Negative selection

Definition

Negative selection is a critical process in the development of T cells, specifically in the thymus, that eliminates those cells which recognize self-antigens too strongly. This mechanism ensures that only T cells that are moderately responsive to foreign antigens are allowed to mature and enter the peripheral immune system. By removing self-reactive T cells, negative selection plays a vital role in preventing autoimmune diseases and maintaining immune tolerance.

5 Must Know Facts For Your Next Test

1. Negative selection primarily occurs in the thymus during T cell maturation, where thymocytes encounter self-antigens presented by thymic epithelial cells.
2. T cells that bind too strongly to self-antigens undergo apoptosis, effectively reducing the risk of autoimmune reactions.
3. This process is crucial for establishing central tolerance, which helps the immune system distinguish between self and non-self.
4. Failure of negative selection can lead to the development of autoimmunity, where self-reactive T cells enter circulation and attack the body’s own tissues.
5. Negative selection is complemented by positive selection, ensuring that only T cells with appropriate affinity for self-MHC molecules are allowed to mature.

Review Questions

• How does negative selection contribute to immune tolerance and the prevention of autoimmune diseases?
  • Negative selection is essential for establishing immune tolerance as it eliminates T cells that react too strongly to self-antigens. By inducing apoptosis in self-reactive thymocytes, negative selection prevents these potentially harmful cells from entering the peripheral immune system. This mechanism significantly reduces the risk of autoimmune diseases, as it ensures that mature T cells are less likely to target the body's own tissues.
• Compare and contrast negative selection and positive selection in the context of T cell maturation.
  • Negative selection and positive selection are two distinct processes critical for T cell maturation. Positive selection occurs first, where thymocytes that can recognize self-MHC molecules are selected for survival. In contrast, negative selection follows, eliminating those T cells that bind too strongly to self-antigens. Together, these processes ensure that only functional and self-tolerant T cells are released into the immune system.
• Evaluate the implications of a defect in negative selection on the overall function of the immune system.
  • A defect in negative selection can have serious implications for immune system function, leading to a higher likelihood of autoimmune diseases. If self-reactive T cells are not adequately eliminated during their development in the thymus, they can circulate throughout the body and initiate inappropriate immune responses against healthy tissues. This breakdown in tolerance not only compromises individual health but also illustrates how tightly regulated processes are necessary for maintaining a balanced and effective immune response.

Related terms

Thymocyte: An immature T cell that is developing in the thymus and undergoes various selection processes before becoming a functional T cell.

Autoimmunity: A condition in which the immune system mistakenly attacks the body's own tissues, often due to a failure in negative selection.

Positive Selection:

The process by which T cells that can recognize self-MHC molecules with a low affinity are selected for survival, allowing them to mature.