Basic Complement System Flashcards
List the process of the Alternative Pathway up until the MAC formation.
C3b that is already found on the surface of the pathogen binds with Factor B
C3b-Factor B binds with Factor D, which cleaves Factor B into Bb and Ba
Ba fucks off and leaves Bb bound to C3b (formation of C3 Convertase)
Properdin binds to C3bBb and stabilizes it
C3 Convertase (C3bBb) cleaves C3 into C3a and C3b
C3b binds to C3 convertase to form C5 convertase (C3bBbC3b) or (C3b)_2Bb for the Kc kid
C5 Convertase cleaves C5 into C5a and C5b
C5a fucks off
Why was C3b already found on the surface of the pathogen?
the alternative pathway is capable of autoactivation because of a process called “tickover” of C3, which means that C3 spontaneously cleaves itself to form C3b.
C3b can also be formed from the Classical Pathway or the Lectin Pathway and serve as an amplification loop.
List the process of the Classical Pathway up until the MAC formation.
1 IgM or 2 IgG antibodies bind to the surface of the pathogen
C1q binds to the antibody
C1r binds to C1q. C1s** binds to C1r and cleaves C2 and C4 into their respective a and b forms
C4bC2a bind to form C3 convertase
C3 convertase cleaves C3 into C3a and C3b
C3a fucks off
C3b binds to C3 convertase to form C5 convertase (C4bC2aC3b)
C5 convertase cleaves C5 into C5a and C5b
Note that C1s has the catalytic capacity to cleave C2 and C4.
List the process of the Lectin Pathway up until the MAC formation.
Pathway is initiated by the binding of Mannose-Binding Lectin to the pathogen.
MBL activates Mannose-Binding Lectin Associated Serine Proteases MASP1 and MASP2
MASP1/2 cleave C2 and C4 into their a and b forms
C4bC2a bind to form C3 convertase
C3 convertase cleave C3 into C3a and C3b
C3b binds to C3 convertase to form C5 convertase (C4bC2aC3b)
C5 convertase cleaves C5 into C5a and C5b
Compare and contrast the Classical Pathway and the Lectin Pathway.
MBL’s structure is similar to C1q
MASP1/2 have similar functions to C1r and C1s, therefore they initiate an identical downstream cascade to the Classical Pathway
Which component from the MAC Complex is inserted into the membrane first and begins the polymerization of the MAX complex?
C8
Key word is inserted. C5b, C6, and C7 bind to the surface but C8 is inserted and begins the polymerization of C9
Differentiate the MAC formation between the Alternative, Classical, and Lectin Pathway.
There is no difference
Tricky Tricky :)
What is the function of DAF (Decay Accelerating Factor)? Which pathways are affected?
Destabilizes C3 convertase by enhancing the dissociation of C4b from C2a and C3b from Bb
Affects both the classical and alternative pathway
Classical Pathway (C4bC2a) Alternative Pathway (C3bBb)
What is the function of CR1? Which pathways are affected?
Cofactor for Factor I mediated cleavage of C3b and C4b. Enhances the dissociation of C4bC2a.
Affects the classical and Lectin pathway
What is the function of Factor H? What pathways are affected?
Binds to C3b and prevents binding for C3/C5 convertases for the alternative pathway
What is the function of CD59?
Blocks the association of C9 with C5b-C8 to prevent the formation of the MAC Complex
What does C3a activate? What does this lead to?
Mast cells and Basophils
Leads to inflammation
What does C5a activate? What does this lead to?
Monocyte and Macrophage
Inflammation
C3a and C5a are both proinflammatory soluble signals. What 4 other ways do they act as anaphylatoxins? Which one is more powerful?
- Contraction of smooth muscles
- Increased permeability of blood vessels
- Degranulation of basophils
- Chemotaxis, release of O2 radicals and lysosomal enzymes
C5a>C3a
What disease is associated with C1 Inhibitor?
Hereditary Angioedema (HAE)
Leads to edema (swelling) in the face, hands, feet, and airway
