Question

Describe the mechanisms by which B-cells and T-cells can recognize self from non-self antigens.

Answer 1

Central tolerance, also known as negative selection, is the process of eliminating any developing T or B lymphocytes that are reactive to self. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides.Lymphocyte maturation (and central tolerance) occurs in primary lymphoid organs such as the bone marrow and the thymus. In mammals, B cells mature in the bone marrow and T cells mature in the thymus.Central tolerance is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs. Central tolerance is essential to proper immune cell functioning because it helps ensure that mature B cells and T cells do not recognize self antigens as foreign microbes. More specifically, central tolerance is necessary because T cell receptors (TCRs) and B cell receptors (BCRs) are made by cells through random somatic rearrangement. This process, known as VDJ recombination, is important because it increases the receptor diversity which increases the likelihood that B cells and T cells will have receptors for novel antigens.

B cell tolerance:Immature B cells in the bone marrow undergo negative selection when they bind self peptides.Properly functioning B cell receptors recognize non-self antigen or pathogen associated molecular proteins (PAMPs).

Outcomes of autoreactivity of BCRs

1. Apoptosis (clonal deletion)
2. Receptor editing: the self-reactive B cell changes specificity by rearranging genes and develops a new BCR that does not respond to self. This process gives the B cell a chance for editing the BCR before it is signaled to apoptose or become anergic.
3. Induction of anergy (a state of non-reactivity).

T cell tolerance:T cell central tolerance occurs in the thymus. T cells undergo positive and negative selection.T cell receptors must have the ability to recognize self major histocompatibility complex (MHC) molecules with bound non-self peptide.

Steps of T cell tolerance

1. During positive selection, T cells are checked for their ability to bind peptide-MHC complexes with affinity. If the T cell cannot bind the MHC class I or MHC class II complex, it does not receive survival signals, so it dies via apoptosis. T cell receptors with sufficient affinity for peptide-MHC complexes are selected for survival.
2. During negative selection, T cells are tested for their affinity to self. If they bind a self peptide, then they are signaled to apoptose (process of clonal deletion).
3. The T cells that do not bind self, but do recognize antigen/MHC complexes, and are either CD4+ or CD8+, migrate to secondary lymphoid organs as mature naïve T cells.