Innate Immunity Part II Flashcards
The activation of the complement system may be inititated by 3 different ativation pathways. What are these pathways?
Classical
Alternative
Lectin
What is the early step 1 of complement activation?
The formation of C3 convertase complex, which trigger inflammation and opsonize microbes.
What is the early step 2 of the complement activation?
The formation of C5 convertase complexes that produce C5a and C5b.
This perpetuates inflammation and initiattes the late steps.
What are the late steps of complement activation?
The formation of membrane attack complexes which form holes in microbial membranes.
Complement activation involves a proteolytic cascade. What is involved in this cascade?
An inactive precursor enzyme (zymogen) is altered to become an active protras that cleaves the next complement protein in the cascade.
What do enzymatic cascades result in?
Tremendous amplification of the amount of proteolytic products that are generated.
What is the function of the by-products of the complement activation?
They perform various effector functions of the complement system.
With what other pathways does the complement system work in cooperatin with?
Blood coagulation pathways
Kinin-kallikrein system (regulates vascular permeability).
What is the result of recognition of microbes by any of the three complement pathways?
It results in sequential recruitment and assembly of additional complement proteins into protease complexes.
What is the function of C3 convertase?
It cleaves C3 to make C3a and C3b fragments.
What is the function of C3a?
It stimulates inflammation by acting as a chemoattractant for neutrophils.
What is the function of the C3b fragment?
It becomes covalently attached to the microbial surface and serves as an opsonin to promote phagocytosis of the microbes.
What is a secondary function of C3 convertase?
It binds a C3b fragment to form a protease complex called C5 convertase.
What is the function of C5 convertase?
It cleaves C5 producing C5a and C5b fragments.
What is the function of C5a?
It is a potent chemoattractant that induces changes in the permeability of blood vessels.
What is the function of C5b?
It is attached to a bacterial membrane that initiates the formation of a complex of C6 - 9 complement proteins called the membrane attack complex.
What complement proteins comprise the membrane attack complex (MAC)?
C6-9
What do multiple MACs cause?
Bacterial leak and lysis
What does the classical complement activation pathway require?
IgM or IgG and C1
C3 and C5 convertases are used.
What occurs during the lectin activation pathway?
MBP binds to bacteria and MASPs are activated.
C3 and C5 convertases are used.
What occurs during the alternative activation pathway?
C3 undergoes spontanous hydrolysis.
Factors B and D are needed.
C3 and C5 convertases are used.
What is factor B?
A serine protease and the active enzyme of C3 and C5 convertases.
What is factor D?
A plamsa serine protease that cleaves factor B when it is bound to C3b.
What is prperdin?
A protein that stabilizes the C3 convertase on microbial surfaces.
What is C1?
It initiates the classical pathway. Fragments of it lead to C4 and C2 activation.
What is C4?
It covalently binds to the surface of a microbe or cell where the antibody is bound and complement is activated.
what is C2?
A serine protease functioning as an active enzyme of C3 and C5 convertase.
What is mannose-binding lectin (MBL)?
It initiates the lectin pathway; it also activates C4 and C2, as in the classical pathway.
How is the alternative pathway capable of autoactivation?
Due to tickover at C3.
It occurs spontaneously and generates C3a and C3b.
What does C3b bind to in the alteranative pathway? What are the results?
C3b binds to factor B.
Factor B is cleaved into Ba and Bb by factor D.
In the alternative pathway, what does Bb associate with?
C3b and C3 convertase, which then cleave additional C3 molecules generating C3b.