Complement Cascade

Question 1

Classical complement pathway, C1q has six specialised binding sites, what do they bind to?

Answer 1

Fc region of the igM and IgG antibody

Question 2

What are c1s and c1r?

Answer 2

Inactive serine proteases

Question 3

How does the classical pathway take place?

Answer 3

C1q binds to fc receptor(igm IgG)
Conformational change c1r, cleaves itself and c1s
C1s then cleaves C4 to C4a and C4b
C4b attaches pathogen membrane covalently
C2 is cleaved leading to the formation of C3 convertase C4bC2a

Question 4

Which is the most major complement pathway?

Answer 4

The alternative then classical and MBL pathways provide increased activation.

Question 5

The Mannose Bilnding Lectin pathway process?

Answer 5

MBL small quantities in the blood.
Macrophages activated by pathogen to secrete cytokine IL-6.
IL-6 stimulates hepatocytes to produce acute phase proteins including MBL
MBL six binding sites, binds to pathogen surface
Activation serine proteases MASP1 and MASP2
Cleaves C2 and C4
C4b binds via a thioester covalent bond to pathogen surface
C2a binds to C4b to create c3 convertase C4bC2a
C5 convertase= C4bC2aC3b

Question 6

The alternative complement pathway, how does soluble C3b become attached to the pathogen surface?

Answer 6

C3 released from liver= thioester bond hydrolysis creates iC3 (some are hydrolysed onto the bacteria surface)
Binds inactive complement factor B making it susceptible to cleavage via factor D.
Small fragment Ba released Bb( has small protease activity) stays attached to iC3.
IC3Bb complex binds C3 molecules and cleaves them to C3a and C3b via protease activity.
Some C3b becomes covalently attached to the pathogen surface.

Question 7

In the alternative pathway how does bound C3b create the C3 convertase?

Answer 7

Pathogen bound C3b binds factor B this facilitates the cleavage of factor B when factor D binds.
This creates the release of C3a and the formation of C3bBb complex on microbial pathogen.

Question 8

Why would an pathogen bound convertase be beneficial?

Answer 8

So when C3 is cleaved into C3b and C3Bb a large proportion of C3b will become bound to the pathogen surface.

Question 9

What form do complement proteins circulate in?

Answer 9

Zymognes

Question 10

C3b binding to pathogen surface is known as?

Answer 10

Complement fixation

Question 11

C3b bound complement function?

C3a function?

Answer 11

. tags pathogen for phagocytosis

Acts as chemoattractant to recruit effector cells

Question 12

Factor P function?

Answer 12

properdin, increases speed and power complement pathway stabalises C3 convertase by by binding to C3bBb

Question 13

Factor H and I function?

Answer 13

Factor H and I prevent formation of C3 convertase. Factor H binds C3b and changes its conformation so C3 is now susceptible to cleavage by Factor I.

Question 14

Decay accelerating factor Function

Membrane co factor protein function

Answer 14

binds to c3b component of alternative convertase=dissociation and inactivation.
Same function, also makes c3b susceptible to clevage and inactivation by factor I.

Question 15

Factor H, function in preventative self cell destruction?

Disadvantages?

Answer 15

Contains site for salic acid mainly found on human cell surface carbohydrates, can lead to a strategy of bacteria host evasion

Question 16

Function complement receptors?

Answer 16

Bind pathogens oponized with complement component

Question 17

CR1 complement receptor on macrophage

Answer 17

Binds C3b with other immune mediators present= phagocytosis. Also has a similar regulatory role to MCP, allows clevage via factor i C3b

Question 18

C5 convertase Fuction?

Answer 18

C3b2Bb (c5 convertase) cleaves c5 to c5a and c5b fragments.

Question 19

C5b function?

Answer 19

Activates the membrane attack complex

Question 20

Membrane attack complex?

Answer 20

C5b binds C6, then C7, this leads to a conformational change, inserts into the bilayer
C8 binds C567 and initiates C9 polymerization
C9 polymerises the complex to form membrane spanning pore that disrupts the cells integrity= cell death.

Question 21

C3a and C5a function?

Answer 21

Inflammatory agents, can induce anaphylactic shock
Phogocytes, enothelial cells and mast cells have specific receptors.
Vasoactive effects blood vessels=increase blood flow and vascular permeability
Induce contraction smooth muscle degranulation mast cells basophils(histamine)
Act as chemoattractant for neutrophils and monocytes.