补体系统在协调人类免疫系统内炎症的激活和调节中起着至关重要的作用。三种不同的激活途径-经典,凝集素,和替代汇聚形成共同的裂解途径,最终形成破坏病原体结构的膜攻击复合物。补体系统活性失调可导致组织损伤,自身免疫性疾病,或者免疫缺陷。在这项研究中,通过使用生物发光微生物探针研究了人血清的抗菌活性,大肠杆菌(pEGFPluxABCDEamp)。该探针先前已用于确定补体系统和多形核中性粒细胞的抗微生物活性。在这项研究中,阻断针对关键血清激活剂和成分的抗体,包括IgG,补体成分1q,因素B,和properdin,被利用。体温和急性期蛋白的影响,如C反应蛋白(CRP)和血清淀粉样蛋白α(SAA),对补体系统也进行了检查。该研究揭示了影响补体系统活性和通路功能的关键因素。除了C1q和IgG等关键因素外,替代途径组成因子B和备解素起了关键作用。结果表明,替代途径约占总血清抗菌活性的三分之一,阻断这条途径破坏了整个补体系统。与预期相反,炎症期间体温升高并没有增强人血清的抗菌活性。CRP表现出补体激活特性,但是在更高的生理浓度下,它表现出拮抗倾向,抑制反应。另一方面,SAA增强了血清的活性。总的来说,这项研究揭示了影响补体系统活性和通路功能的关键因素,强调平衡免疫反应的重要性。
The complement system plays a crucial role in orchestrating the activation and regulation of inflammation within the human immune system. Three distinct activation pathways-classical, lectin, and alternative-converge to form the common lytic pathway, culminating in the formation of the membrane-attacking complex that disrupts the structure of pathogens. Dysregulated complement system activity can lead to tissue damage, autoimmune diseases, or immune deficiencies. In this study, the antimicrobial activity of human serum was investigated by using a bioluminescent microbe probe, Escherichia coli (pEGFPluxABCDEamp). This probe has previously been used to determine the antimicrobial activity of complement system and the polymorphonuclear neutrophils. In this study, blocking antibodies against key serum activators and components, including IgG, complement component 1q, factor B, and properdin, were utilized. The influence of body temperature and acute phase proteins, such as C reactive protein (CRP) and serum amyloid alpha (SAA), on the complement system was also examined. The study reveals the critical factors influencing complement system activity and pathway function. Alongside crucial factors like C1q and IgG, alternative pathway components factor B and properdin played pivotal roles. Results indicated that the alternative pathway accounted for approximately one third of the overall serum antimicrobial activity, and blocking this pathway disrupted the entire complement system. Contrary to expectations, elevated body temperature during inflammation did not enhance the antimicrobial activity of human serum. CRP demonstrated complement activation properties, but at higher physiological concentrations, it exhibited antagonistic tendencies, dampening the response. On the other hand, SAA enhanced the serum\'s activity. Overall, this study sheds a light on the critical factors affecting both complement system activity and pathway functionality, emphasizing the importance of a balanced immune response.