Complement

Question 1

what does the complement systems consist of in steady state conditions (2)

Answer 1

• collection of heat labile serum proteins that circulate the blood
• most are zymogens, inactive precursors of enzymes

Question 2

complement system: evolution (2)

Answer 2

• system is evolutionary conserved
• present in invertebrates to more complex vertebrates

Question 3

complement system abbreviation

Answer 3

C’

Question 4

complement system: characteristic of activation (2)

Answer 4

• acts in a triggered cascade
• each reaction on the cascade results in activation of another C’ component

Question 5

how can the complement system be activated (2)

Answer 5

• IgG and IgM bind to invading pathogens
• C1 binds to the Fc portion of IgG and IgM antibodies

Question 6

what does complement activation results in (3)

Answer 6

• opsonization and destruction of the pathogen
• recruitment of cells involved in inflammation
• direct lysis of gram negative bacteria

Question 7

what occurs to the complement system is the blood is heated

Answer 7

• killing activity of the system disappears due to heat-labile nature of the proteins

Question 8

what are the proteins involved in the complement system (8)

Answer 8

• initiators
• convertase activators
• enzymatic mediators
• opsonins
• anaphalotoxins
• membrane attack complex
• complement receptors
• regulatory proteins

Question 9

complement system: pathways (3)

Answer 9

• classical
• lectin
• alternative

Question 10

what do all complement system pathways generate

Answer 10

• C3 convertase

Question 11

C’: classical pathway activation (2)

Answer 11

• C1 (C1q, C1r, C1s) usually interacts with Ag-Ab complexes
• activates C4 and C2

Question 12

C’: lectin pathway initial activation (2)

Answer 12

• mannose binding lectin (MBL) and ficolins bind carbohydrates on pathogen surface
• activates MBL associated proteases (MASPs)

Question 13

C’: alternative pathway activation

Answer 13

• C3b undergoes spontaneous hydrolysis to C3(H2O)

Question 14

what is the result of C3 convertase generation (2)

Answer 14

• cleavage of C3
• leaves C3b bound to microbial surface and releases C3a

Question 15

C3 convertase: classical or lectin

Answer 15

• C4b2a

Question 16

C3 convertase: alternative

Answer 16

• C3bBb

Question 17

lectin pathway after activation (5)

Answer 17

1. activated MASP-2 cleaves C4 to C4a and C4b
2. C4b binds to microbial surface and C2
3. C2 is cleaved by MASP-2 into C2a and C2b to form the C4b2a complex
4. C4b2a is a C3 convertase, cleaving up to 1000 C3 to C3a and C3b
5. C3b bind to microbial surface or to the C4b2a complex

Question 18

classical pathway after activation (5)

Answer 18

1. activated C1/Ab/Ag complex cleaves C4 to C4a and C4b
2. C4b binds to microbial surface and C2
3. C2 is cleaved by C1/Ab/Ag into C2a and C2b to form the C4b2a complex
4. C4b2a is a C3 convertase, cleaving up to 1000 C3 to C3a and C3b
5. C3b bind to microbial surface or to the C4b2a complex

Question 19

what does C3b deposited onto microbial surface do (3)

Answer 19

1 C3b binds factor B
2. bound factor B is cleaved by plasma protease factor D into Ba and Bb
3. C3bBb complex is a C3 convertase, cleaving many C3 molecules to C3a and C3b

Question 20

alternative pathway after activation (5)

Answer 20

1. C3(H2O) binds to factor B
2. bound factor B is cleaved by factor D into Ba and Bb
3. C3(H2O)Bb complex is a C3 convertase, cleaving many C3 into C3a and C3b
4. C3b is rapidly inactivated unless it binds to cell surface
5. cycle continues as factor B noncovalently binds to C3b on cell surface and is cleaved to Ba and Bb by factor D

Question 21

C’: C5 component activation (3)

Answer 21

1. C3b binds C4b2a or C3bBb to form active C5 convertase: C4b2a3b and C3b(2)Bb
2. C5 binds to Cb3 component of C5 convertase enzyme
3. C5 is cleaved by C2a or Bb to form C5a and C5b

Question 22

C’: C5 component (5)

Answer 22

1. C5b binds C6 and C7
2. C5b67 binds to pathogen membrane via C7
3. C8 binds to complex and inserts into cell membrane
4. C9 molecules bind to complex and polymerize
5. 10-16 molecules of C9 bind to form a pore in the membrane, creating membrane lesions

Question 23

functional components of C’ (3)

Answer 23

• C3a and C5a
• C3b
• membrane attack complex

Question 24

functional components: C3a and C5a (3)

Answer 24

• anaphylatoxins
• increase vascular permeability
• chemotactic (recruit) for inflammatory immune system cells

Question 25

functional components: C3b

Answer 25

- opsonins; tag pathogens for phagocytosis

Question 26

what component initiates formation of the membrane attack complex (MAC)

Answer 26

- C5b

Question 27

what is the MAC composed of (5)

Answer 27

- C5b - C6 - C7 - C8 - multiple C9

Question 28

regulation of C': activation (3)

Answer 28

- C1 esterase inhibitor (C1inh) - inactivates C1r and C1s from active C1 complex - inactivates MASPs

Question 29

regulation of C': amplification (6)

Answer 29

- decay acceleration factor (DAF) - C4 binding protein (C4BP) - complement receptor 1 (CR1 or CD35) - membrane cofactor protein (MCP1) - factor I - factor H

Question 30

regulation of C': factor I (2)

Answer 30

- protease that cleaves C4b - C4BP, CR1 and MCP are cofactors

Question 31

regulation of C': factor H (3)

Answer 31

- cofactor for factor I - factor I cleaves C3b - CR1 acts as a cofactor

Question 32

regulation of C': MAC assembly

Answer 32

- CD59 inhibits insertion of MAC into the membrane - halts MAC at the C8 to C9 stage

Question 33

what regulators of C' affect the C4b2a complex (3)

Answer 33

- DAF - C4BP - CR1

Question 34

regulation of C': DAF, C4BP, and CR1

Answer 34

- displace C2a from C4b2a complex - C4b bound by regulator is cleaved by soluble protease I to inactive forms C4c and C3d

Question 35

regulation of C': CR1 (2)

Answer 35

- displace C3b - act as cofactors in cleavage of C3b by protease I

Question 36

how have pathogens reacted to the complement system

Answer 36

- evolved ways to combat the complement system at various stages