Anergy, within the realm of immunology, characterizes the absence of a response from the body's defense mechanisms when confronted with foreign substances.
Notably, anergy constitutes one of the essential processes fostering tolerance within the immune system, alongside clonal deletion and immunoregulation.
In the immune system, circulating cells called lymphocytes form a primary army that defends the body against pathogenic viruses, bacteria and parasites.
[2] B-cell anergy can be induced by exposure to soluble circulating antigen, and is often marked by a downregulation of surface IgM expression and partial blockade of intracellular signaling pathways.
[2] Understanding the molecular mechanism of anergy induction in T lymphocytes unveils the intricate interplay of signaling pathways governing immune responses.
Under such conditions, the calcium-dependent phosphatase calcineurin acts on the transcription factor NFAT, facilitating its translocation to the nucleus, where it regulates gene expression.
[5] NFAT homodimers play a direct role in the expression of anergy-associated genes, such as the ubiquitin ligase GRAIL and the protease caspase 3.
Tregs, characterized by the expression of the transcription factor Foxp3, exert immunosuppressive effects by inhibiting the activation and function of effector T cells.
[5] Importantly, Tregs can directly interact with anergic T cells, further reinforcing their state of unresponsiveness and promoting peripheral tolerance.
This interaction involves various mechanisms, including the secretion of inhibitory cytokines such as IL-10 and TGF-β, as well as cell-contact-dependent suppression mediated by molecules like CTLA-4.
Anergy may also be used to induce activated lymphocytes to become unresponsive with autoimmune diseases like diabetes mellitus, multiple sclerosis and rheumatoid arthritis.
The anergy in T cells can be induced by Ionomycin, the ionophore capable of raising intracellular concentration of calcium ions artificially.
Blocking of the pathway leading to the anergy can be also done by cyclosporin A, which is capable of inhibiting calcineurin – the phosphatase responsible for dephosphorylating of NFAT priming its activation.