Ch. 6 Complement

Question 1

What is the full name of C3 convertase for the classical pathway?

Answer 1

C4b2a

Question 2

What is the full name of C5 convertase for the classical pathway?

Answer 2

C4b2a3b

Question 3

How is the classical pathway initiated?

Answer 3

by antibody binding (IgM or IgG)

Question 4

How is the lectin pathway initiated?

Answer 4

lectin binds to microbial surfaces

Question 5

How is the alternative tickover pathway inititated?

Answer 5

when C3 undergoes spontaneous hydrolytic cleavage in serum

Question 6

What does the CR1 (CD35) receptor bind and what is the outcome?

Answer 6

• RBCs with Cr1 bind complexes and take them to the liver
• removal of C3b-opsonized immune complexes by liver
• neutrophil phagocytosis

Question 7

What does the CR2 (CD21) receptor bind and what is the outcome?

Answer 7

Binds C3b breakdown products

-promotes uptake of antigens by B cells and FDCs; ehancement of B cell activation and B cell coreceptor

Question 8

What does the CR3 (CD11b with CD18) do?

Answer 8

promotes phagocytosis and extravasation

Question 9

What does the C3aR/C5aR do?

Answer 9

• stimulates release of proinflammatory cytokines and granule components form basophils, eosinophils, neutrophils;
• induce acute phase response protein synthesis in liver
• induced neutrophil respiratory burst

Question 10

What are the three ways complement enhances host defenses against infection?

Answer 10

1. MAC-induced cell death
2. Promotion of Inflammation
3. Promotion of opsonization

Question 11

Which anaphylatoxins bind to receptors on granulocytes, mast cells, and endothelial cells and trigger cascades that secrete IL-6 and TNF-a?

Answer 11

C3a, C4a, C5a

Question 12

What are three separate ways that complement promotes opsonization/phagocytosis?

Answer 12

a. Opsonized microbes easier to ingest/destroy
b. Apoptotic cells express the phospholipid phosphatidyl serine and fragmented DNA on their surface, which binds C1q
c. Opsonized immune complexes easier to clear
i. C3b binds to CR1 on erythrocytes and is carried to the liver and spleen

Question 13

What are two ways that complement is passively regulated?

Answer 13

• protein stability

- cell-surface composition

Question 14

Protein stability regulation

Answer 14

ex. short half-life of C3 convertase unless stabilized by properdin

Question 15

Cell-surface composition regulation

Answer 15

i. Self cells possess different carbohydrate structures (sialic acid) that are more effectively bound by fluid-phase proteases that destroy C3b
1. These more readily inactivate C3b through hydrolysis, protecting self cells

Question 16

C1INH: Membrane bound or soluble? How it regulates complement?

Answer 16

o Serine protease inhibitor (serpin) by binding to and poisoning proteases
o Promotes dissociation of C1 complex by inhibiting proteases C1r and C1s
o MASP-2 of lectin pathway

Question 17

DAF: Membrane bound or soluble? How it regulates complement?

Answer 17

o Decay accelerating factor promote decay of C3 convertases

 Membrane bound

Question 18

CR1: membrane bound or soluble?

Answer 18

membrane bound

Question 19

C4BP

Answer 19

o Soluble components that bind sialic acid/ heparin/heparan sulfate present on the surface of our cells

Question 20

Factor H

Answer 20

o Soluble components that bind sialic acid/heparin/heparan sulfate present on the surface of our cells

Question 21

Factor I

Answer 21

soluble, constitutively active serine protease that cleaves membrane-associated C3b & C4b into inactive fragments
o Decay of C3 convertase leads to C3b and C4b left behind, which are still catalytically active
o Activity is controlled by the presence of decay factors or Membrane Cofactor of Proteolysis (MCP)

Question 22

Protectin

Answer 22

inhibits the MAC attack
o Binds C5b678 complexes deposited on host cells
 Prevents their insertion into the plasma membrane
 Also blocks C9 recruitment, preventing MAC formation

Question 23

Vitronectin

Answer 23

o Soluble protein that binds fluid phase C5b67 to prevent insertion into host cell plasma membranes

Question 24

Carboxypeptidase N,B, and R

Answer 24

inactivate the anaphylatoxins C3a and C5a
 Carboxypeptidases = enzymes that remove amino acids from the carboxyl end of peptides
 Enzymes remove arginine residues from the C termini of C3a & C5a
 Makes them inactive (des-Arg forms, “without Arginine”)
 Helps to shut down unnecessary or dangerous chemotaxis & inflammation induction

Question 25

What are some possible outcomes of deficiencies in the early components of complement cascades, C1-C4?

Answer 25

C1-C4 involved in removing antigen/antibody complexes
Lack in these proteins
• Lupus-like illness
• Chronic renal disease
• Repeated infections
C3 deficiency  severe clinical manifestations
• Needed in large quantities
• Central role in PHAGOCYTOSIS AND MAC FORMATION
C4 deficiency less significant problems
• Needed in small quantities
• Continues role in activating other proteins

Question 26

What are some possible outcomes of deficiencies in the late components of complement cascades, C5-C8?

Answer 26

o Repeated Neisseria infections

o Risk of gonorrhea or meningitis

Question 27

What is a possible outcome of deficiencies in complement regulators, such as C1INH?

Answer 27

• Regulator deficiencies associated with increased inflammatory responses
o Angioedema responses to complement activation

Question 28

What are the 4 categories of complement evasion strategies employed by microbes?

Answer 28

1. Some interfere with the first step of Ig-mediated complement activation
2. Microbial proteins may bind & inactivate complement proteins
3. Microbial proteases destroy complement proteins
4. Some microbes mimic or bind complement regulatory proteins