The Complement System

Question 1

Complement System (Basics)

Answer 1

• Proteins circulating in the blood stream
• Can bind to pathogens (especialy bacteria) resulting in bacterial cell death

Question 2

C3

Answer 2

• Most abundant complement protein
• Synthessized by the liver
• Can be converted to C3b which binds bacteria and causes bacterial death
• All complement activation involves C3 –> C3b

Question 3

Alternative Pathway

Answer 3

• C3 spontaneously converts to C3b
• C3b is rapidly destoryed unless stablized by binding
• C3b binds amino and hydroxyl groups (commonly found on the surface of pathogens)
• Surfaces that bind C3b:
  
  • Bacterial lipopolysaccharides (LPS)
  • Fungal cell walls
  • Viral envelopes

Question 4

C3b positive feedback process

Answer 4

• Stable C3b can bind complement protein B
• Complement protein D clips B bound to C3b
• This forms C3bBb which is a C3 convertase
• Result: Stable C3b can cleave more C3 –> C3b
• Causing rapid accumulation of C3b on surfaces

Question 5

Factor H

Answer 5

• Plasma glycoprotein synthesized in liver
• Blocks alternative pathway on host cells
  
  • Accelerates decay of C3 convertase (C3bBb)
  • Cleaves and inactivates C3b

Question 6

Lectin Pathway

Answer 6

• Mannose-binding lectin (MBL) is produced by the liver and circulates in blood/tissues with MASPS (Mannose associated serine proteases)
• MBL/MASPs complexes bind surfaces with mannose (many microbes)
• Complex bound to mannose cleaves C2 –> C2b
• Complex bound to mannose cleaves C4 –> C4b
• C2b + C4b = C2b4b which is a C3 convertase that converts C3 to C3b

Question 7

Classical Pathway

Answer 7

• Antibody-antigen complexes bind C1 which then:
  
  • Cleaves C2 –> C2b
  • Cleaves C4 –> C4b
• C2b + C4b = C2b4b which is a C3 convertase
• C3 convertase then converts C3 –> C3b

IgM is great at activating this pathway since it is a pentemer

IgG is okay at activating this pathway

Question 8

C3 pathway

Answer 8

• When C3 is cleaved it is broken down into C3a and C3b
  
  • C3a is an anaphylatoxin –> stimulates histamine release from mast cells and increases vascular permeability
  • C3b can lead to the formation of MAC
  • C3b by itself can act as an opsonin

Question 9

Membrane Attack Complex (MAC)

Answer 9

• Stable C3b leads to the formation of the MAC
• MAC is formed from C5, C6, C7, C8, and C9
• Pokes holes in the bacterial cell wall causing it to swell and burst

Question 10

C5a

Answer 10

• Anaphylatoxin
• Also causes neutrophil chemotaxis to that site