NK cells are important in recognising infected cells, and inducing ‘clean deaths’ by apoptosis. MHC I is a cell-surface protein expressed by all self-nucleated cells, and it inhibits the action of NK cells.
However, in some cancers, viral infections, and intracellular bacterial infections, MHC I expression may be downregulated or completely silenced. This silencing can be detected by NK cells, inducing them to secrete perforin.
Perforin is an enzyme that forms channels in the membrane of the target cell, in a similar way to the C9 membrane attack complex formed by the complement system. Through these channels, granzymes are inserted into the target cell. Granzymes induce apoptosis in the target cell, preventing the release of the contents.
Not releasing the contents of the target cell is an important step in the action of NK cells. If a virally-infected cell was lysed, it would release many virions capable of propagating the infection further. By inducing apoptosis, no viruses or toxins are released, helping to resolve the infection.
Cancerous cells can evade NK cells by not changing the expression of MHC I. As this is the only mechanism used to control the activity of NK cells, if it is present on the cell surface it will suppress killing. Due to the high mutation and division rate of cancerous cells, it is possible for a small number to develop this mutation and proliferate.