1-31 Complement

Question 1

what happens if someone is missing c5-c9 of the lytic pathway?

Answer 1

become susceptible to neisseria infections (ghonorreah or memningidits).

Question 2

a child comes in with meningitis for a second time. Whats wrong?

Answer 2

Children with meningitis is rare as it is. Twice indicates a terminal complement component is missing (like c-8)

Question 3

diseases if alternative pathway components are missing?

Answer 3

staph and strep

Question 4

terminal components missing?

Answer 4

neisseria infection

Question 5

classical pathway components missing?

Answer 5

c1, c2, c4 - lupus like immune disease from too many immune complexes not being cleared out.

Question 6

Once a cell starts making IgG what needs to happen to start making IgM again?

Answer 6

You can’t go from IgG back to IgM, the change was a splice in DNA

Question 7

Going from IgM to IgD

Answer 7

edit RNA differently. because more RNA will get made, you can edit it differently later and make IgM again

Question 8

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.

Answer 8

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.

Question 9

Three pathways of complement

Answer 9

alternative (first to act)
lectin (sugar triggered)
classical (antibody leads to lysis, with complement being the third to act)

Question 10

all 3 pathways lead to the same set of events:

Answer 10

1. recruitment of inflammatory molecules
2. opsonization of pathogens
3. perforation of pathogen cell membrane

Question 11

fixation of complement is a series of _____ steps

Answer 11

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.

Question 12

Classical pathway

Answer 12

Requires antibody, initiates with pathogen detection.

1. either a single IgM or two IgG’s must bind antigens on the pathogen surface.
2. C1q binds Fc regions on the antibody or antibodies.
3. starts a cascade of activation of C1r and C1s.
4. makes a protease that cleaves C4 and C2, which then can bind to a surface and cleave C3 into C3a and C3b.
5. C3b then binds the pathogen.

Question 13

Alternative Pathway

Answer 13

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.

Question 14

deposition of ____ onto pathogen surface leads to?

Answer 14

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

Question 15

the end result of either pathway

Answer 15

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

Question 16

while there are several pathways to activate complement, they all end up

Answer 16

fixing c3 to the particle under attack

Question 17

Fixation of complement by the classical pathway requries

Answer 17

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

Question 18

Classical Pathway Steps

Answer 18

1. C1q binds at least 2 Fc regions
2. initiates cascade of activation of C1r and C1s
3. this makes protease that cleaves C4 and C2 which then bind to a surface and cleave C3

Question 19

the alternative pathway does not require antibody but still ends up with

Answer 19

c3 fixed to the particle surface which must be permissive for fixation. our cells are not permissive for fixation

Question 20

the terminal complement components are able to

Answer 20

form a pore in the membrane of a cell. the lytic pathway of complement ends with c9 forming a pore in the target cell

Question 21

Complement can be inhibited at many steps

example?

Answer 21

on human cells, cd59 binds to the c5b678 complex and prevents recruitment of c9 to form a pore.

Question 22

the loss of early classical pathway components leads to

Answer 22

immune complex like disease, NOT AN INCREASED RATE OF BACTERIAL INFECTIONS

Question 23

C3b

Answer 23

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

Question 24

CR1

Answer 24

stimulates phagocytosis and erythrocte transport of immune complexes

Question 25

C1q

Answer 25

binding to two Fc regions sets off a cascade ending in the cleavage of C3

Question 26

a deficiency in c3 can lead to

Answer 26

susceptibility to encapsulated bacteria

Question 27

what does Factor I do?

Answer 27

cleaves/inactivates c3b and c3a

Question 28

factor I deficiency?

Answer 28

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.