immune thrombocytopenia).
- Antibody-dependent cell-mediated cytotoxicity (NK cells).
- Inflammation from complement and Fc receptors (Goodpasture: anti-glomerular basement membrane antibody attacks kidney and lung).
- Receptor dysfunction without cell damage:
- Graves disease: antibodies stimulate the TSH receptor → hyperthyroidism.
- Myasthenia gravis: antibodies block the acetylcholine receptor → muscle weakness.
- Pernicious anaemia: antibodies against intrinsic factor.
Haemolytic disease of the newborn: an Rh-negative mother makes anti-D IgG after exposure to Rh-positive fetal blood (first pregnancy, miscarriage); in a later Rh-positive pregnancy, IgG crosses the placenta and destroys fetal red cells. Prevented by giving anti-D immunoglobulin to the mother.
The direct Coombs test detects antibody on red cells in immune haemolysis.
Type III: immune complex
Antigen–antibody complexes form in the circulation and deposit in vessel walls, glomeruli, joints and skin, or form locally. Complexes activate complement (serum complement levels fall), attract neutrophils, and cause vasculitis with fibrinoid necrosis.
- Systemic immune complex disease:
- Serum sickness: after foreign serum (for example horse antitoxin or anti-snake venom) or some drugs; fever, rash, arthralgia, lymphadenopathy, proteinuria about 7–10 days later.
- SLE (anti-DNA complexes), post-streptococcal glomerulonephritis, polyarteritis nodosa linked to hepatitis B.
- Local immune complex disease (Arthus reaction): injection of antigen into the skin of a person who already has high levels of antibody → local vasculitis and necrosis within hours (for example after too-frequent tetanus booster injections).
Type IV: delayed (T-cell-mediated)
No antibody is involved; reactions peak after 48–72 hours.
- CD4 Th1-mediated (delayed-type hypersensitivity): Th1 cells release IFN-γ → macrophage activation.
- Tuberculin (Mantoux) test: intradermal PPD → induration read at 48–72 hours shows previous exposure or BCG.
- Granulomatous inflammation: TB, leprosy, schistosomiasis, sarcoidosis.
- CD8-mediated cytotoxicity: killing of target cells; virus-infected cells, type 1 diabetes, graft rejection.
- Contact dermatitis: haptens (nickel, chromate, poison ivy, cosmetics, latex additives) bind skin proteins → eczema where the substance touched.
Contact dermatitis is type IV, whereas atopic eczema and urticaria are linked to type I. Latex can cause either: immediate anaphylaxis (type I) or contact dermatitis (type IV).
Expect: the four types with mediators and timing, examples of each (especially anaphylaxis, ABO and Rh reactions, Goodpasture, Graves and myasthenia, SLE, serum sickness, Arthus, Mantoux, contact dermatitis, granulomas), the sequence of type I reactions and late phase, haemolytic disease of the newborn and anti-D, serum sickness timing, and which type is not antibody-mediated.
Quick revision
- I: IgE, mast cells, minutes: anaphylaxis, asthma, hay fever.
- II: antibodies on cells or matrix: transfusion reaction, HDN, Goodpasture, Graves, myasthenia.
- III: immune complexes, complement, vasculitis: SLE, serum sickness, Arthus, PSGN.
- IV: T cells, 48–72 h: Mantoux, contact dermatitis, granulomas, graft rejection.
- Anaphylaxis: IM adrenaline first.
Written by The House Job from standard pathology and immunology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
Which type of hypersensitivity is anaphylaxis?
Type I (immediate), mediated by IgE and mast cells.
Which type of hypersensitivity is the tuberculin test?
Type IV (delayed, T-cell-mediated), read at 48–72 hours.
Why is myasthenia gravis classed as type II hypersensitivity?
Antibodies bind the acetylcholine receptors on muscle and block them; the antibody acts against a fixed cell-surface antigen.
What is the Arthus reaction?
A local type III reaction in which antigen injected into the skin of a person with high antibody levels forms immune complexes in vessel walls, causing local vasculitis and necrosis within hours.