Complement System

Question 1

What type of response is the complement system?

Answer 1

Innate

Question 2

What is the over all response of the complement system?

Answer 2

Recognise pathogens, trigger response
Directly lyse, opsonise (taken up and digested), chemoattractant (recruitment of other cells), degranulation of mast cells

Question 3

How can the level of the components of the complement system be measured in animals?

Answer 3

In serum of all animals

Question 4

How does the complement system use zymogen like proteins?

Answer 4

Recruitment and activation of zymogen like proteins

Zymogen proteins split in two, one is retained, other acts as enzyme/chemoattractant

Question 5

What are the modes of action of the different complement system responses?

Answer 5

Direct inhibitors/blockade
Decay accelerator factors
On WBC surfaces speeds up decay of convertases
CD59 inhibits formtation of the MAC on host cell surfaces?

Question 6

What is MAC?

Answer 6

Membrane attack complex

Question 7

What are the three different types of complement pathways?

Answer 7

Classical
Alternative
Lectin

Question 8

What do all complement systems target and effect?

Answer 8

Effect- phagocytosis, cell lysis, WBC recruitment and activation
Target- Bacteria, viruses, parasites, fungi

Question 9

What is the activating signal and difference of all three complement pathways?

Answer 9

Classic activation- antibody antigen complex
Classic difference- takes longer as needs Ab

Alternative activation- C3 binds to pathogen carbohydrates or protein
Alternative difference- binds directly to pathogen surface

MB-Lectin activation- host mannose binding lectins binding to pathogen mannose
MB-Lectin difference- binds surface via soluble protein

Question 10

Describe the classical pathway (clue 1, 4, 2, 3, 5)

Answer 10

Antigen and antibody activates C1
Activated C1 cleaves C4- C4b and C4a
C2 binds to C4- C4b2
Active C1 cleaves C4b2- C4b2b and C2a
C4b2b cleaves C3- C3b and C3a
C5 binds to C3b- C3b5
C4b2b cleaves C3b5- C3b5b + C5a

Question 11

Describe the alternative pathway (clue C3- B or H)

Answer 11

C3 spontaneously breaks down- C3b and C3a
C3b binds to cell surface
If normal cell factor H causes the C3b to inactivate
If not normal the surface is activating and causes B to bind- C3bB
D cleaves C3bB- C3bBb and Ba
P binds producing C3bBbP

Question 12

Describe the MB-Lectin pathway (clue MASP-2, 4, 2, 3)

Answer 12

Bacterial surface binds to host mannose binding lectin 
Mannose binding lectin activates MASP-2
MASP-2 cleaves C4- C4b and C4a
C4b binds to C2- C4b2
MASP-2 cleaves C4b2- C4b2b + C2a
C4b2b cleaves C3- C3b and C3a

Question 13

Where is C3 made and by what cells?

Answer 13

Made by macrophages in the liver

Question 14

What happens to C3 naturally and what follows?

Answer 14

C3 naturally breaks down to C3a and C3b
C3a acts as an anaphylotoxin or chemoattractant
C3b can bind to microbe surfaces by carbohydrates
C3b can bind to factor H on host cells removing from circulation

Question 15

What is the main similarity between all complement pathways?

Answer 15

All three produce C3 Convertase
MB-Lectin and classical- C4b2b= C3 convertase
Alternative- C3bBb= C3 convertase

Question 16

How does C3 convertase mediate the actions of the complement system?

Answer 16

C3a, C4a, C5a- peptide mediators of inflammation and phagocyte recruitment
C3b- binds to complement receptors on phagocytes, opsonisation of pathogens, removal of immune complexes
C3b and terminal components (C5b, C6, C7, C8, C9)- membrane attack complex

Question 17

Which components of the complement system are anaphylatoxins and what do they do?

Answer 17

C3a, C4a, C5a

Change smooth muscle
Increase vasodilation
Activated mast cells of neutrophils
Increases fluid in the tissue and speeds up lymph flow

Question 18

What is the MAC and what is it composed of?

Answer 18

A central effector mechanism, and an endpoint of all three activation pathways
Composed of C5b, C6, C7, C8 and multiple copies of C9

Question 19

Describe the mechanism of the membrane attack complex

Answer 19

Cleavage of C5- C5a and b
C5b binds to C6- C5bC6
Binds to C7- C5bC6C7
C5bC6C67 allows C7 to insert onto phospholipid bilayer as hydrophobic site is exposed on the C7 protein once in a complex
Surface complex bound by C8 beta, C8 alpha gamma inserts into the cell membrane
This causes 10-16 copies of C9 to polymerise on the cell surface- think Mario pipes

Question 20

What does the MAC do?

Answer 20

Opens the bacterial cell
Loss of cellular components
Homoestasis inhibited
Disrupts protein gradient
Allows host lysosome penetration

Question 21

Why is canine C3 deficiency a problem?

Answer 21

Homozygote dogs have no serum C3
Have trouble in making antibodies against certain pathogens
Increase pyometra, pneumonia, sepsis