Anergy

Anergy

Anergy is a term used in immunology to describe a state of immune unresponsiveness. It occurs when the immune system fails to respond to an antigen that would normally elicit an immune response. This phenomenon is crucial in maintaining self-tolerance and preventing autoimmune diseases.

Mechanism of Anergy

Anergy can occur in both T cells and B cells, the primary cells involved in the adaptive immune response. The mechanisms leading to anergy differ between these cell types.

T Cell Anergy

T cell anergy is typically induced when a T cell receptor (TCR) engages with an antigen presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs) without the necessary second signal, known as co-stimulation. The primary co-stimulatory signal is provided by the interaction between CD28 on T cells and B7 molecules on APCs. In the absence of this co-stimulation, the T cell becomes anergic.

Once anergic, T cells exhibit a reduced ability to proliferate and produce cytokines upon subsequent encounters with the antigen, even if co-stimulation is provided. This state is maintained by various intracellular signaling pathways, including the upregulation of inhibitory receptors such as CTLA-4 and PD-1.

B Cell Anergy

B cell anergy occurs when B cells encounter soluble antigens without T cell help. This can lead to a state where the B cell is unable to mount an effective response upon subsequent antigen exposure. Anergic B cells often have reduced surface expression of the B cell receptor (BCR) and altered signaling pathways that prevent activation.

Role in Immune Tolerance

Anergy plays a critical role in maintaining immune tolerance, particularly peripheral tolerance. It helps prevent the activation of self-reactive lymphocytes that escape central tolerance mechanisms in the thymus and bone marrow. By rendering these cells anergic, the immune system minimizes the risk of autoimmune disease.

Clinical Implications

Understanding anergy has significant implications for autoimmunity, transplantation, and cancer immunotherapy.

• Autoimmunity: Defects in anergy induction can lead to the activation of self-reactive lymphocytes, contributing to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.

• Transplantation: Inducing anergy in T cells specific to donor antigens is a potential strategy to promote graft tolerance and reduce the need for long-term immunosuppression.

• Cancer Immunotherapy: Tumors can exploit anergy mechanisms to evade immune detection. Strategies to reverse T cell anergy, such as checkpoint inhibitors, are being developed to enhance anti-tumor immunity.

Research and Future Directions

Ongoing research aims to better understand the molecular pathways involved in anergy and how they can be manipulated for therapeutic benefit. Advances in this field could lead to novel treatments for autoimmune diseases, improved outcomes in transplantation, and more effective cancer immunotherapies.

See Also

• Immune tolerance
• Autoimmune disease
• Immunotherapy

External Links

• National Center for Biotechnology Information
• World Health Organization