Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Immunol Rev. 2023 Jan;313(1):162-180. doi: 10.1111/imr.13160. Epub 2022 Nov 6.
The alternative pathway (AP) is the phylogenetically oldest arm of the complement system and may have evolved to mark pathogens for elimination by phagocytes. Studies using purified AP proteins or AP-specific serum showed that C3b amplification on bacteria commenced following a lag phase of about 5 min and was highly dependent on the concentration of complement. Most pathogens have evolved several elegant mechanisms to evade complement, including expressing proteases that degrade AP proteins and secreting proteins that block function of C3 convertases. In an example of convergent evolution, many microbes recruit the AP inhibitor factor H (FH) using molecular mechanisms that mimic FH interactions with host cells. In most instances, the AP serves to amplify C3b deposited on microbes by the classical pathway (CP). The role of properdin on microbes appears to be restricted to stabilization of C3 convertases; scant evidence exists for its role as an initiator of the AP on pathogens in the context of serum. Therapeutic complement inhibition carries with it an increased risk of infection. Antibody (Ab)-dependent AP activation may be critical for complement activation by vaccine-elicited Ab when the CP is blocked, and its molecular mechanism is discussed.
替代途径 (AP) 是补体系统中最古老的分支，可能是为了标记病原体以供吞噬细胞清除而进化而来的。使用纯化的 AP 蛋白或 AP 特异性血清进行的研究表明，细菌上的 C3b 扩增始于约 5 分钟的滞后期，并且高度依赖于补体的浓度。大多数病原体已经进化出几种巧妙的机制来逃避补体，包括表达降解 AP 蛋白的蛋白酶和分泌阻止 C3 转化酶功能的蛋白。在趋同进化的一个例子中，许多微生物利用分子机制招募 AP 抑制剂因子 H (FH)，这些机制模拟 FH 与宿主细胞的相互作用。在大多数情况下，AP 用于放大经典途径 (CP) 在微生物上沉积的 C3b。在血清中，对病原体而言，备解素在微生物上的作用似乎仅限于稳定 C3 转化酶；几乎没有证据表明它在 CP 阻断时作为 AP 的起始因子在病原体中发挥作用。补体抑制治疗伴随着感染风险的增加。抗体 (Ab) 依赖性 AP 激活可能对于 CP 阻断时疫苗诱导的 Ab 引起的补体激活至关重要，并且讨论了其分子机制。
