{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:19:42Z","timestamp":1789787982859,"version":"4.0.1"},"reference-count":108,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T00:00:00Z","timestamp":1749340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-112-05"],"award-info":[{"award-number":["TCRD-TPE-112-05"]}]},{"name":"Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-113-09"],"award-info":[{"award-number":["TCRD-TPE-113-09"]}]},{"name":"Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-110-02(2\/3)"],"award-info":[{"award-number":["TCRD-TPE-110-02(2\/3)"]}]},{"name":"Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation","award":["TCRD-TPE-111-01(3\/3)"],"award-info":[{"award-number":["TCRD-TPE-111-01(3\/3)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding the mechanisms of immune activation and deactivation is paramount. A host must initiate effective immunity against pathogenic infections while avoiding triggering immunity against self-antigens, which can lead to detrimental autoimmune disorders. Host immunological pathways can be categorized as Immunoglobulin (Ig)G-dominant eradicable immune reactions and IgA-dominant tolerable immune reactions. Eradicable immune reactions include Th1, Th2, Th22, and Th\u03b1\u03b2 immune responses against four different types of pathogens. Tolerable immune reactions include Th1-like, Th9, Th17, and Th3 immune responses against four different types of pathogens. Here, we try to determine the mechanisms of activation and deactivation of host immune reactions. The spleen and liver play contrasting roles in mediating immune responses: the spleen is primarily involved in immune activation, whereas the liver is responsible for immune deactivation. Similarly, the sympathetic and parasympathetic nervous systems have opposing functions in immune modulation, with the sympathetic system promoting pro-inflammatory responses and the parasympathetic system facilitating anti-inflammatory processes. Furthermore, adrenocorticotropic hormone (ACTH) and glucocorticosteroids exhibit contrasting effects on immune regulation: ACTH is involved in activating adaptive immunity while inhibiting innate immunity, whereas glucocorticosteroids activate natural IgM antibody associated with innate immunity while inhibiting adaptive immunity. Heat shock proteins, particularly molecular chaperones induced by fever, play pivotal roles in immune activation. Conversely, IgD B cells and gamma\/delta T cells contribute to immune deactivation through mechanisms such as clonal anergy. Understanding these mechanisms provides insights into immunological pathways, aiding in the better management of infectious diseases and autoimmune disorders.<\/jats:p>","DOI":"10.3390\/ijms26125503","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"5503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Understanding the Immune System\u2019s Intricate Balance: Activation, Tolerance, and Self-Protection"],"prefix":"10.3390","volume":"26","author":[{"given":"Jui-Yun","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Jane","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, Taoyuan Armed Forces General Hospital, Longtan, Taoyuan City 325, Taiwan"},{"name":"Graduate Institute of Medical Science, National Defense Medical Center, Taipei City114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Tser","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan City 325, Taiwan"},{"name":"Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei City114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Wang","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1360-1422","authenticated-orcid":false,"given":"Wan-Chung","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"Department of Clinical Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"Department of Biotechnology, Ming Chuan University, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hu, W.C. 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