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Flashcards in L4 Deck (28)
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1

Which complement molecules can make thio-ester bonds? Why don't these thio-ester bonds bind self?

C4 - classic and lectin pathways
C3 - alternative pathway
Our cells produce inhibitor of these bonds - thioester bonds will only form to antigens

2

What is the role of C3d?

Breakdown product of C3
Left on antigen
Used for B cell co-activation via CR2
Can also be used for complement binding

3

What are the options of things that can happen to C3b's thioester site when exposed or activated via attachment to an antigen?

1. Inactivated by water
2. Utilized by factor B
3. Inactivated by factor i

4

Explain the steps of the classical pathway.

1. Ab binds antigen
2. C1 complex binds Fc region of Ab
3. Binding creates conformational change in 1q, so 1r can activate 1s
4. 1s cleaves 4 in the blood
5. 4b thio-ester site exposed - binds antigen
5. 4b binds 2, 2 cleaved by 1s
4b + 2a = C3 convertase
6. 4b+2a bind 3, cleave 3
7. 4b+2a+3b = C5 convertase, cleaves 5 into 5a and 5b

5

Which antibodies activate the classical cascade? Why is conformation important for these Abs?

IgM
IgG1
IgG3
(IgG2 = weak activator)
Conformation determines if bind C1
- Free in solution conformation will NOT

6

What are the different molecules of C1? Name the ratio they are present in.

C1q = 6
- non-covalently bind Fc region
C1r = 2, serine protease
C1s = 2, serine protease
r & s are covalently bound

7

Which complement products activate inflammation (anaphylatoxins)?

C3a & C5a

8

Which lectin residues are commonly bound as PAMPs?

Mannose
Sialic acid

9

What are the 2 types of mannose binding proteins?

Mannose binding lectin (made by liver, acute phase reactant)
Ficolin

10

Describe the steps of the lectin binding pathway.

1. MBP + MASP1 + MASP2 bind lectin on antigen
2. MASP2 cleaves 4
3. 4b thio-ester bonds to antigen
4. 4b + 2 cleaved by MASP2
5. 4b + 2a = C3 convertase
6. 4b+2a+3b = C5 convertase

11

Explain the steps of the alternative pathway.

1. C3 in blood randomly --> 3a & 3b
2. 3b thioester binds to antigen, recruits factor B
3. Factor D cleaves factor B - Ba & Bb
4. 3b + Bb = C3 convertase
Causes more C3 binding to the antigen - proliferation and opsonization
5. 3b+Bb+3b = C5 convertase

12

What molecule stabilizes 3b-Bb complex in the alternative pathway?

Factor P

13

What is the active protease in each of the 2 different C3 convertase enzyme complexes?

2a in 4b2a of classical/lectin
Bb in 3b/Bb of alternative

14

What is the basis for having different enzymes governing the alternative vs classical and lectin pathways?

Gene duplication at some point in evolution

15

How does the MAC complex form (lytic pathway)?

C5 cleaved
- 4b2a3b5b
- 3bBb3b5b
5b recruits C6 & C7
C7 brings the complex into the antigen membrane b/c hydrophobic
+ C8
C9 recruited in multiples to form hole

16

What is C1INH?

C1 inhibitor
Binds activated C1r & s/MASP2
Removes them from C1q/MBP

17

What is factor H?

Binds 3b
Can bind Bb

18

What is factor I? What is its cofactor?

= serine protease
Cleaves 4b & 3b
- 3b --> 3bi & 3d
Uses factor H as cofactor

19

What is CD59?

Prevents MAC formation

20

Why do you want complement regulation?

Limit inflam response
Block self responses
Prevent using up all your complement proteins!

21

What disease results from C1 inhibitor mutation/deficiency?

Hereditary angioneurotic edema

22

What are the various roles of 3b breakdown products?

3b = opsonizing --> C5 convertase steps
3bi - opsonization ONLY
3d - stimulates B & dendritic cells

23

What is the role of CR1? What molecule does this receptor bind?

Binds 3b &4bi
On RBCs
Transport complement complex to liver for destruction
How remove immune complexes from the body without clogging up kidneys

24

What is the fxn of CR2? What molecule does this receptor bind?

Bind 3d & 3bi
B cell coactivation! (on FDC & B cells)

25

Which complement receptors are important for phagocytosis? What is the difference between them?

CR3 & CR4 - only bind inactive 3
CRIg - bind 3b & 3bi

26

Where do you find C3a & C5a receptors?

Endothelial cells
Mast cells
Phagocytes
All for inflammatory process!

27

What are the inflammatory fxns of C5a, C3a, and slightly C4a?

Smooth muscle contraction
↑vascular perm
Mast cell release

28

Which complement is in highest concentration in the blood?

C3 = 1st
C4 = 2nd