Complement Flashcards
What co-stimulatory molecules upregulated by DCs by CD4+ T cells to prime them?
Upregultates CD40 and 4-IBBL on DCs (increases their cytokine production too)
What is the classical and alternative C3 convertase?
classical C3 convertase: C4b2b
alternaitve: C3bBb
What is the classical and alternative C5 convertase?
classical C5 conv.: C4b2b3b
alteranative: C3bBb3b
What molecules associte with C1q to cleave C4 and C2?
C1r2s2
What pro thrombin factors assocaite with MBL (and other collections and ficolin)
MASP 1 and MASP 2.
How is the alternative pathway C3 convertase formed?
C3 continously cleaved in fluid phase.
If C3b binds to surface and Factor B is recruited that is cleaved by factor D.
This forms C3bBb.
What role does properdin play? What other theory?
Properdin often as a trimer.
Binds to C3b to stabilise the C3bBb C3 convertase.
May also bind the surface first via charge clusters and recruit C3b and factor B from plasma.
Then also anchors it.
How is C5 alternative convertase formed?
C3bBb anchored by properdin generates C3b.
Forms the C3bBb3b C5 convertase.
Why is C3b mostly inactive in the fluid phase?
Becuase of nucleophilic attack of water on the Cys(SH) and Gln (C=O). Can’t form a thioester bond with surface.
What does C3b and C4b form a thioster bond on surface with?
With proteins or carbohydrates. NH2 or OH domain does nucleophilic attack on the Gln C=O.
Form S-C=O-NH.
What molecule can prevent C1r2s2 complex from binding C1q?
C1 inhibitor!! C INH.
What can displace C2b or Bb from the C3 convertase?
DAF and CR1 and MCP can each do this for classical pathway.
Only CR1 and MCP can displace Bb for an alternative.
What two molecules can work with factor 1 to cleave C3b into iC3b?
CR1 and MCP work with Factor I to form iC3b.
Factor H attracted by charge cluster can also work with Factor I to do this.
What molecules can inhibit the MAC formation?
CD59 can prevent C9 binding and polymerisation.
S protein can bind C7 and remove the C5a,6,7 complex from the membrane.
How does the alternative pathway form an amplification loop?
C3bBb generates more C3b than can bind, recruit Factor B which can be cleaved by Factor D to form more C3bBb.
What might MASP 1 do?
Act as an activator of MAS2P. May be involved in coagulation.
HOw might MASP 3 contribute to the alternative pathway?
By activating Factor D (which cleaves factor B).
What does factor 1 cleavage of to iC3b do?
Prevents further complement activation. But it still acts as a major opsonin.
Which immunoglobulins are especially good at activating classical complement pathway?
IgG3 and IgM (IgG1).
Which Ig doesn’t activate the classical complement pathway?
IgG4.
What things can activate C1q independently from Immunoglbulins?
Can have pentraxins and also other PAMPs, like lipoteichoic acid and LPS, and viruses too.
What synthetic things (used in drug therapy) can activate C1q?
nanoparticles and also medical devices.
What can diminish C1q activation and how?
PEG and heparin (which binds to factor H).
Can MBL bind to postive and negative bacteria?
Both can activate MBL.
Can Ig activate MBL?
yes, by binding to sugars on IgG-GO and polymeric IgA can activate MBL too.
Can IgG and LPS activate the alterantive pathway?
Yes IgG via the Fab’2 portion can activate alternative pathway.
As well as glucans and LPS.
What cells highly express CR1? What effects might this have in adenovirus gene therapy?
CR1 highly expressed by RBC.
Adenovirus actiation of complement can lead to opsonisation and RBC coating that prevents it from reaching target.
What can the Ig complement receptor bind? And what can it stop?
CRIg can bind to C3b and iC3b, and can prevent C3bBb formation.
What does CR2 (CD21) bind?
iC3b and C3d.
What cells highly express CR2? (CD21)
highly expressed by folliciular dedritic cells and B cells.
FDC important for presentation of native antigen to B cells.
difference between MASP and C1r2s2.
MASPs are homologues and form homodimers, Cr12 binds to C1q, and C1s2 binds to the bound C1r2- forms a heterotetramer.
What can inhibit both C1sC1r and MASPs?
serine protease inhibitors (SERPIN) e.g. C1 inhibitor.
Decay destruction and dissocation?
decay: C3 convertases have a short half life.
dissocaition: RCA proteins bind convertases to displace them.
Destruction: proteolytic degradation by RCA of C3b/C4b with factor 1.
Dissociating and destructive RCA cluster proteins?
dissociating: DAF (CD55), MCP and CR1.
destructive: soluble factor H and C4Bp work with factor 1.
Where can fator H and C4Bp inhibit complement?
Inhjibti it in the fluid pahse an bind to damagedd host tissue to prevent excessive activation.
How do pathogens use RCA proteins to protect themselves?
recruit Factor H and C4bp to their cell surface to avoid complement activation.
Or viral genomes have acquired DAF/MCP like genes.
How can pathognes use complement receptors to benefit them?
By using them to adhere to cells e.g. CR2, and DAF as receptors.
Or mild complement activation and C3 binding may enhance uptake.
How is sialic acid on host cells protective?
sialic acid induce inhibitory signals, and regulates the alternative pathway (bids to factor H inhibits C3 convertase formation).
