Bartholomew W R, Shanahan T C
Erie County Medical Center, Erie County Laboratory, Buffalo, New York.
Immunol Ser. 1990;52:33-51.
The complement system, accessory to many immunological functions, consists of a number of interdependent components and receptors. Numerous in vitro approaches have elucidated the biological role of these components and receptors. However, it is the in vivo "natural" experiments that underscore their importance. The phagocytosis and subsequent digestion of pyogenic bacteria is significantly enhanced by the fixation of the third complement component to the bacterial cell wall. Equally important is the intact expression of a receptor (CR3) for the C3b cleavage fragment. Breakdown in this ligand-receptor interaction due to either C3 or CR3 deficiency leads to pyogenic infection. Interestingly, C3-deficient individuals do not demonstrate leukocytic infiltration at the site of infection. Undoubtedly, this is due to the lack of C5 convertase and failure to produce C5a. CR3-deficient individuals, on the other hand, do demonstrate leukocytosis since the third complement component is functional. C3 deficiency is not necessarily a primary lesion and may be secondary to factor I deficiency. In this case, the C3b fragment, along with factor B, acts as a C3 convertase. Inefficient inactivation of C3b, due to factor I deficiency, leads to the uncontrolled consumption of the third component, resulting in C3 deprivation. It appears that phagocytosis by neutrophils and monocytes followed by enzyme-interaction is not sufficient for destruction of the Neisseria organisms. In addition to this leukocyte activity, an intact membrane attack complex, composed of the late complement components C5, 6, 7, 8, and 9, is required for the lysis of these bacteria. This is supported by findings that individuals deficient in late components are highly susceptible to systemic Neisseria infections. Diseases of an autoimmune nature are frequently associated with a deficiency of one of the early complement components C1, C2, or C4 and a deficiency of erythrocytic CR1 receptors as well. This may suggest that proper interaction between a complement fragment of the immune complex with the complement receptor expressed on the erythrocyte is important for proper management and clearance of the complex. Deficiency of the early complement components would prevent the activation of C3 and the fixation of a resulting C3 cleavage product. In this case, erythrocytes would be unable to participate in the transport of the immune complex to the reticuloendothelial system. Instead, tissue deposition of the complex would occur more readily, contributing to the pathologic process. Provided that the early complement cascade were intact, deficiency of erythrocytic CR1 receptors would contribute to the pathologic response for the same reason.(ABSTRACT TRUNCATED AT 400 WORDS)
补体系统辅助多种免疫功能，由许多相互依存的成分和受体组成。众多体外实验方法已阐明了这些成分和受体的生物学作用。然而，正是体内的“自然”实验突出了它们的重要性。化脓性细菌的吞噬作用及随后的消化过程，会因第三补体成分固定于细菌细胞壁而显著增强。同样重要的是C3b裂解片段的受体（CR3）的完整表达。由于C3或CR3缺陷导致这种配体 - 受体相互作用的破坏会引发化脓性感染。有趣的是，C3缺陷个体在感染部位未表现出白细胞浸润。毫无疑问，这是由于缺乏C5转化酶且无法产生C5a。另一方面，CR3缺陷个体确实表现出白细胞增多，因为第三补体成分功能正常。C3缺陷不一定是原发性病变，可能继发于I因子缺乏。在这种情况下，C3b片段与B因子一起充当C3转化酶。由于I因子缺乏导致C3b失活效率低下，会导致第三成分的无节制消耗，从而导致C3缺乏。似乎中性粒细胞和单核细胞的吞噬作用以及随后的酶相互作用不足以破坏奈瑟菌属微生物。除了这种白细胞活性外，由补体晚期成分C5、6、7、8和9组成的完整膜攻击复合物对于裂解这些细菌是必需的。这一观点得到了以下发现的支持：补体晚期成分缺陷的个体极易发生全身性奈瑟菌感染。自身免疫性疾病通常与早期补体成分C1、C2或C4之一的缺乏以及红细胞CR1受体的缺乏有关。这可能表明免疫复合物的补体片段与红细胞上表达的补体受体之间的适当相互作用对于复合物的适当处理和清除很重要。早期补体成分的缺乏会阻止C3的激活以及由此产生的C3裂解产物的固定。在这种情况下，红细胞将无法参与免疫复合物向网状内皮系统的转运。相反，复合物更容易在组织中沉积，从而促进病理过程。如果早期补体级联完整，红细胞CR1受体的缺乏也会因同样的原因导致病理反应。（摘要截选至400字）
