Page 101 - Veterinary Immunology, 10th Edition

VetBooks.ir Activation Pathways

The Alternative Pathway

The alternative pathway is an evolutionary ancient innate pathway.
It is triggered when microbial cell walls meet complement proteins
in the blood.

The most important complement protein is called C3. C3 is a
disulfide-linked heterodimer with α and β chains. It is synthesized
by liver cells and macrophages and is the most abundant
complement component in serum. C3 has a reactive thioester side-
chain, that, when activated, binds to microbes and marks them for

destruction by immune cells. Activation of this thioester side-chain
must be carefully regulated to ensure that C3 does not bind to
normal cells. To prevent such accidents, the thioester group in

inactive C3 is hidden within the folded molecule like a pocket knife.
In healthy normal animals, C3 spontaneously breaks down into
two fragments called C3a and C3b (Fig. 4.3). This breakdown
exposes the reactive thioester group in C3b. The thioester then
generates a carbonyl group that covalently binds the C3b to

carbohydrates and proteins on nearby cell surfaces (Fig. 4.4). The
breakdown of C3 also exposes binding sites for a protein called
factor H (FH). When FH binds to these sites, a protease called factor

I (FI) can then cleave the C3b, preventing further activation and
generating two fragments, iC3b and C3c. iC3b binds receptors on
circulating leukocytes (Fig. 4.5). It stimulates these cells to engulf
pathogens and it activates inflammatory cells. The final breakdown
product of C3, C3dg, targets pathogens to surface receptors on B

cells and so promotes antibody production (Chapter 15).

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