1. Figure 2 Overview of the complement system
Figure 2 | Overview of the complement system. The complement system can be activated by the classical, lectin and alternative pathways. The lectin pathway is activated by binding of mannose-binding lectin (MBL), ficolins or collectins to carbohydrates. C1q activates the classical pathway by binding to IgM and IgG either in antigen-antibody (Ag-Ab) complexes or adsorbed (in denatured conformation) onto material surfaces, or by binding to negatively charged molecules such as DNA, lipopolysaccharide, heparin or C-reactive protein. Activation of the lectin and classical pathways generates proteolytic enzymes in the fluid phase (mannan-binding lectin serine protease 1 (MASP-1), MASP-2, and C1r, C1s, respectively), which promote formation of the classical/lectin pathway C3 convertase C4bC2a. The alternative pathway is activated by the conformational alteration of C3 into C3(H2O) through a process called tick-over, which is amplified by properdin. Activation of the alternative pathway induces formation of the alternative pathway C3 convertase, C3bBbP. The C3 convertases cleave C3 into the anaphylatoxin C3a and the opsonin C3b, which can bind to pathogen surfaces and be further cleaved to iC3b, which facilitates phagocytosis via its interaction with the complement receptors CD35 (also known as CR1) and CD11b/CD18 (also known as CR3). The alternative pathway provides a potent positive feedback loop because each bound C3b moiety is the potential nucleus of a novel C3bBb convertase complex, which can cleave multiple additional C3 molecules. Binding of C3b to the C3 convertases alters their specificity toward C5. Activation of C5 yields the anaphylatoxin C5a, which is involved in inflammatory signalling, and initiates generation of the membrane attack complex (MAC), which can insert into cell membranes and cause lysis. Both C3a and C5a attract and activate polymorphonuclear cells and monocytes to further fuel inflammation.
Ekdahl, K. N. et al. (2017) Cardiovascular disease in haemodialysis: role of the intravascular innate immune system
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