Molecular biology and immunology for clinicians 22: natural killer cell receptors and activation mechanisms

Natural killer (NK) cells (called "third population cells" many years ago because they did not bear surface markers of the first two defined populations, B cells and T cells) are now known to occupy a pivotal position in the immune system, straddling the "divide" between the innate and adaptive responses. Natural killer cells are capable of production of many cytokines, both pro- and anti-inflammatory, and induction of target cell death by lysis and/or programmed cell death (apoptosis). Some of these cytokines are pivotal in the autoimmune and antipathogenic immune responses, implicating NK cells in the pathogenesis of many human diseases. Multiple detection systems allow tight control of the potent effector systems that mediate NK cells' effects. Recent studies have shown that NK cell function is under tight control, with complex inhibitory and activating signaling assuring that these cells can accurately detect intracellular infection and malignant degeneration without damaging healthy cells. Although NK cell receptors do not have antigenic specificity, they do detect certain patterns on the surface of target cells. Their ability to make many cytokines that alter antigen-specific immune responses mediated by other cells puts NK cells in a unique position to influence both innate and adaptive responses.