Complement System

Question 1

Where are complement proteins synthesized?

Answer 1

liver, or myeloid cells during inflammatory response

Question 2

What are the three activation pathways of complement?

Answer 2

classical: antibody-dependent (acquired)
lectin: microbial mannose sugars (innate)
alternative: “activating surfaces” (innate)

Question 3

What is the core process of complement pathways?

Answer 3

sequential activation -> amplification -> regulation

Question 4

Where do the three complement activation pathways converge?

Answer 4

cleavage of C3 to form C3b

Question 5

What is the process of the classical pathway?

Answer 5

antigen-antibody complex binds C1 and activates it -> C4b2a (C3 convertase) -> C3b binds to pathogen

Question 6

In the classical pathway, how many IgM or IgG need to bind to C1 to activate it?

Answer 6

1 IgM

2 IgG

Question 7

What is the process of the lectin pathway?

Answer 7

mannan binding lecting binds terminal mannose sugar -> C4b2a (C3 convertase) formed
*similar to classical

Question 8

What is the process of the alternative pathway?

Answer 8

microbial cell surface activation -> forms C3(H2O) by hydrolysis -> factor B binds C3(H2O) -> forms C3bBb (C3 convertase) -> C3b binds to pathogen

Question 9

Which processes do NOT require an antibody?

Answer 9

lectin & alternative

Question 10

What is cytolysis?

Answer 10

an effector function of the complement, C3 convertase + C3b form C5 convertase -> activates C5 -> Membrane Attack Complex

Question 11

What is opsonization/Phagocytosis?

Answer 11

an effector function of complement, opsonin coats cell -> complement fragments (C3b, iC3b, C4b) bind complement receptors (CR1, CR3, CR4) -> gets phagocytosed by myeloid cells

Question 12

What complement fragments are involved in inflammation mediation? What are they called?

Answer 12

C5a: chemoattracts neutrophils and monocytes
C3a & C4a (lesser extent)
anaphylatoxins

Question 13

How are immune complexes cleared?

Answer 13

C3b deposits on immune complex -> binds with CR1 on RBC -> transferred to macrophages to be destroyed in liver & spleen

Question 14

How are B cells activated?

Answer 14

1. CR2 on B cells bind degraded products of C3b
2. breakdown products of C3 deposit on pathogens
3. B cell antibody binds antigen
4. when antibody & CR2 are engaged it enhances activation

Question 15

How is complement regulated?

Answer 15

C1 Inhibitor
Decay-Accelerating Factor (CD55)
CD59 (protectin)

Question 16

How does C1 inhibitor regulate complement?

Answer 16

prevents C1 activation (affects 1st step of classical & lectin pathways)

Question 17

How does Decay-Accelerating Factor regulate complement?

Answer 17

inactivates classical/lectin pathways: binds C4b2a inactivates alternative: competition with Factor B for binding C3b -> dissociates C3bBb

Question 18

How does CD59 regulate complement?

Answer 18

binds C5b-C8 complex -> prevents addition of C9 -> inhibits membrane attack pathway

Question 19

What complement segments make up the MAC?

Answer 19

C5b through C9

Question 20

What is an opsonin?

Answer 20

coating complement component or antibody