Immune response self-tolerance

The Th-1 /Th-2 paradigma forms a core mechanism regulating the nature of an immune response. More recently, this concept was further developed by identifying Th-subsets with predominantly suppressing properties, T-regulatory cells (Treg). These cells also play a major role in keeping those cells at rest, which have escaped central tolerance (peripheral self tolerance). 

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... 

Besides ensuring self-tolerance, different types of Tregs actively participate in immune responses. 

In addition to having an overabundance of several self-antigens, tumor cells express unique antigens, which can be recognized by the host immune system, provided that the immune system is simultaneously activated. Without this activation, the immune system will become tolerized to the unique antigens known as tumor-associated antigens (TAAs), which are usually small peptides of 8 to 10 amino acids. The potential exists for the eradication of cancers by injection of TAAs and the subsequent immune response. Indeed, there have been many tumor-reactive CTLs identified that recognize specific TAAs (15). 

Sakaguchi S. 2004. Naturally arising CD4+ regulatory T cells for immunologic self tolerance and negative control of immune response. Ann Rev Immunol. 22 531-562. 

Mammalian embryos are extremely tolerant of foreign proteins while still in utero, and all substances within the developing organism are accepted as self. This is essential during development to ensure that immune responses are not raised to proteins and peptides produced during this time. Any immunological response to developmental proteins, hormones and growth factors would have disastrous results. 

H2. Han, S., Zheng, B., Dao Porto, J., and Kelsoe, G., In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl) acetyl IV-affinity-dependent, antigen driven B cell apoptosis in germinal centers as a mechanism for maintaining self-tolerance. J. Exp. Med. 182, 1635-1644 (1995). 

Some speculate that ACAID-based immunotherapy may be beneficial in immune-media ted diseases of the eye and a variety of other organs. This is due to the fact that the immune deviation of ACAID produces T regulatory cells that are effective in inhibiting both Thl and Th2 responses (both primary and secondary responses). Cell d-reac tive NKT cell-dependent tolerance or ACAID induced by inoculation of antigen into the eye may contribute to self-tolerance and prevention of autoimmune responses in organs and tissues in general. 

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