Complement

Question 1

Complement can be an indicator of … ?

Answer 1

Inflammation

Question 2

What is the role of complement?

Answer 2

Recognises pathogen or danger signals and triggers responses that can:

• Directly lyse pathogens
• Oponise pathogens
• Act as a chemoattractant
• Trigger degranulation of mast cells

Question 3

Where can complement proteins be measured?

Answer 3

In the serum of all animals. The proteins are already there, so don’t need to be made, only switched on

Question 4

How does complement work using proteins?

Answer 4

Through recruitment and activation of zymogen-like proteins (pro-enzymes)

Question 5

What happens to the zymogen-like proteins on the cell surface?

Answer 5

The zymogen splits into two. The larger part is retained on the cell surface whilst the smaller part acts as a chemoattractant or cell activator

Question 6

What is the role of CD59 as a method of action?

Answer 6

Inhibits the formation of the membrane attack complex on host cell surfaces

Question 7

Complement is a part of which immune system?

Answer 7

The innate immune system

• non-specific
• must possess broad activation mechanisms

Question 8

What are the 3 complement systems called?

Answer 8

• Classical pathway
• Alternative pathway
• Lectin pathway

Question 9

Describe the classical pathway

Answer 9

• Antigen-antibody complex (activating signal) binds to inactive C1, which then activates it
• The small molecules e.g. C2a, C3a can act as activation triggers
• This pathway is longer due to the need for antibodies

Question 10

Describe the alternative pathway

Answer 10

• Dominant pathway
• Starts with C3 which undergoes spontaneous breakdown giving C3a and C3b
• C3b binds to the surface of a host cell
• If its a healthy cell it is recycled
• It is activated if it is an abnormal cell

Question 11

Describe the lectin pathway

Answer 11

• Relies on a host receptor first binding to a bacterial carbohydrate
• MASP-2 becomes active and cleavage begins
• productions of C4b2 and C3b
• binds directly to pathogen surface

Question 12

All 3 pathogens converge on which molecule?

Answer 12

C3

Question 13

Where is C3 made?

Answer 13

By macrophages in the liver

Question 14

Describe C3 and the products of its breakdown

Answer 14

C3 - breaks down into C3a and C3b
C3b - can bind microb surfaces via carbohydrate
C3a acts as an anaphylatoxin or chemoattractant

Question 15

C3a, C4a & C5a are all?

Answer 15

Anaphylatoxins

Question 16

Describe complement and inflammation triggering

Answer 16

• changes smooth muscle
• increases vasodilation
• activates mast cells or neutrophils
• Increases fluid in the tissue and speeds up lymph flow, which forces debris into the lymphatic system

Question 17

What is the end point of all 3 activation pathways?

Answer 17

The membrane attack complex

Question 18

The MAC is composed of which pro-enzymes?

Answer 18

C5b, C6, C7, C8 and multiple copies of C9

Question 19

How does assembly of the MAC begin?

Answer 19

Cleavage of C5 to C5a and C5b

Question 20

C5b then binds to…?

Answer 20

C6 and C7

Question 21

What happens to the C5b:C6:C7 complex?

Answer 21

Allows insertion of C7 into the phospholipid bilayer as a hydrophobic site is exposed on the C7 protein once in a complex

Question 22

Once bound to the phospholipid bilayer, how is the MAC completed?

Answer 22

• C8 binds to the C5b:C6:C7 complex and inserts into the cell membrane
• This causes 10-16 copies of C9 to polymerize on the cell surface forming a ring like structure – pore in the membrane

Question 23

What is the role of the MAC?

Answer 23

• opens the bacterial cell cytosol
• dramatic loss of cellular homeostasis
• disrupts proton gradient

Question 24

What are the consequences of a canine C3 deficiency?

Answer 24

• inherited disorder
• Have trouble in making antibodies against certain pathogens – E. coli etc
• Increased pyometra, pneumonia, sepsis etc

Question 25

What are the consequences of Porcine Factor H deficiency?

Answer 25

- Carriers born normal up to a few weeks thereafter production problems. - Die of anaemia and renal failure. - Factor H stops C3b activation - In animals C3 accumulates on surface and basal membranes of kidneys – no serum C3