Complement System Flashcards

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1
Q

What is the complement system

A

Effector system of the humoral response (both innate and adaptive)

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2
Q

What are the 4 roles of complement system proteins

A

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

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3
Q

What are the 3 pathways

A

Classical

Alternative

Lectin

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4
Q

What initiates classical pathway

A

Antigen and antibody complex

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5
Q

Which complements make up classical pathway

A

C1 (q,r,s)

C4 , C3 and C2

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6
Q

Which complements are in alternative pathway

A

Factor D,B,P

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7
Q

Which complement is in both alternative and classical pathway

A

C3

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8
Q

Which enzyme is produced in all 3 pathways

A

C3 convertase

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9
Q

What are complements cleaved into

A

a and b fragments

A are always smaller
B are larger

(Apart from in C2 A = large)

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10
Q

What do a and b fragments do

A

Inflammation = a

B = opsonins and surface binding

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11
Q

Which opsonin is produced from C3 convertase (why it’s so important)

A

C3b

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12
Q

Why complement binds to the antibody via globular heads

A

C1q (part of the c1)

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13
Q

How does c1 q bind to antibodies

A

Fc binding globules on antibodies

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14
Q

What is the c1 complex made of

A

2 x s

2 x r

1 x q

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15
Q

Which antibody has 5 fc binding globules (meaning only 1 needed to bind c1 q)

A

Igm

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16
Q

Why are 2 igg needed for c1 q to bind

A

IgG are smaller and 2 globular heads of c1 q need to bind to be activated

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17
Q

What is activated (conformation change) via c1 q binding to antibody and what happens

A

C1 r

This then cleaves c1 s to activate it

18
Q

What is c1 s

A

A serine protease

19
Q

Explain the events which lead to c4b2a (C3 convertase)

A

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

20
Q

What does the c4b2a then cleave

A

C3 into C3a (inflammation) and c3b (opsonin)

21
Q

Which bond on c3b (exposed via c4b2a cleavage) allows into to bind as an opsonin to pathogen

A

Thioester bond

22
Q

How does c3b also cause phagocytosis

A

Via c3b receptors

23
Q

What is produced if c3b binds to c4b2a (C3 convertase)

A

Produces C5 convertase

24
Q

What does c5 convertase (c4b2ac3b) do if c5 binds

A

Cleaves it to c5a for inflammation

C5b then can bind to pathogen recruiting c6,7,8,9 = MAC

25
Q

What does c 5,6,7,8,,9 form which kills pathogen

A

A pore by displacing membrane lipids (mac complex)

26
Q

What activates alternative pathway

A

C3b opsonin binding to pathogen surface

27
Q

What produces the C3 convertase in the alternative pathway

A

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

28
Q

Which factor stabilises the c3bBb convertase to surface

A

Factor P

29
Q

How is c5 convertase produce from c3bBb

A

Another c3b is added to surface forming c3b2Bb = c5 convertase

30
Q

How is production of c5 convertase c3b2Bb in the alternative pathway allowing recruitment of mac

A

Cleaves c5 into c5a for inflammation and c5b which binds to 6,7,8,9 = mac

31
Q

What are lectins and where are they made

A

Carb binding Proteins made in liver

32
Q

What do lectin recognise on pathogens

A

Mannose

Forming mannose binding lectin complex (MBL)

33
Q

What are produced from the MBL complex

A

Masp 1 and 2 (mannose serine protease)

34
Q

How is C3 convertase c4b2a produced from masp

A

They cleave c4 and c2

C4b and c2a bind

35
Q

What happens once the C3 convertase c4b2a in lectin pathway is produced

A

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

36
Q

Why complement has chemotaxis properties for inflammation eg increase permeability

A

C1s

37
Q

What would happen if someone had C3 deficiency

A

Can’t produce c3b to be opsonin which can’t then bind to c4b2a to produce a c5 convertase = no cytolysis for mac

38
Q

What do C1 inhibitors do

A

Bind to the qrs to stop classical pathway

Also remove MBL so that masp can’t be produced

39
Q

Which regulator binds to c4b which displaces c2a and C3b or Bb(in alternative pathway)

A

Complement receptor 1

40
Q

What does factor 1 regulator cleave

A

C3b and c4b