long term if they trigger a predominantly IgE response. This response could trigger an allergic reaction to future immunizations with the same antigens (IOM, 1994a).

To prevent the body's immune system from destroying its own tissues in what is known as an autoimmune response, immature T cells that react against self-antigens are thought to be destroyed in the thymus gland, creating what is known as central tolerance. Peripheral tolerance might also occur, whereby those T cells that could potentially react to self-antigens and that are not destroyed in the thymus are somehow prevented from causing an autoimmune reaction. Although studies suggest that peripheral tolerance exists, at least in experimental animals, the mechanism for the process is not yet known. If peripheral tolerance exists in people, an autoimmune response might occur in response to vaccination if the vaccine somehow disrupts that peripheral tolerance or if peripheral tolerance is not strong on the day of vaccination (Miller et al., 1989).

Some people have suggested that vaccines can stimulate autoimmune reactions if some of the antigen fragments in vaccines resemble a person's self-antigens. However, it is unclear why an immune system that is tolerant of its own self-antigens would respond to a self-antigen mimic in a vaccine. Berkower speculated that vaccines might counter peripheral tolerance and foster an autoimmune reaction if they contain molecular mimics of self-antigens that are usually not exposed to T cells, because peripheral tolerance seems to depend on the continuous presence of an antigen.

Nakhasi suggested that an autoimmune response might be instigated by a vaccine or by natural infection if the microbial antigens bind to self-antigens in infected cells and change the antigens' shape such that they are no longer tolerated and can elicit an immune response.

According to McFarland, researchers suspect that molecular mimicry, which could possibly lead to an autoimmune disorder, might be occurring between self-antigens and antigens from microbes or vaccines if the two antigens share much of the same chemical structure. Recent studies suggest, however, that they need to have a similar structure only in the narrow region that binds to the T-cell receptor (Vogt et al., 1994; Wucherpfennig et al., 1994). In addition, the amino acids in this region do not have to be identical; rather studies suggest that they must have the same basic chemical and charge properties (Vogt et al., 1994; Wucherpfennig et al., 1994; Vergelli et al., 1996).

Some researchers have hypothesized that autoimmune diseases may be stimulated by viruses (Fujinami et al., 1985; Westall and Root-Bernstein, 1983). Westall and Root-Bernstein have postulated that this may occur if three criteria are met. The first one is that antigens are present that have molecular structure similar to self antigens found in certain human tissue (Westall and Root-

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement