Maison » Natural Killer (NK) Cell Cytotoxicity

Natural Killer (NK) Cell Cytotoxicity

1975
  • Rolf Kiessling
  • Eva Klein
  • Hans Wigzell
Natural Killer cells in a laboratory setting, examining cytotoxicity mechanisms.

Natural Killer (NK) cells are cytotoxic lymphocytes of the innate immune system, critical for early defense against viral infections and cancer. Unlike T cells, they do not require prior sensitization. NK cells identify and kill target cells that have downregulated MHC class I molecules—a common immune evasion tactic by tumors and viruses—through a “missing-self” recognition mechanism, inducing apoptosis via perforin and granzymes.

Natural Killer (NK) cells provide a rapid, first-line defense against cellular threats. Their function is governed by a balance of signals from activating and inhibitory receptors on their surface. Healthy cells express MHC class I molecules, which are recognized by inhibitory receptors on NK cells (like KIRs and NKG2A). This interaction sends a strong “don’t kill me” signal, preventing the NK cell from attacking. This is known as “missing-self” recognition: the absence of the ‘self’ MHC class I signal is what triggers the attack.

When a cell becomes cancerous or is infected by certain viruses, it often reduces the expression of MHC class I molecules to evade detection by cytotoxic T cells. This, however, makes it a prime target for NK cells. The lack of an inhibitory signal, often coupled with the presence of stress-induced ligands recognized by activating NK cell receptors (like NKG2D), tips the balance towards activation. Once activated, the NK cell’s cytotoxic mechanism is very similar to that of a CTL. It releases perforin and granzymes to induce apoptosis in the target cell. NK cells can also induce cell death through other pathways, such as the Fas/FasL interaction, and are key players in antibody-dependent cell-mediated cytotoxicity (ADCC), where they kill target cells coated with antibodies.

UNESCO Nomenclature: 2415
– Immunology

Type

Biological Mechanism

Disruption

Substantial

Utilisation

Widespread Use

Precursors

  • distinction between innate and adaptive immunity
  • identification of lymphocytes as key immune cells
  • discovery of interferons and their role in antiviral defense
  • development of in vitro cell killing assays
  • understanding of tumor immune evasion mechanisms

Applications

  • NK cell-based cancer immunotherapies
  • therapies for viral infections
  • monitoring immune status in patients
  • understanding pregnancy immunology (NK cells are abundant in the uterus)
  • development of antibody-dependent cell-mediated cytotoxicity (ADCC) drugs

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Related to: natural killer cell, NK cell, innate immunity, missing-self recognition, MHC class I, immunology, cancer surveillance, perforin, granzyme, ADCC.

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