Browse the corpus

Natural killer or NK cells are a subpopulation of large granular lymphocytes that arise from a common NK/T-cell progenitor. Accumulating evidence indicates that NK cells can develop and mature both in the bone marrow and secondary lymphoid tissues including tonsils, spleen, and lymph nodes.[1] In the innate immune system, NK cells participate in early cytotoxic responses against viruses, parasites, microbial pathogens, as well as tumor immunosurveillance. Also, their protective and pathogenic roles have been more defined in the development of autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease.[2] NK cell's function is regulated by various activating or inhibitory receptors. These germ-line encoded immunoreceptors on the surface of NK cells sense nonspecific alterations of self-cells caused by cellular stress, infections, or malignant transformation.[3] In contrast, B and T lymphocytes in the adaptive arm, undergo gene rearrangement to generate surface receptors and mediate the antigen-specific immune responses.[4][5] While encountering normal cells, inhibitory receptors override activating receptors. However, molecular changes on the cell surface due to viral infection or tumor formation can stimulate the activating receptors. Upon activation, NK cells release granzyme, perforin, effector molecules of the tumor necrosis factor family, and Fas-ligand to induce apoptosis of the target cells. In addition, NK cells synthesize and release other cytokines and chemokines such as Il-10, gamma-interferon, and granulocyte-macrophage colony-stimulating factor, to recruit other immune effector cells to the target site. NK cells also exhibit antibody-dependent cell cytotoxicity against cells or target antigens which are marked with specific antibodies. Recently, therapeutic applications modulating the inhibition-activation dynamic of NK cells have been developed for multiple conditions including cancer, autoimmune disease, and diabetes.[6]

In addition to NK cell roles in defense against viral infections and tumor immunosurveillance, they have been linked to several other diseases including asthma [21], inflammatory bowel disease [22], and autoimmune diseases [23]. Advancements in understanding the pathophysiology of NK cells resulted in the development of new therapeutic options and treatments. For instance, NK cells are found in the pancreas of patients with diabetes type I, and they enhance the disease development. Reducing the NK cell activation using specific blocking antibodies will prevent further disease progression.[6]