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• Allergic and Other Hypersensitivity Disorders
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In autoimmune disorders, the immune system produces antibodies to an endogenous antigen. It may involve the following hypersensitivity reactions:

• Type II: Antibody-coated cells, like any similarly coated foreign particle, activate the complement system (see Biology of the Immune System: Complement System), resulting in tissue injury.
• Type III: The mechanism of injury involves deposition of antibody-antigen complexes.
• Type IV: Injury is T-cell–mediated.

For specific autoimmune disorders, see elsewhere in The Manual (see also Table 1: Allergic and Other Hypersensitivity Disorders: Putative Autommune Disorders).

Etiology

Several mechanisms may account for the body's attack on itself.

Autoantigens may become immunogenic because they are altered chemically, physically, or biologically. Certain chemicals can couple with body proteins, making them immunogenic (as in contact dermatitis). Drugs can produce several autoimmune reactions by binding covalently to serum or tissue proteins (see Allergic and Other Hypersensitivity Disorders: Drug Hypersensitivity). Photosensitivity exemplifies physically induced autoimmunity: Ultraviolet light alters skin protein, to which the patient becomes allergic. In animal models, persistent infection with an RNA virus that combines with host tissues alters autoantigens biologically, resulting in an autoimmune disorder resembling SLE.

Antibodies produced in response to a foreign antigen may cross-react with normal autoantigens (eg, cross-reaction between streptococcal M protein and human heart muscle).

Normally, potentially pathologic autoimmune reactions are avoided because of the immunologic tolerance mechanisms of clonal deletion and clonal anergy. Any autoreactive lymphocytes not controlled by these mechanisms are usually restrained by Foxp3+ regulatory T cells. A regulatory T-cell defect may accompany any of these mechanisms for autoimmunity. Anti-idiotype antibodies (antibodies to the antigen-combining site of other antibodies) may interfere with regulation of antibody activity.

Genetic factors play a role. Relatives of patients with autoimmune disorders often have the same type of autoantibodies, and incidence of autoimmune disorders is higher in identical than in fraternal twins. Most autoimmune disorders have a polygenic etiology, and allelic variants within the HLA gene locus nearly always contribute. Women are affected more often than men. In genetically predisposed people, environmental factors may provoke disease (eg, certain drugs can trigger hemolytic anemia in patients with G6PD deficiency).

Last full review/revision September 2008 by Peter J. Delves, PhD

Content last modified September 2008