Zinkernagel R M, LaMarre A, Ciurea A, Hunziker L, Ochsenbein A F, McCoy K D, Fehr T, Bachmann M F, Kalinke U, Hengartner H
Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland.
Adv Immunol. 2001;79:1-53. doi: 10.1016/s0065-2776(01)79001-3.
Neutralizing antibodies are evolutionarily important effectors of immunity against viruses. Their evaluation has revealed a number of basic insights into specificity, rules of reactivity (tolerance), and memory—namely, (1) Specificity of neutralizing antibodies is defined by their capacity to distinguish between virus serotypes; (2) B cell reactivity is determined by antigen structure, concentration, and time of availability in secondary lymphoid organs; and (3) B cell memory is provided by elevated protective antibody titers in serum that are depending on antigen stimulation. These perhaps slightly overstated rules are simple, correlate with evidence as well as clinical observations, and appear to largely demystify many speculations about antibodies and B cell physiology. The chapter also considers successful vaccines and compares them with those infectious diseases where efficient protective vaccines are lacking, it is striking to note that all successful vaccines induce high levels of neutralizing antibodies (nAbs) that are both necessary and sufficient to protect the host from disease. Successful vaccination against infectious diseases such as tuberculosis, leprosy, or HIV would require induction of additional long-lasting T cell responses to control infection.
中和抗体是抗病毒免疫中具有进化重要性的效应分子。对它们的评估揭示了一些关于特异性、反应性规则(耐受性)和记忆的基本见解,即:(1)中和抗体的特异性由其区分病毒血清型的能力定义;(2)B细胞反应性由抗原结构、浓度以及在次级淋巴器官中可获得的时间决定;(3)血清中保护性抗体滴度升高提供了B细胞记忆,这取决于抗原刺激。这些或许略显夸张的规则很简单,与证据以及临床观察结果相关,并且似乎在很大程度上揭开了许多关于抗体和B细胞生理学猜测的神秘面纱。本章还考量了成功的疫苗,并将它们与缺乏有效保护性疫苗的传染病进行比较,值得注意的是,所有成功的疫苗都会诱导高水平的中和抗体(nAbs),这些抗体对于保护宿主免受疾病侵害既是必要的也是充分的。针对结核病、麻风病或HIV等传染病成功接种疫苗将需要诱导额外的持久T细胞反应来控制感染。