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Clonal anergy
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==Mechanism== 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 ineffective at mounting immune responses. Later [[Ronald Schwartz]] and [[Marc Jenkins (immunologist)|Marc Jenkins]] described a similar process operating in the T lymphocyte. Many [[viruses]] ([[HIV]] being the most extreme example) seem to exploit the immune system's use of tolerance induction to evade the immune system, though the suppression of specific antigens is done by fewer pathogens (notably ''[[Mycobacterium leprae]]'').<ref name=Janeway>{{cite book | vauthors = Janeway Jr CA, Travers P, Walport M, Shlomchik M |author-link=Charles Janeway |title=Immunobiology | edition = Fifth |publisher=Garland Science |year = 2001 |location = New York and London |url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10 |isbn=0-8153-4101-6}}</ref> At the cellular level, "anergy" is 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 [[virus]]es, [[bacteria]] and [[parasite]]s. There are two major kinds of lymphocytes β 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 cells must be recruited and allowed to multiply rapidly. This process β called "clonal expansion" β allows the body to quickly mobilise an army of clones, as and when required. Such immune response is anticipatory and its specificity is assured by pre-existing clones of lymphocytes, which expand in response to specific [[antigen]] (process called "[[clonal selection]]"). This specific 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.<ref name=Janeway/> 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]] [[cellular signaling|signaling]] pathways.<ref name=Janeway/>
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