Complement Cascade

Question 1

3 functions of complement cascade

Answer 1

1. anaphylatoxin production, inflammatory mediators that activate vascular epithelium and recruit phagocytes
2. opsonization
3. formation of MAC

Question 2

alternative pathway

Answer 2

innate, first to be activated

Question 3

lectin pathway

Answer 3

innate, second to be activated

Question 4

classical pathway

Answer 4

acquired (has an innate function as well), last to be activated

Question 5

T/F all complement components produced by liver in inactive form

Answer 5

true

Question 6

C3bBb

Answer 6

C3 convertase of the alternative pathway

Question 7

C4bC2a

Answer 7

C3 convertase of lectin and classical pathway

Question 8

Importance of C3b deposition

Answer 8

1. it’s a component of the C5 convertase which is necessary for formation of the MAC
2. opsonin

Question 9

C3a

Answer 9

anaphylatoxin

Question 10

C3b2Bb

Answer 10

C5 convertase-important for generation of the MAC

Question 11

Formation of C3bBb

Answer 11

C3b binds pathogen, then factor B binds that, then factor D cleaves resulting in the C3 convertase C3bBb

Question 12

C3b

Answer 12

opsonin

Question 13

C5 convertase

Answer 13

Cleaves C5 into C5a and C5b

Question 14

C5a

Answer 14

anaphylatoxin, IMPORTANT chemotactic factor for neutrophils (along with IL-8)

Question 15

C5b

Answer 15

first component of the MAC

Question 16

MAC formation

Answer 16

C5b joins with C6 and C7 which then joins with C8 which then recruits 10-16 of C9 resulting in the production of a pore in the bacterial cell membrane resulting in disintegrity and death

Question 17

MBP/MBL

Answer 17

mannose binding protein of the lectin pathway, binds mannose residues of the bacteria

Question 18

MASP-1/2

Answer 18

MBP recruits these, they bind and then result in the cleavage of C4 and C2 which results in the formation of the C4aC2b convertase of the lectin pathway (C3 convertase does the same thing as in the alternative path)

Question 19

Classical pathway involves ____

Answer 19

antibodies

Question 20

Classical pathway initiation

Answer 20

when complement component C1 binds to antibody that is bound to its cognate antigen

Question 21

C1 molecule

Answer 21

has 6 C1q stalks with C1r and C1s. When C1 binds to an antigen-engaged antibody C1r cleaves C1s which then cleaves C4 and C2 to create the C4aC2b convertase of the classical pathway (C3 convertase does the same thing as in the other two pathways)

Question 22

C4a

Answer 22

anaphylatoxin

Question 23

C2b

Answer 23

anaphylatoxin

Question 24

Most efficient isotopes for initiation classical complement cascade?

Answer 24

IgM and IgG3

Question 25

Deposition of C3b leads to

Answer 25

1. uptake and destruction of pathogen by phagocytes that have receptors for C3b 2. creation of the MAC

Question 26

C4b2a3b

Answer 26

C5 convertase

Question 27

T/F Alternative pathway amplifies the other two pathways

Answer 27

true

Question 28

Innate classical pathway

Answer 28

C reactive protein produced by the liver during septic bacterial infections binds to phosphocholine residues on bacteria and mimics the IgM antibody and thus recruits the C1 molecule and initiates the classical complement cascade

Question 29

Complement is important for encapsulated bacteria because____

Answer 29

phagocytes can't recognize PRRs on them bc they're covered by the capsule but complement factors can be deposited on their surface which leads to phagocytic activity

Question 30

T/F there are no Fc receptors for IgM

Answer 30

true

Question 31

CR1

Answer 31

found on phagocytes | recognizes C3b and results in phagocytosis

Question 32

CR1 on RBCs

Answer 32

clearance of immune complex-IMPORTANT-if not cleaned up they cause vasculitis and kidney disfunction

Question 33

CR3 and CR4

Answer 33

found on phagocytes | recognize iC3b, breakdown of C3b and stimulate phagocytosis

Question 34

CR2

Answer 34

B cell co-receptor it increases the signaling that results from B cell receptor binding to cognate antigen, decreasing the amount of costimulation signal needed from helper T cells

Question 35

C3a and C5a

Answer 35

role in activating mast cells | anaphylatoxins

Question 36

2 forms of regulation of complement

Answer 36

1. passive | 2. active

Question 37

passive regulation

Answer 37

hydrolization of thioester bonds

Question 38

C1 inhibitor

Answer 38

binds C1r:C1s and causes them to disassociate from C1q so they cannot cleave C4 and C2

Question 39

Deficiency of C1 inhibitor (HANE)

Answer 39

results in the overproduction of anaphylatoxins (which remember can stimulate mast cells) and cause angioedema episodes

Question 40

C4 binding protein

Answer 40

binds to the C4b component of the classical pathway C3 convertase, causing a displacement of the C2b fragment and making the C4 fragment susceptible to cleavage by factor I, permanently disabling that copy of the C3 convertase enzyme

Question 41

factor H

Answer 41

H binds to C3b, making it susceptible to cleavage by factor I. Once C3b is cleaved to form iC3b, it can no longer serve as a template for factor B binding, so that copy of C3b can never become part of a functional C3 convertase of the alternative pathway

Question 42

factor I

Answer 42

protease that cleaves C4b once C2 has been dissociated from it by C4-binding protein and it cleaves C3b that has been bound by factor H

Question 43

Factor I deficiency

Answer 43

this leads to depletion of C3, preventing activation of the complement cascades when they are really needed also results in deficiency of iC3b

Question 44

decay accelerating factor (CD55)

Answer 44

a membrane-bound protein that gets its name from its ability to dissociate C3 convertase enzymes

Question 45

MCP

Answer 45

MCP binds to either C3b or C4b, they become susceptible to cleavage by factor I membrane bound

Question 46

CR1

Answer 46

membrane-bound protein that binds to C3b and C4b, making them susceptible to factor I cleavage.

Question 47

CD59/protectin

Answer 47

prevents membrane attack complex formation on host cells by binding to the C5b,6,7,8 complex and preventing C9 from binding to the complex

Question 48

paroxymal noctural hemoglobulinuria

Answer 48

the inability to produce a phospoinositol glycolipid tail that anchors decay accelerating factor and CD59 (or protectin) into the membrane of host cells results inperiodic episodes of intravascular erythrocyte lysis