Nonspecific Defenses of the Host |
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24. Describe the complement pathways. 25. Differentiate between the classical and alternative pathways. 26. Describe the outcomes of complement fixation. 27. Define opsonization. 28. Describe the effects of deficiencies of specific complement proteins. |
The complement system consists of a group of serum proteins that activate one another to destroy invading microorganisms. (Serum is the liquid remaining after blood plasma is clotted.)
There are three pathways to complement activation but they all end up forming a C3 convertase complex which activates C3 and results in three things:
C3 is cleaved to C3a and C3b
C3a stimulates inflammation
C3b opsonizes and cleaves C5 to produce C5a and C5b
C5a stimulates inflammation
C6, C7, C8, and C9 associate to form the MAC, which causes cell lysis.
Stimulates Inflammation
Cytolysis
Classical Pathway
C1 binds to antigen – antibody complexes. (Antibody binding to antigen is called "antigen fixation"; when an antigen-antibody complex binds C1 this is called "complement fixation")
C2 and C4 associate and this acts as C3 convertase.
Alternative Pathway
Factor B, factor D, factor P, and C3b bind to certain cell wall polysaccharides (i.e. peptidoglycan) to activate C3b.
C3 undergoes autolysis to provide C3b, which is very unstable and has a short half-life.
Factor B stabilizes the C3b.
Factor D cleaves factor B to produce a C3b-factorBb molecule; this acts as C3 convertase.
Properdin, Factor P, stabilizes the C3b-factorBb C3 convertase.
The Lectin Pathway
Phagocytosis by macrophages induces release of chemicals that stimulate the liver to produce carbohydrate binding proteins (lectins).
One such lectin, mannose-binding lectin (MBL) binds to mannose on bacterial cells walls and on some viruses.
MBL opsonizes and activates C2 and C4 to activate C3.
Complement is deactivated by host-regulatory proteins and water.
Complement deficiencies can result in an increased susceptibility to disease.