How Complement Works

The Lectin Pathway

Stage 1

• Microbes enter the body through wounds, respiratory means, digestion, etc.

Microbes

Person

Stage 2

• Microbes that have entered the body stimulate the innate immune system (in all age groups)

• This acts as the first line of defence

Microbes

C3

Macrophage

Natural Killer Cells

Neutrophils

MBL

C3bC3a

Stage 3• Complement is

activated and comprises of two pathways in the innate immune system– The alternative pathway– The lectin pathway

• The classical pathway is part of the adaptive immune system

Microbes

C3

MBL

C3bC3a

C3

C3bC3a

C3

C3bC3a

• In the lectin pathways, the MBL attaches to the mannose on the microbe

MBL

Stage 4

Microbe

Mannose

Stage 5

a) The MASP2 on the MBL breaks down the C4 protein into C4b and C4a. C4a leads to inflammation and cell recruitment

b) The protein C2 is also broken down into its ‘b’ (major) and ‘a’ (minor) components

C4 C4b C4a

a)

b) C2

C2a

C2b

Stage 6

• The ‘b’ components of the C4 and C2 proteins bind together to the microbe to form a C3 convertase

MBL

Microbe

C4b2b

C3 convertase

Stage 7• The protein C3 is broken

into its ‘b’ and ‘a’ components by the C3 convertase

• The C3a leads to inflammation and cell recruitment

• The C3b leads to opsonisation and removal of immune complexes

• It is thought that this process happens spontaneously and thus the C3 convertase would catalyse the breakdown

C3

C3b

C3a

Stage 8

• The C3b protein binds to the microbe and the C3 convertase molecule to make a C5 convertase

Microbe

C3bC3b C4b2b3b

C5 convertase

Stage 9• C5 is broken down

into C5b and C5a• The C5a protein leads

to inflammation and cell recruitment

C5

C5b

C5a

Stage 10

• C6 binds to C5b and accepts C7, C7binds to the lipid membrane and C8 then initiates binding and polymerization of C9

• C6, C5b, C7 and C8 are all components of MAC (membrane attack complex)

C5b

C7

C6

C8

Plasma Membrane

Stage 11• C9 is another

component of MAC• It binds to C5b, C6,

C7 and C8, and polymerizes to form membrane pores

• MAC leads to cell lysis and death of the microbe through osmotic lysis

C5b

C7

C6

C8

Plasma Membrane

C9

MAC