CorpusHuman Anatomy
Lymphatic & ImmunePhysiological process

Hypersensitivity reactions

Also known as: hypersensitivity, allergy, Gell and Coombs classification, type I hypersensitivity, type II hypersensitivity, type III hypersensitivity, type IV hypersensitivity, delayed-type hypersensitivity, immune-complex disease, atopy

Excessive or misdirected immune responses that damage the host, classified by Gell and Coombs into type I (IgE-mediated, immediate), type II (antibody against cell-bound antigen), type III (immune complexes) and type IV (T-cell-mediated, delayed).

Overview

Hypersensitivity requires prior sensitisation; tissue damage occurs on subsequent exposure. The triggering antigen may be environmental (allergens, drugs), microbial or self (autoimmunity).

Type I — immediate (anaphylactic). In atopic individuals, Th2 cells drive IgE production; IgE binds FcεRI on mast cells and basophils. On re-exposure, allergen cross-links the IgE, triggering degranulation within minutes (histamine, tryptase) and synthesis of prostaglandin D2 and leukotrienes, followed 2–24 hours later by a late-phase reaction dominated by eosinophils and Th2 cells. Examples: anaphylaxis, allergic rhinitis (hay fever), allergic asthma, urticaria and angioedema, food, venom, latex and drug (e.g. penicillin) allergy. Tests: skin-prick testing (wheal and flare in 15–20 min), specific IgE, serum mast-cell tryptase.

Type II — antibody-mediated (cytotoxic). IgG or IgM bind antigens on cell surfaces or in extracellular matrix, causing opsonisation and phagocytosis, complement-mediated lysis and inflammation, ADCC, or receptor dysfunction without cell death (stimulating antibodies in Graves disease; blocking antibodies in myasthenia gravis and pernicious anaemia). Examples: ABO-incompatible transfusion reaction, haemolytic disease of the newborn, autoimmune haemolytic anaemia (positive direct antiglobulin/Coombs test), immune thrombocytopenia, Goodpasture syndrome (anti-type IV collagen; linear IgG on the glomerular basement membrane), pemphigus vulgaris (anti-desmoglein), bullous pemphigoid, acute rheumatic fever and hyperacute graft rejection.

Type III — immune-complex. Soluble antigen–antibody complexes (especially when antigen is in slight excess) deposit in vessel walls, glomeruli, joints and skin, activate complement (low C3/C4) and attract neutrophils, causing vasculitis, glomerulonephritis and arthritis. Examples: SLE, post-streptococcal glomerulonephritis (granular "lumpy-bumpy" deposits ≈ 1–3 weeks after pharyngitis, longer after skin infection), serum sickness (fever, rash, arthralgia and proteinuria 1–2 weeks after foreign protein or some drugs), the local Arthus reaction, polyarteritis nodosa (hepatitis B), cryoglobulinaemia (hepatitis C) and IgA vasculitis.

Type IV — delayed-type (cell-mediated). No antibody: sensitised CD4 Th1/Th17 cells release cytokines that recruit and activate macrophages, or CD8 T cells kill target cells; reactions peak at 48–72 hours. Examples: tuberculin (Mantoux) test, contact dermatitis (nickel, poison ivy, hair dye — haptens; diagnosed by patch testing), granulomas (TB, sarcoidosis), type 1 diabetes, multiple sclerosis, coeliac disease, acute cellular graft rejection, graft-versus-host disease and many drug eruptions (DRESS, Stevens–Johnson syndrome/TEN).

Parts & subdivisions

  1. Type I — IgE, mast cells (minutes)
    Anaphylaxis, asthma, hay fever, urticaria, food allergy.
  2. Type II — IgG/IgM against cell-bound antigen
    Transfusion reactions, HDFN, AIHA, ITP, Goodpasture, Graves, myasthenia gravis, pemphigus.
  3. Type III — immune complexes
    SLE, post-streptococcal GN, serum sickness, Arthus reaction, PAN.
  4. Type IV — T cells (48–72 h)
    Mantoux test, contact dermatitis, granulomas, T1DM, MS, graft rejection.

Function

  • Represents protective immune mechanisms (anti-helminth IgE, antibody, immune complexes, T-cell responses) directed at the wrong target or acting in excess.

Clinical significance

Anaphylaxis

The most dangerous type I reaction: airway, breathing or circulation compromise within minutes of exposure. Treat with intramuscular adrenaline (adult 0.5 mg into the anterolateral thigh, repeated after 5 minutes if needed), airway support, oxygen and IV fluids; measure mast-cell tryptase; provide adrenaline auto-injectors and refer to an allergy service.

Prevention of Rh disease

Giving anti-D immunoglobulin to RhD-negative pregnant women (routinely in the third trimester and after delivery of an RhD-positive baby or other sensitising events) prevents maternal sensitisation and therefore type II haemolytic disease in later pregnancies.

Testing by type

Type I: skin-prick test, specific IgE, tryptase. Type II: direct/indirect antiglobulin (Coombs) tests, autoantibody assays. Type III: complement levels, immunofluorescence of biopsies (granular deposits). Type IV: patch test, Mantoux test, interferon-γ release assays (IGRAs).

Mnemonics

"ACID"

Type I — Anaphylactic/allergic (IgE); Type II — Cytotoxic (antibody against cells); Type III — Immune complex; Type IV — Delayed (T cells). Types I–III are antibody-mediated; type IV is cell-mediated — the "4th T": T cells.

Test yourself

A patient develops a firm, red induration 48–72 hours after an intradermal tuberculin (Mantoux) test. This is an example of…
  1. Type I hypersensitivity
  2. Type II hypersensitivity
  3. Type III hypersensitivity
  4. Type IV hypersensitivity

Answer: Type IV hypersensitivity

The Mantoux reaction is a classic delayed-type (type IV) hypersensitivity: memory Th1 cells recognise the antigen, secrete IFN-γ and recruit and activate macrophages. Contact dermatitis (nickel, poison ivy) is another example.

More lymphatic & immune system questions

Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.