Complement

Question 1

Where are complement proteins produced and found?

Answer 1

Mostly in the liver, found in the plasma. They can be soluble or expressed on cell surfaces.

Question 2

Functions of Complement

Answer 2

Acts as pattern recognition system and facilitates killing and disposal of pathogens. Waste disposal (clearance of immune complexes and apoptotic cells). Bridge between innate and adaptive immunity.

Question 3

3 Ways to Initiate Complement

Answer 3

1) Mannose binding lectin
2) Classical Pathway - antibody attached to antigen
3) Alternative Pathway - spontaneous low level activation on pathogen surfaces

Question 4

Classical Pathway

Answer 4

C1 binds to antibodies, C4 binds, C4a leaves, C4b attracts and cleaves C2, so only C2a remains. C4b2a is a C3 convertase, that attracts C3, which forms thioester bond with pathogen membrane and cleaves away C3a, leaving C3b. C3 convertases can repeatedly deposit C3bs all over a cell.

Question 5

Alternative Pathway

Answer 5

Independent of PRR. C3b can bind directly to cells via their reactive TED. Then, Factor B and Factor D bind. Factor D cleaves factor B into Ba and Bb. Bb remains, thus creating C3bBb, another C3 convertase. This pathway is most dominant after initiation.

Question 6

Complement Termination

Answer 6

After C3 binds and C3a is released, the molecule is a C5 convertase, which cleaves bound C5 into C5a (anaphylatoxin) and C5b. This complex is now a recognition site for opsnization or the formation of the MAC

Question 7

MAC

Answer 7

Membrane attack complex. Formation occurs when C6 binds to C5b, C7 to C6, C8 to C7. Many C9’s added to C8 to form a pore that causes cell lysis.

Question 8

Anaphylatoxin

Answer 8

Mediators of inflammation and phagocyte recruitment. C3a and C5a

Question 9

iC3b

Answer 9

Inactive C3b that has had its TED cleaved. This is one way to prevent activation of complement cascade. Created by factor H and I

Question 10

Consequences of Complement

Answer 10

Bacteria is killed by lysis, bacteria is opsonized by phagocytes, engulfed bacteria are killed by phagocytic granules activated by anaphylatoxins.

Question 11

C1qINH

Answer 11

Blocks classical pathway from occurring by changing C1q arm and preventing C4 binding.

Question 12

DAF

Answer 12

Decay Accelerating Factor, fits into C3bBb of alternate pathway and blocks it, causing Bb to dissociate, preventing C3 convertase activity, and preventing binding of next C3.

Question 13

Factor H

Answer 13

Has DAF activity and Cofactor activity to work with Factor I and turn C3b into iC3b.

Question 14

CD59

Answer 14

AKA Protectin, blocks completion of MAC by preventing C9 binding.

Question 15

Can pathogens subvert the complement system?

Answer 15

Of course, that’s what makes them pathogens