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Flashcards in L4 Deck (28)
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1
Q

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

A

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

2
Q

What is the role of C3d?

A

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

3
Q

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

A
  1. Inactivated by water
  2. Utilized by factor B
  3. Inactivated by factor i
4
Q

Explain the steps of the classical pathway.

A
  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
  6. 4b binds 2, 2 cleaved by 1s
    4b + 2a = C3 convertase
  7. 4b+2a bind 3, cleave 3
  8. 4b+2a+3b = C5 convertase, cleaves 5 into 5a and 5b
5
Q

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

A
IgM
IgG1 
IgG3
(IgG2 = weak activator)
Conformation determines if bind C1
- Free in solution conformation will NOT
6
Q

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

A
C1q = 6
- non-covalently bind Fc region
C1r = 2, serine protease
C1s = 2, serine protease 
r & s are covalently bound
7
Q

Which complement products activate inflammation (anaphylatoxins)?

A

C3a & C5a

8
Q

Which lectin residues are commonly bound as PAMPs?

A

Mannose

Sialic acid

9
Q

What are the 2 types of mannose binding proteins?

A

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

Ficolin

10
Q

Describe the steps of the lectin binding pathway.

A
  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
Q

Explain the steps of the alternative pathway.

A
  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
Q

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

A

Factor P

13
Q

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

A

2a in 4b2a of classical/lectin

Bb in 3b/Bb of alternative

14
Q

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

A

Gene duplication at some point in evolution

15
Q

How does the MAC complex form (lytic pathway)?

A
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
Q

What is C1INH?

A

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

17
Q

What is factor H?

A

Binds 3b

Can bind Bb

18
Q

What is factor I? What is its cofactor?

A

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

19
Q

What is CD59?

A

Prevents MAC formation

20
Q

Why do you want complement regulation?

A

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

21
Q

What disease results from C1 inhibitor mutation/deficiency?

A

Hereditary angioneurotic edema

22
Q

What are the various roles of 3b breakdown products?

A

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

23
Q

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

A

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

24
Q

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

A

Bind 3d & 3bi

B cell coactivation! (on FDC & B cells)

25
Q

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

A

CR3 & CR4 - only bind inactive 3

CRIg - bind 3b & 3bi

26
Q

Where do you find C3a & C5a receptors?

A

Endothelial cells
Mast cells
Phagocytes
All for inflammatory process!

27
Q

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

A

Smooth muscle contraction
↑vascular perm
Mast cell release

28
Q

Which complement is in highest concentration in the blood?

A
C3 = 1st
C4 = 2nd