Complement.

Abstract

The complement system mediates a wide range of important biological functions. The use of modern techniques in protein chemistry and molecular biology has greatly facilitated our understanding of the interactions between the fluid phase and cell-bound components of the system. Structural and genetic analysis has shown that while many of these components are polymorphic, there are major similarities between many of the proteins serving enzymatic and regulatory roles in both the alternative and classical pathways. The regulation of complement activation and Class III genes, on chromosomes 1 and 6 respectively, encode nine of the major proteins in the system. The genetic basis of C4 and C3 polymorphisms is now well established, and further study may reveal functional differences between polymorphic variants of other components. The study of individuals with either genetic or acquired deficiencies of complement proteins and receptors has provided insight into the function of these components, leukocyte adherence deficiency (LAD) providing the best example. An appreciation of the genetics, structure and functions of the regulatory proteins decay-accelerating factor (DAF) and homologous restriction factor has enhanced our understanding of the pathogenesis of paroxysmal nocturnal haemoglobinuria. The full importance of CD59 glycoprotein, the newest member of the complement family, remains to be determined.