Page 110 - Veterinary Immunology, 10th Edition

therefore called classical C3 convertase. The newly generated C3b
VetBooks.ir binds and activates C5. Subsequent reactions lead to formation of

the terminal complement complex and microbial killing.
In addition to binding immune complexes, C1 can also be

activated directly by some viruses, or by bacteria such as Escherichia
coli and Klebsiella pneumoniae. C1q can also bind to apoptotic and
necrotic cells, extracellular matrix proteins, pentraxins such as C-
reactive protein, amyloid and prion proteins, and DNA. However,

all these substances (with the exception of immune complexes) can
also bind the complement inhibitors C1-BP and FH so that full
complement activation does not occur. If these inhibitory processes
are blocked, uncontrolled complement activation may lead to

unwanted inflammation.

The Amplification Pathway

All surface-bound C3 convertases, regardless of their origin, can

induce the next steps in complement activation, the amplification
pathway (Fig. 4.10). Once C5 binds to C3b, substrate modulation
occurs, and the C5 is then cleaved by C3bBb (Fig. 4.11). The
convertases break C5 (195 kDa) into a small fragment called C5a,
leaving a large fragment C5b attached to the C3b. This cleavage also

exposes a site on C5b that can bind two new proteins, C6 and C7, to
form a multimolecular complex called C5b67 (Fig. 4.12). The C5b67
complex can then insert itself into the microbial cell wall. Once

inserted in the surface of an organism, the complex first binds a
molecule of C8 to form C5b678. Twelve to 18 C9 molecules then
polymerize with the C5b678 complex to form a tubular structure
called the terminal complement complex (TCC), (also called the
membrane attack complex [MAC] or C5b6789). The TCC inserts

into microbial cell membranes and punches a hole in the invader. If
sufficient TCCs are formed on an organism, it will be killed by
osmotic lysis. These TCCs can be seen by electron microscopy as

ring-shaped structures on the microbial surface with a central
electron-dense area surrounded by a lighter ring of poly C9 (see
Fig. 4.12).

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