Editing Complement system (section)

=== Alternative pathway ===
{{Main|Alternative complement pathway}}
The [[alternate complement pathway|alternative pathway]] is continuously activated at a low level, analogous to a car engine at idle, as a result of spontaneous [[complement component 3|C3]] hydrolysis due to the breakdown of the internal [[thioester]] bond (C3 is mildly unstable in aqueous environment). The alternative pathway does not rely on pathogen-binding antibodies like the other pathways.<ref name="Abbas_2010" /> C3b that is generated from C3 by a C3 convertase enzyme complex in the fluid phase is rapidly inactivated by [[factor H]] and [[complement factor I|factor I]], as is the C3b-like C3 that is the product of spontaneous cleavage of the internal thioester. In contrast, when the internal thioester of C3 reacts with a hydroxyl or amino group of a molecule on the surface of a cell or pathogen, the C3b that is now covalently bound to the surface is protected from factor H-mediated inactivation. The surface-bound C3b may now bind [[complement factor B|factor B]] to form C3bB. This complex in the presence of [[factor D]] will be cleaved into Ba and Bb. Bb will remain associated with C3b to form C3bBb, which is the alternative pathway C3 convertase.<ref>{{Cite journal |display-authors=6 |vauthors=Rooijakkers SH, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, Ricklin D, Lambris JD, Janssen BJ, van Strijp JA, Gros P |date=July 2009 |title=Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor |journal=Nature Immunology |volume=10 |issue=7 |pages=721–7 |doi=10.1038/ni.1756 |pmc=2729104 |pmid=19503103}}</ref>

The C3bBb complex is stabilized by binding oligomers of [[properdin|factor P]] (properdin). The stabilized C3 convertase, C3bBbP, then acts enzymatically to cleave much more C3, some of which becomes covalently attached to the same surface as C3b. This newly bound C3b recruits more B, D and P activity and greatly amplifies the complement activation. When complement is activated on a cell surface, the activation is limited by endogenous complement regulatory proteins, which include [[CD35]], [[CD46]], [[CD55]] and [[CD59]], depending on the cell. Pathogens, in general, don't have complement regulatory proteins (there are many exceptions, which reflect adaptation of microbial pathogens to vertebrate immune defenses). Thus, the alternative complement pathway is able to distinguish self from non-self on the basis of the surface expression of complement regulatory proteins. Host cells don't accumulate cell surface C3b (and the proteolytic fragment of C3b called iC3b) because this is prevented by the complement regulatory proteins, while foreign cells, pathogens and abnormal surfaces may be heavily decorated with C3b and iC3b. Accordingly, the alternative complement pathway is one element of [[innate immunity]].{{citation needed|date=May 2015}}

Once the alternative C3 convertase enzyme is formed on a pathogen or cell surface, it may bind covalently another C3b, to form C3bBbC3bP, the C5 convertase. This enzyme then cleaves C5 to C5a, a potent [[anaphylatoxin]], and C5b. The C5b then recruits and assembles C6, C7, C8 and multiple C9 molecules to assemble the [[membrane attack complex]]. This creates a hole or pore in the membrane that can kill or damage the pathogen or cell.<ref name=":1" />