Editing Natural killer cell (section)

{{Short description|Type of cytotoxic lymphocyte}}
{{Distinguish|Natural killer T cell}}
{{Infobox cell|Name=Natural killer cell|Image=Human Natural Killer Cell (29120480442).jpg|Caption=Human natural killer cell, colorized scanning electron micrograph|System=[[Immune system]]|Function=Cytotoxic [[lymphocyte]]}}

'''Natural killer cells''', also known as '''NK cells''', are a type of [[cytotoxic]] [[lymphocyte]] critical to the [[innate immune system]]. They are a kind of large granular lymphocytes<ref>{{Cite journal |last=Oshimi |first=Kazuo |date=2017 |title=Clinical Features, Pathogenesis, and Treatment of Large Granular Lymphocyte Leukemias |url=https://www.jstage.jst.go.jp/article/internalmedicine/56/14/56_56.8881/_article |journal=Internal Medicine |language=en |volume=56 |issue=14 |pages=1759–1769 |doi=10.2169/internalmedicine.56.8881 |issn=0918-2918}}</ref><ref>{{Cite web |title=Large granular lymphocytic (LGL) leukemia |url=https://www.lls.org/leukemia/large-granular-lymphocytic-leukemia |access-date=2024-08-24 |website=www.lls.org}}</ref> (LGL), and belong to the rapidly expanding family of known [[innate lymphoid cell]]s (ILC) and represent 5–20% of all circulating lymphocytes in humans.<ref>{{cite journal | vauthors = Perera Molligoda Arachchige AS | title = Human NK cells: From development to effector functions | journal = Innate Immunity | volume = 27 | issue = 3 | pages = 212–229 | date = April 2021 | pmid = 33761782 | pmc = 8054151 | doi = 10.1177/17534259211001512 | doi-access = free }}</ref> The role of NK cells is analogous to that of [[cytotoxic T cell]]s in the vertebrate [[adaptive immune response]]. NK cells provide rapid responses to [[virus]]-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors.  Most [[immune cells]] detect the antigen presented on [[MHC class I|major histocompatibility complex I]] (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of [[antibodies]] and MHC, allowing for a much faster immune reaction.  They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of [[MHC class I]].<ref name="Vivier2011">{{cite journal | vauthors = Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S | display-authors = 6 | title = Innate or adaptive immunity? The example of natural killer cells | journal = Science | volume = 331 | issue = 6013 | pages = 44–49 | date = January 2011 | pmid = 21212348 | pmc = 3089969 | doi = 10.1126/science.1198687 | bibcode = 2011Sci...331...44V }}</ref> This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

NK cells can be identified by the presence of [[Neural cell adhesion molecule|CD56]] and the absence of [[CD3 (immunology)|CD3]] (CD56<sup>+</sup>, CD3<sup>&minus;</sup>).<ref name="pmid32477340">{{cite journal | vauthors = Pfefferle A, Jacobs B, Haroun-Izquierdo A, Kveberg L, Sohlberg E, Malmberg KJ | title = Deciphering Natural Killer Cell Homeostasis | journal = Frontiers in Immunology | volume = 11 | pages = 812 | year = 2020 | pmid = 32477340 | pmc = 7235169 | doi = 10.3389/fimmu.2020.00812 | doi-access = free }}</ref> NK cells differentiate from [[Interleukin-7 receptor-α|CD127<sup>+</sup>]] common [[Innate lymphoid cell|innate lymphoid]] progenitor,<ref name=":7">{{cite journal | vauthors = Kansler ER, Li MO | title = Innate lymphocytes-lineage, localization and timing of differentiation | journal = Cellular & Molecular Immunology | volume = 16 | issue = 7 | pages = 627–633 | date = July 2019 | pmid = 30804475 | pmc = 6804950 | doi = 10.1038/s41423-019-0211-7 }}</ref> which is downstream of the [[Lymphopoiesis#The old model: lymphoid vs myeloid|common lymphoid progenitor]] from which [[B cell|B]] and [[T cell|T lymphocyte]]s are also derived.<ref name=":7" /><ref>{{cite journal | vauthors = Harly C, Cam M, Kaye J, Bhandoola A | title = Development and differentiation of early innate lymphoid progenitors | journal = The Journal of Experimental Medicine | volume = 215 | issue = 1 | pages = 249–262 | date = January 2018 | pmid = 29183988 | pmc = 5748853 | doi = 10.1084/jem.20170832 }}</ref> NK cells are known to differentiate and mature in the [[bone marrow]], [[lymph node]]s, [[spleen]], [[tonsil]]s, and [[thymus]], where they then enter into the circulation.<ref name=Lannello2008>{{cite journal | vauthors = Iannello A, Debbeche O, Samarani S, Ahmad A | title = Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS | journal = Journal of Leukocyte Biology | volume = 84 | issue = 1 | pages = 1–26 | date = July 2008 | pmid = 18388298 | doi = 10.1189/jlb.0907650 | s2cid = 26975415 | citeseerx = 10.1.1.619.9639 }}</ref> NK cells differ from [[natural killer T cell]]s (NKTs) phenotypically, by origin and by respective effector functions; often, NKT cell activity promotes NK cell activity by secreting [[IFNγ|interferon gamma]]. In contrast to NKT cells, NK cells do not express [[T-cell antigen receptors]] (TCR) or pan T marker [[CD3 (immunology)|CD3]] or surface [[immunoglobulin]]s (Ig) [[B cell receptor]]s, but they usually express the surface markers [[CD16]] (FcγRIII) and [[CD57]] in humans, NK1.1 or NK1.2 in [[C57BL/6]] [[mouse|mice]]. The [[NKp46]] cell surface marker constitutes, at the moment, another NK cell marker of preference being expressed in both humans, several strains of mice (including [[BALB/c|BALB/c mice]]) and in three common monkey species.<ref>{{cite journal | vauthors = Walzer T, Bléry M, Chaix J, Fuseri N, Chasson L, Robbins SH, Jaeger S, André P, Gauthier L, Daniel L, Chemin K, Morel Y, Dalod M, Imbert J, Pierres M, Moretta A, Romagné F, Vivier E | display-authors = 6 | title = Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 9 | pages = 3384–3389 | date = February 2007 | pmid = 17360655 | pmc = 1805551 | doi = 10.1073/pnas.0609692104 | doi-access = free | bibcode = 2007PNAS..104.3384W }}</ref><ref>{{cite journal | vauthors = Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, Moretta L, Moretta A | display-authors = 6 | title = p46, a novel natural killer cell-specific surface molecule that mediates cell activation | journal = The Journal of Experimental Medicine | volume = 186 | issue = 7 | pages = 1129–1136 | date = October 1997 | pmid = 9314561 | pmc = 2211712 | doi = 10.1084/jem.186.7.1129 }}</ref>

Outside of [[innate immunity]], both activating and inhibitory NK cell receptors play important functional roles in self tolerance and the sustaining of NK cell activity.  NK cells also play a role in the [[adaptive immune response]]:<ref name=Arina2007>{{cite journal | vauthors = Arina A, Murillo O, Dubrot J, Azpilikueta A, Alfaro C, Pérez-Gracia JL, Bendandi M, Palencia B, Hervás-Stubbs S, Melero I | display-authors = 6 | title = Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer | journal = Expert Opinion on Biological Therapy | volume = 7 | issue = 5 | pages = 599–615 | date = May 2007 | pmid = 17477799 | doi = 10.1517/14712598.7.5.599 | s2cid = 43003664 }}</ref> numerous experiments have demonstrated their ability to readily adjust to the immediate environment and formulate antigen-specific [[immunological memory]], fundamental for responding to secondary infections with the same antigen.<ref>{{cite book | vauthors = Watzl C | title = How to trigger a killer: modulation of natural killer cell reactivity on many levels | series = Advances in Immunology | volume = 124 | pages = 137–70 | date = 2014 | pmid = 25175775 | doi = 10.1016/B978-0-12-800147-9.00005-4 | isbn = 9780128001479 }}</ref>  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]] and HIV therapy.<ref>{{Cite journal |last=Perera Molligoda Arachchige |first=Arosh S |date=2022-03-25 |title=NK cell-based therapies for HIV infection: Investigating current advances and future possibilities |url=https://academic.oup.com/jleukbio/article/111/4/921/6885120 |journal=Journal of Leukocyte Biology |language=en |volume=111 |issue=4 |pages=921–931 |doi=10.1002/JLB.5RU0821-412RR |issn=0741-5400|url-access=subscription }}</ref><ref>{{Cite journal |last=Arachchige |first=Arosh S. Perera Molligoda |date=2021 |title=A universal CAR-NK cell approach for HIV eradication |url=http://www.aimspress.com/rticle/doi/10.3934/Allergy.2021015 |journal=AIMS Allergy and Immunology |language=en |volume=5 |issue=3 |pages=192–194 |doi=10.3934/Allergy.2021015 |issn=2575-615X |doi-access=free }}{{Dead link|date=August 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>