Type III hypersensitivity (immune complexes) !

Process

Antibodies clump with a soluble antigen in the blood. The clumps lodge in small vessels, mostly in the kidney, joints and skin, and inflame them.

Updated 2026-11-01

See it in 3D: Kidneys · Skin

What it is

In type III hypersensitivity the antigen is soluble. When antibody and antigen meet in the right proportions, small complexes form that the body clears poorly; they settle in places where blood is filtered under pressure, such as glomeruli, synovium and small vessels. There they activate the classical complement pathway and attract neutrophils, which damage the vessel wall (vasculitis). The disease appears where the complexes land, not where the antigen came from.

Key facts

Serum sickness: fever, rash, joint pain and sometimes proteinuria about 1–2 weeks after a foreign protein (antivenom, some monoclonal antibodies or antithymocyte globulin), earlier on re-exposure.
Arthus reaction: a local complex reaction in the skin; painful swelling and redness hours after a vaccine booster, peaking around a day.
Post-streptococcal glomerulonephritis follows throat or skin infection with Streptococcus pyogenes; C3 is low and antistreptococcal antibodies are high.
Lupus nephritis is driven by anti-DNA and nucleosome complexes; low C3 and C4 with rising anti-dsDNA suggest active disease.

Step by step

A soluble antigen (a foreign protein, a microbe, or nuclear material in lupus) meets its antibody.
With a slight excess of antigen, small complexes form that escape clearance by macrophages.
The complexes deposit in glomeruli, joints, skin vessels or alveoli.
They activate classical complement; C3 and C4 fall in the blood and C5a draws in neutrophils.
Neutrophil enzymes and oxygen radicals injure the vessel wall: vasculitis, nephritis, arthritis.

In the lab

Low C3, C4 and CH50 from consumption.
Biopsy with immunofluorescence shows granular (lumpy) IgG and C3 deposits, unlike the smooth linear pattern of anti-GBM disease.
Small-vessel biopsy may show leukocytoclastic vasculitis.

Test yourself

Think of the answer, then tap the question to see it.

Why are complement levels low in active lupus nephritis?

Immune complexes deposited in the glomeruli activate the classical pathway and use up C3 and C4 faster than the liver replaces them.

What does granular immunofluorescence on a kidney biopsy suggest, compared with a linear pattern?

Granular deposits mean immune complexes (type III, such as lupus or post-streptococcal disease); a smooth linear pattern means antibody against the basement membrane itself (anti-GBM, type II).

What is an Arthus reaction?

A local type III reaction: painful swelling and redness at an injection site hours after a booster, from complexes forming in small skin vessels of a person with high antibody levels.

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See it in 3D

The structures of Durgical's 3D anatomy where it is found.

Microorganisms

Streptococcus pyogenes

← All of immunology

Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.

Sources: Type III Hypersensitivity Reaction (StatPearls Publishing (NCBI Bookshelf), 2025); Systemic lupus erythematosus (El Rosario University Press (NCBI Bookshelf), 2013).

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Representative model, for educational purposes only.