Complement Flashcards
functions of complement
lysis
opsonization
activation of inflammatory response
clearance of immune complexes
describe the classical pathway
- Ab (IgM or 2 IgG) binds C1q
- C1r C1s (2 of each) bind C1q - Ca2+
- C4, C2 - C4bC2a (C3 convertase) - Mg 2+
- C3 activated & C3b binds = amplification
- C4bC2aC3b = C5 convertase
- C5b678-C9 = MAC
- split off products = C3a, C4a, C5a
describe the alternative pathway of complement
- no Ab involved
- spontaneous hydrolysis of C3
- fluid phase (plasma) and cell bound
- sialic acid on host cell inactivates C3b
- proteins involved = factor B, D (serine protease), Properdin
pathogen activators of alt pathway
gram neg = LIPOPOLYSACCH
gram pos = teichoic acid
fungi & yeast cell wall = zymosan
some viruses
non-pathogen activators of alt pathway
IgG, IgA, IgE
cobra venom
pur carbs (agarose, inulin)
anionic polymers = dextran sulphate
describe the lectin pathway
- lectins acute phase reactants produced in liver = collectins
- mannose-binding lectin (MBL)
> mannose, N-acetyl glucosamine, D-glucose, L-fucose - proteins involved = MBL, MBL-associated serine proteases = MASP1, MASP2, MASP3
what happens in the lectin pathway?
MBL binds CHO residues on microbes
MASP binds and is activated
C4 C2 cleaved to C4BC2a
C3 activated
pathogens with D-mannose, L-fucose
gram neg = Salmonella
gram pos = Streptococci
yeast = C. albicans
viruses = influenza A, HIV
parasites = Leishmania
complement receptors
bind complement coated organisms to aid in clearance
- used in conjunction with regulator proteins (PROTECT HOST CELLS)
- amplify B cell signal
- used by some pathogens to enter cell
examples of complement receptors
CR1
CR2
CR3/4
CR1
- aid phagocytosis by monocytes, macs, and neuts
- binds C3b, C4b
- help with immune complex clearance via rbc delivery to spleen
- required for factor I to function
- receptor for P. falciparum
CR2
- co-receptor on B cell surface
- amplification signalling with associated CD19 and CD81 (TAPA-1)
- EBV uses CR2 as receptor
CR3 and CR4
CD11b/c/CD18 integrins
- aid phagocytosis by monos, macs, neuts
- help neuts and monos with extravasation
- present on NK cells
describe the three components of complement regulation
- inhibitors regulate complement cascade = localize activation, protect host
- soluble (plasma proteins)
- membrane bound (host clls and some pathogens)
list the soluble complement inhibitors
C1-inhibitor (C1-Inh)
factor H
factor I