complement II Flashcards
3 reasons why C1`q can bind to so many ligands like Pentraxins, ECM LPS, HIV, PS etc?
Because it is modular (heterotrimeric) charge depndent , and flexibility
Structure of C1q?
2 x A+B chain dimer associates with a C-C dimer to form a dimer with two heterotrimeric globular head domains.
These dimers themselves trimerise to form a structure of 18 polypeptides with 6 glubular domains.
Which chain of C1q is thought to be most important for binding?
Thought that B chain most important and that A and C chains help to stabilise it.
2 ways C1q can be involved in B cell responses-
can help stimulate IgG production. And then binds to Fc receptors.
How is it involved in coagulation?
Can regulate platelet aggregation. C3 deficiency leads to thrombosis (formation of blood clots).
How can bind both IgM and IgG?
Uses different amino acids and charge clusters to do this.
Flexibiilty at hinge region also allows this.
What molecules can C1q bind to on apoptotic cells?
Phosphatidyl serine. C1q then binds its other end with calreticulin and CD91.
Or can also bind to pentraxins like CRP and SAP.
good and bad outcomes of complement activation in the brain?
Can be important for neuronal trimming. if deficient then mice have epilepsy and in mine normal optical development is impaired.
Howver may also be associated with binding amyloid plaques to contribute to neuroinflammation and neuronal death.
How might C1q and Wnt signalling contribute to ageing?
C1q can bind to frizzled and cleave LRP5/6 to activate Wnt signalling that is associated with ageing.
What can deficiency in C1q, C1s/, C4 and C2 lead to?
Reduced removeal of apoptotic cells, and SLE.
Upon complement treatment this can lead to tissue damage.
What can C3 deficiency lead to?
No opsonisation and MAC complex formation not possible.
Susceptible to severe recurrent infections (pyrogenic and neisseria), and lupus like disease.
properdin , factor D and B deficeincy?
Neisseria and recurrnet infections.
C1 inhibitor deficiency disease?
No inhibition of serine proteases.
hereditry agio-odema, but thought to be mainly because C1 inhibitor also inhibits kallikrein, so overproduction of bradykinin.
deficiency in CD59?
CD59 doesn’t inhibit C9 polymerisation.
More MAC formation that may lead to haemolysis and thrombosis.
factor H and factor I deficiency?
Can lead to seoncdary C3 deficiney and susceptibility to infection and susceptible to SLE + renal failure too.
Higher C5a C3a leads to vasopermeabilty and leakage.
aHUS.
