Deficiency Causes of<unk>  deficiency include lymphocytopenia of<unk> s and/or defects on function of individual<unk> s. Complete insufficiency of<unk>  function can result from hereditary conditions such as severe combined immunodeficiency (SCID), Omenn syndrome, and cartilage–hair hypoplasia. Causes of partial insufficiencies of<unk>  function include acquired immune deficiency syndrome (AIDS), and hereditary conditions such as DiGeorge syndrome (DGS), chromosomal breakage syndromes (CBSs), and<unk>  and<unk>  combined disorders such as ataxia-telangiectasia (AT) and Wiskott–Aldrich syndrome (WAS). The main pathogens of concern in<unk>  deficiencies are intracellular pathogens, including Herpes simplex virus, Mycobacterium and Listeria. Also, fungal infections are also more common and severe in<unk>  deficiencies. Cancer Cancer of<unk> s is termed<unk>  lymphoma, and accounts for perhaps one in ten cases of non-Hodgkin lymphoma. The main forms of<unk>  lymphoma are: * Extranodal<unk>  lymphoma * Cutaneous<unk>  lymphomas: Sézary syndrome and Mycosis fungoides * Anaplastic large<unk>  lymphoma * Angioimmunoblastic<unk>  lymphoma Exhaustion<unk>  exhaustion is a poorly defined term that scholars do not necessarily mean the same thing. There are three different approaches to how it is defined. "The first approach primarily defines as exhausted the<unk> s that present the same<unk> ular dysfunction (typically, the absence of an expected effector response). The second approach primarily defines as exhausted the<unk> s that are produced by a given cause (typically, but not necessarily, chronic exposure to an antigen). Finally, the third approach primarily defines as exhausted the<unk> s that present the same molecular markers (typically, programmed<unk>  death protein 1 PD-1)." Dysfunctional<unk> s is characterized by progressive loss of function, changes in transcriptional profiles and sustained expression of inhibitory receptors. At first<unk> s lose their ability to produce IL-2 and TNFα followed by the loss of high proliferative capacity and cytotoxic potential, eventually leading to their deletion. Exhausted<unk> s typically indicate higher levels of CD43, CD69 and inhibitory receptors combined with lower expression of CD62L and CD127. Exhaustion can develop during chronic infections, sepsis and cancer. Exhausted<unk> s preserve their functional exhaustion even after repeated antigen exposure. During chronic infection and sepsis<unk>  exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4<unk>  help. Antigen exposure also has effect on the course of exhaustion because longer exposure time and higher viral load increases the severity of<unk>  exhaustion. At least 2–4 weeks exposure is needed to establish exhaustion. Another factor able to induce exhaustion are inhibitory receptors including programmed<unk>  death protein 1 (PD1), CTLA-4,<unk>  membrane protein-3 (TIM3), and lymphocyte activation gene 3 protein (LAG3). Soluble molecules such as cytokines IL-10 or TGF-β are also able to trigger exhaustion. Last known factors that can play a role in<unk>  exhaustion are regulatory<unk> s. Treg<unk> s can be a source of IL-10 and TGF-β and therefore they can play a role in<unk>  exhaustion. Furthermore,<unk>  exhaustion is reverted after depletion of Treg<unk> s and blockade of PD1.<unk>  exhaustion can also occur during sepsis as a result of cytokine storm. Later after the initial septic encounter anti-inflammatory cytokines and pro-apoptotic proteins take over to protect the body from damage. Sepsis also carries high antigen load and inflammation. In this stage of sepsis<unk>  exhaustion increases. Currently there are studies aiming to utilize inhibitory receptor blockades in treatment of sepsis. During transplantation While during infection<unk>  exhaustion can develop following persistent antigen exposure after graft transplant similar situation arises with alloantigen presence. It was shown that<unk>  response diminishes over time after kidney transplant. These data suggest<unk>  exhaustion plays an important role in tolerance of a graft mainly by depletion of alloreactive CD8<unk> s. Several studies showed positive effect of chronic infection on graft acceptance and its long-term survival mediated partly by<unk>  exhaustion. It was also shown that recipient<unk>  exhaustion provides sufficient conditions for NK<unk>  transfer. While there are data showing that induction of<unk>  exhaustion can be beneficial for transplantation it also carries disadvantages among which can be counted increased number of infections and the risk of tumor development. During cancer During cancer<unk>  exhaustion plays a role in tumor protection. According to research some cancer-associated<unk> s as well as tumor<unk> s themselves can actively induce<unk>  exhaustion at the site of tumor.<unk>  exhaustion can also play a role in cancer relapses as was shown on leukemia. Some studies have suggested that it is possible to predict relapse of leukemia based on expression of inhibitory receptors PD-1 and TIM-3 by<unk> s. Many experiments and clinical trials have focused on immune checkpoint blockers in cancer therapy, with some of these approved as valid therapies that are now in clinical use. Inhibitory receptors targeted by those medical procedures are vital in<unk>  exhaustion and blocking them can reverse these changes.
T cell
Dendritic cell
Natural killer cell
Mast cell
Reactive lymphocyte
Prolymphocyte
Cytokine-induced killer cell
Monocyte