Why in the news?

• Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi have won the Nobel Prize in medicine for their discoveries concerning peripheral immune tolerance.

Peripheral Immune Tolerance

• What is it?: Peripheral immune tolerance refers to the mechanisms that prevent immune cells (especially T and B lymphocytes) from attacking the body’s own tissues after they have matured and left the thymus or bone marrow.
• Where does it occur: Occurs in peripheral lymphoid organs such as lymph nodes, spleen, mucosal tissues, and throughout the bloodstream.
• Mechanism:
  • Anergy (Functional Inactivation): Self-reactive lymphocytes become inactive when they recognize self-antigens without co-stimulatory signals (e.g., absence of CD28-B7 interaction).
  • Suppression by Regulatory T Cells (Tregs): CD4⁺CD25⁺FOXP3⁺ Tregs secrete IL-10 and TGF-β, suppressing self-reactive immune responses.
  • Deletion (Apoptosis): Self-reactive T or B cells undergo programmed cell death when repeatedly stimulated by self-antigens.
  • Immune Privilege: Certain sites (e.g., eye, brain, testis, placenta) are naturally shielded from immune attack — antigens here induce tolerance rather than response.
• Importance:
  • Prevents autoimmune diseases such as Type-1 Diabetes, Rheumatoid Arthritis, and Multiple Sclerosis.
  • Maintains immune homeostasis and self-tissue protection.
  • Ensures tolerance to commensal microbes and dietary antigens in mucosal surfaces.
• Failure Leads to:
  • Leads to autoimmune disorders, chronic inflammation, and transplant rejection.
  • Can be caused by genetic mutations