Immune tolerance

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The immune tolerance comprises immunological processes in vertebrates to avoid immune response .


Immune tolerance is divided into two areas, central and peripheral tolerance. The central tolerance describes the negative selection through induced apoptosis or anergy of B and T cells in the bone marrow or in the thymus . The peripheral tolerance describes the reduction of the immune response outside these lymphatic organs, e.g. B. with a desensitization or with autoreactive T and B cells, which have survived the negative selection.

Central tolerance arises from the development of T lymphocytes in the thymus . The process of negative and positive selection plays the most important role here. In order to develop into mature T-lymphocytes, the so-called double-positive lymphocytes (CD4 + CD8 +) have to go through a series of "tests". Here, the binding T-cell receptor (engl .: T cell receptor , TCR) of MHC-I and MHC-II molecules , of the thymus epithelial cells expressed are and endogenous peptides carry. If this binding is not possible, i.e. if the TCR is not able to recognize MHC molecules, the cell does not receive a survival signal and goes into apoptotic cell death . One speaks of death by neglect , death through neglect. The T cell is not selected positively. However, if the binding to MHC is too strong, the T cell is overactivated and it also perishes apoptotically, it is selected negatively. Ultimately, only T cells that can bind MHC with moderate affinity survive. These have proven that they are able to recognize MHC (functional), but on the other hand cannot be activated by MHC complexes with endogenous peptides, i.e. are not autoreactive. The expression of autoantigens in thymus cells is induced by AIRE .

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

However, since not all of the body's own peptides - the self-antigens - are presented in the thymus, but rather further antigenic epitopes occur in the body's periphery, the organism tries to achieve peripheral tolerance. It is mainly sustained through three mechanisms:

  1. Anergy
    If an antigen is presented to a T-cell without co-stimulation, this T-cell goes into anergy, that is, it continues to live but can no longer be activated, not even by later antigen presentation by an APC.
  2. Deletion
    If an antigen is continuously presented to a T cell in high concentrations, this T cell dies in apoptosis. The same thing happens if a T cell is activated again a short time after activation.
  3. Regulatory T cell suppression .
    There is still a lot of research going on in this area. So far, only the existence of a so-called CD25 + regulatory T cell is certain. This releases the cytokines TGF-β and interleukin-10 and thus inhibits other T cells in their environment. Direct cellular contact is also necessary for this inhibiting effect.

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

  • The TH3 cell that secretes TGF-β .
  • The Tr1 cell that 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, testes and the fetus during pregnancy.

Self tolerance

As a self-tolerance ability is immune systems of higher organisms designated body's to recognize substances on their own, to distinguish it from averted exogenous to distinguish substances. In order to be able to ward off pathogens such as bacteria , viruses , fungi and parasites , an organism must be able to clearly recognize them as foreign. On the other hand, antigens that are identified as endogenous are tolerated by the immune system. The development of self-tolerance occurs both centrally and peripherally.

Foreign tolerance

Antigens foreign to the body are not formed in the thymus or bone marrow, so they do not occur in the course of developing central tolerance. Nevertheless, some exogenous antigens are tolerated as long as there are no simultaneous activation signals from the immune system, e.g. B. in the mucous membranes of the intestines, mouth, lungs or on the skin. These organs contain a particularly large number of exogenous antigens and an immune response can also occur there, but non- pathogenic molecules are normally tolerated, e.g. B. from food. The tolerance formation therefore takes place peripherally. Food tolerance is mediated with the participation of the M cells in the intestine . In the case of allergies , although antigen-specific immune cells are present, a peripheral external tolerance is induced in the course of desensitization.