Complement 2 Flashcards
(22 cards)
what are the 2 additional roles of complement?
phagocytosis
clearance
how is complement involved in phagocytosis?
- antibodies bound to bacteria activate complement and bonding of C3b to bacteria
- engulfment of bacteria by neutrophils is mediated by Fc receptors + complement receptors
- granules fuse with phagosomes, releasing toxic oxygen metabolites that kill bacteria
how is complement involved in clearance?
- small antigen-antibody complexes form and activate complement
- complex gated with C3b
- bound C3b binds to Cr1 on erythrocyte surface
- delivers immune complexes to spleen + liver, where they are removed
what are the 4 main complement receptors and their ligands?
where are these found?
CR1
- CD35
- erythrocytes
CR2
- CD21
- B and T cells
CR3
- CD11b+CD18
- neutrophils
CR4
- CD11c+CD18
- neutrophils
what do the 4 main complement receptors have in common?
complement control repeat protein receptors
beta-2 intern family adhesion molecules
what are the 2 anaphylatoxin receptors?
where are they expressed?
what type of receptors are these?
C3a receptor
- widely expressed
C5a receptor
- lymphoid cells
GPCR
which molecules are important for regulating complement activation?
DAF
= decay accelerating factor
factor I
= C3b/C4b inactivator
factor H
= co=factor for factor I
MCP
= membrane cofactor protein
CR1
= complement receptor 1
C4BP
= C4 binding protein
what do CR1 and DAF do?
compete with Factor B in binding with C3b on the cell surface
they can even remove Bb from an already formed C3bBb complex
what does factor I do?
which other molecules does it require?
cleaves C3b into its inactive form iC3b
-> brevets C3 convertase formation
requires a C3b-binding protein like factor H, CR1 + MCP
what does factor H do?
what does it preferentially bind too and what does this result in?
inhibits formation of C3 convertase by competing with factor B for binding to C3b
accelerates the decay of C3 convertase
acts as a cofactor for factor I-mediated cleavage of C3b
vertebrate cells (high affinity for GAGs) -> protects host cells from complement-mediate damage
describe the structure of factor H
what do these domains bind to?
4 complement control repeat units at the N terminus
- binds to C3b on surface of cells
2 domains (19 +20)
- bind to C3b
- bind to sugars on host cells
how does factor H react differently to self and non-self cells?
non-self
= weak binding
-> activation
self
= strong binding to GAGs and C3b
-> regulation
what have some microbes now developed?
immune evasion proteins that help factor H bind
-> breakdown of C3b
= evade complement activation on their surfaces
what are these immune evasion proteins/mechanisms that microbes have evolved?
C3 convertase inhibitors
protease production
-> breakdown +ve complement fragments of microbial surface
RCA-like expression
binding of RCA
(complement regulators)
explain how C4bp and factor H promote the dissociation of C3 convertases
what else are these molecules involved in?
C4bp acts on C4b2b
factor H acts on C3bBb
they bind to the covalently bound component (C4b or C3b)
-> displaces the associated cofactor
C4bp, fH, CR1 + MCP
catalyse the permanent inactivation of C3b and C4b via proteolytic cleavage by factor I
what do complement deficiencies result in?
increased susceptibility to bacterial infections e.g. meningococcal disease
autoimmune diseases
what is the name of the disease caused by a C4 deficiency?
systemic lupus erythematosus (SLE)
what are the features of C2 deficiency?
most common of the inherited classical complement component deficiencies in Caucasians
most common cause of death = sepsis
most common organisms: S. pneumoniae and H. influenzae
what are the features of C3 deficiency?
rarest fo the 4 early component deficiencies
most severe phenotype
Membranoproliferative glomerulonephritis
neutrophil dysfunction
humoral deficiencies
complement deficiencies
what are the features of factor B deficiency?
single case has been reported
meningococcemia
what are the features of factor D deficiency?
Neisserial infections are the most common manifestation
what are the features properdin deficiency?
X-linked complement deficiency
1 of more common complement deficiencies + occurs largely in Caucasians
1 or more episodes of meningococcal disease
high fatality rate
