Hypersensitivity reactions
Also known as: Gell and Coombs reactions, allergic reactions
Hypersensitivity reactions are exaggerated or inappropriate immune responses that damage the host. The Gell and Coombs system classifies them into four types: I (IgE-mediated), II (antibody-mediated cytotoxic), III (immune complex), and IV (T-cell-mediated delayed).
Hypersensitivity reactions are immune responses that are excessive or misdirected, causing tissue damage rather than protection. The classic Gell and Coombs classification divides them into four types, remembered by the mnemonic ACID: Anaphylactic/Atopic (I), Cytotoxic (II), Immune complex (III), and Delayed (IV).
Type I reactions are immediate and IgE-mediated: allergen cross-links IgE on mast cells and basophils, triggering histamine release. Examples include anaphylaxis, allergic rhinitis, and urticaria. Type II reactions involve IgG or IgM antibodies binding antigens on cell surfaces, causing destruction by complement or phagocytes — as in hemolytic transfusion reactions, autoimmune hemolytic anemia, and Goodpasture syndrome. Type III reactions occur when circulating antigen-antibody complexes deposit in vessels and tissues, activating complement — as in serum sickness, poststreptococcal glomerulonephritis, and lupus nephritis. Type IV reactions are delayed, cell-mediated responses driven by T lymphocytes rather than antibodies — contact dermatitis (poison ivy, nickel), the tuberculin skin test, and transplant rejection.
Drugs are among the most common triggers across all four types: penicillins and sulfonamides can cause anaphylaxis, drug-induced hemolysis, serum sickness-like reactions, or delayed rashes, which is why allergy history matters before dispensing antimicrobials.
USMLE Step 1 tests hypersensitivity heavily — classifying a clinical vignette into the correct type is a staple question — and the PTCE touches the same territory through antibiotic and antiviral adverse reactions and allergy screening.
Key takeaways
- Hypersensitivity reactions are damaging, exaggerated immune responses, classified into Gell and Coombs types I-IV (mnemonic: ACID).
- Type I is immediate and IgE/mast-cell mediated — anaphylaxis and atopy.
- Type II is antibody against cell-surface antigens; type III is immune complex deposition.
- Type IV is delayed and T-cell mediated, with no antibody involvement — contact dermatitis and the TB skin test.
- USMLE Step 1 tests vignette classification by type; the PTCE covers drug allergies and antibiotic adverse effects.