C5C9

C5-C9, also referred to as C5C9 in some texts, denotes the terminal components of the complement system, the proteins numbered C5 through C9. These proteins are solubleRecognition proteins produced by the liver and circulating in serum as inactive precursors that become activated during immune responses.

Activation and assembly occur when C5 is cleaved by the C5 convertase into C5a and C5b. C5a acts as a potent inflammatory mediator and chemoattractant, while C5b initiates the formation of the membrane attack complex (MAC). The MAC is assembled in a stepwise fashion as C5b binds C6, C7, C8, and multiple copies of C9, ultimately creating a transmembrane pore in target cell membranes and leading to lysis. The terminal components are especially effective against certain bacteria and are a key effector mechanism of innate immunity.

Regulation of C5-C9 is crucial to protect host cells from unintended damage. Regulatory proteins such as CD55 (decay-accelerating factor) and CD59 (protectin) limit MAC formation on host cells. Deficiencies or dysregulation of the terminal complement pathway increase susceptibility to infections with encapsulated bacteria, most notably Neisseria meningitidis, and can contribute to complement-mediated diseases. Conversely, excessive MAC activity can contribute to tissue damage in inflammatory and autoimmune conditions.

Clinical testing commonly uses the CH50 assay to assess the functional integrity of the entire classical pathway, including C5-C9, while assays detecting the terminal complement complex or C5b-9 can help evaluate complement activity in various disorders. The term C5-C9 is used in immunology to designate these late-acting components of the cascade.