{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:11:12Z","timestamp":1785449472265,"version":"3.56.0"},"reference-count":127,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T00:00:00Z","timestamp":1712448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"New York State Department of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Immune responses to influenza (flu) antigens reflect memory of prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed \u201coriginal antigenic sin\u201d or, more recently, \u201cimmune imprinting\u201d and \u201cseniority\u201d. We have researched a comparison between the immune response to live flu infections and inactivated flu vaccinations. A brief history of antibody generation theories is presented, culminating in new findings about the immune-network theory and suggesting that a network of clones exists between anti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells, like natural killer (NK) cells and macrophages, are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes is described. New vaccines in development are mentioned along with the results of some clinical trials. The manuscript concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.<\/jats:p>","DOI":"10.3390\/vaccines12040389","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T09:31:23Z","timestamp":1712568683000},"page":"389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cellular and Molecular Immunity to Influenza Viruses and Vaccines"],"prefix":"10.3390","volume":"12","author":[{"given":"Jane","family":"Kasten-Jolly","sequence":"first","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-9640","authenticated-orcid":false,"given":"David A.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA"},{"name":"Departments of Biomedical Science and Environmental Health Science, University at Albany School of Public Health, Rensselaer, NY 12144, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/eji.1830020416","article-title":"Original antigenic sin at the cellular level 1. 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