Description
The three distinct activation pathways of complement converge with the formation of a C5 convertase and it is cleavage of C5 by these convertases that initiates the lytic or terminal pathway. In contrast to the activation pathways, which require enzymatic cleavage for activation, the terminal pathway relies on conformational changes induced by binding. Binding of C6 facilitates binding of C7 which alters the conformation of the complex. After binding of C8 a variable number of C9 molecules associate with the C5b678 complex, the so called terminal complement complex (TCC) or Membrane Attack Complex (MAC). The formation of the membrane form of TCC causes lysis of cells or can trigger a variety of cellular metabolic pathways resulting in the synthesis and release of inflammatory mediators. The TCC contains neoantigens that are absent from the individual native components. Neoantigens are present both in the membrane-bound (MAC) and the fluid-phase (SC5b-9) complex. TCC is present in normal human plasma, < 1 AU/ml, and increases in patients with complement activation