Complement Flashcards
Complement components generate products that: (4 things)
- Recruit inflammatory cells
- opsonize microbial pathogens and immune complexes (facilitating antigen clearance)
- Kill microbial pathogens
- Generate an inflammatory response
where does complement activation takes place
on antigenic surfaces (Antigen-Ab complexes, microbial surfaces, mammalian cell surfaces
the three pathways of activation of complement
classical, lectin, and alternative
Designation of components of the alternative pathway
Capital letters such as factor B, and factor D
designation for the lectin pathway
acronyms such as MASP-2
Classical pathway activation is initiated after
immune complex formation
what does C1 bind to
A site on the Fc portion of an antibody that is exposed after it has bound to antigen
C1 structure
macromolecule, of
Clq: 6 globular heads and extended tails
C1r
C1s
what activates C1qrs
at least 2 of the C1q globular heads are simulaneously bound to antibody. This requires 2 Fc portions to be close together on the antigenic surface. (would need 2 antigens with IgG but only one on IgM due to its pentameric structure)
C1r is activated by _____ and does _____
C1q binding to antigen; C1r cleaves C1s which activates C1s
C1s becomes active after
it is cleaved from the C1qrs molecule by C1r
Why does IgM require a smaller concentration to activate complement?
bc of its pentameric structure one IgM bound to antigen can bind to multiple of the globular heads of C1q
The Lectin pathway is itiated by
a protein- Mannan Binding Lectine (MBL) or ficolis (which are homologous to C1q)
MBL binds to
Mannose and other complex carbohydrates on the surface of many microbial pathogens
Ficolins bind
oligosaccharides
MASP- and MASP-2
Mannose binding lectin-associated serine protease: serine proteases that are physically associated with MBL/ficolins. similar to C1r and C1s
MASP-1 and MASP-2 are activated by
MBL/ficolins binding to a surface and undergoing a conformational change
difference between MBL and ficolins
similar structures but bind different carbohydrate domains
MBL-mannose and fructose residues
Ficolins- oligosaccharides w/ acetylated sugars
acitivated C1qrs or activated MASP- and MASP-2 cleave
C4 to C4a and C4b
C4b
binds to a cell surface (eg a microorganism) and the bound C4b binds C2
C2 bound to C4b
C2 is cleaved by C1s forming the C4b2a complex which remains bound to the cell surface.
C4b2a
cleaves C3 to C3a and C3b ( C3 convertase)