What Is Peripheral Tolerance?

Mary McMahon

Peripheral tolerance involves the failure of circulating T and B cells to attack antigens carried on the cells of the body. The development of immune tolerance prevents the body from attacking itself. It can also be induced medically to limit transplant rejection or treat people with severe allergies. Several mechanisms are involved in the development of peripheral tolerance. This is a subject of study for immunologists, transplant researchers, and allergy specialists, all of whom interact with both central and peripheral tolerance in the course of their work.

Anatomical model of the human body
Anatomical model of the human body

T cells develop inside the thymus, while B cells mature in the bone marrow. During the development process, they are subject to central tolerance, where the body identifies cells that will react to self-antigens and destroys them. These cells never enter the peripheral immune system and thus do not have an opportunity to cause autoimmune disease. Some slip through the net, requiring a secondary screening through peripheral tolerance.

One way the body manages the peripheral immune system is by creating what are known as “privileged areas,” where T-cells cannot enter. Cells that could react to antigens found in these areas never come into contact with them. Another factor is negative selection, which allows the body to destroy cells that might react with self-antigens, just as it does in the bone marrow and thymus. Peripheral tolerance can also occur when cells fail to exhibit costimulation, a necessary part of the reaction process the immune system uses to lock on and destroy antigens.

Some tissues in the body continuously produce enzymes that trigger cell death in response to the presence of specific compounds on the surface of cells. This allows the body to maintain peripheral tolerance in special areas by killing off T cells that drift into the region, since they contain special proteins that will react with the enzymes. Regulatory T-cells are also involved, as they identify and mop up hazardous T-cells that might cause autoimmune reactions.

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Studies on immunological tolerance provide important information for care providers. In patients with autoimmune diseases, something has gone wrong and the body is no longer tolerant. Many treatments focus on suppressing the whole immune system, which poses risks to the patient. Another option could be the induction of immune tolerance to prevent immune attacks on the body itself while leaving the ability to attack foreign antigens intact. Induced tolerance is also important for the treatment of severe allergies and the management of transplant rejection.

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