Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, Massachusetts 02139, USA.
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
Nat Rev Immunol. 2018 Jan;18(1):46-61. doi: 10.1038/nri.2017.106. Epub 2017 Oct 24.
Antibodies play an essential role in host defence against pathogens by recognizing microorganisms or infected cells. Although preventing pathogen entry is one potential mechanism of protection, antibodies can control and eradicate infections through a variety of other mechanisms. In addition to binding and directly neutralizing pathogens, antibodies drive the clearance of bacteria, viruses, fungi and parasites via their interaction with the innate and adaptive immune systems, leveraging a remarkable diversity of antimicrobial processes locked within our immune system. Specifically, antibodies collaboratively form immune complexes that drive sequestration and uptake of pathogens, clear toxins, eliminate infected cells, increase antigen presentation and regulate inflammation. The diverse effector functions that are deployed by antibodies are dynamically regulated via differential modification of the antibody constant domain, which provides specific instructions to the immune system. Here, we review mechanisms by which antibody effector functions contribute to the balance between microbial clearance and pathology and discuss tractable lessons that may guide rational vaccine and therapeutic design to target gaps in our infectious disease armamentarium.
抗体通过识别微生物或感染细胞，在宿主防御病原体中发挥着重要作用。尽管预防病原体进入是一种潜在的保护机制，但抗体可以通过多种其他机制来控制和消除感染。除了结合和直接中和病原体外，抗体还通过与先天和适应性免疫系统相互作用，利用我们免疫系统中锁定的多种抗菌过程，来驱动细菌、病毒、真菌和寄生虫的清除。具体来说，抗体协同形成免疫复合物，从而驱动病原体的隔离和摄取、清除毒素、消除感染细胞、增加抗原呈递并调节炎症。抗体通过对抗体恒定区的差异修饰来动态调节其多样化的效应功能，这为免疫系统提供了特定的指令。在这里，我们综述了抗体效应功能在微生物清除和病理学之间的平衡中所起的作用，并讨论了一些可行的经验教训，这些经验教训可能有助于指导合理的疫苗和治疗设计，以填补我们在传染病武器库中的空白。
