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Tolerance Testing

Immune tolerance is the process of training an immune system to not mount an immune response to normal healthy tissues and cells in its own body.

This is achieved by passing candidate B and T cells through a series of antigen exposures then modifying or killing those that mount an inappropriate response.

Tolerance testing can be broadly split into 2 stages:
- Central, where cells learn to differentiate between self and non-self antigens, and
- Peripheral, where cells learn not to overreact to antigens of benign or helpful entities.

Immature lymphocytes, which differentiated from lymphoid precursor, undergo central tolerance test. When they pass the test, they differentiate further into either regulatory T cells, or transitional lymphocytes. If they don’t pass the test, they undergo apoptosis, or modify the antibodies displayed on their cell surface. The regulatory T cells and transitional lymphocytes go through second, peripheral tolerance, test. When they pass it, they differentiate into mature lymphocytes. If they don’t pass it, they undergo apoptosis, suppression, or anergy. Central tolerance test happens in generative lymphoid organs - thymus and bone marrow, whereas peripheral tolerance test happens in peripheral tissues.

Figure 1. Outcomes of immune cell tolerance testing.

Central tolerance testing

During this stage, cells that bind too tightly to presented self-antigen are eliminated from the immune repertoire by induction of cell death, anergy or for some B cells triggering a rearrangement of the receptor gene to make a new expressable version.

Peripheral tolerance testing

During this process any self-reactive B or T cells that might have sneaked through central testing are eliminated. Sometimes the cells only properly encounter self-antigen in large volume once they emigrate from the primary tissues. Such cells are ordinarily eliminated quickly in the peripheral tissues.
Clonal deletion is the term that is applied to the elimination of B cells that strongly bind antigen in the peripheral tissues and then undergo apoptosis. There is no opportunity for the cells to rearrange their genes at this stage - they simply are removed.