Hunter-Complement Flashcards
Who came up with the term complement?
Jules Bordet
studying cholera
What is complement?
> 30 constitutively expressed serum & cell surface proteins
help with innate immune response
helps antibodies in adaptive humoral immune response
helps eliminate immune complexes
What would complement deficiencies do?
increase susceptibility to pyogenic bacteria
precipitate immune complex diseases
Complement shares features with which 2 pathways?
the coagulation & kinin pathways
What are zymogens?
substrate proteins (proenzymes) are cleaved and acquire proteolytic activity
amplification, one protease cleaves a protein to activate it. etc.
zymogens are the inactive form
What are the 4 major fcns of complement?
- opsonization (binding to promote phagocytosis)
- inflammation, chemotaxis, activation of immune cells
- clearance of immune complexes
- form pores in pathogen membranes–death
T/F 50% of all bacteria can be destroyed via the pore-forming function of complement.
FALSE. ONly like 2 bacteria in a trillion can be killed this way. Even though it is cool.
What are immune complexes?
antigen-antibody bound
What part of a pathogen does the complement respond to in the classical pathway?
antigen antibody complex
Which parts of the complement start the classical pathway by doing their thing & recognizing stuff?
C1q, r, s complex
C4
C2
**then we get to the C3 convertase
Which parts of the pathogen start the lectin pathway by being recognized by the complement?
mannose-binding lectin or ficolin binds carbs on pathogen surfaces
Which parts of the complement do the recognizing of the pathogen in the lectin pathway?
MBL/ficolin, MASP-2
C4
C2
**then we get to the C3 convertase
Which part of the pathogen is recognized by the complement in the alternative pathway?
pathogen surfaces
Which part of the complement does the recognizing in the alternative pathway?
C3
B
D
**then we get to C3 convertase
After we get to C3 convertase…what kinds of by-products do we get?
C3a, C3b, C5a
What is the effect of C3a & C5a being produced?
peptide mediators of inflammation
phagocyte recruitment
What is the effect of C3b?
binds to complement receptors on phagocytes
opsonization of pathogens
removal of immune complexes
What are the terminal complement components that you can get after you get C3b? What do these terminal components cause?
C5b C6 C7 C8 C9 **membrane-attack complex, lysis of certain pathogens & cells
Typically, in the complement system what does a capital letter identify? What does a lower case letter identify?
Capital Letter: complement protein
Lower Case Letter: cleavage fragment (except for r & s)
What is the order of activation in the classical pathway?
C1, C4, C2, C3, C5-9
Which indicates the smaller fragment & which the larger fragment: a & b? What is the exception to this rule?
a is small.
b is large.
Exception: C2b is the small fragment.
What does the letter i before a protein indicate?
the enzymatically inactive form
Which parts of the complement fit this description? binding to antigen-antibody complexes and pathogen surfaces
C1q
Which parts of the complement fit this description? binding to carb structures such as mannose or GlcNAc on microbial surfaces
MBL Fincolins C1q Properidin factor P
Which parts of the complement fit this description? Activating enzymes
C1r C1s C2a D MASP-2
Which parts of the complement fit this description? Membrane-binding proteins & opsonins
C4b & C3b
Which parts of the complement fit this description? Peptide mediators of inflammation
C5a, C3a, C4a
Which parts of the complement fit this description? membrane-attack proteins
C5b C6 C7 C8 C9
Which parts of the complement fit this description? complement receptors
CR1 CR2 CR3 CR4 CRIg
Which parts of the complement fit this description? Complement-regulatory proteins
C1NH C4BP CR1 MCP DAF H I P CD59
Describe the structure of the C1 complex.
C1q is the collagen region C1r & C1s is also there. looks like a tulip detects bacteria as a unit. complexes for the other pathways look similarly
What are all of the things that C1q recognizes?
pattern recognition receptor
bacterial porins & LPS
IgM, IgG, C-reactive protein
Describe the classical pathway in more detail.
C1 complex comes together & the C1s becomes active (serine protease). It cleaves C4 into a &b.
C4b binds to pathogen surface or is hydrolyzed.
Enzyme cleaves C2. C2a stays on pathogen surface w/ C4b.
C4b2a=C3 convertase. Cleaves C3 into C3a & b. C3b stays.
What happens to C4b or C3b if they don’t stick to the pathogen surface right away?
They are hydrolyzed!!! Water is added to the bond.
What is the effect of having iC3b on a bacterial surface?
it opsonizes it for destruction via phagocytosis. CR3 on macrophages, neutrophils, and dendritic cells attaches to iC3b–endocytosis & phagocytosis!
