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. 2021 Jul 27;6:93. doi: 10.1038/s41541-021-00354-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Intrinsic and extrinsic modulators may either challenge or strengthen the immune system. External challenges can result in either A the loss in immune system homeostasis (unhealthy state) in the absence of intrinsic capabilities or B the maintenance of homeostasis in the presence of intrinsic capabilities (healthy state). Vaccination may potentially have a positive influence through trained immunity, by creating a flexible memory pool, by direct and indirect prevention of diseases triggered by infections and associated inflammation.