acquired immunological tolerance
Acquired immunological tolerance
An induced state in which antigens originally regarded as foreign become regarded as self by the immune system. Tolerance can be induced (tolerization) in all of the cells of the immune system, including T cells (also known as T lymphocytes), the antibody-forming B cells (also known as B lymphocytes), and natural killer cells. Artificially induced immunological tolerance can be helpful in a number of clinical settings. Inducing self-tolerance in the immune system could be an approach to curing autoimmune diseases.
Tolerization can also be used to facilate organ transplantation. Despite improvements in immunosuppressive drug therapy, teaching the immune system to regard a set of foreign antigens presented by the organ graft as self (that is, tolerance induction) has become an important goal for several reasons: (1) It would eliminate the need for chronic immunosuppressive therapy, which is associated with lifelong increased risks of infection and malignancy, and other side effects. (2) It would prevent chronic rejection (a major problem even with immunosuppressive therapy), which often leads to late graft loss. (3) It presents a less toxic alternative to the unacceptably high levels of nonspecific immunosuppressive therapy that would likely be required to prevent rejection of xenografts (grafts from a donor of another species). See Transplantation biology
Many strategies for inducing immunological tolerance involve reproducing the mechanisms involved in natural central tolerance—the phenomenon by which self-tolerance is maintained among immature lymphocytes developing in the central lymphoid organs. For developing T cells, tolerance occurs in the thymus, the central organ for T cell development. For B cells, development occurs in the bone marrow, and an encounter with self antigens can induce tolerance there among the immature cells.
The transplantation of bone marrow or other sources of hematopoietic (blood cell-producing) stem cells provides a very powerful means of inducing T cell central tolerance. The clinical potential of bone marrow or other types of hematopoietic cell transplantation for the induction of transplantation tolerance in humans has not yet been realized.
Peripheral tolerance comprises mechanisms to prevent immune responses among mature lymphocytes in the peripheral tissues. One major mechanism of T cell and B cell peripheral tolerance is anergy, in which the cells cannot be fully activated by encounter with the antigens that their receptors recognize. Numerous methods of inducing T and B cell anergy have been described.
Another major mechanism of peripheral tolerance is suppression, in which both B cells and T cells may be rendered tolerant of a specific antigen through the activity of substances or cells that actively suppress the lymphocyte's function. Numerous means of inducing B cell and T cell suppression have been described, and convincing evidence implicates cells with the ability to suppress T cell alloresponses (immune responses to alloantigens) in transplantation models. See Immunosuppression