Question

Define “self-tolerance”? and what are the situations that may led to the loss of self-tolerance (three at least)?. Define each situation and give one example for each. (100 – 150 words)

Answer 1

Self-tolerance is the ability of the immune system to recognise self produced antigens as a non-threat while appropriately mounting a response to foreign substance. Some situations that may lead to loss of self-tolerance include reduced deletion or enhanced activation of autoreactive CD4+T helper lymphocytes, defective immunomodulation by CD4+regulatory and CD8+ suppressor T-lymphocytes, dysregulated signalling . Three major conceptual situations are clonal deletion, ligand-induced activation, and active suppression.

Clonal deletion leads to an example of B cell development. Antigenic determinants present as highly expressed membrane components cause the apoptotic death of the earliest progenitor with a functional BCR. This process is analogous to clonal deletion of autoreactive T cells in the thymus. Ligand induced activation example as adoptive transfer that elimination of energic B cells requires functional fas on the B cell and functional Fas ligand on the T cell. The activation state of the B cell determines the functional outcome of the T/B cell interactions. Active suppression leads to an example of B cell repertoire, central tolerance is made by clonal deletion of developing B cells that can recognise self antigens associated with cell membranes or solid surfaces. The establishment of helper T cells tolerance to antigens by clonal deletion is of paramount importance to hold back the activation suppression of B cells clones through negative selection.