Complement component C5b-9 complex (MAC (Membrane attack complex) or TCC (Terminal complement complex))

The **complement component C5b–9 complex**, also known as the membrane attack complex (**MAC**) or terminal complement complex (**TCC**), is a multi-protein structure formed during activation of the classical, lectin, or alternative pathways within the human complement system. It consists sequentially of components **C5b**, **C6**, **C7**, **C8**, and multiple copies (~12–18) of **C9**, which assemble on pathogen surfaces. Once formed, it inserts into lipid bilayers creating transmembrane pores that disrupt cellular integrity—leading to osmotic lysis and death. While essential for defense against microbes, uncontrolled deposition can cause host tissue injury seen in various autoimmune/inflammatory diseases. Regulatory proteins such as clusterin, vitronectin, and CD59 limit its action on self-cells. Therapeutically targeting this pathway—most commonly by inhibiting upstream cleavage events—has proven effective for several rare hematologic disorders but carries infection risk due to impaired bacterial killing.

Other names

Membrane attack complexTerminal complement complexMACTCC

For drugs like eculizumab/ravulizumab: - Inhibition of C5 cleavage prevents generation of both pro-inflammatory peptide C5a and initiator fragment C5b, thus blocking downstream MAC formation. - This prevents pore formation on host cells, reducing cell lysis and tissue damage in conditions with excessive complement activation. Other mechanisms could involve stabilizing regulatory proteins such as CD59 to prevent inappropriate MAC insertion into host membranes.