Hypersensitivity Types III and IV
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Direct answer
Type III hypersensitivity is an immune complex reaction in which soluble antigen-antibody complexes deposit in vessels, glomeruli or joints and attract neutrophils through complement activation. Type IV hypersensitivity is a delayed reaction in which sensitised T cells, not antibodies, cause tissue injury over 48 to 72 hours. The Mantoux tuberculin test and contact dermatitis are classic examples of type IV reactions.
What you must remember
- Type III mechanism: soluble antigen-antibody complexes that escape clearance deposit in vessels, glomeruli and joints, then activate complement.
- Neutrophil injury: C3a and C5a recruit neutrophils, which release lysosomal enzymes that damage vessel walls and the glomerular basement membrane.
- Serum sickness: a type III reaction to foreign serum proteins, appearing about one to two weeks after exposure with fever, rash, arthralgia and lymphadenopathy.
- Arthus reaction: a local type III injury in an individual with preformed IgG, peaking within several hours of intradermal antigen.
- Type IV timing: a delayed reaction that peaks at 48 to 72 hours and is mediated by sensitised T cells rather than antibodies.
- Tuberculin test: the Mantoux test is a type IV reaction, read as transverse induration 48 to 72 hours after intradermal PPD.
- Contact dermatitis: a type IV reaction to haptens such as nickel or urushiol, with Langerhans cells carrying the hapten to lymph nodes.
- Granulomas: type IV reactions form granulomas in tuberculosis and leprosy when the organism cannot be cleared.
How an immune complex lesion develops
Type III injury is a sequence of events that begins with antigen and ends with inflammation in a distant tissue. The steps below show why the damage lands in vessels, kidney and joints rather than at the site where the antigen first entered.
- Antigen persistence: a soluble antigen, such as a foreign serum protein or a microbial protein, remains in the circulation long enough to be bound by specific IgG or IgM.
- Complex formation: antigen and antibody combine into immune complexes, which are normally cleared by phagocytes in the liver and spleen.
- Deposition: when clearance fails, complexes lodge in vessel walls, the glomerular basement membrane or the synovium, depending on their size and charge.
- Complement activation: C3a and C5a are generated at the deposit, attracting neutrophils to the site.
- Tissue injury: neutrophils release lysosomal enzymes and reactive oxygen species, causing vasculitis, glomerulonephritis or arthritis.
The Arthus reaction is this same pathway played out locally, while serum sickness is the systemic form seen after large doses of foreign serum. Both are type III reactions, and the difference lies mainly in the extent of the complexes rather than in the mechanism.
High-yield distinctions for the viva
Type III and type IV both cause inflammation, but the timing and the effector cell separate them clearly. Three traps below catch many candidates.
- Trap: thinking the Mantoux test measures antibody Correct: the tuberculin test is a type IV reaction, read at 48 to 72 hours, that measures T cell memory to purified protein derivative.
- Trap: placing the Arthus reaction in type IV because it looks local Correct: Arthus is a type III reaction caused by preformed IgG and complexes, and it peaks within hours rather than days.
- Trap: calling contact dermatitis a type I reaction because it itches Correct: contact dermatitis is a type IV reaction with no major antibody role, mediated by sensitised T cells after a hapten binds skin proteins.
Frequently asked questions
What is the typical time course of a Mantoux tuberculin reaction?
The Mantoux tuberculin reaction is read at 48 to 72 hours, because it is a delayed type IV response driven by memory T cells. The result is measured as transverse induration, and the size that counts as positive depends on the patient group being tested.
Which kidney lesion is a classic example of type III hypersensitivity?
Post-streptococcal glomerulonephritis is a classic type III example, in which immune complexes containing streptococcal antigens deposit in the glomeruli. Lupus nephritis is also a type III immune complex disease, since complexes of nuclear antigen and antibody lodge in the kidney.
Why does contact dermatitis count as a type IV hypersensitivity reaction?
Contact dermatitis counts as type IV because sensitised T cells, not antibodies, cause the skin injury after a hapten such as nickel binds skin proteins. The rash typically appears a day or more after re-exposure, and patch testing is used to identify the culprit allergen.
Which lesion is characteristic of a type IV reaction in tuberculosis?
A type IV reaction in tuberculosis forms granulomas, compact collections of epithelioid macrophages surrounded by lymphocytes, often with caseous necrosis at the centre. The same delayed mechanism explains the positive Mantoux test and the granulomas seen in tuberculosis and leprosy.