Anergy

Anergy is a theory in immunobiology that describes a lack of reaction by the body's defence mechanisms to foreign substances, and consists of a direct induction of peripheral lymphocyte tolerance. A state of anergy often indicates that the immune system is unable to mount a normal immune response against a specific antigen, usually a self-antigen.

This phenomenon was first described in B lymphocytes by Gustav Nossal and termed "Clonal Anergy." The clones of B lymphocytes in this case can still be found alive in the circulation, but are very ineffective at mounting immune responses. Later Ronald Schwartz and Marc Jenkins described a similar process operating in the T lymphocyte. It is interesting to note that many viruses (notably HIV) seem to exploit this phenomenon to evade the immune system.

At the cellular level, the term "anergy" defines the inability of an immune cell to mount a complete response against its target. In the immune system, circulating cells called lymphocytes form a primary army that defends the body against pathogenic viruses, bacteria and parasites. There are two major kinds of lymphocytes - the T lymphocyte and the B lymphocyte. Among the millions of lymphocytes in the human body, only a few actually are specific for any particular infectious agent. At the time of infection, these few cell must be recruited and allowed to multiply rapidly. This process - called "clonal expansion" - allows the body to quickly mobilise an army of clones, as and when required. This clonal army then combats the pathogen until the body is free of the infection. Following clearance of the infection, the clones that are no longer needed die away naturally.

However, a small number of the body's army of lymphocytes are able to react with proteins that are normally present in a healthy body. The clonal expansion of those cells can lead to autoimmune diseases, wherein the body attacks itself. In order to prevent this process, lymphocytes possess an intrinsic quality-control mechanism. This machinery shuts down the lymphocytes' ability to expand, if the trigger for the expansion turns out to be the body's own protein. T-cell anergy can arise when the T-cell does not receive appropriate co-stimulation in the presence of specific antigen recognition. 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.