1-31 Complement Flashcards
what happens if someone is missing c5-c9 of the lytic pathway?
become susceptible to neisseria infections (ghonorreah or memningidits).
a child comes in with meningitis for a second time. Whats wrong?
Children with meningitis is rare as it is. Twice indicates a terminal complement component is missing (like c-8)
diseases if alternative pathway components are missing?
staph and strep
terminal components missing?
neisseria infection
classical pathway components missing?
c1, c2, c4 - lupus like immune disease from too many immune complexes not being cleared out.
Once a cell starts making IgG what needs to happen to start making IgM again?
You can’t go from IgG back to IgM, the change was a splice in DNA
Going from IgM to IgD
edit RNA differently. because more RNA will get made, you can edit it differently later and make IgM again
T or F Once an immune response shifts to making IgG it is impossible for that individual to make IgM to that antigen in the future.
False, THAT cell can’t make IgM about, but some of the millions of b cells you make that day will be reactive to IgM. Even in secondary response, there is a blip of IgM made.
Three pathways of complement
alternative (first to act)
lectin (sugar triggered)
classical (antibody leads to lysis, with complement being the third to act)
all 3 pathways lead to the same set of events:
- recruitment of inflammatory molecules
- opsonization of pathogens
- perforation of pathogen cell membrane
fixation of complement is a series of _____ steps
irreversible steps. Cleavage steps lead to new molecule being formed and a piece floating away. One fixes to surface of bacteria (c3b) and c3a floating away.
Classical pathway
Requires antibody, initiates with pathogen detection.
- either a single IgM or two IgG’s must bind antigens on the pathogen surface.
- C1q binds Fc regions on the antibody or antibodies.
- starts a cascade of activation of C1r and C1s.
- makes a protease that cleaves C4 and C2, which then can bind to a surface and cleave C3 into C3a and C3b.
- C3b then binds the pathogen.
Alternative Pathway
doesnt require antibody. proactive (initiates wtihout antigen detection)
Begins with a C3 convertase that ultimately cleaves C3 into C3a and C3b. C3b then binds the pathogen.
deposition of ____ onto pathogen surface leads to?
C3b.
binding of complement receptors. This further leads to opsonization and/or perforation of pathogens, recruitment of inflammatory cells, and clearance of immune complexes to the liver and spleen
the end result of either pathway
cleavage of c3. This leads to the activation of a common sequence of events leading to cell lysis.
the components c5-c9 form the membrane attack complex, which lyses the target cell
while there are several pathways to activate complement, they all end up
fixing c3 to the particle under attack
Fixation of complement by the classical pathway requries
C1q binding to at least 2 Fc regions
- a single pentomeric IgM
- or two adjacent IgG - more efficient as immune response matures and there are more IgG
Classical Pathway Steps
- C1q binds at least 2 Fc regions
- initiates cascade of activation of C1r and C1s
- this makes protease that cleaves C4 and C2 which then bind to a surface and cleave C3
the alternative pathway does not require antibody but still ends up with
c3 fixed to the particle surface which must be permissive for fixation. our cells are not permissive for fixation
the terminal complement components are able to
form a pore in the membrane of a cell. the lytic pathway of complement ends with c9 forming a pore in the target cell
Complement can be inhibited at many steps
example?
on human cells, cd59 binds to the c5b678 complex and prevents recruitment of c9 to form a pore.
the loss of early classical pathway components leads to
immune complex like disease, NOT AN INCREASED RATE OF BACTERIAL INFECTIONS
C3b
Deposition of c3b leads to binding of complement receptors
- opsonizing - bacteria or yeast
- clearance of immune complexes - if we have antibody forming complexes with antigen, if we don’t clear them out, can deposit in organs and cause damage. Need to clear complexes out. Cause kidney disease
CR1
stimulates phagocytosis and erythrocte transport of immune complexes
C1q
binding to two Fc regions sets off a cascade ending in the cleavage of C3
a deficiency in c3 can lead to
susceptibility to encapsulated bacteria
what does Factor I do?
cleaves/inactivates c3b and c3a
factor I deficiency?
similar to c3 deficiency, will be susceptible to encapsulated bacteria.
The thing that chops up c3 leads to no c3?
Opposite of expectation. Normally c3 is activated at low levels, fixes to surfaces, and because of correct inhibitors, factor I cleaves the active c3b before it starts fixing more
-no factor I? you fix c3b everywhere. Run out of it. By controlling it, you have more.
