Lecture 2: The Complement System Flashcards
What is complement?
inactive plasma proteins (often pro-enzymes), activated (by proteolysis) to carry out various immunological functions
Where is complement found?
widely distributed in tissues and body fluids
What does complement do?
promotes lysis of bacteria, infected cells, transplanted cells etc. promotes opsonisation (i.e. phagocytosis of targeted cells) promotes inflammation (i.e. recruitment of leukocytes)
How many complement proteins are there and what are they produced by?
there are more than 30 complement proteins and they are produced by liver cells (hepatocytes), monocytes, macrophages and some epithelial (skin) cells
What does complement activation involve? When do proteins carry out their function?
an enzyme “cascade”
many active proteins exist but will not carry out their function until a trigger is fired e.g. first inactive protein in the “cascade” is activated
What are the terms given to cleaved products of enzyme cascade?
“a” for smaller fragment and “b” for larger fragment e.g. C3 cleaved to C3a and C3b
What is the trigger for the complement cascade?
C1 (inactive) -> C1 (active)
Where does activation of the complement system occur?
on the surface of pathogens (or other cells)
How do the products of complement activation bind to cell surfaces?
either alone, or bound to antibody
Why do host cell surface proteins regulate complement activation?
to minimise host damage
these proteins are found on normal (healthy) cells and are absent on microbes (e.g. bacteria)
What is the state of soluble complement components?
they are often inactive or transiently active
What are the stages of complement action?
pattern recognition trigger -> protease cascade amplification / C3 convertase -> inflammation / phagocytosis / membrane attack
What does the classical pathway of the complement system involve?
antigen-antibody complexes
- > IgM and IgG
- > formally an “effector mechanism of humoral immunity”
What does the alternative pathway of the complement system involve?
directly involves pathogen (bacterial surfaces)
antibody independent
part of the innate response
What does the lectin pathway of the complement system involve?
mannan binding lectin
How is the complement cascade initiated?
three pathways for activation which utilise different but often homologous components, e.g. C4 and C3, C2 and B
results in formation of different but homologous C3 convertases for classical/lectin and alternative pathways
What are the early common stages of the complement cascade?
up to (including) cleavage of C3 -> can be by C3 convertase
What are the late steps (effector phase) of the complement cascade?
after C3 cleavage, C5 convertases are formed, and C5 hydrolysis results in pore formation, cell lysis and inflammation
Which processes and proteins are involved in the common steps of the complement cascade?
proteolysis of C3 to C3a (inflammatory mediator) + C3b
binding of C3b to microbe surface
C3 activated by enzyme complex
C3 convertases form the C5 convertases
How does C3b act as an opsonin?
reactive thioester groups exposed on C3b bind amino and hydroxyl groups on microbial surfaces
What is C3 convertase in the different pathways of the complement system?
lectin pathway - C4b2a
classical pathway - C4b2a
alternative pathway - C3bBb
fluid phase - C3(H2O)Bb
What is C3 convertase in the different pathways of the complement system?
lectin pathway - C4b2a
classical pathway - C4b2a
alternative pathway - C3bBb
fluid phase - C3(H2O)Bb
What is C5 convertase in the different pathways of the complement system?
lectin pathway - C4b2a3b
classical pathway - C4b2a3b
alternative pathway - C3b2Bb
How is the alternative pathway of the complement system activated?
C3 undergoes spontaneous hydrolysis to C3(H2O), which binds to factor B, allowing it to be cleaved by factor D into Ba and Bb -> the C3(H2O)Bb complex is a C3 convertase, cleaving more C3 into C3a and C3b -> factor B binds noncovalently to C3b on a cell surface and is cleaved by Bb by factor D
