"Immune tolerance:The concept of immune tolerance was first introduced by Owen in 1945. Later on Medawar andBillingham worked and introduced the term immune tolerance. Immune tolerance is a condition of ignorance of the adaptive immune system towardssubstances or tissue that has the capacity to induce an immune response in host organism.Immune Tolerance is classified into central tolerance or peripheral tolerance depending on wherethe tolerance is originally induced.Tolerance induced in the thymus and bone marrow is called central) and tolerance induced inother tissues and lymph nodes is termed as peripheral tolerance.Immune tolerance is important for normal physiology and functioning of the organism. Central tolerance is the main way in which the immune system learns to discriminate self fromnon-self antigens However many auto-reactive T cells escape central tolerance due to absence of antigens orinsufficient numbers of antigens. To cope up the situation, tolerance is maintained bymechanisms in peripheral lymphoid organsPeripheral tolerance is a crucial part of defense system in preventing hypersensitivity of theimmune system to various environmental contaminants such as allergens(pollen and intestinalmicrobes, etc. malfunctioning of the immune tolerance may lead to autoimmune disease,resulting in syndromes such as systemic lupus erythematosus. Some of the mechanism by which peripheral tolerance acts in described below in the form of Bcell tolerance and T cell tolerance T-cell tolerance:1-Sequestration of antigens in some tissues:Many self antigens are hidden in tissues that are anatomically located away from T lymphocytes2- Privileged sites are protected by regulatory mechanisms: Privileged sites include brain, testes and anterior champers of the eye. In these sites lymphocytesare controlled by apoptosis or cytokines such as TNF ß and IL103- T cell death can be induced by persistent activation or neglect:Cells possess Fas receptor, when it cross-links with its ligand FasL it promote apoptopic celldeath. Activated lymphocyte will die by passive cell death (PCD) when deprived from its antigen4- Regulation by suppressive cytokinesIL-2 and IL-2 receptor regulate sensitivity to Fas mediated apoptosis B cell tolerance: ? High affinity IgG production is T cell dependento Lack of T cell leads to non-self reactivity by B cells ? Self reactive B cells either edit their receptors to become non-reactive or die by theprocess of apoptosis In peripheral B cell tolerance, self reactive cells are removed bynegative selection in the spleen in a process that is similar to T cell removal in thethymus.? During B cell development in the bone marrow the complete antigen receptor (IgM) isfirst expressed on 'immature' B cells. If those cells encounter their target antigen in aform which can cross-link their IgM then such cells are programmed to die. Therequirement for cross-linking means that the antigen has to be polyvalent Central tolerance:The process of central tolerance involves mechanisms of tolerance acting during lymphocytedevelopment in the thymus or bone marrow. Experimental studies show that central tolerance ismostly due to the elimination or inactivation of those T and B cells that recognise self-antigens.These cells are destroyed or inactivated after they have expressed receptors for self-antigens andbefore they develop into fully immunocompetent lymphocytes. Deletion of self-reactive cells atan early stage in their development has been termed 'clonal deletion'. In early foetal life, self-reactive lymphocytes that are part of the developing immune system aredeleted when exposed to self-antigens. New immunologically competent cells are generatedthroughout life and these must be continuously deleted or inactivated also., Peripheral tolerance: "