17.7: Hypersensitivity Reactions: Immune-Complex Reactions

Type III hypersensitivity reactions occur when antigen–antibody complexes form and activate the complement system. Normally, these complexes help the clearance of antigens by phagocytes and red blood cells. However, when large numbers of immune complexes are present, they can deposit in tissues—particularly in the walls of blood vessels—leading to inflammation and tissue injury. These deposits trigger complement activation and neutrophil recruitment, resulting in serum sickness, a systemic reaction characterized by fever, rash, joint pain, and lymph node enlargement that typically appears 7–14 days after antigen exposure and resolves once the antigen is eliminated.

The Arthus reaction is a localized Type III hypersensitivity reaction that occurs when an antigen is injected into the skin of a sensitized individual with high levels of circulating IgG antibodies, such as after repeated vaccination. Large immune complexes form at the site, causing an inflammatory response within 4–10 hours, marked by redness, swelling, and tissue necrosis. Similar localized immune complex–mediated reactions can occur in the lungs following repeated exposure to inhaled antigens such as mold or animal proteins, leading to farmer’s lung or pigeon fancier’s disease.

Type III hypersensitivity, or immune complex reactions, result from antibodies binding to soluble antigens in the circulation, forming immune complexes. These circulating complexes then activate the complement system, triggering an inflammatory cascade.

When not efficiently cleared by the immune system, these complexes can deposit in the walls of blood vessels and tissues. This deposition recruits complement proteins and neutrophils, which manifests as serum sickness. It is a systemic immune response characterized by fever, rash, joint pain, and lymph node enlargement. It can happen in response to some commonly used antibiotics, among other things.

Another example of the type III hypersensitivity is the Arthus reaction. In previously sensitized individuals, exposure to antigens, like those from insect bites or fungal spore inhalation, can lead to the formation of large quantities of antigen–antibody complexes at the exposure site. This triggers a localized inflammatory response, resulting in redness, swelling, and tissue damage at the site.