The Complement System

Key points

• • Complement is a set of blood proteins that, once triggered, activate one another in a cascade to help destroy microbes.
• • It can be switched on by three routes: the classical pathway (antibody bound to a microbe), the lectin pathway (mannose on microbes) and the alternative pathway (directly on microbe surfaces).
• • All three routes meet at the central step of splitting the protein C3, which is the heart of the system.
• • Its main jobs map to its fragments: C3b coats microbes for phagocytosis (opsonisation), C3a and C5a drive inflammation and recruit cells (C5a is a chemoattractant), and C5b to C9 build the membrane attack complex.
• • The membrane attack complex (C5b to C9) makes a pore in the microbe's surface, letting it swell and burst, and is especially important against Neisseria and some other Gram-negative bacteria.
• • An inherited lack of certain complement proteins leads to repeated infections, and a lack of the C1 inhibitor causes hereditary angioedema.