Immune tolerance

The immune tolerance includes immunological processes in vertebrates, in order to avoid an immune response.

Properties

Immune tolerance is divided into two portions, the central and peripheral tolerance. The central tolerance describes the negative selection by induced apoptosis or anergy of B and T cells in the bone marrow or in the thymus. Peripheral tolerance describes the reduction of the immune response outside of these lymphoid organs, eg in a desensitization or autoreactive T and B cells, which have survived the negative selection.

Central tolerance is created in the development of T lymphocytes in the thymus. Here, the process of negative and positive selection plays the most important role. In order to develop into mature T lymphocytes, the so-called double-positive lymphocytes have to go through (CD4 CD8 ) a series of " tests ". Here, the T-cell receptor binds (English: T cell receptor, TCR) to MHC I and MHC II molecules which are expressed by thymic epithelial cells and carry endogenous peptides. This binding is not possible, therefore, the TCR is not able to recognize MHC molecules, given the cell survival signal and no changes to the apoptotic cell death. One speaks of the death by neglect, the death by neglect. The T cell is selected not positive. Is the binding to MHC but too strong, there is an over-activation of the T cell and it is also based on apoptotic, it is negatively selected. Ultimately survive only T cells that can bind with moderate affinity MHC. They have proven that they are able to recognize MHC ( functional ), but can not be activated by MHC complexes with endogenous peptides on the other side, that are not autoreactive.

Only about 1-2 % of all T cells that mature in the thymus, survive this process of selection.

However, since not all endogenous peptides - the self- antigens - are presented in the thymus, but occur more antigenic epitopes in the periphery, the organism strives to peripheral tolerance. It is mainly maintained by three mechanisms:

Furthermore, the existence of two additional regulatory T cells, it is postulated:

• TH3 the cell, TGF- β secreted.
• The Tr1 cell, which secretes interleukin -10.

Regulatory T cells play a major role in the formation of the functional barrier of the immune system in the so-called immune- privileged organs such as the eye, testis and fetus during pregnancy.

Self-tolerance

As a self- tolerance, the ability of the immune systems of higher organisms is called to recognize the body's own substances as such in order to distinguish them from defended against exogenous substances. In order to fend off pathogens, such as bacteria, viruses, fungi and parasites, it must be possible an organism, they clearly recognize as foreign. Antigens, which are identified as endogenous, however, are tolerated by the immune system. The formation of self-tolerance occurs both centrally and peripherally.

Foreign tolerance

Exogenous antigens are not formed in the thymus or bone marrow, so they do not occur in the course of training of central tolerance. However, some nonself antigens are tolerated as long as no concurrent activation of the immune system signals are present, such as in the mucous membranes of the intestine, mouth, lungs, or skin. In these organs, particularly many exogenous antigens occur and it can also be an immune response there, but non-pathogenic molecules are usually tolerated, eg from food. The tolerance formation is therefore peripherally. The food tolerance is mediated with the involvement of M cells in the intestine. For allergies, although antigen-specific immune cells are present, induces peripheral tolerance in the wake of a foreign desensitization.