Krzych Urszula, Zarling Stasya, Pichugin Alexander
Department of Cellular Immunology, Branch of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States.
Department of Cellular Immunology, Branch of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States.
Immunol Lett. 2014 Oct;161(2):189-95. doi: 10.1016/j.imlet.2014.03.011. Epub 2014 Apr 5.
Immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. Adequately maintained memory T and B cell pools assure a fast, effective and specific response against re-infections. However, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, Plasmodium spp., the causative agents of malaria. For example, memory responses to Plasmodium antigens amongst residents of malaria endemic areas appear to be either inadequately developed or maintained, because persons who survive episodes of childhood malaria remain vulnerable to intermittent malaria infections. By contrast, multiple exposures of humans and laboratory rodents to radiation-attenuated Plasmodium sporozoites (γ-spz) induce sterile and long-lasting protection against experimental sporozoite challenge. Multifactorial immune mechanisms maintain this protracted and sterile protection. While the presence of memory CD4 T cell subsets has been associated with lasting protection in humans exposed to multiple bites from Anopheles mosquitoes infected with attenuated Plasmodium falciparum, memory CD8 T cells maintain protection induced with Plasmodium yoelii and Plasmodium berghei γ-spz in murine models. In this review, we discuss our observations that show memory CD8 T cells specific for antigens expressed by P. berghei liver stage parasites as an indispensable component for the maintenance of protracted protective immunity against experimental malaria infection; moreover, the provision of an Ag-depot assures a quick recall of memory T cells as IFN-γ-producing effector CD8 T cells and IL-4- producing CD4 T cells that collaborate with B cells for an effective antibody response.
免疫记忆是抗原特异性免疫反应的主要特征之一，记忆细胞的持久性有助于针对感染因子的预防性免疫接种。充分维持的记忆性T细胞和B细胞库可确保对再次感染做出快速、有效且特异性的反应。然而，免疫记忆的许多方面仍未得到充分理解，尤其是寄生虫诱导的免疫记忆，例如疟原虫属，即疟疾的病原体。例如，疟疾流行地区居民对疟原虫抗原的记忆反应似乎发育不足或维持不佳，因为童年时期患过疟疾的幸存者仍易受间歇性疟疾感染。相比之下，人类和实验啮齿动物多次接触经辐射减毒的疟原虫子孢子（γ-子孢子）可诱导对实验性子孢子攻击的无菌且持久的保护。多因素免疫机制维持这种持久的无菌保护。虽然记忆性CD4 T细胞亚群的存在与暴露于感染减毒恶性疟原虫的按蚊多次叮咬的人类的持久保护有关，但记忆性CD8 T细胞在小鼠模型中维持由约氏疟原虫和伯氏疟原虫γ-子孢子诱导的保护。在本综述中，我们讨论了我们的观察结果，即针对伯氏疟原虫肝期寄生虫表达的抗原的记忆性CD8 T细胞是维持针对实验性疟疾感染的持久保护性免疫的不可或缺组成部分；此外，提供抗原储存库可确保作为产生IFN-γ的效应性CD8 T细胞和产生IL-4的CD4 T细胞快速召回记忆性T细胞，这些细胞与B细胞协作以产生有效的抗体反应。
