Antigen-antibody complexes, which are produced during normal immune responses, cause disease only when they are formed in excessive amounts, are not efficiently removed by phagocytes, and become deposited in tissues. Complexes containing positively charged antigens are particularly pathogenic because they bind avidly to negatively charged components of the basement membranes of blood vessels and kidney glomeruli. Once deposited in the vessel walls, the Fc regions of the antibodies activate complement and bind Fc receptors on neutrophils, activating the cells to release damaging proteases and reactive oxygen species. This inflammatory response within the vessel wall, called vasculitis, may cause local hemorrhage or thrombosis leading to ischemic tissue injury. In the kidney glomerulus, the vasculitis can impair the nor mal filtration function, leading to renal disease.

The first immune complex disease studied was serum sickness, seen in subjects who received antitoxin- containing serum from immunized animals for the treatment of infections. Some of these treated individuals subsequently developed a systemic inflammatory disease. This illness could be recreated in experimental animals by systemic administration of a protein antigen, which elicits an antibody response and leads to the formation of circulating immune complexes. This can occur as a complication of any therapy involving injection of foreign proteins, such as antibodies against microbial toxins, snake venoms and T cells that are usually made in goats or rabbits, and even some humanized monoclonal antibodies that are used to treat different diseases and may differ only slightly from normal human Ig.

A localized immune complex reaction called the Arthus reaction was first studied in experimental animals. It is induced by subcutaneous administration of a protein antigen to a previously immunized animal; it results in the formation of immune complexes at the site of antigen injection and a local vasculitis. In a small per centage of vaccine recipients who have previously been vaccinated or already have antibodies against the vaccine antigen, a painful swelling that develops at the injection site represents a clinically relevant Arthus reaction.

In human immune complex diseases, the antibodies may be specific for self-antigens or microbial antigens. In several systemic autoimmune diseases, many of the clinical manifestations are caused by vascular injury when complexes of the antibodies and self-antigens deposit in vessels in different organs. For example, in systemic lupus erythematosus, immune complexes of anti-DNA antibodies and DNA can deposit in the blood vessels of almost any organ, causing vasculitis and impaired blood flow, leading to a multitude of different organ pathologies and symptoms. Several immune complex diseases are initiated by infections. For example, in response to some streptococcal infections, individuals make antistreptococcal anti bodies that form complexes with the bacterial antigens. These complexes deposit in kidney glomeruli, causing an inflammatory process called poststreptococcal glomerulonephritis that can lead to renal failure. Other immune complex diseases caused by complexes of antimicrobial antibodies and microbial antigens lead to vasculitis. This may occur in patients with chronic infections with certain viruses (e.g., the hepatitis virus) or parasites (e.g., malaria).

مواضيع ذات صلة

Diseases Caused by T Lymphocytes

Examples and Treatment of Diseases Caused by Cell- or Tissue-Specific Antibodies

Mechanisms of Antibody-Mediated Tissue Injury and Disease

Hypersensitivity Disorders Caused by Immune Responses : Clinical Syndromes and Therapy

Activation of Mast Cells and Secretion of Mediators

Activation of Th2 Cells and Production of IgE Antibody

Transplantation of Blood Cells and Hematopoietic Stem Cells

Prevention and Treatment of Graft Rejection

Monocytes–Macrophages: Host Defense Functions: Phagocytosis

Mononuclear Phagocyte System

Immune Mechanisms of Graft Rejection

Induction of Immune Responses Against Transplants