11.4. Mechanism of tolerance induction
Unit 11 - Immunologic tolerance11.4. Mechanism of tolerance induction
The exact mechanism of induction and maintenance of tolerance is not fully understood, but there are several mechanism to induce tolerance. They are:-
T and B lymphocytes during development come across self antigens and such cells undergo clonal deletion through a process known as apoptosis or programmed cell death. But sometimes these cells can escape and can trigger autoimmune disease.
The clonal deletion is not a fool proof system and often T and B cells fail to undergo deletion but enter the periphery, here the regulatory T cells recognize these cells and prevent these cells form exerting autoimmunity.
Activation-induced cell death
T cells upon activation not only produce cytokines or carryout their effector functions but also die through programmed cell death or apoptosis. In this process, the death receptor (Fas) and its ligand (FasL) play a crucial role. Thus, normal T cells express Fas but not FasL. Upon activation, T cells express FasL which binds to Fas and triggers apoptosis.
Auto-reactive T cells when exposed to antigenic peptides on antigen presenting cells (APC) that do not possess the co-stimulatory molecules become anergic (nonresponsive) to the antigen. B cells when exposed to large amounts of soluble antigen down-regulate their surface IgM and become anergic. These cells also up-regulate the Fas molecules on their surface. An interaction of these B cells with Fas-ligand bearing T cells results in their death via apoptosis.
Sometimes T cells reactive to self-antigen mature and migrate to the periphery, but they may not come across the appropriate antigen because it may embedded in the tissue and inaccessible to T cells. These cells may die later. Likewise, the B cells capable of autoimmunity that escape deletion, may not find the antigen or the specific T-cell help and thus not be activated and die out.
These are antibodies that are produced against the specific idiotypes of other antibodies. Anti-idiotypic antibodies are produced during the process of tolerization and have been demonstrated in tolerant animals. These antibodies may prevent the B cell receptor from interacting with the antigen.
Regulatory T cells (Formerly called suppressor cells)
These regulatory T cells suppress the function of other T cells which are engaged in combating the pathogen. But the exact mechanism through which regulatory T cells suppress other T cell function is unclear.
Last modified: Thursday, 21 June 2012, 9:02 AM