{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:58:15Z","timestamp":1793383095718,"version":"4.5.0"},"reference-count":177,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021-EGA10"],"award-info":[{"award-number":["TKP2021-EGA10"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["-EGA13"],"award-info":[{"award-number":["-EGA13"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021"],"award-info":[{"award-number":["TKP2021"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["HUHR-1901-3.1.1-0032 HU HR CBC"],"award-info":[{"award-number":["HUHR-1901-3.1.1-0032 HU HR CBC"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["CABCOS III"],"award-info":[{"award-number":["CABCOS III"]}]},{"name":"Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund","award":["FK-139028"],"award-info":[{"award-number":["FK-139028"]}]},{"name":"Hungarian National Research, Development and Innovation Fund","award":["TKP2021-EGA10"],"award-info":[{"award-number":["TKP2021-EGA10"]}]},{"name":"Hungarian National Research, Development and Innovation Fund","award":["-EGA13"],"award-info":[{"award-number":["-EGA13"]}]},{"name":"Hungarian National Research, Development and Innovation Fund","award":["TKP2021"],"award-info":[{"award-number":["TKP2021"]}]},{"name":"Hungarian National Research, Development and Innovation Fund","award":["HUHR-1901-3.1.1-0032 HU HR CBC"],"award-info":[{"award-number":["HUHR-1901-3.1.1-0032 HU HR CBC"]}]},{"name":"Hungarian National Research, Development and Innovation Fund","award":["CABCOS III"],"award-info":[{"award-number":["CABCOS III"]}]},{"name":"Hungarian National Research, Development and Innovation Fund","award":["FK-139028"],"award-info":[{"award-number":["FK-139028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural autoantibodies (nAAbs) recognize self-antigens and are an important component of the immune system, having evolved from invertebrates to vertebrates, and are viewed as stable byproducts of immune function and essential players in health and disease. Initially characterized by their conserved nature and multi-reactivity, primarily as IgM isotypes, nAAbs are now recognized for their adaptability in response to infections and vaccinations, bridging innate and adaptive immunity. The nAAbs and the cellular elements, such as \u03b3\u03b4 T, iNKT, and MAIT cells, of the natural immune system perform a primary defense network with moderate antigen-specificity. This comprehensive literature review was conducted to analyze the role of natural autoantibodies (nAAbs) in health and disease. The review focused on research published over the past 40 years, emphasizing studies related to infectious diseases, vaccinations, and autoimmune disorders. Recent studies suggest that nAAbs engage in complex interactions in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and type 1 diabetes. Their roles in immunological processes, such as maternal tolerance during pregnancy, further underscore their complexity. Emerging evidence indicates that nAAbs and the cellular elements of the natural immune system may contribute to both disease pathogenesis and protective mechanisms, highlighting their dual nature. Continued research on nAAbs is vital for improving our understanding of immune responses and developing therapeutic strategies for autoimmune disorders and infectious diseases.<\/jats:p>","DOI":"10.3390\/ijms26115413","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:49:22Z","timestamp":1749102562000},"page":"5413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulators and Conductors of Immunity: Natural Immune System in Health and Autoimmunity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6126-1840","authenticated-orcid":false,"given":"Katalin","family":"B\u00f6r\u00f6cz","sequence":"first","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1276-3141","authenticated-orcid":false,"given":"D\u00e1vid","family":"Szinger","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di\u00e1na","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-8127","authenticated-orcid":false,"given":"Timea","family":"Berki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Biotechnology, Clinical Center, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3406-2010","authenticated-orcid":false,"given":"P\u00e9ter","family":"N\u00e9meth","sequence":"additional","affiliation":[{"name":"Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0167-5699(92)90071-E","article-title":"The Cognitive Principle Challenges Clonal Selection","volume":"13","author":"Cohen","year":"1992","journal-title":"Immunol. 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