Complement System

Question 1

Complement

Answer 1

complex system of proteins that interact to kill invading microbes. Trigger inflammation and regulate immunity.

Question 2

What initiates the classical complement pathway?

Answer 2

when 1 IgM or 2 IgG molecules bind to antigenic surface

Question 3

What initiates the alternative pathway

Answer 3

triggered by the presence of bacterial PAMPs. FH and FI destroy C3b and stop the pathway, preventing the continuous activation of complement and production of the MAc

Question 4

C3 Convertase

Answer 4

when C3b binds to bacteria, FB and FD form C3 convertase to activate more C3 and kill the bacterial cells. Very unstable. Amplification step because it is stabilized by FP to kill as many cells as possible

Question 5

What does the terminal sequence operate?

Answer 5

tubular complex of poly-C9 that causes cell lysis

Question 6

Why does complement have to be regulated

Answer 6

so healthy cells are not attacked/prevent autoimmunity

Question 7

Basic mechanism of complement inhibition

Answer 7

1. C1 inhibitor inhibits activation of classical pathway
2. other inhibitors block C3 and C5 convertases
3. CD55 protects healthy cell membranes
4. vitronectin, clusterin, and CD59 inhibit amplification pathway

Question 8

Opsonization

Answer 8

bacterial coated by antibodies and/or complement bind to neutrophil receptors and are readily ingested

Question 9

Complement Proteins Labelling

Answer 9

labeled numerically with the prefix C or designated as factors by letters of the alphabet

Question 10

Where are complement proteins found?

Answer 10

free in serum or cell-surface receptors

Question 11

What is the most common complement protein in serum?

Answer 11

C3

Question 12

Which complement proteins are made in the liver?

Answer 12

C3, C6, C8, and FB

Question 13

Which complement proteins are made by macrophages?

Answer 13

C2, C3, C4, C5, FB, FD, FP, and FI

Question 14

What is C1q produced by?

Answer 14

Mast cells

Question 15

Alternate Pathway

Answer 15

innate pathway that accounts for most complement activated

Question 16

Lectin Pathway

Answer 16

innate pathway triggered by mannose on microbial surfaces. They activate MBL associated serine protease (MASP). This activates C4

Question 17

Classical Pathway

Answer 17

triggered by antibody binding and hence part of the adaptive response. Triggered when 1 IgM or 2 IgG bind to an antigenic surface

Question 18

Pathways triggered by bacterial PAMPs

Answer 18

alternative and lectin pathways

Question 19

What do all three pathways activate?

Answer 19

C3, which in turn initiates the amplification pathway and generates the terminal complement complex

Question 20

Is alternative C3 convertase stable?

Answer 20

no, so Factor P binds to the complex and it forms a stable C3bBbP complex

Question 21

Substrate Modulation

Answer 21

Constraint- FD can act on FB only after it has bound to C3b but not before. This regulates several reactions in the complement pathways. It ensures that the activities of enzymes such as FD are confined to the correct molecules

Question 22

Activated C3b

Answer 22

binds covalently to microbial surfaces and will not come off. Potent opsonin. Triggers the terminal pathway and inactivated by FH and FI

Question 23

Terminal Pathway

Answer 23

triggered by the activation of C3b. Components come together to trigger C9 polymerization. Poly-C9 forms a tubular complex that inserts into a target cell membrane. The target then undergoes osmotic lysis

Question 24

C3a target

Answer 24

eosinophils

Question 25

C5a target

Answer 25

neutrophils, eosinophils, macrophages

Question 26

Canine C3 Deficiency

Answer 26

Occurs in Brittany Spaniels as a result of a mutation in the C3 gene. Results in increased susceptibility to disease, most notably bacterial pneumonia. Inherited as an autosomal recessive condition

Question 27

Factor H Deficiency in Pigs

Answer 27

Uncontrolled activation of the alternate pathway results. Massive amounts of C3 are deposited in the kidneys. Renal failure results

Question 28

Type 1 Phagocytosis

Answer 28

mediated by antibodies through CD32

Question 29

Type 2 Phagocytosis

Answer 29

mediated by complement through CD35

Question 30

What stops the alternative pathway?

Answer 30

factor H