Complement

Question 1

3 complement pathways in short

Answer 1

Lectin - MBL and ficolins recognize and bind carbs on pathogen surface

Classical - C1q interacts with pathogen surface or antibodies bound to surface

Alternative pathway - C3 undergoes spontaenous hydrolysis to C3(H2O) to initiate eventual deposition of C3 convertase on microbial surfaces

Question 2

All pathways

Answer 2

Generate a C3 convertase which cleaves C3…leaving C3b bound to membrane and releasing C3a

Question 3

3 consquences of comlement

Answer 3

c3a and c5a recruit phagocytic cells to site of infeciton and promote inflammation

Phagocytes with receptors for C3b engulf and destroy pathogen (opsonization)

Completion of cascade leads to membrane-attack complex

Question 4

Lectin pathway

Answer 4

MASP-2 associated with MBL (or ficolin) cleaves C4 to C4a and C4b, C4b binds to microbial surface…C4b then binds C2, which is cleaved by MASP-2 to C2a and C2b…C2a forms C4b2a complex and C2b released…C4b2a is a C3 convertase that cleaves C3 into C3a and C3b…c3b bind to microbial surface and complex with C4b2a3b to make a C5 convertase

Question 5

Classical pathway

Answer 5

C1q associated with serine proteases C1r and C1s binds antibody…C1r and C1s cleave C4 and then same as lectin

Question 6

Alternative pathway

Answer 6

Amplification of other pathways

C3b deposied by classical or lectin pathway…C3b binds factor B…Factor B cleaved by factor D into Ba and Bb…C3bBb complex is a C3 convertase that cleaves more C3 molecules into C3a and C3b

Question 7

Tickover

Answer 7

C3 undergoes spontaneous hydrolysis to form C3(H2O) which binds factor B…allows it to be cleaved by factor D into Ba and Bb…C3(H2O)Bb complex is a c3 convertase…C3b rapidly inactivated unless near cell surface…Factor B binds C3b on cell surface and cleaved to Bb by factor D

Question 8

What do pathogens lack and what is present to help?

Answer 8

Properdin (factor) P because lack complement-regulatory proteins…binds C3 convertase and pathogen surface to stabilize

Question 9

C5 convertase formation

Answer 9

C3b binds C4b2a or C3bBb to form C4b2a3b or C3b2Bb…C5 binds to C3b component of the enzyme…C5 is cleaved by C2a or Bb to form C5a or C5b…C5b remains bound

Question 10

MAC

Answer 10

C5b binds C6 and C7…C5b67 complexes with membrane via C7…C8 binds and inserts into membrane…C9 binds and polymerize…10-16 molecules of C9 form pore into membrane

Question 11

Regulation of C1q/C1r/C1s complex

Answer 11

C1INH dissociates C1r and C1s from active C1 complex (classical)

Question 12

Regulation of C4b2a (c3 convertase)

Answer 12

DAF, C4BP, and CR1 displace C2a from complex….C4b bound by C4BP, MCP, or CR1 is cleaved by protease I into C4d and C4c

Question 13

Regulation of C5 convertase

Answer 13

CR1 and H displace C3b. CR1 and H act as cofactors in cleave of C3b by I

Question 14

Regulation of MAC

Answer 14

CD59 prevents final assembly of C9 onto the complex

Question 15

Low C3 levels

Answer 15

Lead to increased numbers of bacterial infection

Question 16

What leads to hemolytic anemia and how

Answer 16

uncontrolled MAC formation…could be absense of CD59 that inhibits MAC formation

Question 17

C3b does NOT

Answer 17

Increase vascular permeability

Question 18

C2b is important in which system

Answer 18

Kinin

Question 19

MAC complex deficiency

Answer 19

Neisseria recurrent infection

Question 20

Cleave products of ____ pathway interact with kinin system

Answer 20

Classical pathway

Question 21

Factor I deficiency

Answer 21

Leads to recurrent bacterial infections…Factor B would be undetectable