Type III Hypersensitivity (Immune Complex)
Type III (immune-complex) hypersensitivity results from antibodies binding soluble antigens to form circulating immune complexes that deposit in vessel walls and tissues. The deposited complexes activate complement and recruit neutrophils, producing inflammation and tissue injury at the site of deposition.
Definition
Type III hypersensitivity is immune-complex-mediated injury in which antibodies bind soluble antigens to form complexes that deposit in blood-vessel walls and tissues, where they activate complement and attract neutrophils, causing inflammation.
Scope
This entry covers how soluble antigen-antibody complexes form, why they deposit in particular sites such as small vessels, glomeruli, joints, and skin, and how complement and neutrophils mediate the resulting injury. It is a mechanistic reference within immunopathology, not clinical guidance.
Core questions
- How do soluble immune complexes form and circulate?
- Why do complexes deposit at particular sites?
- How do complement and neutrophils translate deposition into tissue damage?
- What distinguishes a local (Arthus) reaction from systemic serum sickness?
Key concepts
- Soluble antigen-antibody (immune) complexes
- Complex size and antigen-antibody ratio
- Complement activation and C3a/C5a
- Neutrophil recruitment and tissue injury
- Arthus reaction (local)
- Serum sickness (systemic)
- Sites of deposition: glomeruli, small vessels, joints, skin
Mechanisms
When antibody meets soluble antigen, the size and solubility of the resulting complexes depend on the antigen-antibody ratio; intermediate-sized complexes formed near antigen excess are poorly cleared and tend to deposit in vessel walls and filtering tissues. Deposited complexes activate the classical complement pathway, generating anaphylatoxins that increase vascular permeability and chemoattract neutrophils. Neutrophils attempting to phagocytose tissue-bound complexes release proteases and reactive oxygen species, injuring the vessel wall and surrounding tissue. A localised version is the Arthus reaction, while widespread complex formation after foreign-protein exposure produces systemic serum sickness.
Clinical relevance
Type III mechanisms contribute to immune-complex glomerulonephritis, systemic lupus erythematosus, serum sickness, and certain vasculitides, explaining their characteristic vascular and glomerular involvement and complement consumption. This entry describes mechanisms for orientation and is not a basis for diagnosis or treatment of these conditions.
Epidemiology
Immune-complex disease is encountered across a range of conditions whose individual frequencies differ widely; systemic lupus erythematosus, a prototypical immune-complex disorder, shows a strong female predominance. Specific burden is covered in disease entries.
Evidence & guidelines
The mechanistic account derives from immunology textbooks and disease reviews; condition-specific evidence and guidelines lie in the relevant clinical entries.
History
Immune-complex injury was first illuminated by Arthus's early-twentieth-century description of local necrotising reactions to repeated antigen injection and by studies of serum sickness following antiserum therapy, phenomena later codified as Type III in the Gell and Coombs scheme.
Key figures
- Robin Coombs
- Philip Gell
- Nicolas Maurice Arthus
Related topics
Seminal works
- coombs-gell-1963
Frequently asked questions
- What determines where immune complexes deposit?
- Complex size, charge, and local haemodynamics matter: intermediate-sized complexes formed in slight antigen excess are cleared poorly and tend to lodge in sites of plasma filtration and turbulence such as glomeruli, small vessels, joints, and skin.
- What is serum sickness?
- Serum sickness is the systemic form of Type III hypersensitivity, classically following exposure to a foreign protein, in which circulating immune complexes deposit widely and cause fever, rash, joint symptoms, and sometimes nephritis.