{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:42:11Z","timestamp":1791416531656,"version":"4.3.3"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immunologists generally view the notion of self and non-self as part of a broader, more contextual understanding of immune function, rather than a rigid dogma. While the classical paradigm that the primary role of the immune system is to recognize and eliminate anything foreign once provided a unifying basis for explaining tolerance and rejection, numerous discoveries have focused attention on how immune responses are finely tuned by a range of contextual cues, including tissue signals, hygienist theory, molecular mimicry, symbiotic microbes, metabolic factors and epigenetic modifications. Maternal-fetal tolerance and the persistence of microchimeric cells in adults demonstrate that genetically foreign cells can be actively integrated into the host, challenging the simple assumption that \u2018foreign\u2019 equals unconditional attack. Similarly, research into the microbiome, the virome and the phenomenon of trained innate immunity has shown that there can be beneficial or even essential relationships between the body and what has traditionally been labelled \u2018non-self\u2019. Over the last decade, the idea that the immune system strictly enforces a binary distinction has instead evolved towards a model in which it continuously interprets signals of damage or perturbation, manages complex ecological relationships with commensal or latent organisms, and recalibrates according to the organism\u2019s life stage and environment. There remains a recognition that clonal deletion and negative selection in the thymus, together with MHC-bound peptide recognition, still underlie many core processes, and in certain clinical contexts, such as acute transplant rejection or the prevention of autoimmunity, an approximate self-non-self-categorization is directly relevant. Overall, however, the field recognizes that \u2018self\u2019 is not a static attribute defined once and for all, but rather a dynamic and context-dependent state that continues to be shaped by microbial symbioses, epigenetic reprogramming and immunoregulatory networks throughout an individual\u2019s lifespan.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1595764","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:13:09Z","timestamp":1746677589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Self or nonself: end of a dogma?"],"prefix":"10.3389","volume":"16","author":[{"given":"Marie","family":"Duhamel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Salzet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"B1","volume-title":"A general review of the recent work in immunity","author":"Ehrlich","year":"1906"},{"key":"B2","volume-title":"Lectures on the comparative pathology of inflammation delivered at the Pasteur Institute in 1891.","author":"Metchnikoff","year":"1893"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.5962\/bhl.title.29861","volume-title":"Immunity in infective diseases","author":"Metchnikoff","year":"1905"},{"key":"B4","volume-title":"Trait\u00e9 de l\u2019immunit\u00e9 dans les maladies infectieuses","author":"Bordet","year":"1920"},{"key":"B5","first-page":"289","article-title":"Sur l\u2019existence de substances sensibilisatrices dans la plupart des s\u00e9rums anti-microbiens","volume":"1901","author":"Bordet","year":"1901","journal-title":"Annales de l\u2019institut Pasteur"},{"key":"B6","volume-title":"Essai philosophique, concernant l\u2019entendement humain","author":"Locke","year":"1742"},{"key":"B7","first-page":"505","article-title":"On the origin of the vaccine inoculation","volume":"5","author":"Jenner","year":"1801","journal-title":"Med Phys J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3406\/rmv.1882.2953","article-title":"Quatri\u00e8me Congr\u00e8s international d\u2019hygi\u00e8ne et de d\u00e9mographie \u00e0 Gen\u00e8ve, du 4 au 9 septembre 1882.\u2014Communication de M. 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