Complement (year 2)

Question 1

what responses does the complement system trigger?

Answer 1

direct lysis of pathogens
opsonisation
act as chemoattractant
trigger degranulation of mast cells

Question 2

can complement be measured?

Answer 2

compliment proteins can be measured in serum of all animals, they don’t need to be synthesised just switched on

Question 3

what type of proteins are needed for the complement system to work?

Answer 3

recruitment/activation of zymogen-like proteins - these split to form an enzyme and cell activator

Question 4

why must the complement system be under tight regulation?

Answer 4

it is an extremely potent system

Question 5

what are the modes of action of the complement system?

Answer 5

direct inhibitors
decay accelerator factors
CD59 inhibits the formation of MAC on host cell surfaces

Question 6

what immune system is the complement system apart of? what does this tell you about the system?

Answer 6

innate

it is non-specific with a broad range of activation mechanisms

Question 7

what are the three pathways of the complement system?

Answer 7

classical
alternative
MB-lectin

Question 8

what is the activation signal of the three pathways?

Answer 8

classical - antigen/antibody complexes
alternative - host lectin binding to pathogen surface
MB-lectin - C3 binding to pathogen surface carbohydrates/proteins

Question 9

what microorganisms can the system tarted?

Answer 9

bacteria, virus, parasite, fungi

Question 10

what are the small molecules that are formed known as a?

Answer 10

anaphylotoxins

Question 11

what are the functions of anaphylotoxins?

Answer 11

chemoattractant

activate inflammatory cells

Question 12

describe the classical pathway

Answer 12

antigen/antibody complex binds to inactive C1 to activate it this cleaves C4 to starts a cascade of reactions ending with a variety of anaphylotoxins

Question 13

what is the most dominant pathway?

Answer 13

alternative

Question 14

what protein is central to all three pathways?

Answer 14

C3

Question 15

describe the alternative pathway

Answer 15

C3 undergoes spontaneous breakdown to C3b and C3a under normal circumstances factor H will bind to C3b and inactivate it
in the presence of an activating surface (pathogen) C3 will bind to factor B this is then cleaved by factor D and factor P is incorporated the final molecule then has positive feedback to speed up the breakdown of C3

Question 16

what does the alternative pathway rely on?

Answer 16

soluble pathogen carbohydrates

Question 17

describe the process of the MB-lectin pathway

Answer 17

mannose-binding lectin activates MASP2 which cleaves C4

Question 18

where is C3 made?

Answer 18

by macrophages in liver

Question 19

anaphylotoxins trigger inflammation, what are the results of this?

Answer 19

changes to smooth muscle leading to vasodilation and oedema
this increases the fluid in tissue speeding up the flow of lymph so mast cells/macrophages follow a chemotactic gradient back to the anaphylotoxins that are present by the antigen

Question 20

what is an endpoint of all 3 pathways?

Answer 20

membrane attack complex (MAC)

Question 21

what is MAC composed of?

Answer 21

C5, C6, C7 C8, multiple C9

Question 22

how is the MAC assembled?

Answer 22

C5b and C6 bind to C7 that inserts into the phospholipid bilayer, C8 then binds and inserts
C9 binds and polymerises 15 molecules to form a pore in the membrane

Question 23

what does the pore formed in the membrane from the MAC do?

Answer 23

opens the cell so cytosol leaks out and lysozymes can invade

this causes dramatic loss of cellular function, homeostasis and disruption to proton gradient (signalling disrupted)