Hypersensitivity reactions can arise following treatment with soluble antigens such as animal antisera. The pathology is caused by the deposition of antigen:antibody aggregates, or immune complexes, in particular tissues and sites. Immune complexes are generated in all antibody responses, but their pathogenic potential is determined, in part, by their size and by the amount, affinity, and isotype of the responding antibody. Larger aggregates fix complement and are readily cleared from the circulation by the mononuclear phagocyte system. However, the small complexes that form when antigen is in excess tend to be deposited in blood vessel walls. There they can ligate Fc receptors on leukocytes, leading to leukocyte activation and tissue injury.
A local hypersensitivity reaction called an Arthus reaction (Fig. 14.17) can be triggered in the skin of sensitized individuals who possess IgG antibodies against the sensitizing antigen. When antigen is injected into the skin, circulating IgG antibody that has diffused into the skin forms immune complexes locally. The immune complexes bind Fc receptors such as FcγRIII on mast cells and other leukocytes, generating a local inflammatory response and increased vascular permeability. Fluid and cells, especially polymorphonuclear leukocytes, then enter the site of inflammation from local blood vessels. The immune complexes also activate complement, leading to the production
C5a Local in˜ammation, increased ˜uid and protein release, phagocytosis, and blood vessel occlusion 1–2 hours Locally injected antigen in immune individual with IgG antibody Activation of Fc˜RIII on mast cells induces their degranulation Local immune-complex formation activates complement. C5a binds to and sensitizes the mast cell to respond to immune complexes
Fig. 14.17 The deposition of immune complexes in tissues activation of complement, and the complement component C5a causes a local inflammatory response known as an Arthus contributes to sensitizing the mast cell to respond to immune reaction. In individuals who have already made IgG antibody against complexes. As a result of mast-cell activation, inflammatory cells an antigen, the same antigen injected into the skin forms immune invade the site, and blood vessel permeability and blood flow are complexes with IgG antibody that has diffused out of the capillaries. increased. Platelets also accumulate inside the vessel at the site, Because the dose of antigen is low, the immune complexes are ultimately leading to vessel occlusion. If the reaction is severe, all formed only close to the site of injection, where they activate mast these changes can lead to tissue necrosis. cells bearing Fcγ receptors (FcγRIII). The immune complex induces of the complement fragment C5a. This is a key participant in the inflammatory reaction because it interacts with C5a receptors on leukocytes to activate these cells and attract them to the site of inflammation (see Section 2-5). Both C5a and FcγRIII have been shown to be required for the experimental induction of an Arthus reaction in the lung by macrophages in the walls of the alveoli, and they are probably required for the same reaction induced by mast cells in the skin and the synovial linings of joints. Recruitment and activation of C5a receptor-bearing leukocytes leads to tissue injury, sometimes resulting in frank necrosis.