Antibodies also bind soluble antigen, and the resulting antibody-antigen complexes normally get cleared by the reticuloendothelial system. Problems arise when complexes are small enough to stay in circulation but large enough to activate complement, and when they deposit in tissues with high filtration pressure or fenestrated capillaries — the glomerulus, synovium, skin, and choroid plexus are typical sites.
Once deposited, complexes activate complement locally. C5a recruits neutrophils, and the neutrophils attempt to phagocytose complexes that are stuck to the tissue surface. This is the key step: the neutrophil cannot internalize the fixed complex, so it releases its lysosomal enzymes, reactive oxygen species, and neutrophil extracellular traps into the surrounding tissue. The damage is therefore caused by the frustrated phagocyte, not by the complex itself.
The injury appears roughly four to ten hours after exposure, when complexes have had time to deposit and neutrophils have arrived, and it can persist as long as complexes continue to form. Because deposition depends on where complexes lodge rather than on where the antigen originated, the injury can appear in tissues far from the original antigen source. This is the type III hypersensitivity pattern.