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Medicine Nobel for scientists who demystified the immune system

Why in News

  • The 2025 Nobel Prize in Physiology or Medicine was awarded to Shimon Sakaguchi (Japan), Mary Brunkow, and Fred Ramsdell (USA).
  • Recognition is for discoveries related to the human immune system, particularly regulatory T cells (Tregs) and peripheral immune tolerance.
  • Significance: Findings have paved the way for novel therapies in cancer, autoimmune diseases, and organ transplantation.

Relevance

  • GS-3 (Science & Technology):
    • Advances in immunology and biotechnology
    • Implications for healthcare, personalized medicine, and public health
  • GS-2/3 (Ethics & Innovation):
    • Research ethics, translational research, and equitable access to advanced therapies

Human Immune System

  • Components:
    • B cells: Produce antibodies to neutralize pathogens.
    • T cells: Mediate cellular immunity; can kill infected cells or regulate immune response.
    • Neutrophils & Macrophages: Innate immune cells; engulf pathogens.
  • Function: Identify and eliminate foreign antigens while maintaining tolerance to self-cells.
  • Tolerance: Prevents immune system from attacking body’s own tissues. Two types:
    • Central tolerance: Elimination of self-reactive T cells in thymus.
    • Peripheral tolerance: Mechanisms outside the thymus, ensuring immune cells do not attack self-cells in circulation.

Key Discoveries by the Laureates

  1. Shimon Sakaguchi (1995):
    1. Identified a previously unknown class of regulatory T cells (Tregs) in mice.
    2. Showed these cells suppress autoimmunity by controlling other T cells.
    3. Introduced the concept of peripheral immune tolerance beyond central tolerance.
  2. Mary Brunkow & Fred Ramsdell (2001):
    1. Discovered that mutations in the Foxp3 gene cause severe autoimmune disease (IPEX syndrome) in humans.
    2. Demonstrated the mechanistic link between Foxp3 and Tregs, establishing Tregs as the immune system’s “security guards.”

Mechanism of Peripheral Immune Tolerance

  • Regulatory T Cells (Tregs):
    • Express Foxp3 gene.
    • Monitor and regulate other immune cells to prevent self-reactivity.
    • Deficiency or mutation leads to autoimmune disorders, where the body attacks its own tissues.
  • Impact on Disease:
    • Cancer: Manipulating Tregs can boost anti-tumor immunity.
    • Autoimmune Diseases: Treg-targeted therapies reduce abnormal immune attacks (e.g., Type 1 diabetes, IPEX).
    • Transplantation: Enhances graft acceptance by controlling immune rejection.

Clinical & Research Significance

  • Peripheral Tolerance: Launched a new field of research.
  • Medical Applications:
    • Novel immunotherapies for cancer (checkpoint inhibitors, CAR-T).
    • Treatments for autoimmune diseases (immune modulation via Tregs).
    • Organ transplantation: Reduces rejection risk.
  • Ongoing Research: Several therapies targeting Tregs are in clinical trials.

Broader Scientific Context

  • Previously, immune tolerance was thought to occur only through central tolerance (elimination in thymus).
  • Discoveries reveal multi-layered immune regulation, highlighting:
    • Complexity of immune system
    • Need for balance between immunity against pathogens and self-tolerance
  • Showcases how basic research can translate into therapeutic breakthroughs.

Numbers & Facts

  • Foxp3 mutations: Cause IPEX syndrome, a rare but life-threatening autoimmune disorder.
  • Treg discovery timeline:
    • 1995: Sakaguchi identifies Tregs in mice
    • 2001: Brunkow & Ramsdell link Foxp3 mutations to autoimmune disease
  • Clinical trials: Multiple Treg-based therapies underway globally for autoimmunity, cancer, and transplantation.

October 2025
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