Get Complete Information on the Origin of Self Tolerance (Immune tolerance)

Different possible ways for origin of self tolerance are as follows.

Clonal Deletion Theory:

Burnet has proposed clonal deletion theory to explain origin of self tolerance.

According to his theory destruction of self-reactive lymphoid cells takes place during the development of the immune system. T and B lymphocytes undergo positive and negative selection during their development and maturation within the primary lymphoid organs.

During this process, cells that can react with self antigens undergo clonal deletion. Thus clonal deletion plays a key role in ensuring tolerance to self antigen. If any T and B cells fail to undergo deletion, the immune system has devised several additional check points to maintain tolerance.

For example T cells upon activation not only produce cytokines or carryout their effectors functions but also die through programmed cell death or apoptosis.

Clonal Anergy:

According to Nossal, self-reactive T- or B-cells become inactivated in the normal individual and cannot amplify the immune response.

T cells when exposed to auto-reactive antigenic peptides on antigen presenting cells (APC) that do not possess the co-stimulatory molecules become anergic (nonresponsive) to the antigen.

B cells when exposed to large amounts of soluble antigen down-regulate their surface IgM and become anergic.

Clonal Ignorance:

Host immune responses are directed to ignore self-antigens. T cells reactive to self-antigen, not represented in the thymus may mature and migrate to the periphery but they may never encounter the appropriate antigen because it is sequestered in inaccessible tissues (tissue not drained directly by the lymphocytes) such as central nervous tissue, testicular tissue etc. Hence cells reactive to self-antigen may die for lack of stimulus.

Auto-reactive B cells that escape deletion may not find the antigen or the specific T-cells help and thus not get activated and die out.

Anti-Idiotype Antibody

According to this theory a network of antibodies capable of neutralizing self-reactive antibodies exists naturally within the body.

Anti-idiotypic antibodies are produced during the process of tolerization and have been demonstrated in tolerant animals. These antibodies may prevent the B cell receptor from interacting with the antigen