15-28 Autoimmune diseases involve the host immune system attacking host proteins

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• A second mistake that can be made by the immune system is the recognition of self-antigens. This causes autoimmune diseases that are characterized by constant overstimulation of the immune system.
• Autoimmune diseases are often triggered by infection or exposure to certain antigens in the environment.

Under normal conditions, the body is able to distinguish self from non-self antigens. This immune tolerance develops by several mechanisms as described earlier in the chapter. When this tolerance breaks down, autoimmunity occurs, which is characterized by an immune response against antigens present on host tissue. As an individual ages, various types of infections and other encounters with foreign antigens can precipitate the formation of antibodies that react against self-antigens. These are usually benign and under normal circumstances disappear as soon as the offending antigen is removed. Autoimmune disease is often precipitated by the activation of self-reactive T and B cells following stimulation by infection or exposure to certain antigens present in the environment. These illnesses can be extremely debilitating and cause significant suffering in afflicted individuals. Figure 15-32 summarizes various autoimmune diseases.

Autoimmune disease is mitigated by four factors.

1. There seems to be a genetic predisposition for some autoimmune diseases. For example, there is a correlation between a person's susceptibility to Graves' disease and the presence of a specific antigenic determinant on the MHC molecule. Genes encoding MHC molecules actually have a number of alleles in humans, and as a result, their protein sequence is not the same from person to person.
2. Viral or bacterial infections of some sorts can precipitate autoimmune disease. It seems an infection with certain pathogens triggers an immune response that cross-reacts with antigens present in the body. One emerging example is Guillain-Barré syndrome where at least some of the cases appear to be caused by a previous infection with Campylobacter jejuni. After infection, the immune system begins attacking the nervous system causing weakness, sometimes to the point of impeding breathing.
3. Endocrine hormones (hormones secreted directly into the blood or lymph) affect the severity of autoimmune disease. Estrogen promotes autoimmune reactions, while androgen inhibits them through yet unknown mechanisms and this partially explains the predominance of autoimmune disorders in women.
4. Stress and neurotransmitters (those with effects on the nervous system) can cause physiological changes that make autoimmune diseases worse.

For example, autoimmune diseases cause a progressive degeneration of the tissues attacked by the immune system. In systemic lupus erythematosus, the immune response is errantly directed against a number of different self-antigens including DNA, nucleoproteins and blood-clotting factors. The illness results in the accumulation of antigen-antibody complexes that migrate to the kidneys and joints causing immune complex-mediated hypersensitivity. If untreated, this leads to kidney failure and severe arthritis. Type 1 diabetes is an autoimmune disease, where the immune system responds to the cytoplasm and surface proteins present on islets cells of the pancreas. Destruction of these cells results in the inability to make insulin. Many of these diseases are extremely difficult to treat.

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