Complement

Question 1

What co-stimulatory molecules upregulated by DCs by CD4+ T cells to prime them?

Answer 1

Upregultates CD40 and 4-IBBL on DCs (increases their cytokine production too)

Question 2

What is the classical and alternative C3 convertase?

Answer 2

classical C3 convertase: C4b2b

alternaitve: C3bBb

Question 3

What is the classical and alternative C5 convertase?

Answer 3

classical C5 conv.: C4b2b3b

alteranative: C3bBb3b

Question 4

What molecules associte with C1q to cleave C4 and C2?

Answer 4

C1r2s2

Question 5

What pro thrombin factors assocaite with MBL (and other collections and ficolin)

Answer 5

MASP 1 and MASP 2.

Question 6

How is the alternative pathway C3 convertase formed?

Answer 6

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.

Question 7

What role does properdin play? What other theory?

Answer 7

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.

Question 8

How is C5 alternative convertase formed?

Answer 8

C3bBb anchored by properdin generates C3b.

Forms the C3bBb3b C5 convertase.

Question 9

Why is C3b mostly inactive in the fluid phase?

Answer 9

Becuase of nucleophilic attack of water on the Cys(SH) and Gln (C=O). Can’t form a thioester bond with surface.

Question 10

What does C3b and C4b form a thioster bond on surface with?

Answer 10

With proteins or carbohydrates. NH2 or OH domain does nucleophilic attack on the Gln C=O.
Form S-C=O-NH.

Question 11

What molecule can prevent C1r2s2 complex from binding C1q?

Answer 11

C1 inhibitor!! C INH.

Question 12

What can displace C2b or Bb from the C3 convertase?

Answer 12

DAF and CR1 and MCP can each do this for classical pathway.

Only CR1 and MCP can displace Bb for an alternative.

Question 13

What two molecules can work with factor 1 to cleave C3b into iC3b?

Answer 13

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.

Question 14

What molecules can inhibit the MAC formation?

Answer 14

CD59 can prevent C9 binding and polymerisation.

S protein can bind C7 and remove the C5a,6,7 complex from the membrane.

Question 15

How does the alternative pathway form an amplification loop?

Answer 15

C3bBb generates more C3b than can bind, recruit Factor B which can be cleaved by Factor D to form more C3bBb.

Question 16

What might MASP 1 do?

Answer 16

Act as an activator of MAS2P. May be involved in coagulation.

Question 17

HOw might MASP 3 contribute to the alternative pathway?

Answer 17

By activating Factor D (which cleaves factor B).

Question 18

What does factor 1 cleavage of to iC3b do?

Answer 18

Prevents further complement activation. But it still acts as a major opsonin.

Question 19

Which immunoglobulins are especially good at activating classical complement pathway?

Answer 19

IgG3 and IgM (IgG1).

Question 20

Which Ig doesn’t activate the classical complement pathway?

Answer 20

IgG4.

Question 21

What things can activate C1q independently from Immunoglbulins?

Answer 21

Can have pentraxins and also other PAMPs, like lipoteichoic acid and LPS, and viruses too.

Question 22

What synthetic things (used in drug therapy) can activate C1q?

Answer 22

nanoparticles and also medical devices.

Question 23

What can diminish C1q activation and how?

Answer 23

PEG and heparin (which binds to factor H).

Question 24

Can MBL bind to postive and negative bacteria?

Answer 24

Both can activate MBL.

Question 25

Can Ig activate MBL?

Answer 25

yes, by binding to sugars on IgG-GO and polymeric IgA can activate MBL too.

Question 26

Can IgG and LPS activate the alterantive pathway?

Answer 26

Yes IgG via the Fab’2 portion can activate alternative pathway.
As well as glucans and LPS.

Question 27

What cells highly express CR1? What effects might this have in adenovirus gene therapy?

Answer 27

CR1 highly expressed by RBC.

Adenovirus actiation of complement can lead to opsonisation and RBC coating that prevents it from reaching target.

Question 28

What can the Ig complement receptor bind? And what can it stop?

Answer 28

CRIg can bind to C3b and iC3b, and can prevent C3bBb formation.

Question 29

What does CR2 (CD21) bind?

Answer 29

iC3b and C3d.

Question 30

What cells highly express CR2? (CD21)

Answer 30

highly expressed by folliciular dedritic cells and B cells.

FDC important for presentation of native antigen to B cells.

Question 31

difference between MASP and C1r2s2.

Answer 31

MASPs are homologues and form homodimers, Cr12 binds to C1q, and C1s2 binds to the bound C1r2- forms a heterotetramer.

Question 32

What can inhibit both C1sC1r and MASPs?

Answer 32

serine protease inhibitors (SERPIN) e.g. C1 inhibitor.

Question 33

Decay destruction and dissocation?

Answer 33

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.

Question 34

Dissociating and destructive RCA cluster proteins?

Answer 34

dissociating: DAF (CD55), MCP and CR1.
destructive: soluble factor H and C4Bp work with factor 1.

Question 35

Where can fator H and C4Bp inhibit complement?

Answer 35

Inhjibti it in the fluid pahse an bind to damagedd host tissue to prevent excessive activation.

Question 36

How do pathogens use RCA proteins to protect themselves?

Answer 36

recruit Factor H and C4bp to their cell surface to avoid complement activation.
Or viral genomes have acquired DAF/MCP like genes.

Question 37

How can pathognes use complement receptors to benefit them?

Answer 37

By using them to adhere to cells e.g. CR2, and DAF as receptors.
Or mild complement activation and C3 binding may enhance uptake.

Question 38

How is sialic acid on host cells protective?

Answer 38

sialic acid induce inhibitory signals, and regulates the alternative pathway (bids to factor H inhibits C3 convertase formation).