Editing Natural killer cell (section)

===Missing 'self' hypothesis===
[[File:Missing self.svg|thumb|right|400px| Schematic diagram indicating the complementary activities of [[cytotoxic T cells]] and NK cells]]
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 [[Receptor (biochemistry)|receptor]]s:  activating receptors and inhibitory receptors, including [[killer-cell immunoglobulin-like receptors]]. Most of these receptors are not unique to NK cells and can be present in some [[T cell]] subsets, as well.

The inhibitory receptors recognize [[MHC class I]] [[allele]]s, which could explain why NK cells preferentially kill cells that possess low levels of MHC class I molecules. This mode of NK cell target interaction is known as "missing-self recognition", a term coined by [[Klas Kärre]] and co-workers in the late 90s. MHC class I molecules are the main mechanism by which cells display viral or tumor antigens to cytotoxic T cells. A common evolutionary adaptation to this is seen in both intracellular [[microbes]] and tumors: the chronic down-regulation of MHC I molecules, which makes affected cells invisible to T cells, allowing them to evade T cell-mediated immunity. NK cells apparently evolved as an evolutionary response to this adaptation (the loss of the MHC eliminates CD4/CD8 action, so another immune cell evolved to fulfill the function).<ref name=Lodoen>{{cite journal | vauthors = Lodoen MB, Lanier LL | title = Viral modulation of NK cell immunity | journal = Nature Reviews. Microbiology | volume = 3 | issue = 1 | pages = 59–69 | date = January 2005 | pmid = 15608700 | doi = 10.1038/nrmicro1066 | s2cid = 16655783 }}</ref>