Lecture 25 - Complement Proteins Flashcards Preview

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Flashcards in Lecture 25 - Complement Proteins Deck (55)
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1

When and how were complement discovered?

1900.
A heat-labile factor in fresh serum that complements the function of antibodies is discovered

2

What are complement proteins?

Inactive proteins (often pro-enzymes, zymogens) in serum activated by proteolysis to carry out a range of immune functions

3

Complement protein functions
1)
2)
3)

1) Bacterial, infected cell, foreign cell lysis
2) Chemotaxis
3) Inflammation

4

Number of C' proteins

Over 30

5

What produce C' proteins?
1)
2)
3)
4)

1) Hepatocytes
2) Macrophages/monocytes
3) Some epithelial cells
4) Neutrophils (less commonly)

6

Proportion of globin plasma that is C'

10%

7

Globin plasma

Protein component of plasma

8

How are C' activated?

Enzymatic cascade

9

Significance of 'a' and 'b' fragments of a C'

'a' is smaller fragment, 'b' is larger fragment.

Exception is C2, where 'a' is larger

10

Where does activation of C' often occur?

Surface of pathogen

11

How do host cells minimise self damage by C'?

Self cells have regulatory factors on their surfaces for reducing C' activity.
Pathogens lack these

12

Activity of soluble/fluid phase C'

Often transiently active, inactive.

13

Which C' pathway is an effector of humoral immunity?

Classical pathway

14

Alternative pathway origins

Evolutionarily older than the lectin or classical pathways

15

Antibody-independent pathways

Lectin, alternative

16

Steps in C' cascade
1)
2)
3)

1) Initiation
2) Early
3) Late

17

Initiation
1)
2)
3)

1) 3 pathways for activation
2) Different pathways use different, but homologous components
3) Result in formation of different, but homologous C3 convertases

18

Early stages
1)
2)

1) Cleavage of C3
2) Formation of C5 convertase

19

How can C3 be cleaved?
1)
2)

1) C3 convertase (C4b/C2a, C3b/Bb)
2) Spontaneous hydrolysis of C3 (tickover)

20

Types of C3 convertase
1)
2)

1) Classical/lectin - C4b/C2a
2) Alternative - C3b/Bb

21

Late steps (effector phase)
1)
2)

1) After C3 cleavage, C5 convertases are formed
2) C5 activation results in pore formation, inflammation, cell lysis

22

Common steps in complement activation
1)
2)
3)

1) C3 convertase cleaves C3 (C4b/C2a or C3b/Bb)
2) C3 is cleaved, C3a is an inflammatory mediator, C3b binds to the surface of microbe (acts as an opsonin)
3) C3 convertases form the C5 convertases (C4b/C2a/C3b or C3b/Bb/C3b)

23

How does C3b bind to microbial surface?

Cleavage exposes reactive thioester groups on C3b
Reactive thioester groups bind amino and hydroxyl groups on microbial surface

24

Two types of C5 convertase

1) Classical/lectin - C4b/C2a/C3b
2) Alternative - C3b/Bb/C3b

25

Alternative pathway initiation
1)
2)
3)
4)
5)
6)

1) Low-levels of C3 hydrolysis initiate formation of active intermediates
2) Intermediates cleave C3 to C3a and C3b. In fluid, C3b is short-lived
3) C3b thioester group is revealed, C3b binds to microbial surface
4) B cleaved by factor D to Bb
5) C3b and Bb form C3 convertase on microbial surface
6) Properdin binds and stabilises C3 convertase on microbial surface

26

What cleaves B into Bb?

Factor D

27

What stabilises C3 convertase on microbial surface in alternative pathway?

Properdin

28

How is C5 convertase formed in the alternative pathway?

When C3 convertase cleaves C3, C3b joins C3b/Bb on cell surface, forms C5 convertase

29

Factor Bb
1)
2)
3)

1) Active form of factor B
2) Cleaved by factor D
3) Forms alternative C3 convertase with C3b, and alternative C5 convertase with two C3b's

30

Factor D
1)
2)

1) Serine protease
2) Cleaves factor B when bound to C3b