Central 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). 

During differentiation of T- or B-lymphocytes antigen recqrtors are generated which react to self or autoantigens. These are generally eliminated by the mechanisms of central tolerance or kept silent by the mechanisms of peripheral tolerance ( autoimmune disease). 

Central Diabetes Insipidus Central Tolerance Centrosome... 

Although central tolerance is the major mechanism to establish the T-cell repertoire by positive and negative selection mechanisms, thymic deletion of harmful T-cell populations is incomplete. Therefore, the immune system has developed mechanisms that deal with tolerance in the peripheral lymphoid organs providing the necessary... 

Chen Z, Benoist C, Mathis D. 2005. How defects in central tolerance impinge on a deficiency in regulatory T cells. Proc Natl Acad Sci USA. 102 14735-14740. 

Nemazee, D. 2006. Receptor editing in lymphocyte development and central tolerance. Nat. Rev. Immunol. 6 728-740. 

T-cells are primed in the thymus, where they undergo two selection processes (central tolerance) the first, positive selection process selects only those T-ceUs with the correct set of receptors that can recognise the MHC molecules responsible for self-recognition then a negative selection process begins, whereby only T-ceUs that can recognise MHC molecules complexed with foreign peptides are allowed to pass out of the thymus. 

Clonal deletion of self-reactive T- and B-ceUs during development, which removes lymphocytes with high-avidity receptors for ubiquitous self-antigen present in the thymus and marrow. This is known as central tolerance. 

Briefly describe the development of central tolerance to myelin. 

Wliich cells interaction leads to development of the central tolerance in thymus ... 

Kyewski B, Klein L (2006) A central role for central tolerance. Annu Rev Immunol 24 571-606. 

In experimental models, the immunosuppressant cyclosporine A blocks T-cell signalling pathways by inhibiting the phosphatase calcineurin and may induce autoimmunity by impairing central tolerance... 

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