Negative Selection

Definition

Negative selection is a critical process in the immune system where developing immune cells that strongly recognize self-antigens are eliminated to prevent autoimmunity. This mechanism ensures that only those cells with the appropriate affinity for foreign antigens and tolerance to self-antigens survive, maintaining the body's immune balance and preventing harmful responses.

5 Must Know Facts For Your Next Test

1. Negative selection occurs primarily in the thymus for T cells and in the bone marrow for B cells, ensuring self-tolerance before these cells enter circulation.
2. During negative selection, T cells that bind too strongly to self-antigens undergo apoptosis, while those with moderate or weak binding can proceed to mature.
3. B cells also undergo a similar process in the bone marrow, where those that recognize self-antigens are either deleted or undergo receptor editing.
4. The efficiency of negative selection is crucial for preventing autoimmune diseases, as it reduces the likelihood of autoreactive lymphocytes being activated.
5. Defects in negative selection can lead to the survival of autoreactive T or B cells, contributing to autoimmune disorders such as rheumatoid arthritis or lupus.

Review Questions

• How does negative selection contribute to the development of a functional and self-tolerant T cell repertoire?
  • Negative selection plays a vital role in shaping a functional T cell repertoire by removing those T cells that react too strongly with self-antigens. This process occurs in the thymus where T cells are presented with various self-antigens. Only T cells that show weak or no reactivity are allowed to mature and enter circulation. By eliminating potentially harmful autoreactive cells, negative selection ensures that the majority of T cells are capable of responding effectively to foreign pathogens without attacking the body's own tissues.
• In what ways does negative selection differ between T cell and B cell development regarding their respective environments?
  • Negative selection for T cells occurs in the thymus, where they interact with thymic epithelial cells presenting self-antigens. If T cells bind too strongly, they undergo apoptosis. In contrast, B cell negative selection takes place in the bone marrow and involves interactions with bone marrow stromal cells. B cells that bind self-antigens can either be deleted or undergo receptor editing to alter their specificity. This difference highlights how each cell type adapts its selection process to its unique developmental environment while achieving self-tolerance.
• Evaluate the potential consequences of impaired negative selection on the immune system's ability to distinguish between self and non-self antigens.
  • Impaired negative selection can have significant consequences for an individual's immune system, primarily leading to the survival of autoreactive lymphocytes. When this mechanism fails, it can result in autoimmune diseases where the immune system mistakenly targets and attacks the body's own tissues. Conditions such as multiple sclerosis and type 1 diabetes exemplify how a lack of proper negative selection allows harmful immune responses against self-antigens. Additionally, understanding these implications provides insights into potential therapeutic strategies aimed at restoring tolerance and preventing autoimmunity.

Related terms

Central Tolerance:

The process by which developing T and B cells are screened in primary lymphoid organs to eliminate those that strongly bind to self-antigens.

Thymus:

A primary lymphoid organ where T cells mature and undergo selection processes, including negative selection, to ensure self-tolerance.

Autoimmunity:

A condition in which the immune system mistakenly attacks the body's own tissues due to a failure in tolerance mechanisms.