Central tolerance

Definition

Central tolerance is a crucial mechanism in the immune system that helps prevent the body from attacking its own tissues by eliminating self-reactive immune cells during their development in the thymus and bone marrow. This process ensures that T cells and B cells that recognize self-antigens are either destroyed or rendered inactive, maintaining immune system balance and preventing autoimmune diseases. Understanding central tolerance is essential for grasping how adaptive immunity protects the body while also guarding against harmful autoimmunity.

5 Must Know Facts For Your Next Test

1. Central tolerance primarily occurs in the thymus for T cells and in the bone marrow for B cells, where self-reactive cells are identified and eliminated.
2. The efficiency of central tolerance is vital for preventing autoimmune diseases, as failure in this process can lead to conditions like lupus or rheumatoid arthritis.
3. Not all self-reactive immune cells are eliminated during central tolerance; some may persist but are rendered non-functional through other mechanisms.
4. Both positive and negative selection processes are involved in shaping the repertoire of T cells, with negative selection being key to establishing central tolerance.
5. Research into central tolerance has implications for therapies aimed at modulating immune responses, including treatments for autoimmune diseases and cancer immunotherapy.

Review Questions

• How does central tolerance differ from peripheral tolerance in terms of mechanisms and locations within the immune system?
  • Central tolerance occurs during the development of T and B cells primarily in the thymus and bone marrow, where self-reactive cells are eliminated through negative selection. In contrast, peripheral tolerance takes place outside these primary lymphoid organs, involving mechanisms that prevent activation of any self-reactive cells that may escape central tolerance. Peripheral tolerance can involve regulatory T cells and other suppressive signals to ensure that self-reactive immune cells do not cause harm in the body.
• What role does negative selection play in central tolerance, and why is it essential for maintaining a healthy immune system?
  • Negative selection is a critical process within central tolerance that eliminates T cells with high affinity for self-antigens during their maturation. This ensures that potentially harmful self-reactive T cells do not enter circulation and trigger autoimmune responses. By effectively reducing the number of self-reactive immune cells, negative selection helps maintain immune homeostasis and protects against autoimmune diseases, allowing the body to respond appropriately to foreign pathogens without attacking its own tissues.
• Evaluate how failures in central tolerance can lead to autoimmune diseases and discuss potential therapeutic strategies to address these failures.
  • Failures in central tolerance can result from genetic predispositions or environmental factors that lead to the survival of self-reactive immune cells. When these cells escape elimination, they can initiate an autoimmune response, attacking healthy tissues and resulting in diseases such as type 1 diabetes or multiple sclerosis. Therapeutic strategies may include enhancing central tolerance through gene therapy or using regulatory T cell therapies to re-establish proper immune regulation. Such approaches aim to restore balance within the immune system, reducing the incidence of autoimmunity while maintaining effective defenses against infections.

Related terms

negative selection: The process by which developing T cells that strongly recognize self-antigens are induced to undergo apoptosis, preventing them from entering circulation.

autoimmunity:

A condition in which the immune system mistakenly attacks the body's own cells and tissues, often due to a breakdown in tolerance mechanisms.

peripheral tolerance: A secondary mechanism of tolerance that occurs outside of the thymus and bone marrow, helping to prevent self-reactive immune cells from becoming activated in the peripheral tissues.