Complement System

Question 1

what is the complement system?

Answer 1

system comprised of proteins that help to kill microbes, induce inflammation, increase phagocytosis by opsonization and clear soluble immune complexes

Question 2

what is the lectin pathway initiated by?

Answer 2

lectins that bind mannose

Question 3

what is the alternate pathway activated by?

Answer 3

cell wall of bacteria and yeast

Question 3

what is the classical pathway initiated by?

Answer 3

antigen-antibody complex

Question 3

what are the steps for activation of the complement system?

Answer 3

1. recognition
2. enzyme activation
3. expression of biological activity

Question 4

what are some similarities/differences on the paths?

Answer 4

S: end result
D: unique proteins & enzymes for first step

Question 5

all three pathways make:

Answer 5

C3 convertase (and cleave C3)

Question 6

what proteins are involved in the classical pathway?

Answer 6

C1-9

Question 6

what makes up the C1 complex?

Answer 6

C1q, C1s, C1r

Question 6

what is the first step of the classical pathway?

Answer 6

binding of C1 to antibody

Question 7

the conformational change that occurs when C1 is bound activates:

Answer 7

C1s

Question 8

what is needed for binding onto the C1 complex?

Answer 8

2 IgG OR 1 IgM (cause IgM so big)

Question 9

what is C1s?

Answer 9

C1 esterase that cleaves C4 and C2
(cleaves C4 to C4a + C4B, C2 to C2a, C2b)

Question 10

what steps occur to form MAC?

Answer 10

c6 binds to c5b
c7 binds to that
c8 binds to that
C5bc6c7c8 acts as receptor for c9

Question 11

What happens after C3 cleaves C4 and C2?

Answer 11

C4b and C2a form a complex called C3 convertase that can cleave C3 into C3a&b

Question 11

what is the largest amplification step?

Answer 11

C3 convertase cleaving hundreds of copies of C3, forms amplification or cascade of reactions

Question 12

C4bC2aC3b forms a complex called ____

Answer 12

C5 convertase (cleaves C5 to C5a&b)

Question 13

what does C5b do?

Answer 13

initiates the formation of membrane attack complex

Question 14

what does c9 do?

Answer 14

polymerizes into tube that inserts onto membrane punching holes that allow water and ions to ender making the cell lyse (causes direct death of microorganisms)

Question 15

what is a lectin?

Answer 15

proteins that bind to carbohydrates

Question 16

mannose binding lectin bind to _______________

Answer 16

carbs on surface of bacteria and yeast

Question 17

MBL cleaves _______

Answer 17

C4 and C2 (thus making C3 convertase) (picks up classical pathway from here)

Question 18

In the alternate pathway PAMPS begin the pathway how?

Answer 18

they hydrolyze C3 to make C3 a&b

Question 19

after C3bFactorB complex is formed what ccurs?

Answer 19

factor D cleaves factor B forming c3bBb which is C3 convertase

Question 19

what binds to C3bBb and why?

Answer 19

properdine to make it more stable becomes C3bBbP

Question 20

after c3b binds to the cell surface what happens?

Answer 20

binds factor B forming C3bFactorB complex,

Question 21

what does C3bBbP do?

Answer 21

cleaves C3 to C3b (positive feedback loop)

Question 22

what does C3bBbC3b do?

Answer 22

cleave C5, C5b then can initiate process to make MAC

Question 23

how does the complement system induce inflammation?

Answer 23

C3a, C4a, C5a strongly stimulate chemotaxis for neutrophils and basophils/mast cells

Question 24

what is C reactive protein?

Answer 24

protein produced by inflammation to tart classic pathway, used as a marker to detect inflammation in the body

Question 25

how does the complement system facilitate phagocytosis?

Answer 25

opsonization (immune system recognizing and destroying pathogens)

Question 26

what binds to the complement receptors?

Answer 26

C3b, iC3b, C4b

Question 27

how are immune complexes cleared?

Answer 27

after complement cascade is activated, complex binds to complement receptors enhancing phagocytosis and destruction of antigen

Question 28

deficiency in complement components C1, C4, C2 is associated with ______ because ______

Answer 28

Lupus impaired ability to clear immune responses (exhausts quantities of complement proteins)

Question 29

deficiency in the alternate pathway can lead to what?

Answer 29

increased susceptibility to recurrent infection with pus producing bacteria

Question 30

what is the first thing that inhibits the classical pathway?

Answer 30

Cleavage of C4 and C2 blocked by C1 inhibitor

Question 31

what is the second thing that blocks a later stage of the classical pathway?

Answer 31

decay accelerating factor binds to C4 dissociating C4bC2a blocking formation of C3 convertase

Question 32

what is associated with deficiency of C1 INH?

Answer 32

angioedema or uncontrolled activation of C'

Question 33

what blocks C3 convertase in the alternate pathway?

Answer 33

factor H (displaces Bb from C3bBb)

Question 34

what forms inactive C3b?

Answer 34

factor I and membrane cofactor protein

Question 35

what blocks C3 convertase in the alternative pathway?

Answer 35

DAF

Question 36

what blocks C9 binding and precents MAC?

Answer 36

C59

Question 37

what are serum carboxypeptidase inactive anaphylatoxins?

Answer 37

C3a, C5a, C4a

Question 38

Phagocytic removal of microbes and immune complexes from our tissues is helped by which of the following? a) IgG b) C3bi c) C3b d) All of the above

Answer 38

d) All of the above

Question 39

Although compliments are considered part of the innate defense, which of the three pathways may require time and acts with antigen specificity? a) Classical b) Lectin c) Alternate d) C reactive protein

Answer 39

a) Classical