Complement Activation Flashcards
What is a complement?
Proteins
When does complement activation occur?
Early immediate response upon exposure to tissue damage
The principle of the complement system
Involved in cascade to destroy cell
What was the Ehrlich experiment?
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
What did Ehrlich experiment suggest?
Not only antibodies, bacteria themselves can activate this cascade
-> therefore a way to destroy an infected cell
What are the 3 pathways of complement activation?
- Classic Activation Pathway
- Mannose-binding lectin activation pathway
- Alternative activation pathway
What activates the classic activation pathway?
Antigen/antibody immune complex
What activates the mannose-binding lectin activation pathway?
Microbes with terminal mannose groups
What activates the alternative activation pathway?
Bacteria, fungi, virus or tumour cells
What are the major functions of the complement system?
- Lysis of bacterial cells/pathogens
- Opsonisation
- Inflammation
4.Immune Clearance
What are the components of the complement system?
Complement proteins
C1- C9 proteins
Classical Pathway - Antibodies
Alternative pathway - Factors B,D and P
Lectin pathway - Lectin -> further needs 2 proteins: MASP1 + MASP2
How do you activate C proteins?
Cleaved in 2 fragments
a and b
a - smaller, inactive
b- larger, active
What the exception for C2 complement protein?
C2a - active and larger
C2b - inactive and smaller
All the 3 pathways lead to the activation of which complement?
C3
After C3 - common pathway
What are the key steps in classical activation complement pathway?
- Antigen-antibody complex (IGg or IgM)
- C1 complex binds to antibody - C1qr2 s2
- Starts cleavage of complement
C2 -> C2a (active form) and C2b
C4 -> C4b (active form) and C4a - Enzyme complex = C3- convertase
- Cleaves complement C3
C3 -> C3a -> inflammation
-> C3b - C5-convertase
- Cleaves complement C5
- C5b recruitment of C6 and C7 (gets in to membrane of pathogen)
- Recruits C8 complement
- Able to polymerise C9 molecules into pathogen membrane
- Poly C9 :forms the pore in the pathogen membrane
-> MAC: Membrane attack complex - Via MAC: Influx of Ca2+ and electrolytes into target cell
- Bursting of cell: osmotic lysis
What is the C1 complex?
C1qr2s2
What is the active form of complement C2?
C2a
What are the 2 main enzyme complex in the classical activation complement pathway?
C3-convertase
C5-convertase
What is the pore formed in the pathogen membrane called?
MAC
Membrane attack complex
C3a complement is used for?
Inflammation
What enzyme polymerises C9 complement?
C5b678
How does the cell burst open?
Osmotic lysis
Influx of calcium ions
Burst cell open
What is MBL?
Mannose binding lectin
How does the mannose-binding lectin pathway get activated?
MBL binds to mannose carbohydrate on pathogen membrane
What is the C1 like complex?
Mannose-binding lectin activation pathway
1 MBL
MASP1
MASP2
What is the unique convertase in the alternative pathway?
Fluid phase C3 convertase
Works on few molecules of C3
Explain the steps in the alternative pathway?
- C3 undergoes thioester hydrolysis -> C3(H20)
2.Factor B in plasma
->acted upon factor D
->2 fragments -> Bb (larger and active)
-> Ba - Bb combines with C3(H20)
-> Fluid phase C3 convertase - Acts on C3
-> C3b
-> C3a
5.Bb present in plasma combines with C3b - fully stable C3 convertase - C3b joins c3 convertase + properdin -> C5 convertase
- Acts on C5 , C5b gets into target membrane
- Recruits further 3 complement proteins C6,C7 and C8
- Forms complex, polymerises C9
- Poly C9 = MAC
- Osmotic lysis
What is the key role in defense against pathogens?
