Proposed Mechanisms for Induction of Autoimmunity

A variety of mechanisms have been proposed to account for the T-cell-mediated generation of autoimmune diseases (Figure 20-8). Evidence exists for each of these mechanisms,

VISUALIZING CONCEPTS

VISUALIZING CONCEPTS

Release of sequestered antigen

Inappropriate MHC expression on non-APCs

Release of sequestered antigen

Inappropriate MHC expression on non-APCs

IL-2

TH cell TC cell

Tissue damage

Activated TH cell

IFN-y TH cell

IL-2

TH cell TC cell

Tissue damage

IFN-y TH cell

Activated TH cell

TH cell B cell Plasma cell

TH cell B cell Plasma cell

B cell

Ab to self-antigens

B cell

FIGURE 20-8

Proposed mechanisms for inducing autoimmune responses. Normal thymic selection appears to generate some self-reactive TH cells; abnormalities in this process may generate even more self-reactive THcells. Activation of these self-

reactive T cells in various ways, as well as polyclonal activation of

B cells, is thought to induce an autoimmune response, in this case resulting in tissue damage. In all likelihood, several mechanisms are involved in each autoimmune disease. [Adapted from V. Kumar et al, 1989, Annu. Rev. Immunol. 7:657.]

and it is likely that autoimmunity does not develop from a single event but rather from a number of different events.

In addition, susceptibility to many autoimmune diseases differs between the two sexes. As noted earlier, Hashimoto's thyroiditis, systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and scleroderma preferentially affect women. Factors that have been proposed to account for this preferential susceptibility, such as hormonal differences between the sexes and the potential effects of fetal cells in the maternal circulation during pregnancy, are discussed in the Clinical Focus.

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Essentials of Human Physiology

Essentials of Human Physiology

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