Complement system Flashcards
Basic functions of complement system
Lysis of cells, bacteria and virus
Opsonization
Immune clearance
Bind complement receptors
What does Lysis entail
Antibody dependent or antibody independent mechanisms
Opsonization?
The uptake of particulate antigens by phagocytosis
What are the fragments generated during activation called
A and B
With a and b, which is larger and which is smaller?
A is smaller, b is larger
Where do larger fragments bind?
large fragments binds to the target near the site of activation
What do the smaller fragments do?
They diffuse from the site and can initiate receptor mediated local inflammatory responses
What happens when fragments interact with each other?
They form functional complexes such as C4b2a
The classical, lectin and alternative pathway all create what?
C5b
What molecules activates the classical pathway?
IgM and IgG
What are the components involved in the classical pathway?
C1,C2,C3 and C4
What happens when IgM binds to an antigen?
There is a change that exposes a binding site for C1
What domains does C1r and C1’s have?
Catalytic and interaction
For C1q to have a stable interaction, what needs to happen?
C1q needs to bind to at least two Fc sites
What happens to C1s when C1r converts it
It becomes an active enzyme with two substrates C4 and C2
What is C4
C4 is a glycoprotein with 3 polypeptide chains α, β, γ
C1s cleave the amino terminal end of the a chain, what happens?
A binding site on C4b is exposed (it is the larger fragment)
What are the two forms of IgM
Pentameric when in solution and monomeric when attached to the cell
C4b binds to the target vicinity of C1, then what happens
C2 attaches to the exposed site on C4b, C1 then cleaves it leaving C2a and C2b, C2b then diffuses away leaving C3 convertase
How many polypeptide chains does C3 have?
two, a and b
what is generated when C3a is cleaved?
C3b
C3b binds to C4b2a3b to form what
C4b2a3b aka C5 convertase
when C4b2a cleaves C5 and C5a diffuses away, what happens to C5b
C5b attaches to C6 which starts the formation of MAC
Where do all the reactions take place?
They take place on the hydrophilic surfaces of membranes or immune complexes
The terminal sequence of compliment activation involves what molecules
C5b,C6,C7,C8 and C9
What is MAC
Mac is a large channel through the target cell membrane
Where does C5b bind?
C5b binds to the surface of the target cell which allows the binding of other components
C5b is inactivated unless what molecule stabilises it?
C6
What happens when C5b6 binds to C7?
The hydrophobic residues on the complex are exposed which messes with the membrane phospholipids and inserts into the bilayer
What are the final two steps in the formation of MAC
C8 binds to C5b67 and then a bunch of C9 joins the C5b678 complex
When MAC occurs what goes on?
The cell cant stay stable and is killed by the water flushing in
What immune system is the alternative pathway
Innate
What does the alternative pathways include
C3, factor B, factor D and properdin
C3b binds to foreign surface antigens which then binds factor B. What site is then exposed?
the enzyme Factor D
What does factor D do?
Factor D cleaves off a small fragment Ba which then generates C3 convertase activity
C3bBb has an activity of five minutes. what needs to bind to it to extend its life to 30 minutes?
Properdin
What does protein and glycoproteins circulate in the serum as?
Zymogens
