4. The complement system Flashcards
where are complement proteins produced
the liver
what is opsonization
coating of the pathogen with antibodies for recognition by phagocytic cells
complement proteins in circulation
circulate in their inactive forms, “activated” in the presence of pathogens or antibodies bound to pathogens
3 different proteolytic pathways that lead to complement activation
first to act = alternative pathway
second to act = lectin pathway
third to act = classical pathway
many complement proteins are proteases and zymogens, what does this mean
complement proteins are synthesized as their inactive forms (zymogens) and successively cleave each other to become activated (proteases)
stages of complement activation
- pattern recognition trigger
- protease cascade amplification/C3 convertase
- 1 of 3 effector pathways (inflammation, phagocytosis or MAC)
outcome of complement activation: inflammation
C3a and C5a recruit and activate leukocytes at site of infection
outcome of complement activation: opsonization
C3b bound to microbe surface is recognized by C3b receptor on phagocyte which destroys the pathogen
outcome of complement activation: membrane attack complex
insertion of complement proteins C5b-C9 into the pathogen membrane forms pores which disrupts the osmotic balance across the membrane and promotes pathogen death
exceptions in complement protein nomenclature
- C2 product C2a is a larger fragment than C2b
- C1q, C1r and C1s are not cleavage products but distinct proteins that compose C1
extra proteins in the alternative pathway
factor B (Ba and Bb) and factor D
complement proteins were named by…
their order of discovery (C1-4-2-3-5…)
* C4 acts before C2 and 3 but it was discovered first
which complement proteins are NOT in the alternative pathway
C1, 4 and 2
which complement protein is NOT in the lectin pathway
C1
lectin pathway initiation
initiated by mannose-binding lectin and ficolins
bind to carbohydrate structures on microbial surfaces
MASPs trigger the cleavage of complement routines (since there is no C1)