Self-antigens

T-Lymphocytes (4,5) and other cellular components of the immune system also have equally wide implications in regulation of the normal immune system. The T-lymphocytes play a central role in the body s response to harmful antigens and tumor—host interaction (4). Responses involve antigens derived from vimses, bacteria, parasites, and tumors. T-ceUs also participate in the immune surveillance response, where self-antigens are recognized, but usually sequestered within the cell and, when exposed, become markers of cellular damage. 

Part of these T-lymphocytes transform into memory cells. These cells are different from their ancestors in that they are activated by a much lower antigen binding strength and also much less depend on signal 2. Now self-antigens can activate these T-lymphocytes. As during activation continuously new memory cells are formed, autoreactivity is sustained and autoimmune disease follows (Fig. 2). 

Evasion of tolerance to self antigens. Hidden or sequestered antigens do exist, for instance spermatozoa and eye-lens tissue. These are confined to anatomical sites which do not have access to lymphoid tissue, and exposure of the above to lymphoid cells as a result of surgery or accident results in the production of the corresponding antibodies. 

Vt Self-antigen mDC r Danger-antigen mDC (Q Naive pDC Primed or effector pDC... 

Autoimmune diseases in which immunological self-tolerance breaks down and the immune system launches an attack on self-antigens. 

The mechanism most commonly invoked to explain the association of infection with autoimmune disease is molecular mimicry that is, the concept that antigens (or more properly, epitopes) of the microorganism closely resemble self-antigens.50 The induction of an immune response to the microbial antigen thus results in cross-reactivity with selfantigens and the induction of autoimmunity. Although epitope specific cross-reactivity has been shown in some animal models,48,51 53 molecular mimicry is clearly demonstrated to be the causative mechanism in few, if any, human diseases.3 54,55... 

There is considerable interest in the role of infectious agents in the development of autoimmune diseases. Some of this interest is based on the concept of molecular mimicry as a causal mechanism. Molecular mimicry refers to the possible pathologic role of cross-reactive antibodies or T cells to a self-antigen that is structurally similar to, and thus shares epitopes with, a viral or other infectious agent. For most autoimmune diseases, however, evidence of molecular mimicry leading to disease is not conclusive.1819 Viruses and other infections also have a less-specific immune effect, stimulating toll-like receptors and proinflammatory cytokine secretion, which is another mechanism that has been postulated to influence autoimmune disease risk.20... 

Kubicka-Muranyi, M. et al., Mercuric-chloride-induced autoimmunity in mice involves up-regulated presentation by spleen cells of altered and unaltered nucleolar self antigen. Int. Arch. Allergy Immunol., 108, 1, 1995. 

Dighiero, G., Lymberi, J., Marie, J.C., Rouyse, S., Butler-Browne, G.S., Whalen, R.G. and Avrameas, S. (1983). Murine hybridomas secreting natural monoclonal antibodies reacting with self antigens. J. Immunol. 135 2267-2271. 

Regulatory T (T ) cells represent a distinct T-cell lineage that plays a key role in tolerance to self antigen and prevention of autoimmune diseases, as well as in inappropriate immune responses involved in allergic diseases [1-3]. Tr cells are characterized by a set of phenotypic and functional... 

Wong J, Mathis D, Benoist C TCR-based hneage tracing no evidence for conversion of conventional into regulatory T cells in response to a natural self-antigen in pancreatic islets. J Exp Med 2007 204 2039-2045. 

Regulatory T-cell immunotherapy for tolerance to self antigens and alloanti-gens in humans. Nat Rev Immunol 2007 7 585-598. 

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