Bit · Rheum/Immuno
Hypersensitivity Types I–IV
Four mechanisms of immune-mediated tissue damage. The pivot is which immune component drives the reaction: IgE, antibody-on-cell, immune complex, or T cell.
Mechanism
Hypersensitivity reactions are exaggerated or misdirected immune responses. Four types, classified by the Coombs and Gell scheme by mechanism:
- Type I — Immediate (IgE) — preformed IgE on mast cells/basophils crosslinks on re-exposure to antigen → degranulation → histamine/leukotrienes → anaphylaxis, urticaria, asthma. Minutes.
- Type II — Antibody-mediated — IgG or IgM binds antigen on a cell or matrix → complement activation, opsonisation, ADCC. Cytotoxic, or functional (receptor-modulating).
- Type III — Immune complex — antigen-antibody complexes deposit in vessels/tissues → complement activation → neutrophil recruitment → tissue damage. Hours to days.
- Type IV — Delayed / T-cell-mediated — sensitised CD4⁺ Th1 (or CD8⁺) cells respond to antigen → cytokine release, macrophage activation. Days. No antibody involved.
Differentiator Table
| Type I | Type II | Type III | Type IV | |
| Mechanism | IgE on mast cells | IgG/IgM vs cell-surface or matrix antigen | Antigen-antibody complexes deposit | T cells (CD4 Th1 or CD8) |
| Speed | Minutes | Hours | Hours to days | Days (24–72 h) |
| Mediators | Histamine, leukotrienes, tryptase | Complement (MAC), opsonisation, ADCC | Complement, neutrophils | IFN-γ, cytokines, macrophages |
| Classic examples | Anaphylaxis, atopy, asthma, hives, food allergy | Goodpasture, AIHA, ITP, pemphigus, rheumatic fever, hyperacute transplant rejection, Graves (functional) | SLE, post-strep GN, serum sickness, Arthus reaction, polyarteritis nodosa | PPD/TB test, contact dermatitis (poison ivy, nickel), MS, T1DM, granulomas, chronic transplant rejection |
| Test / clue | Skin prick test, tryptase | Direct/Indirect Coombs, biopsy with linear immunofluorescence | Biopsy with 'lumpy-bumpy' granular immunofluorescence | PPD induration, patch test |
The Pivot
Two questions tell you which type:
- How fast? Minutes → I. Hours → II. Hours–days → III. Days → IV.
- Is there antibody? No → IV. Yes → I (IgE), II (antibody on a cell), or III (antibody in a complex).
Immunofluorescence pattern on biopsy: linear (II, e.g. Goodpasture) vs granular/lumpy-bumpy (III, e.g. post-strep GN).
NBME-Style Stem
A 24-year-old man presents 10 days after starting a new antibiotic with fever, urticaria, joint pain, and proteinuria. Renal biopsy shows granular immunofluorescent deposits along the glomerular basement membrane. Which type of hypersensitivity reaction best explains these findings?
Concept Anchor
Four types, four drivers: IgE on mast cells (immediate), antibody on a cell surface (cytotoxic), antibody in a complex (lumpy-bumpy deposition), T cells (delayed). Speed + presence of antibody decide the type.