Immunological Tolerance

Immunological Tolerance

Immunological tolerance is a state of specific immunologic unresponsiveness to a particular antigen to which a person has been exposed earlier. The immune tolerance prevents the body to mount immune response against the self-antigen.

Mechanisms of Tolerance

Suggested mechanism of tolerance includes (a) clonal deletion, (b) clonal anergy, and (c) suppression.

i.         Clonal deletion: Clones of B and T lymphocytes thatrecognize self-antigens are selectively deleted in embryonic life, hence are not available to respond on subsequent exposure to antigen. This is known as clonal deletion.

ii.        Clonal anergy: Clonal anergy means a condition in whichclones of B and T lymphocytes that recognize self-antigens might be present but cannot be activated.

iii.               Suppression: In this mechanism, clones of B and T lym-phocytes expressing receptors that recognize self-antigens arepreserved. However, expression of immune responses following antigen recognition might be inhibited by active suppression.

Types of Immune Tolerance

The immune tolerance may be of two types: natural or acquired.

Natural tolerance: Natural tolerance is nonresponsivenessto self-antigens. It develops during the embryonic life, and any antigen that comes in contact with the immune system during its embryonic life is recognized as self-antigen. The self-antigen would not induce any immune response. Burnet and Fenner (1949) also postulated that foreign antigens would not induce immune response if they were administered during the embryonic life.

Acquired tolerance: Acquired tolerance develops when apotential immunogen induces a state of unresponsiveness to itself. The antigen needs to be repeatedly or persistently admin-istered to maintain the acquired tolerance. This is probably necessary because of the continuous production of new B and T cells that must be rendered tolerant. Induction of immune tolerance depends on a number of factors. These include (a) species and immune competence of the host and (b) physical nature, dose, and route of administration of antigens

·           Species and immune competence of the host: Tolerance dependson the immunological maturity of the host. Embryos and neonatal animals are immunologically immature, hence are more susceptible for induction of tolerance. Rabbits and mice can be made tolerant more rapidly than guinea pigs and chickens.

·           Physical nature, dose, and route of administration of antigens:Soluble antigens and haptens can induce more immune tolerance than the aggregated antigens. For example, heat aggregated human gamma globulin is more tolerogenic than deaggregated gamma globulin in mice. It may possi-bly be due to enhanced phagocytosis of aggregated proteins than soluble antigens by macrophages, in which they can be presented to antibody-forming cells, thus inducing antibody synthesis. The induction of tolerance is dose dependent also. For example, a very simple molecule induces tolerance more readily than a complex one. Repeated minute doses as well as high doses of antigen induce B-cell tolerance, whereas a moderate degree of same antigen may be immunogenic. The route of administration is also important. In guinea pigs, intravenous or oral administration of certain hap-tens causes tolerance, whereas intradermal administration causes induction of immunity. T cells become tolerant more readily than B cells and also remain tolerant longer than B cells. Tolerance is overcome spontaneously or by injection of cross-reacting antigens. For example, in rabbits, tolerance to bovine serum albumin can be abolished by immunization with cross-reacting human serum albumin. Tolerance can be enhanced by administration of immunosuppressive drugs. For example, tolerance is enhanced in patients who have received organ transplants.