Complement: coming full circle

The complement system has long been known to be a major element of innate immunity. Traditionally, it was regarded as the first line of defense against invading pathogens, leading to opsonization and phagocytosis or the direct lysis of microbes. However, from the second half of the twentieth century on, it became clear that complement is also intimately involved in the induction and “fine tuning” of adaptive B- and T-cell responses as well as lineage commitment. This growing recognition of the complement system’s multifunctional role in immunity is consistent with the recent paradigm that complement is also necessary for the successful contraction of an adaptive immune response. This review aims at giving a condensed overview of complement’s rise from a simple innate stop-and-go system to an essential and efficient participant in general immune homeostasis and acquired immunity.