Lecture 22 - Complement FINISH

Question 1

What is the complement system

Answer 1

part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen’s cell membrane.

Question 2

What is the human complement system

Answer 2

~20 plasma proteins
1- regulators or receptors on cell membranes

Function - defend the host against microbial infections and removal of cell debris

Question 3

How does the human complement system fight microbial infections

Answer 3

release of small bioactive fragments
(anaphylatoxins)

fragments of complement proteins
bind to the activating agents
opsonization (covalently)

destroy the invader organism
by forming pores
on the target cell (MAC)

Question 4

What is the classical pathway

Answer 4

Antigen-antibody complexes

C1q, C1r, C1s
C4
C2
C3 convertase
C3b opsonisation clearance

Question 5

What is the MBLectin pathway

Answer 5

Mannose on pathogen surfaces
MBL, MASP-1, MASP-2
C4
C2
C3 Converts
C3b (opsonisation clearance)

Question 6

What is the alternative pathway

Answer 6

Pathogen surfaces
C3
B
D
C3 converts
C3b

Question 7

What are the Lysis mechanisms

Answer 7

C5b, C6, C7, C8, C9

Question 8

What is phagocyte recruitment complexes

Answer 8

C4a
C3a
C5a

Question 9

What is the order of complement activation

Answer 9

Alternative, Lectin, Classical

Question 10

What does C3b bind to

Answer 10

Basic component - covalently bound to surface component of pathogen

Question 11

Slide 9

Question 12

slide 10

Question 13

How do Anaphylatoxins work

Answer 13

Act on blood vessels to increase vascular permeability (with C3a, C5a, C4a) - and chemoattract immune system

leads to:
Increase permeability which allows increased fluid leakage from blood vessels and extravasation of antibodies and complement at side of infection (w IgG and IgM)

Migration of macrophages, neutrophils and lymphocytes into tissue is increased. Microbcidal activity of macrophages and neutrophils is also increased

Question 14

What s complement factor 1 composed of

Answer 14

consists of Collagen structure with 6 heads - C1q with C1r and C1s - 2 serine proteases.
Contains a flexible hinge

(slides 14+15)

Question 15

Slide 18

Question 16

Once C1 is bound to the surface, what happens next

Answer 16

Activated MASP-2 cleaves C4 to C4a and C4b, with some C4b binding covalently to microbial surface

Activated MASP-2 also cleaves C2 to C2a and C2b

C2a binds to surface C4b forming classical C3 convertase - C4b2a

C4b2a binds C3 and cleaves it to C3a and C3b, C3b binds covalently to the microbial surface

Question 17

C3 most abundant in blood

Question 18

What is complement factor C3

Answer 18

Large protein, multi-domain, important in all 3 pathways activation, Slide 21 ADD

Question 19

How does Spontaneous C3 cleavage occur

Answer 19

C3 floats about, spontaneously hydrolysed producing C3a, if excess pathogen around, it attacks, if not, gets destroyed in liver

If pathogen is around, alternative pathway occurs - ADD SLIDE 23

Question 20

How is the fluid phase of C3 converts undergone

Answer 20

C3 undergoes spontaneous hydrolysis to C3(H2O) which binds to factor B allowing it to be cleaved by factor D into Ba and Bb

The C3(H2O)Bb complex is a C3 convertase, cleaving more C3 into C3a and C3b.

C3b is rapidly inactivated unless it binds to cell surface

Factor B binds noncovalently to C3b on a cell surface and is cleaved to Bb by factor D

Question 21

regulators slide 26

Question 22

slide 28+29

Question 23

termination - Complement factor 6-9 pathway slide 30

Question 24

slide 31 onwards