Histology, Natural Killer Cells

Excerpt

Natural killer or NK cells are a sub-population of Large Granular Lymphocytes (LGLs) which 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 (SLTs) including tonsils, spleen, and Lymph nodes (LNs). 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. 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. In contrast, B and T lymphocytes in the adaptive arm, undergo gene rearrangement to generate surface receptors and mediate the antigen-specific immune responses .

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 TNF 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, GM-CSF 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, diabetes, etc.