Complement Cascade Flashcards Preview

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Flashcards in Complement Cascade Deck (61):
0

C'

complement

1

what systems does complement "complement"?

humoral and innate immunity

2

complement is central to what?

inflammatory reactions

triggering and amplifying inflammation, attraction of phagocytes, clearance of immune complexes, cellular activation, direct microbial killing, and important in development of the humoral responses

3

larger and smaller fragment of complement?

a - smaller
b - larger

b binds and a diffuses

4

anaphylotaxins

a fragments of complement

are chemotactic peptides

5

role of anaphylatoxins

play a role in initiating a localized inflammatory response

6

all pathways of complement end where?

formation of the MAC

7

classical pathway

activated by antigen binding to antigen

assists in the humoral response

8

alternative pathway

not necessary for a prior exposure
-doesn't need antibody
plays a role in surveillence

more primitive than classical

9

lectin pathway

activated by binding of mannose binding protein in bacteria

10

initiation of classical pathway?

IgG or IgM antibody is bound and results in the binding of C1
-C1 binds to Fc portion of antibodies

11

overview of classical complement pathway

most efficient and fast

1) IgG and IgM antibodies bind antigen and Fc portion binds C1
-binds to C1q domains (cleavage of C1r and C1s)
enzymatically active C1qrs

12

structure of C1

one hexamer C1q subunit, two C1r, and two C1s subunits

forms a large complex

13

what activates C1?

cleavage of C1r and C1s
-yields active C1qrs

*the C1 is a C1q hexamer, two C1r, and two C1s subunits

14

how many of each antibody to activate classical pathway?

IgM is a pentamer
-only requires one to initiate cascade

IgG is a monomer
-requires at least two to initiate cascade

15

activity of enzymatically active C1qrs?

cleaves C4
-release C4a and C4b

C4b attaches to the cell membrane which form clusters around the area of the antibody interaction

C4a diffuses away

also cleaves C2

16

activity of C4b?

recruits C2, which is also cleaved by C1qrs
-C2a diffuses away and C2b binds to C4b

17

what is the C3 convertase of classical pathway?

C4b2b
-cleaves C3

C3b will opsonize and also associate with the C3 convertase
-forms the C4b2b3b (C5 convertase)

18

importance of C3

responsible for the distinction between self and non-self

self surfaces limit the deposition of C3b
-C3b rapidly associates with non-self surfaces

19

C5 convertase of the classical pathway?

C4b2b3b

initiates the formation of the MAC complex

C5b associates with C6 and C7 which inserts into the membrane
-forms pore - which will lead to slow lysis

C8 then bind the C5b67 which
-forms C5b678 which recruits 10-16 copies of C9
forms the MAC

20

what is the MAC complex?

C5b6789

creates large pores in the membrane
-results in more rapid osmotic lysis of the cell

21

alternative pathway of complement?

slow and less efficient

surveillence system

22

initiation of alternative pathway?

spontaneous conversion of C3 to C3b
-important in recognizing self from non-self

23

how is C3b involved in the recognition of self membrane?

sialic acid levels are high on the self membranes
-result in the inactivation of C3b

bacterial and viral envelopes have low sialic acid
-C3b remains associated with membrane

24

C3 convertase of the alternative pathway?

factor B binds to C3b and is cleaved
-factor D cleaves factor B

forms C3bBb (alternative C3 convertase)
results in the cleavage of C3 (amplifies process)

25

Factor B

binds to membrane associated C3b

cleaved by Factor D

26

Factor D

cleaves factor B bound to C3b
-results in C3bBb (C3 convertase of the alternative pathway)

27

properdin

binds the C3 convertase of alternative pathway and stabilizes it

*increases its half-life

28

C5 convertase of alternative pathway?

C3bBbP3b

Properdin is stabilizing the C5 convertase

C5 convertase cleaves C5 and formation of MAC complex occurs

29

lectin pathway?

antibody-independent

involves the lectin
-MBLs and MASPs

30

activation of the lectin pathway?

MBL binds MASP on bacterial surface polysaccharides

this structure is similar to the C1q
-cleaves C4 and C2

forms C4b2b (C3 convertase of the classical pathway)
-everything occurs as classical pathway
forms the C3 convertase C4b2b

31

RCA proteins?

regulators of complement activation

32

two main function of RCA?

bind and cause dissociate

cause the proteolytic cleave of components

33

first level of control of convertases?

decay acceleration

34

decay acceleration

many of the components have short half lives

C3b is hydrolyzed rapidly**

35

C1inh

in both classical and lectin pathway

binds to the C1r and C1s to dissociate them from C1q

removes MASP enzymes from MBL complex

36

Factor I

plasma protein

cleaves C4b or C3b

has several cofactors - C4-bp, MCP, CR1

prevents formation of C3 and C5 convertases
-C3 - C4 degradation
-C5 - C3 degradation

37

cofactors of Factor I

C4-bp, MCP, CR1

38

C4-binding protein

binds to C4b
-prevents its association with C2b
-causes C4b to dissociate from the C3 convertase

C4-bp/C4b is target for digestion by Factor I

39

Complement Receptor I

binds C3b and allows for the cleavage by Factor I

**mechanism for distinguishing between self and non-self

(CR1;CD35)

40

Membrane Co-factor protein

MCP;CD46

co-factor for factor I
binds to either C4b or C3b

found on self membranes
*allows self vs. non-self recognition

41

Factor H

analagous to C4-bp

binds to C3b and prevents C5 convertase formation

Factor H/C3b is a target for factor I

42

protected site concept

factor H binding only occurs if the C3b has been deposited on surface of cell

43

decay-accelerating factor

DAF;CD55

promotes the dissociation of the C3 convertase
-C2b from C4b and Bb from C3b
-in classical and alternative pathways

44

CD59

blocks C9 binding to C5b678 on cell surface

45

vitronectin (S protein)

binds to the fluid phase (C5b67)
-prevents binding to membrane

**doesn't prevent C8 or C9 association
-forming MAC, but they aren't in the membrane

46

opsonization

-major one in body?

major one is C3b

C4b is also an opsonin

Complement receptors on the phagocytic cells bind to the C3b or C4b
-increases phagocytosis
-also the a fragments increase phagocytosis

47

activity of anaphylatoxins?

increase the number of complement receptors on the cell surface of phagocytes
greatly facilitate their phagocytosis of complement opsonized cells

48

waste management

removal of immune complexes from circulation

-antibodies bind extracellular antigens

antibody with bound C3b
-binds to erythrocytes complement receptor
-taken to the spleen and liver (degradation)
-erythrocytes offload the antibody/complement

49

MAC activity on erythrocytes?

only single MAC to lyse an RBC

50

nucleated cells and MAC?

usually requires several MACs

there are certain cells that can internalize the MAC and degrade it

51

complement and inflammation?

instrumental role

activation of complement results in influx of fluid

52

anaphylatoxins function?

increase inflammation

bind to receptors on mast cells and basophils - histamine
smooth muscle contraction - vascular permeability
monocytes and neutrophils to adhere to endothelial cells


53

C5a

most potent in mediating the processes of inflammation in response to complement cascade

54

C2a

prokinin

cleaved by plasmin to yield kinin
-results in edema

55

C3 deficiency

can lead to life-threatening situations
-noticed early after birth

can be mimicked by deficiency in factor H and factor I

**why?

56

MAC deficiency?

C5, 6, 7, 8, 9
generally healthy

except infection by Neisseria gonorrhoeae and N. meningitidis

57

deficiency in C1, 2, and 4

most common is C2
-patients have a high degree of systemic lupus erythematois
SLE

58

C1inh deficiency

HANE

chronic low levels of C4 and C2

swelling with no obvious cause

commonly involves the extremities

59

DAF deficiency

decay-accelerating factor

leads to paroxysmal nocturnal hemoglobinuria

hemolytic disorders
-degrades RBCs

treat with erythropoietin

60

viruses and complement?

use them to increase its infectivity

epstein-barr - CR2 as a receptor for attachment
measles - MCP as a receptor
West Nile virus - C3b to gain entry into cells via CR3 recepor