Natural Killer Cells

Natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the function of the innate immune system. NK cells provide rapid responses to viral-infected cells, and respond to tumor formation. They are "natural killers" because they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because virus-infected or cancerous cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T cells. 

NK cells are large granular lymphocytes (LGL) and constitute the third kind of cell differentiated from the common lymphoid progenitor-generating B and T lymphocytes. NK cells differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus. NK cells do not express T-cell antigen receptors (TCR), the T Cell maker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans.

In addition to the knowledge that natural killer cells are effectors of innate immunity, recent research has uncovered information on both activating and inhibitory NK cell receptors that play important functional roles, including self-tolerance and the sustaining of NK cell activity. The role of NK cells in both the innate and adaptive immune responses is becoming increasingly important in research using NK cell activity as a potential cancer therapy.

NK cells are cytotoxic; small granules in their cytoplasm contain granzymes, proteins such as perforin and proteases. Upon release in close proximity to a targeted cell, perforin forms pores in the cell membrane of the cell, creating an aqueous channel through which the granzymes and associated molecules can enter, inducing either apoptosis or osmotic cell lysis. The distinction between apoptosis and cell lysis is important in immunology: lysing a virus-infected cell could potentially only release the virions, whereas apoptosis leads to destruction of the virus inside. α-defensins, antimicrobial molecules, are also secreted by NK cells, and directly kill bacteria by disrupting their cell walls.

Cytokines play a crucial role in NK cell activation. Cytokines are stress molecules released by cells upon viral infection, they signal to the NK cell the presence of viral pathogens in the affected area. Cytokines involved in NK activation include IL-12, IL-15, IL-18, IL-2, and CCL5. NK cells limit the spread of viral infections while the adaptive immune response generates antigen-specific cytotoxic T cells that can clear the infection. NK cells work to control viral infections by secreting IFNγ and TNFα. IFNγ activates macrophages for phagocytosis and lysis, and TNFα acts to promote direct NK tumor cell killing.

Human NK Cell Expansion Kit New!
Expands human CD3-CD56+ cytokine-induced killer (CIK) cell populations from PBMCs.

Resources for in vitro Differentiation and Expansion: