Immune responses to antigenic material in immune privileged sites

The manner in which these features create immune privilege and the associated 'deviant' systemic immune response (to privileged antigens) is the subject of intense investigation at the present. Current evidence indicates that privilege may result from an actively acquired, dynamically regulated, antigen-specific immune response that is able to express itself within the privileged site while avoiding nonspecific, tissue-destructive inflammation. Since this 'deviant' immune response is systemic in nature, the selective deficiencies (delayed hypersensitivity and production of complement fixing antibodies) are evident when the same antigens are encountered at other, nonpriv-ileged sites of the body. The unique features of immune responses to antigens expressed on grafts placed in privileged sites are also elicited when other types of nongraft antigens are inoculated into the privileged site, including antigens associated with tumors, haptens, virally encoded antigens, soluble heterologous protein antigens, and tissue-restricted autoantigens.

In the past, immune privilege has been regarded largely as a laboratory curiosity. However, it now appears that privilege is actively acquired and maintained, leading investigators to wonder whether privileged sites serve physiologic purposes. For example, it has been proposed that privilege in the anterior chamber of the eye, including the deviant systemic immune response to antigens placed within this site, serves to limit/prevent immunogenic inflammation at that site. As a consequence, the microanatomic integrity of the eye, which is essential for vision, is spared from blinding distortion by inflammation. Privileged sites may have in common a unique vulnerability to the nonspecific, destructive potential of immunogenic inflammation, and therefore immune privilege may be an evolutionary adaptation designed to mitigate this possibility. In addition, privileged tissues, such as the eye, contain strong tissue-restricted autoantigens that can readily cause autoimmune disease. Immune privilege is considered to be one mechanism that is used by tissues with strong 'sequestered1 autoantigens to avoid destructive autoimmunity.

See also: Autoantigens; Autoimmune diseases; Autoimmunity; Transplantation.

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