Lecture 7: Complement

Question 1

what is complement

Answer 1

a collection of soluble proteins present in blood and other body fluids that serves to ‘complement’ antibody activities

*many complement proteins are proteases

Question 2

when is complement activated

Answer 2

in response to pathogens or antibodies bound to pathogens

Question 3

what is required in order for complement proteins to become active

Answer 3

proteolytic cleavage of C3—> C3a and C3b

Question 4

what results in the rapid inactivation of C3b ?

Answer 4

if it becomes unbound to pathogen

Question 5

what triggers the activation of the Lectin Pathway?

Answer 5

• by pattern recognition receptors MBL (Mannose Binding Lectin) and ficolins

Question 6

what are the key molecules in the LECTIN pathway

Answer 6

• MBL/Ficolin
• MASP2
• C4
• C2

Question 7

what are the key molecules in the CLASSICAL pathway

Answer 7

• C1q
• C1r
• C1s
• C4
• C2

Question 8

what are the key molecules in the ALTERNATIVE pathway

Answer 8

• Factor D
• Factor B
• properdin
• C3

Question 9

explain the steps in the lectin pathway

Answer 9

• activated MASP2 associated w/ MBL or Ficolin cleaves C4 into C4a + C4b
• C4b binds to microbial surface
• C4b binds to C2
• C2 cleaved by MASP2 —> C2b and C2a
• C4bC2a complex forms
• C4bC2a = C3 convertase

Question 10

what initiates the classical pathway

Answer 10

IgG binding to an antigen on pathogen surface

Question 11

what are the 2 ways in which the alternative pathway can be activated

Answer 11

• C3b deposited by classical or lectin pathway C3 convertase
• spontaneous hydrolysis of C3

Question 12

What is different about the alternative pathway’s C3 convertase

Answer 12

it is C3b bound to Bb

Question 13

what are the C3 convertases from the classical, lectin and alternative pathways

Answer 13

classical & lectin: C4bC2a
alternative: C3bBb

Question 14

role of C3b

Answer 14

binds to pathogen, opsonizes it, signals for its destruction

Question 15

how is C5 convertase formed in each pathway

Answer 15

Classical and lectin: C3b binds C4bC2a –> C4bC2aC3b
alternative pathway: C3b binds C3Bb –> C3bC3bBb

Question 16

what are the 3 main functions of the complement system

Answer 16

• destroy invading pathogens via phagocytosis
• initiate localized inflammatory response
• Membrane Attack Complex

Question 17

effects of C3a, C4a and C5a

Answer 17

• they bind to receptors on endothelial and mast cells to produce inflammation
• C5a acts on neutrophils to increase adherence

Question 18

What are the regulatory mechanisms of the complement system

Answer 18

• C1 inhibitor
• Factor I
• Factor H
• DAF, C4BP, CR1
• CD59

Question 19

how does C1 inhibitor work

Answer 19

dissociates C1r and C1s from the active C1 complex

Question 20

role of Factor I in regulation of complement

Answer 20

inactivates C3b by cleaving it to iC3b

Question 21

role of Factor I in regulation of complement

Answer 21

inactivatesC3b by cleaving it to iC3b

Question 22

role of DAF, C4BP, CR1 in regulation of complement

Answer 22

displace C2a from C4bC2a complex

Question 23

role of CD59 in regulation of complement

Answer 23

prevents the final assembly of MAC at C8-9 stage

Question 24

waht is Atypical hemolytic uremic syndrome

Answer 24

mutations of Factor I, Factor H or MCP
* unable to effectively regulate complement
* leads to damage of platelets and RBCs

Question 25

what is Accelerated macular degeneration

Answer 25

leading cause of blindness in elderly * base change in factor H genes * complement is activated on host photoreceptors