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Natural killer cell
Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis.
NK-cells are defined as large granular lymphocytes that do not express T-cell antigen receptors (TCR) or Pan T marker CD3 or surface immunoglobulins (Ig) B cell receptor but that usually express the surface markers CD16 (FcγRIII) and CD56 in humans, and NK1.1/NK1.2 in certain strains of mice.
They were named "natural killers" because of the initial notion that they do not require activation in order to kill cells that are "missing self" markers of major histocompatibility complex (MHC) class I. However, it is now known that the cells are activated.
Given their strong cytolytic activity and the potential for auto-reactivity, Natural Killer cell activity is tightly regulated. Natural Killer cells must receive an activating signal, which can come in a variety of forms, the most important of which are listed below.
NK cells are cytotoxic; small granules in their cytoplasm contain proteins such as perforin and proteases known as granzymes. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis. The distinction between apoptosis and cell lysis is important in immunology: lysing a virus-infected cell would only release the virions, whereas apoptosis leads to destruction of the virus inside.
NK cells are activated in response to interferons or macrophage-derived cytokines. They serve to contain viral infections while the adaptive immune response is generating antigen-specific cytotoxic T cells that can clear the infection. Patients deficient in NK cells prove to be highly susceptible to early phases of herpes virus infection.
In order for NK cells to defend the body against viruses and other pathogens, they require mechanisms that enable the determination of whether a cell is infected or not. The exact mechanisms remain the subject of current investigation, but recognition of an "altered self" state is thought to be involved. To control their cytotoxic activity, NK cells possess two types of surface receptors: activating receptors and inhibitory receptors. Most of these receptors are not unique to NK cells and can be present in other T cell subsets as well.
NK cell receptor types (with inhibitory as well as some activating members) are differentiated by structure:
History and discovery
The discovery of NK cells occurred in the early 1970s during research on the well-characterized ability of T-lymphocytes to lyse tumor cells against which they had been previously immunized. During these experiments, investigators consistently observed what was termed a natural reactivity, that is, a certain population of cells seemed to be able to lyse tumor cells without having been previously sensitized to them. As these discoveries were incompatible with established model at the time, many of these observations were initially considered artifacts.
However, by 1973, 'natural killing' activity was established across a wide variety of species, and the existence of a separate lineage of cells possessing this ability was postulated. Through the use of monoclonal antibodies, natural killing ability was mapped to the subset of large, granular lymphocytes known today as NK-cells.
The cells were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self" recognition ("missing-self" recognition is a term used to describe cells with low levels of MHC class I cell surface marker molecules — a situation that could arise due to viral infection, or in tumors under strong selection pressure of killer T cells).
With the discovery of activating receptors almost two decades after the discovery of the inhibitory receptors these cells continue to be called by the same name, though “natural” no longer means the same thing. The term “natural killer” continues to be justified by:
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Natural_killer_cell". A list of authors is available in Wikipedia.|