Flashcards in Lecture 25 - Complement Proteins Deck (55)
When and how were complement discovered?
A heat-labile factor in fresh serum that complements the function of antibodies is discovered
What are complement proteins?
Inactive proteins (often pro-enzymes, zymogens) in serum activated by proteolysis to carry out a range of immune functions
Complement protein functions
1) Bacterial, infected cell, foreign cell lysis
Number of C' proteins
What produce C' proteins?
3) Some epithelial cells
4) Neutrophils (less commonly)
Proportion of globin plasma that is C'
Protein component of plasma
How are C' activated?
Significance of 'a' and 'b' fragments of a C'
'a' is smaller fragment, 'b' is larger fragment.
Exception is C2, where 'a' is larger
Where does activation of C' often occur?
Surface of pathogen
How do host cells minimise self damage by C'?
Self cells have regulatory factors on their surfaces for reducing C' activity.
Pathogens lack these
Activity of soluble/fluid phase C'
Often transiently active, inactive.
Which C' pathway is an effector of humoral immunity?
Alternative pathway origins
Evolutionarily older than the lectin or classical pathways
Steps in C' cascade
1) 3 pathways for activation
2) Different pathways use different, but homologous components
3) Result in formation of different, but homologous C3 convertases
1) Cleavage of C3
2) Formation of C5 convertase
How can C3 be cleaved?
1) C3 convertase (C4b/C2a, C3b/Bb)
2) Spontaneous hydrolysis of C3 (tickover)
Types of C3 convertase
1) Classical/lectin - C4b/C2a
2) Alternative - C3b/Bb
Late steps (effector phase)
1) After C3 cleavage, C5 convertases are formed
2) C5 activation results in pore formation, inflammation, cell lysis
Common steps in complement activation
1) C3 convertase cleaves C3 (C4b/C2a or C3b/Bb)
2) C3 is cleaved, C3a is an inflammatory mediator, C3b binds to the surface of microbe (acts as an opsonin)
3) C3 convertases form the C5 convertases (C4b/C2a/C3b or C3b/Bb/C3b)
How does C3b bind to microbial surface?
Cleavage exposes reactive thioester groups on C3b
Reactive thioester groups bind amino and hydroxyl groups on microbial surface
Two types of C5 convertase
1) Classical/lectin - C4b/C2a/C3b
2) Alternative - C3b/Bb/C3b
Alternative pathway initiation
1) Low-levels of C3 hydrolysis initiate formation of active intermediates
2) Intermediates cleave C3 to C3a and C3b. In fluid, C3b is short-lived
3) C3b thioester group is revealed, C3b binds to microbial surface
4) B cleaved by factor D to Bb
5) C3b and Bb form C3 convertase on microbial surface
6) Properdin binds and stabilises C3 convertase on microbial surface
What cleaves B into Bb?
What stabilises C3 convertase on microbial surface in alternative pathway?
How is C5 convertase formed in the alternative pathway?
When C3 convertase cleaves C3, C3b joins C3b/Bb on cell surface, forms C5 convertase
1) Active form of factor B
2) Cleaved by factor D
3) Forms alternative C3 convertase with C3b, and alternative C5 convertase with two C3b's