Pangburn M K
Fed Proc. 1983 Jan;42(1):139-43.
Activation of complement via the alternative pathway represents one means of natural resistance to infection because it is capable of neutralizing a wide variety of potential pathogens in the total absence of antibody. The pathway involves six serum proteins and possesses a unique amplification system capable of depositing large numbers of C3b molecules on the surfaces of activating particles. C3b deposition enhances phagocytosis and results in activation of the membrane attack pathway of complement. C3b attachment is covalent, arising from a reaction between an intramolecular thiolester bond in nascent C3b and nucleophiles such as hydroxyl groups on surface carbohydrates. The reactions that initiate C3b attachment are not specific interactions like those initiating other biological cascade systems, but involve slow, spontaneous hydrolysis of the thiolester bond in C3 and subsequent random deposition of C3b onto all nearby surfaces. Once bound, C3b is capable of discriminating between host-derived cells and activating particles. Recognition is evidenced by a lower affinity between activator-bound C3b and the complement control protein factor H. Measurements of the association constant between unbound, soluble C3b and factor H suggest that activator-bound C3b recognizes structures on activators that inhibit factor H binding.
通过替代途径激活补体是机体天然抗感染的一种方式，因为在完全没有抗体的情况下，它能够中和多种潜在病原体。该途径涉及六种血清蛋白，并拥有一个独特的放大系统，能够在激活颗粒表面沉积大量C3b分子。C3b沉积可增强吞噬作用，并导致补体膜攻击途径的激活。C3b的附着是共价的，源于新生C3b分子内硫酯键与表面碳水化合物上的亲核试剂（如羟基）之间的反应。引发C3b附着的反应不像引发其他生物级联系统的反应那样是特异性相互作用，而是涉及C3中硫酯键的缓慢自发水解，随后C3b随机沉积到所有附近的表面上。一旦结合，C3b就能区分宿主来源的细胞和激活颗粒。激活剂结合的C3b与补体调节蛋白H因子之间较低的亲和力证明了这种识别。对未结合的可溶性C3b与H因子之间结合常数的测量表明，激活剂结合的C3b识别激活剂上抑制H因子结合的结构。
