An Introduction to Complement System

Complement System History

The complement system comprises a far-reaching and vital component of innate immunity and represents one of the major effector mechanisms of the innate immune system. Discovered in 1896 by Bordet as a heat-labile component of serum, it was so named for its ability to 'complement' the antibacterial properties of antibody in the heat-stabile fraction of serum.

It is now appreciated that complement is a complex network of plasma and membrane-associated serum proteins which can elicit highly efficient and tightly regulated inflammatory and cytolytic immune responses to infectious organisms (bacteria, viruses, parasites), tissue damaged by physical, chemical, or neoplastic insults, and other surfaces identified as 'nonself'.

For many years after its discovery, the role of complement in immunity was thought to be confined to innate immune responses with no impact on adaptive immune responses, in much the same way as innate immunity, in general, was relegated to those functions of immunity that involved prevention and confinement of infection while adaptive immunity provided effectors required to clear the infection.

The ability to separate the functions of the two arms of immunity was called into question as early as the 1970s, and since then the body of knowledge illustrating the interplay between the adaptive and innate wings of immunity has grown dramatically.

Similarly, the ability of complement to not only affect robust innate immune responses but also to interface with and influence T-cell and B-cell biology and adaptive responses has become increasingly appreciated.

Complement System Origins

Complement is a system of more than 30 proteins in the plasma and on cell surfaces, amounting to more than 3 g/L and constituting more than 15% of the globular fraction of plasma.

This array of proteins is organized into a hierarchy of proteolytic cascades that start with the identification of pathogenic surfaces and lead to the generation of potent proinflammatory mediators (anaphylatoxins), opsonization ('coating') of the pathogenic surface through various complement opsonins (e.g., C3b), and targeted lysis of the pathogenic surface through the assembly of membrane-penetrating pores known as the membrane attack complex (MAC).

Complement system represents an evolutionarily ancient component of host defense, and the evolutionary survival value of complement serves to accentuate the important roles it plays in host defense. Originally, it was thought to be a unique vertebrate feature, showing high degrees of homology in structure and function among the higher vertebrates as phylogentically ancient as the nurse shark.

What is Complement System References

1. Nesargikar P, et al. (2012). The complement system: history, pathways, cascade and inhibitors. European Journal of Microbiology and Immunology, 2(2), 103-111.
2. Dunkelberger J R, et al. (2010). Complement and its role in innate and adaptive immune responses. Cell research, 20(1), 34-50.