Complement

Question 1

what is the complement system?

Answer 1

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

Question 2

who named this the complement system and why?

Answer 2

Ehrlich

because this heat-labile, anti-microbial component in the blood complements the immune system

Question 3

what is the function of the human complement system?

Answer 3

defend the host against microbial infections

Question 4

what are the 3 parts of the complement system?

Answer 4

1. release of small bioactive fragments
   (anaphylatoxins)
   -> recruits cells to site of infection based on the conc grad of components
   (can cause inflammation)
2. opsonisation = fragments of complement proteins bind to activating agents
   - tag for removal
3. destroy invading organism by forming pores on target cell

Question 5

what are the 3 pathways?

what do they involve/what are they triggered by?

Answer 5

classical
(antigen-antibody complexes)
- acts last

MBLectin
(Mannose sugars on pathogen surfaces)

alternative
(pathogen surfaces)

Question 6

what are the complement components in each pathway?

Answer 6

Classical:
C1q, C1r, C1s
C4
C2

MBLectin:
MBL, MASP-1, MASP-2
C4, C2

Alternative:
C3
B, D

Question 7

what do all the complement components converge to form?

what does this enzyme do?

what does this product do?

Answer 7

C3 convertase

cleaves C3 into C3b

C3b is an opsinin that can tag onto microbial surfaces

Question 8

which 3 components are involved in phagocyte recruitment?

which 5 components are involved in lysis?

Answer 8

c4a
c3a
c5a

c5b
c6
c7
c8
c9

Question 9

describe what happens in the classical pathway process

Answer 9

1. antibodies bind to surface of microbe
2. C1 binds to antibodies and becomes activated
3. C1 cleaves C2+C4…
   - > C2a + C4b become the C3 Convertase
4. C3 converts cleaves C3 into C3a (goes away) and C3b (opsonin that joins the complex forming C5 convertase)
5. C5 convertase produces C5b
   - > helps form MAC (membrane attack complex)
   - > tiggers terminal pathway leading to pore formation

Question 10

what are the 2 components of C1 that cleave C4 and C2?

what are the names of C4a and C4b?

what is the difference between C2a and C2b?

Answer 10

C1r and C1s

C4a = anaphylatoxin
C4b = opsonin

C2a = bigger + binds to cell surface 
C2b = smaller

Question 11

what effect do anaphylatoxins have on blood vessels?

why is this beneficial?

Answer 11

increase vascular permeability

allows increased fluid leakage from blood vessels + extravasation of antibodies + complement at site of infection

migration of macrophages, neutrophils + lymphocytes into tissues is increased
microbicidal activity of macrophages + neutrophils is also increased

Question 12

describe the structure of complement factor 1 (C1)

Answer 12

C1q

+ C1r and C1s (enzymatic)

= intact C1

Question 13

what is the main function of C1q?

Answer 13

binds to antibodies
- either 2 closely bound IgG molecules
OR 1 IgM

-> triggers the classical pathway

Question 14

how does MASP-2 (C1) cleave C4 and C2?

what happens after this?

Answer 14

C4
-> C4a + C4b

C2
-> C2a + C2b

C4b covalently attaches to microbial surface
->C2a binds to C4b
= forms classical C3 convertase C4bC2a

Question 15

describe the process of C3 cleavage

Answer 15

C3a (potent anaphylatoxin) is cleaved off

• > C3b attaches to surface of pathogen
• > after a while, inactive component iC3b is cleaved
• > leaves C3d

Question 16

describe the alternative pathway process

up to rapid opsonisation

Answer 16

1. spontaneous cleavage of C3
2. C3b binds to microbe surface
3. factor B binds to C3b
4. factor D cleaves factor B into Bb + Ba
   - > C3bBb complex forms C3 convertase
5. factor P stabilises C3 convertase
6. C3b creates many more C3b molecules
   = amplifies pathway
7. lots of C3b attach to microbe surface = rapid opsonisation

Question 17

describe the alternative pathway

from C5 convertase formation

Answer 17

1. another C3b binds to C3bBb complex
   - > forms C5 convertase
2. cleaves C5 into C5a + C5b
3. leads to formation of MAC

Question 18

what is the fluid-phase C3 convertase in the alternative pathway?

Answer 18

when you have spontaneous cleavage of C3

-> it can attach factor B + D
so the enzyme becomes a soluble C3 enzyme

C3bBb complex is stabilised by factor P on the cell surface

C3 convertase deposits many C3b molecules on the pathogen surface

-> opsonisation + activation of terminal complement components

Question 19

what is dangerous about the fluid-phase C3 convertase?

Answer 19

highly reactive

so host cells in blood stream + vascular tissue must be protected

Question 20

how are host cells protected from fluid-filled C3 convertase?

Answer 20

host cells have complement-control proteins:
Cr1, H, MCP + DAF
that bind to C3b

these help to breakdown host cell-attached C3b
-> so C3 convertase cannot form

results in no activation of complement on host cell surfaces

Question 21

how similar are complement factors 3, 4 + 5?

Answer 21

almost identical in structure

Question 22

what allows c3/c4 to bind to microbes?

Answer 22

internal thiolactone ring (thioester bond)

covalently binds to a hydroxyl (e.g. in mannose) on the microbe surface

Question 23

which pathway are C6, 7, 8 + 9 part of?

Answer 23

terminal pathway

Question 24

describe the process of the terminal pathway

Answer 24

1. C5b binds C6 + C7
2. C5b67 complexes bind to membrane via C7
3. C8 binds to complex and inserts into the cell membrane
4. C9 molecules bind to the complex + polymerise
5. 1-16 molecules of C9 bind to form a pore in the membrane
   = MAC pore
6. lysis of microbe