Natural killer (NK) cell

NK cells are large granular lymphocytes, ≈ 5–15% of blood lymphocytes, that develop in the bone marrow under the control of IL-15. They lack rearranged antigen receptors and are therefore part of innate immunity (classified as group 1 innate lymphoid cells), yet they share cytotoxic machinery with CD8 T cells. Most blood NK cells are CD56^dim CD16⁺ and highly cytotoxic; a minority (CD56^bright), enriched in lymph nodes, mainly secrete cytokines.

NK-cell activity is set by a balance of signals. Activating receptors such as NKG2D detect stress-induced ligands (MICA/MICB) on infected or transformed cells; inhibitory receptors — killer-cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A — recognise MHC class I on healthy cells. Viruses and tumours often down-regulate MHC I to escape CD8 T cells, which removes NK inhibition — the "missing-self" hypothesis. NK cells also kill antibody-coated targets through CD16 (FcγRIIIa) — antibody-dependent cell-mediated cytotoxicity (ADCC).

Killing is by directed release of perforin and granzymes, inducing apoptosis of the target, and through death-receptor ligands (FasL, TRAIL). NK cells also secrete IFN-γ, activating macrophages and steering T cells towards Th1. They are activated by IL-12, IL-15, IL-18 and type I interferons, and peak in number early in viral infections, before the T-cell response. Specialised uterine NK cells help remodel the spiral arteries in pregnancy.