Complement Activation Flashcards

1
Q

What is a complement?

A

Proteins

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2
Q

When does complement activation occur?

A

Early immediate response upon exposure to tissue damage

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3
Q

The principle of the complement system

A

Involved in cascade to destroy cell

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4
Q

What was the Ehrlich experiment?

A

Hemolysis of red blood cells mediated by antibody involves complement
-> serum added to red blood cell
->serum contained antibodies that can bind to surfaces leading to destruction of R.B.C

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5
Q

What did Ehrlich experiment suggest?

A

Not only antibodies, bacteria themselves can activate this cascade
-> therefore a way to destroy an infected cell

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6
Q

What are the 3 pathways of complement activation?

A
  1. Classic Activation Pathway
  2. Mannose-binding lectin activation pathway
  3. Alternative activation pathway
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7
Q

What activates the classic activation pathway?

A

Antigen/antibody immune complex

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8
Q

What activates the mannose-binding lectin activation pathway?

A

Microbes with terminal mannose groups

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9
Q

What activates the alternative activation pathway?

A

Bacteria, fungi, virus or tumour cells

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10
Q

What are the major functions of the complement system?

A
  1. Lysis of bacterial cells/pathogens
  2. Opsonisation
  3. Inflammation
    4.Immune Clearance
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11
Q

What are the components of the complement system?

A

Complement proteins
C1- C9 proteins
Classical Pathway - Antibodies
Alternative pathway - Factors B,D and P
Lectin pathway - Lectin -> further needs 2 proteins: MASP1 + MASP2

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12
Q

How do you activate C proteins?

A

Cleaved in 2 fragments
a and b
a - smaller, inactive
b- larger, active

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13
Q

What the exception for C2 complement protein?

A

C2a - active and larger
C2b - inactive and smaller

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14
Q

All the 3 pathways lead to the activation of which complement?

A

C3
After C3 - common pathway

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15
Q

What are the key steps in classical activation complement pathway?

A
  1. Antigen-antibody complex (IGg or IgM)
  2. C1 complex binds to antibody - C1qr2 s2
  3. Starts cleavage of complement
    C2 -> C2a (active form) and C2b
    C4 -> C4b (active form) and C4a
  4. Enzyme complex = C3- convertase
  5. Cleaves complement C3
    C3 -> C3a -> inflammation
    -> C3b
  6. C5-convertase
  7. Cleaves complement C5
  8. C5b recruitment of C6 and C7 (gets in to membrane of pathogen)
  9. Recruits C8 complement
  10. Able to polymerise C9 molecules into pathogen membrane
  11. Poly C9 :forms the pore in the pathogen membrane
    -> MAC: Membrane attack complex
  12. Via MAC: Influx of Ca2+ and electrolytes into target cell
  13. Bursting of cell: osmotic lysis
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16
Q

What is the C1 complex?

A

C1qr2s2

17
Q

What is the active form of complement C2?

A

C2a

18
Q

What are the 2 main enzyme complex in the classical activation complement pathway?

A

C3-convertase
C5-convertase

19
Q

What is the pore formed in the pathogen membrane called?

A

MAC
Membrane attack complex

20
Q

C3a complement is used for?

A

Inflammation

21
Q

What enzyme polymerises C9 complement?

A

C5b678

22
Q

How does the cell burst open?

A

Osmotic lysis
Influx of calcium ions
Burst cell open

23
Q

What is MBL?

A

Mannose binding lectin

24
Q

How does the mannose-binding lectin pathway get activated?

A

MBL binds to mannose carbohydrate on pathogen membrane

25
Q

What is the C1 like complex?

A

Mannose-binding lectin activation pathway
1 MBL
MASP1
MASP2

26
Q

What is the unique convertase in the alternative pathway?

A

Fluid phase C3 convertase
Works on few molecules of C3

27
Q

Explain the steps in the alternative pathway?

A
  1. C3 undergoes thioester hydrolysis -> C3(H20)
    2.Factor B in plasma
    ->acted upon factor D
    ->2 fragments -> Bb (larger and active)
    -> Ba
  2. Bb combines with C3(H20)
    -> Fluid phase C3 convertase
  3. Acts on C3
    -> C3b
    -> C3a
    5.Bb present in plasma combines with C3b - fully stable C3 convertase
  4. C3b joins c3 convertase + properdin -> C5 convertase
  5. Acts on C5 , C5b gets into target membrane
  6. Recruits further 3 complement proteins C6,C7 and C8
  7. Forms complex, polymerises C9
  8. Poly C9 = MAC
  9. Osmotic lysis
28
Q

What is the key role in defense against pathogens?

A