Trained immunity

Trained immunity is the modification of cells in the innate immune system (the one with which an organism is born) to create a "memory" of a pathogen. Trained immunity creates no antibodies in preparation for a second encounter. Instead, the immunity is mediated mostly by epigenetic modifications, alterations in gene expression and cellular function without changes to the original DNA sequence. The resulting immunity lasts up to several months, in contrast to the classical immunological memory (which may last up to a lifetime), and is usually unspecific because there is no production of specific antibodies/receptors.[1]

The term "trained immunity" is relatively new – immunological memory has previously been considered only as a part of adaptive immunity – and refers only to changes in innate immune memory of vertebrates.[2][3] The term "innate immune memory" is sometimes used as a synonym for the term trained immunity which was first coined[4] by the scientist Mihai Netea and his colleagues Jessica Quintin and Jos W.M.van der Meer on 18 May 2011 in their research titled Trained Immunity: A Memory for Innate Host Defense.[5][6][7] In a separate paper published on 30 April 2020 and set out in the Lancet on 16 May 2020, Mihai Netea and his colleagues Nigel Curtis, Annie Sparrow and Tedros A Ghebreyesus suggested that, in addition to its specific effect against tuberculosis, the trained immunity provided by the BCG vaccine might have beneficial nonspecific (off-target) effects on the immune system that protect against a wide range of other infections and that vaccination with BCG might have a role in protecting health-care workers and other vulnerable individuals against severe coronavirus disease 2019 (COVID-19).[8][9] Innate immunity rendered by BCG vaccination is a non-specific protective response against a wide spectrum of pathogens, including, viruses, such as SARS-CoV-19, as well as bacteria (Francisella), parasites (Leishmania, Malaria), and other intracellular microbes.[10] This protective response is shown to be nitric oxide mediated.[11]

Evidence of trained immunity is found mainly at monocytes/macrophages and NK cells and, less at γδ T cells and innate lymphoid cells.[12]

Monocytes and macrophages

Monocytes/macrophages can undergo epigenetic modifications after a ligation of their pattern recognition receptors (PRRs). This ligation prepares these cells for a second encounter with the training pathogen.[12] The secondary response may be heightened not only against the training pathogen, but also against different pathogens whose antigens are recognized by the same PRRs. This effect has been observed when stimulating cells by β-glucan, Candida Albicans, or by vaccination against tuberculosis with a vaccine containing BCG.[13][3] Monocytes are very short-lived cells; however, the heightened secondary response can be spotted even several months after the primary stimulation. This shows that the immune memory is created at the level of progenitor cells, but so far it is not known how this memory is achieved.[3]

NK cells

The trained immunity involving NK cells looks more like classic immunological memory, because there is development of at least partially-specific clones of NK cells. These cells have receptors on their surface against the antigens with which they came in contact during the first stimulation.[1] For example, after the encounter with cytomegalovirus, certain clones of NK cells (those that have a Ly49H receptor on their surface) expand and then show signs of immunological memory.[14]

References
  1. Pradeu T, Du Pasquier L (May 2018). "Immunological memory: What's in a name?" (PDF). Immunological Reviews. 283 (1): 7–20. doi:10.1111/imr.12652. PMID 29664563.
  2. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, et al. (April 2016). "Trained immunity: A program of innate immune memory in health and disease". Science. 352 (6284): aaf1098. doi:10.1126/science.aaf1098. PMC 5087274. PMID 27102489.
  3. Gourbal B, Pinaud S, Beckers GJ, Van Der Meer JW, Conrath U, Netea MG (May 2018). "Innate immune memory: An evolutionary perspective". Immunological Reviews. 283 (1): 21–40. doi:10.1111/imr.12647. PMID 29664574.
  4. "A Prime Time for Trained Immunity: Innate Immune Memory in Newborns & Infants". US National Library of Medicine Introduction Line 6 Netea and colleagues recently coined the term trained immunity. Retrieved 2020-09-02.
  5. "Trained Immunity: A Memory for Innate Host Defense" (PDF). Science Direct. Retrieved 2020-09-02.
  6. "Trained Immunity: A Memory for Innate Host Defense". Cell Host & Microbe. Retrieved 2020-09-02.
  7. "Trained Immunity: A Memory for Innate Host Defense". National Library of Medicine. Retrieved 2020-09-02.
  8. "Considering BCG vaccination to reduce the impact of COVID-19". The Lancet. Retrieved 2020-09-03.
  9. "Netherlands to Test Century-Old Tuberculosis Shot for Coronavirus". Bloomberg. Retrieved 3 January 2020.
  10. Green, Shawn J. (June 11, 1995). "Nitric oxide in mucosal immunity". Nature Medicine. 1 (6): 515–517. doi:10.1038/nm0695-515 – via www.nature.com.
  11. . PMID 8423095. Cite journal requires |journal= (help); Missing or empty |title= (help)
  12. Gardiner CM, Mills KH (August 2016). "The cells that mediate innate immune memory and their functional significance in inflammatory and infectious diseases". Seminars in Immunology. 28 (4): 343–50. doi:10.1016/j.smim.2016.03.001. PMID 26979658.
  13. "Landmark trial shows trained immunity reduces respiratory infections in the elderly by 80%". Today in Science. Retrieved 2020-09-02.
  14. Sun JC, Beilke JN, Lanier LL (January 2009). "Adaptive immune features of natural killer cells". Nature. 457 (7229): 557–61. Bibcode:2009Natur.457..557S. doi:10.1038/nature07665. PMC 2674434. PMID 19136945.
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