我们的免疫防御系统依赖于免疫系统区分入侵病原体和自身的能力来抵御感染。对于已经几乎完全融入宿主的逆转录病毒来说，这项任务非常具有挑战性，甚至看似不可能完成。本次回顾研究了内源性逆转录病毒和其他逆转录元素引发的先天免疫和适应性免疫反应的限制、免疫识别的目标以及它们对宿主健康和疾病的影响。与理论预期相反，内源性逆转录元素保留了相当的免疫原性，在其表观遗传抑制受损时表现得最为明显，有助于自身炎症和自身免疫性疾病以及与年龄相关的炎症。然而，最近的证据表明，对内源性逆转录元素的调节免疫反应对于免疫系统的发展和功能是至关重要的，在癌症免疫监视、抵抗感染和对微生物群落的反应中起着基础作用。因此，阐明与内源性逆转录元素的相互作用点将深化我们对免疫系统功能和对疾病的贡献的理解。《免疫学年度评论》第41卷的最终在线出版日期预计是2023年4月。请访问http://www.annualreviews.org/page/journal/pubdates获取修订后的预估日期。

Our defenses against infection rely on the ability of the immune system to distinguish invading pathogens from self. This task is exceptionally challenging, if not seemingly impossible, in the case of retroviruses that have integrated almost seamlessly into the host. This review examines the limits of innate and adaptive immune responses elicited by endogenous retroviruses and other retroelements, the targets of immune recognition, and the consequences for host health and disease. Contrary to theoretical expectation, endogenous retroelements retain substantial immunogenicity, which manifests most profoundly when their epigenetic repression is compromised, contributing to autoinflammatory and autoimmune disease and age-related inflammation. Nevertheless, recent evidence suggests that regulated immune reactivity to endogenous retroelements is integral to immune system development and function, underpinning cancer immunosurveillance, resistance to infection, and responses to the microbiota. Elucidation of the interaction points with endogenous retroelements will therefore deepen our understanding of immune system function and contribution to disease. Expected final online publication date for the Annual Review of Immunology, Volume 41 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.