Autoimmunity Immunological Tolerance

By Dr. Ananya Mandal, MDReviewed by Sally Robertson, B.Sc.

The term autoimmunity refers to a failure of the body’s immune system to recognize its own cells and tissues as “self.” Instead, immune responses are launched against these cells and tissues as if they were foreign or invading bodies.

Research conducted by Noel Rose and Witebsky in New York and Roitt and Doniach at University College London showed that diseases such as rheumatoid arthritis and thyrotoxicosis were linked to an inadequate immune tolerance and these conditions were caused by the body’s inability to fight “non-self” substances while also being able to ignore “self” substances.

This lack of immunological tolerance means the immune system mounts an attack against self determinants, through the production of antibodies. These reactive molecules are referred to as autoantibodies. How immunological tolerance develops is not yet understood, but three popular theories among immunologists are described below.

• The “Clonal Deletion theory,” suggests that self-reactive lymphoid cells are eliminated during immunological development. Pioneers Frank Burnet and Pete MedMedawar were awarded the 1960 Nobel Prize in Physiology or Medicine for proposing their research into acquired immunological tolerance.
• Proposed by Gustav Nossal, the “Clonal Anergy theory” suggests that reactive T- or B-cells become deactivated during development and fail to increase immune responses.
• The “Idiotype Network theory,” first described by Jerne, held that certain antibody networks could neutralize autoantibodies.

Further theories currently being investigated include the “Clonal Ignorance theory,” and the “Suppressor population or Regulatory T cell theory.” The “Clonal Ignorance theory” suggests that self-reactive T cells not present in the thymus move to the periphery where they fail to encounter target antigens. Self-reactive B cells then fail to find the correct helper T-cell or antigen. The “Suppressor population or Regulatory T cell theory,” holds that regulatory T-lymphocytes such as CD4+FoxP3+ cells prevent, down regulate or reduce aggressive immune responses to self tissues.

Further Reading

• All Autoimmunity Content
• What is Autoimmunity?
• Low-Level Autoimmunity
• Autoimmunity Genetic Factors
• Autoimmunity Sex