The immune system must be able to discriminate between self and non-self. When self/non-self discrimination fails, the immune system destroys cells and tissues of the body and as a result causes autoimmune diseases.<unk> s actively suppress activation of the immune system and prevent pathological self-reactivity, i.e. autoimmune disease. The critical role<unk> s play within the immune system is evidenced by the severe autoimmune syndrome that results from a genetic deficiency in<unk> s (IPEX syndrome – see also below). Diagram of<unk> , effector<unk> s and dendritic cell showing putative mechanisms of suppression by<unk> s. The molecular mechanism by which<unk> s exert their suppressor/regulatory activity has not been definitively characterized and is the subject of intense research. In vitro experiments have given mixed results regarding the requirement of cell-to-cell contact with the cell being suppressed. The following represent some of the proposed mechanisms of immune suppression: *<unk> s produce a number of inhibitory cytokines. These include TGF-β, Interleukin 35, and Interleukin 10. It also appears that<unk> s can induce other cell types to express interleukin-10. *<unk> s can produce Granzyme B, which in turn can induce apoptosis of effector cells.<unk> s from Granzyme B deficient mice are reported to be less effective suppressors of the activation of effector<unk> s. * Reverse signalling through direct interaction with dendritic cells and the induction of immunosuppressive indoleamine 2,3-dioxygenase. * Signalling through the ectoenzymes CD39 and CD73 with the production of immunosuppressive adenosine. * Through direct interactions with dendritic cells by LAG3 and by TIGIT. This review of<unk>  interactions with dendritic cells provides distinction between mechanisms described for human cells versus mouse cells. * Another control mechanism is through the IL-2 feedback loop. Antigen-activated<unk> s produce IL-2 which then acts on IL-2 receptors on<unk> s alerting them to the fact that high<unk>  activity is occurring in the region, and they mount a suppressory response against them. This is a negative feedback loop to ensure that overreaction is not occurring. If an actual infection is present other inflammatory factors downregulate the suppression. Disruption of the loop leads to hyperreactivity, regulation can modify the strength of the immune response. A related suggestion with regard to interleukin 2 is that activated<unk> s take up interleukin 2 so avidly that they deprive effector<unk> s of sufficient to avoid apoptosis. * A major mechanism of suppression by<unk> s is through the prevention of co-stimulation through CD28 on effector<unk> s by the action of the molecule CTLA-4.
Regulatory T cell
Regulatory B cell
Cytokine-induced killer cell
Natural killer T cell
Memory B cell
Naive T cell
Nonspecific immune cell
Natural killer cell