The complement system

The complement system is a collection of blood and cell surface proteins that is a major primary defense and a clearance component of innate and adaptive immune responses. At least 30 different complement proteins act sequentially to produce a wide ranges of activities, from cell lysis to augmentation of the adaptive response. The complement system has four major antimicrobial functions.

Lysis – Polymerization of specific activated complement components on a foreign cell or enveloped virus leads to the formation of pores. The lipid bilayer of the cell or virus is disrupted.

Activation of inflammation РSeveral peptides produced by proteolytic cleavage of complement proteins bind to vascular endothelial cells and lymphocytes. These cells then produce cytokines which stimulate inflammation and enhances responses to foreign antigens.

Opsonization – Certain complement proteins can bind to virions. Phagocytic cells with receptors for these complement proteins can then engulf the virus particles and destroy them. This process is called opsonization.

Solubilization of immune complexes – Some virus infections that are not cytopathic – the virus does not kill cells – lead to the accumulation of antibody-virus complexes. When these immune complexes lodge in blood vessels they can cause damage. An example is glomerulonephritis caused by deposition of antibody-antigen complexes in the kidney. Some complement proteins can disrupt these complexes and facilitate their clearance from the circulatory system.

There are three different complement pathways: classical, alternative, and mannan-binding. Unfortunately the nomenclature of the complement proteins is confusing, because they were named as they were discovered, not according to their function (see illustration below of the classical pathway). We’ll discuss the different pathways in the course of several posts. Don’t be daunted by the apparent complexity; stay with me and you’ll have a good appreciation of an extremely important part of our immune defense system.

And yes, viruses have evolved to modify the complement system.

classical-complement-s(click for a large version)