NK cells ( natural killer cells ) belong to the lymphocytes (subgroup of white blood cells or leukocytes ). They are able to recognize and kill abnormal cells such as tumor cells and virus-infected cells. NK cells have no antigen- specific receptors and are part of the innate immune system . Healthy people have a proportion of 5–15% NK cells in peripheral mononuclear blood cells.
The development of cells
Like the other lymphocytes, NK cells develop from lymphatic precursor cells in the bone marrow and later circulate in the bloodstream. They are larger than T lymphocytes and B lymphocytes . The target structures of an NK cell are virus-infected cells and cancer cells, which it recognizes via unchangeably encoded receptors.
The CD56 receptor is an important marker for NK cells. NK cells in the blood are defined as CD3-CD56 +. NK cells that express high levels of CD56 (CD56bright) are more likely to produce cytokines, while NK cells that express little CD56 are more likely to exert cytotoxic functions.
NK cells differentiate tumor cells and cells infected by intracellular microorganisms of normal, endogenous cells by means of specific receptors (. U. A KIR-molecules , NKG2 with CD94 and natural cytotoxic receptors ) associated with MHC class I molecules on the Surface of the target cells interact. Tumor and infected cells are normally recognized and eliminated by the cytotoxic T lymphocytes on the basis of foreign antigens that they present in complex with the MHC-I molecules on their surface. Some viruses are able to suppress the presentation of MHC-I molecules on the surface of their host cells and thus avoid being destroyed by T lymphocytes. The decreased expression of MHC molecules on tumor cells and infected by microorganisms cells will now be recognized by NK-cells and leads to apoptosis of the target cell, a principle that by the Swedish immunologists Klas Kärre was postulated and as the missing-self hypothesis is referred to .
NK cells seem to play an important role at the interface between innate and acquired immunity : apparently the interaction between natural killer cells and dendritic cells leads to a selection of antigen-presenting cells and thus promotes the modeling of the acquired immune response.
Knowledge from the laboratory
NK cells do not need to be activated, but their activity can be increased by interleukins ( IL-2, IL-12 ) or interferons such as IFN-α and IFN-β, which are secreted by macrophages . After increasing their activity, they can produce large amounts of IFN-γ, which is relevant for the containment of various infections. They can destroy cells with cytotoxic granules released on the surface of the hostile cell and cause them to die through apoptosis . The activity of the NK cells can be determined in the laboratory using an in vitro analysis (NK cell activity analysis). Recently there was a report on the use of special bioreactors in which NK cells can be generated in high yield and purity. The NK cells produced in this way under GMP conditions showed a high degree of cytotoxicity against tumor cells in vitro .
theory and practice
For a long time it was not exactly clear how NK cells without inhibitory receptors produce self-tolerance. A model to explain this was provided by work that showed that in addition to NK cell maturation, there is a process known as “ licensing ”. In this case, NK cells which do not express inhibitory MHC class I receptors that match the organism would either not be activated presystemically ( arming model ) or the last activation step would be prevented ( disarming model ).
- Charles A. Janeway Jr. u. a .: immunology. 5th edition, Spektrum Akademischer Verlag, Heidelberg / Berlin 2002, ISBN 3-8274-1078-9 .
- Hans-Gustaf Ljunggren, Klas Kärre: In search of the 'missing self': MHC molecules and NK cell recognition . In: Immunology Today . tape 11 , 1990, pp. 237-244 , doi : 10.1016 / 0167-5699 (90) 90097-S , PMID 2201309 .
- The weapons of the immune system: how killer cells differentiate between endogenous and exogenous Carsten Watzl, University of Heidelberg
- ^ Maren Claus, Johann Greil, Carsten Watzl: Comprehensive analysis of NK cell function in whole blood samples . In: Journal of Immunological Methods . tape 341 , no. 1-2 , p. 154–164 , doi : 10.1016 / j.jim.2008.11.006 ( elsevier.com [accessed July 27, 2017]).
- ↑ Megan A Cooper, Todd A Fehniger, Michael A Caligiuri: The biology of human natural killer-cell subsets . In: Trends in Immunology . tape 22 , no. 11 , p. 633-640 , doi : 10.1016 / s1471-4906 (01) 02060-9 .
- ↑ F. Brilot, T. Strowig, C. Munz: NK cells interactions with dendritic cells shape innate and adaptive immunity. In: Frontiers in bioscience: a journal and virtual library. Volume 13, 2008, pp. 6443-6454, ISSN 1093-4715 . PMID 18508671 . (Review).
- ↑ A. Moretta, E. Marcenaro et al. a .: NK cells at the interface between innate and adaptive immunity. In: Cell death and differentiation. Volume 15, Number 2, February 2008, pp. 226-233, ISSN 1350-9047 . doi: 10.1038 / sj.cdd.4402170 . PMID 17541426 . (Review).
- ↑ A. Reschner, P. Hubert u. a .: Innate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response. In: Clinical and Experimental Immunology. Volume 152, Number 2, May 2008, pp. 219-226, ISSN 1365-2249 . doi: 10.1111 / j.1365-2249.2008.03624.x . PMID 18336590 . PMC 2384094 (free full text). (Review).
- ↑ Xavier Michelet, Lydia Dyck et al. a .: Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. In: Nature Immunology. 19, 2018, p. 1330, doi : 10.1038 / s41590-018-0251-7 .
- ↑ Bröker K, Sinelnikov E, Gustavus D, Schumacher U, Pörtner R, Hoffmeister H, Lüth S, Dammermann W: Mass Production of Highly Active NK Cells for Cancer Immunotherapy in a GMP Conform Perfusion Bioreactor. , Front Bioeng Biotechnol. 2019 Aug 13; 7: 194, PMID 31457007
- ↑ Sungjin Kim et al .: Licensing of natural killer cells by host major histocompatibility complex class I molecules . In: Nature . tape 436 , no. 7051 , August 4, 2005, p. 709-713 , doi : 10.1038 / nature03847 .