Complement System Flashcards
What is the complement system
Effector system of the humoral response (both innate and adaptive)
What are the 4 roles of complement system proteins
Act as opsonins - opsonisation then phagocytosis via receptor activation
Some recruit phagocytes for inflammation (chemokines)
Some activate B cells to produce antibodies
Some make up MAC for cell lysis
What are the 3 pathways
Classical
Alternative
Lectin
What initiates classical pathway
Antigen and antibody complex
Which complements make up classical pathway
C1 (q,r,s)
C4 , C3 and C2
Which complements are in alternative pathway
Factor D,B,P
Which complement is in both alternative and classical pathway
C3
Which enzyme is produced in all 3 pathways
C3 convertase
What are complements cleaved into
a and b fragments
A are always smaller
B are larger
(Apart from in C2 A = large)
What do a and b fragments do
Inflammation = a
B = opsonins and surface binding
Which opsonin is produced from C3 convertase (why it’s so important)
C3b
Why complement binds to the antibody via globular heads
C1q (part of the c1)
How does c1 q bind to antibodies
Fc binding globules on antibodies
What is the c1 complex made of
2 x s
2 x r
1 x q
Which antibody has 5 fc binding globules (meaning only 1 needed to bind c1 q)
Igm
Why are 2 igg needed for c1 q to bind
IgG are smaller and 2 globular heads of c1 q need to bind to be activated
What is activated (conformation change) via c1 q binding to antibody and what happens
C1 r
This then cleaves c1 s to activate it
What is c1 s
A serine protease
Explain the events which lead to c4b2a (C3 convertase)
C1s cleaves c4 into c4 a and b
C4a goes to inflammation site
C4 b binds to the pathogen and then c2 is recruited
C2 is also cleaved via c1s protease
C2a (large fragment) then binds to c4b = C3 convertase
What does the c4b2a then cleave
C3 into C3a (inflammation) and c3b (opsonin)
Which bond on c3b (exposed via c4b2a cleavage) allows into to bind as an opsonin to pathogen
Thioester bond
How does c3b also cause phagocytosis
Via c3b receptors
What is produced if c3b binds to c4b2a (C3 convertase)
Produces C5 convertase
What does c5 convertase (c4b2ac3b) do if c5 binds
Cleaves it to c5a for inflammation
C5b then can bind to pathogen recruiting c6,7,8,9 = MAC
What does c 5,6,7,8,,9 form which kills pathogen
A pore by displacing membrane lipids (mac complex)
What activates alternative pathway
C3b opsonin binding to pathogen surface
What produces the C3 convertase in the alternative pathway
factor B binding to c3b on pathogen surface
The factor B is then cleaved by factor D
Bb and 3b then bind (c3bBb) to produce C3 convertase
Which factor stabilises the c3bBb convertase to surface
Factor P
How is c5 convertase produce from c3bBb
Another c3b is added to surface forming c3b2Bb = c5 convertase
How is production of c5 convertase c3b2Bb in the alternative pathway allowing recruitment of mac
Cleaves c5 into c5a for inflammation and c5b which binds to 6,7,8,9 = mac
What are lectins and where are they made
Carb binding Proteins made in liver
What do lectin recognise on pathogens
Mannose
Forming mannose binding lectin complex (MBL)
What are produced from the MBL complex
Masp 1 and 2 (mannose serine protease)
How is C3 convertase c4b2a produced from masp
They cleave c4 and c2
C4b and c2a bind
What happens once the C3 convertase c4b2a in lectin pathway is produced
Cleaves C3 into C3 a and c3b
C3b can be an opsonin and also bind to c4b2a to form a c5 convertase
This c5 convertase can then cleave c5 and c5b recruits 6,7,8,9 = mac
Why complement has chemotaxis properties for inflammation eg increase permeability
C1s
What would happen if someone had C3 deficiency
Can’t produce c3b to be opsonin which can’t then bind to c4b2a to produce a c5 convertase = no cytolysis for mac
What do C1 inhibitors do
Bind to the qrs to stop classical pathway
Also remove MBL so that masp can’t be produced
Which regulator binds to c4b which displaces c2a and C3b or Bb(in alternative pathway)
Complement receptor 1
What does factor 1 regulator cleave
C3b and c4b
