Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
Immunol Rev. 2013 Jul;254(1):10-33. doi: 10.1111/imr.12072.
Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection, but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of 'symbiotic' intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high-level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4(+) T-cell responses, binding anti-bodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Furthermore, immune therapies specifically directed toward boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients.
近年来,人类免疫缺陷病毒(HIV)感染的免疫学、发病机制和预防方面的进展不断揭示出与感染相关的进行性免疫缺陷的机制线索,但更重要的是,阐明了感染和疾病进展的免疫相关性。HIV 选择性感染、消除和/或失调人类免疫系统的几个关键细胞,破坏宿主免疫反应的多个分支,并对黏膜屏障造成严重损伤,导致“共生”肠道细菌和病毒的组织浸润,这些细菌和病毒实际上成为促进全身免疫激活的机会性感染。这导致激活和募集或更多的靶细胞来维持 HIV 感染,导致淋巴组织中持续、高水平的病毒复制、耐药株的快速进化以及持续逃避免疫反应。然而,疫苗研究和自发控制者的研究最终提供了从保护和疾病进展中获得免疫的相关性,包括病毒特异性 CD4(+) T 细胞反应、结合抗体、先天免疫反应和产生具有强大抗体依赖性细胞介导的细胞毒性活性的抗体。新出现的免疫相关性表明,通过有效的疫苗策略预防 HIV 感染是可能的,这些疫苗策略可以保护和刺激易感宿主中的关键调节细胞和免疫反应。此外,专门针对增强免疫系统特定方面的免疫疗法最终可能导致 HIV 感染患者的治愈。