NEWS & RESOURCES

Natural killer (NK) cells are lymphocytes of the innate immune system which are able to kill different targets such as cancer cells and virally infected cells without prior activation making then attractive candidates for cancer immunotherapy. Furthermore, its defence system has been extended into antimicrobial response, elimination of senescent cells, resolution of inflammation and induction of adaptive immune response. NK cells are defined as CD56+ and CD3-, which is naturally located in most of our organs and tissues, especially peripheral blood, skin, lymph nodes, bone marrow, thymus, liver, intestines, lungs, uterus etc. NK cells are classified into two distinct populations as based on surface density of CD56 expression, which are CD56bright and CD56dim NK cells and both of them have a unique functional characteristics. In brief, CD56bright NK cell represent a minimal (10%) population in the circulatory system and has low or no cytotoxic response; however this NK cell subset produces an array of cytokines and chemokines which influence the immune modulation and thus this cells are commonly referred as “cytokine producers”. On other side, CD56dim NK cell is predominant (90%) in circulatory system and is a potent mediator of natural and antibody dependent cytotoxicity. 

 Mechanism of Action
1. Paracrine Action



 
 
 






2. Recognition of the target cells
Natural killer (NK) cells can discriminate between infected and uninfected target cells and between some tumour and normal cells through sensing the appearance of MHC class I (major histocompatibility class I) molecules. Most of the nucleated normal cells express MHC class I molecules on their surface but the infected and most of the tumour cells do not express MHC class I molecules and thus the NK cell can distinguish the target cells from healthy & normal cells.   
                                                                              
3. Killing the target cell
NK cell Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell.
                                                                                    
The schematic representation shows how NK cells kill tumour cells. Normal cells are not killed because inhibitory signals from MHC class 1 molecules override the activating signals. In tumour cells or virus-infected cells, reduced expression or alteration of MHC molecules interrupts the inhibitory signals, allowing activation of NK cells and lysis of target cells. Cytokines are small cell-signalling protein molecules secreted by the immune cells to kill the cancer cells. These cytokines enter the cancer cells, disrupt their functions and eventually lysing them. Later, these dead cells are flushed out of our body through the detoxification system.
 
4. Migration towards target
Chemokines are chemotactic cytokines that control the migratory patterns and positioning of NK cells. NK cells can respond to a large array of chemokines and can be recruited to different points of the body and to sites of inflammation. Cytolytic CD56dim CD16bright NK cell subset expresses CXCR1, CX3CR1 and ChemR23 chemokine receptors; therefore, it is mainly recruited to inflamed peripheral tissues. Whereas, CD56bright CD16neg/dim NK cells preferentially express CCR7 and are primarily attracted by secondary lymphoid organs (lymph nodes, tonsils and spleen). These cells are highly express CD62L (L-selectin) which provides important adhesion to endothelial surfaces required for extravasation of CD56bright NK cells.