Lecture 14, Compliment Flashcards
What are the 3 main effects of compliment activation?
- Recruit inflammatory cells
- Opsonization
- Kill via MAC
What are the names of the 3 compliment pathways?
- Lectin pw
- Classical pw
- Alternative pw
What molecule recognizes pathogen in the classical complement pw?
C1 (macromolecule)
Name the 3 different parts of C1
- Which is the biggest part?
- C1q (6 globular heads that bind AB and extended tails)
- C1r
- C1s
How is the C1qrs complex activated?
When at least 2 of the heads are bound to AB (on Ag); binding induces conformational change on AB constant region
- Single molecule bound to pentameric IgM can activate C1
What happens to the C1qrs complex upon binding 2+ ABs on Ag?
- Once C1q bound, C1r undergoes conformational change to become active
- C1r cleaves C1s, C1s active now as well
What molecule recognizes pathogen in the lectin complement pw?
Mannan Binding Lectin (MBL, a protein)
- Or Ficolins
(trimeric clusters)
While MBL binds mannose, ficolins bind ___________.
Oligosaccharides
What 2 serine proteases are MBL associated w/?
What classical pw complement molecules are they similar in function to?
MASP 1 and MASP 2
- Similar to C1r and C1s
How are MASP 1/2 activated?
How does this differ from the classical complement pw?
Activated upon MBL binding to Ag surface
- Bind directly to pathogen surface, not to AB
Upon initial activation of C1s in the classical complement cascade, what important convertase is first created? (name and function)
C4b2a, a C3-convertase
Once C4b2a (C3-convertase) is created in the classical complement pw, what convertase is created next? (name and function)
C4b2a3b, a C5-convertase
Upon initial activation of MASP-2 in the lectin complement cascade, what important convertase is first created? (name and function)
C4b2a, a C3-convertase
Once C4b2a (C3-convertase) is created in the lectin complement pw, what convertase is created next? (name and function)
C4b2a3b, a C5-convertase
What is MAC?
Does it mostly kill gram - or + ? (give e.g.)
How is it created?
Membrane Attack Complex: creates a pore in a pathogen to lyse it (many viruses)
- Gram-negative (Neisseria spp.)
- Once a C5-convertase is formed, C5 -> C5b. Then C6, C7, C8, and up to 16 C9’s join to form the MAC
How does the alternative complement pw get started?
- Hydrolysis of C3 (slowly occurs spontaneously in plasma)
How is the C3-convertase formed in the alternative pw? (name it as well)
- C3b binds factor B (Bb; cleaved by factor D) to form C3bBb, a C3-convertase
What products are formed with the hydrolysis of C3?
Which is bound to the pathogen and which is released (soluble)?
- C3a (soluble)
- C3b (bound to pathogen; rapidly degraded if not bound to pathogenic surface)
Are C3 and C5 convertases always bound to the pathogen or sometimes soluble?
Always bound (I think)
In the alternative complement pw, once the C3-convertase C3bBb is formed, how is the C5-convertase formed? (name it as well)
Active C3-convertase creates more C3a and C3b. When another molecule of C3b binds the C3bBb, a C5 convertase is formed: C3bBbC3b
Review: name the C3- and C5-convertases of each of the pw’s
C3-convertase of classical/lectin: C4b2a
C3- convertase of alternative: C3bBb
C5-convertase of classical/lectin: C4b2a3b
C5-convertase of alternative: C3bBbC3b
What is opsonization?
What receptors are used?
What do these receptors sense?
Basically ingestion of Ag that was coated via complement cascade
- CR1
- C3b
(C4a assists in adherence, C5b in phagocytosis)
How are Ag-AB complexes removed from the body?
Depends on C3b
- Bind to CR1 on circulating RBCs
- Ag-AB’s stripped off by resident macrophages as they pass thru liver, spleen
What complement components contribute to chemotaxis and vascular changes during inflammation? (not on the list of things to know)
- C5a is a chemoattractant for different granulocytes
- C3a, C4a, C5a trigger mast cells and basophils to increase vascular permeability
