Natural killer cell

Natural killer cell
Human natural killer cell, colorized scanning electron micrograph
SystemImmune system
FunctionCytotoxic lymphocyte
Anatomical terms of microanatomy

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans.[1] The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Most immune cells detect the antigen presented on major histocompatibility complex (MHC) 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.[2] 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 CD56 and the absence of CD3 (CD56+, CD3).[3] NK cells differentiate from CD127+ common innate lymphoid progenitor,[4] which is downstream of the common lymphoid progenitor from which B and T lymphocytes are also derived.[4][5] NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation.[6] NK cells differ from natural killer T cells (NKTs) phenotypically, by origin and by respective effector functions; often, NKT cell activity promotes NK cell activity by secreting interferon gamma. In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD57 in humans, NK1.1 or NK1.2 in C57BL/6 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 mice) and in three common monkey species.[7][8]

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:[9] 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.[10] 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.[11][12]

  1. ^ Perera Molligoda Arachchige AS (April 2021). "Human NK cells: From development to effector functions". Innate Immunity. 27 (3): 212–229. doi:10.1177/17534259211001512. PMC 8054151. PMID 33761782.
  2. ^ Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, et al. (January 2011). "Innate or adaptive immunity? The example of natural killer cells". Science. 331 (6013): 44–49. Bibcode:2011Sci...331...44V. doi:10.1126/science.1198687. PMC 3089969. PMID 21212348.
  3. ^ Pfefferle A, Jacobs B, Haroun-Izquierdo A, Kveberg L, Sohlberg E, Malmberg KJ (2020). "Deciphering Natural Killer Cell Homeostasis". Frontiers in Immunology. 11: 812. doi:10.3389/fimmu.2020.00812. PMC 7235169. PMID 32477340.
  4. ^ a b Kansler ER, Li MO (July 2019). "Innate lymphocytes-lineage, localization and timing of differentiation". Cellular & Molecular Immunology. 16 (7): 627–633. doi:10.1038/s41423-019-0211-7. PMC 6804950. PMID 30804475.
  5. ^ Harly C, Cam M, Kaye J, Bhandoola A (January 2018). "Development and differentiation of early innate lymphoid progenitors". The Journal of Experimental Medicine. 215 (1): 249–262. doi:10.1084/jem.20170832. PMC 5748853. PMID 29183988.
  6. ^ Iannello A, Debbeche O, Samarani S, Ahmad A (July 2008). "Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS". Journal of Leukocyte Biology. 84 (1): 1–26. CiteSeerX doi:10.1189/jlb.0907650. PMID 18388298. S2CID 26975415.
  7. ^ Walzer T, Bléry M, Chaix J, Fuseri N, Chasson L, Robbins SH, et al. (February 2007). "Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46". Proceedings of the National Academy of Sciences of the United States of America. 104 (9): 3384–3389. Bibcode:2007PNAS..104.3384W. doi:10.1073/pnas.0609692104. PMC 1805551. PMID 17360655.
  8. ^ Sivori S, Vitale M, Morelli L, Sanseverino L, Augugliaro R, Bottino C, et al. (October 1997). "p46, a novel natural killer cell-specific surface molecule that mediates cell activation". The Journal of Experimental Medicine. 186 (7): 1129–1136. doi:10.1084/jem.186.7.1129. PMC 2211712. PMID 9314561.
  9. ^ Arina A, Murillo O, Dubrot J, Azpilikueta A, Alfaro C, Pérez-Gracia JL, et al. (May 2007). "Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer". Expert Opinion on Biological Therapy. 7 (5): 599–615. doi:10.1517/14712598.7.5.599. PMID 17477799. S2CID 43003664.
  10. ^ Watzl C (2014). How to trigger a killer: modulation of natural killer cell reactivity on many levels. Advances in Immunology. Vol. 124. pp. 137–70. doi:10.1016/B978-0-12-800147-9.00005-4. ISBN 9780128001479. PMID 25175775.
  11. ^ Perera Molligoda Arachchige, Arosh S (2022-03-25). "NK cell-based therapies for HIV infection: Investigating current advances and future possibilities". Journal of Leukocyte Biology. 111 (4): 921–931. doi:10.1002/JLB.5RU0821-412RR. ISSN 0741-5400.
  12. ^ Arachchige, Arosh S. Perera Molligoda (2021). "A universal CAR-NK cell approach for HIV eradication". AIMS Allergy and Immunology. 5 (3): 192–194. doi:10.3934/Allergy.2021015. ISSN 2575-615X.

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