Complement system

The complement system is a large family of proteins that circulate in blood and tissue fluid in an inactive form, most of them made by the liver. It belongs to innate immunity but also works closely with antibodies, and its name reflects how it was first seen to complete, or complement, the killing of bacteria by antibodies. Its main proteins are numbered C1 to C9.

Activation can start in three ways. The classical pathway is triggered by antibodies bound to a microbe, the lectin pathway by a protein that binds sugars on microbial surfaces, and the alternative pathway by C3 that activates spontaneously and sticks to microbes. Each activated protein cuts and switches on the next, so a small trigger is greatly amplified. All three routes meet at C3. Its fragment C3b coats the microbe so phagocytes can seize it, a process called opsonization. The small fragments C3a and C5a promote inflammation and attract neutrophils, and the late proteins C5b to C9 assemble into the membrane attack complex, a pore that can make bacteria burst.

Regulatory proteins protect the body's own cells from attack. Doctors measure C3 and C4 in blood to follow disorders such as lupus, in which their levels can drop.