Complement Flashcards

1
Q

what is complement

A

very complex system of 50 diff proteins in serum or receptors on white cells
wide rage functions
involves enzyme cascade

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2
Q

what do all components of enzyme cascade do

A

circulate as inactive precursors

makes proteolytic enzymes activating other enzymes

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3
Q

what is the central protein of complement

A

C3

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4
Q

what does a deficiency of C3 lead to

A

recurrent bacterial infections

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5
Q

what do all three complement pathways result in

A

proteolytic cleavage of C3 to C3b and C3a

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6
Q

what is C3b and C3a

A

C3b - large fragment

C3a - small fragment

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7
Q

what does C3b then do after having been cleaved

A

deposited onto surface of micro organism and marks it out for destruction via lysis or opsonisation

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8
Q

what enzyme is used during cleavage

A

C3 convertase

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9
Q

where is a thioester bond

A

between Cys and Glu on alpha chain

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10
Q

after cleavage what happens to the thioester bond

A

becomes exposed and unstable

nucleophilic attack by electrons on -OH and -NH2 group

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11
Q

what happens after the thioester bon is nnucelophillic attacked

A

covalent bond formed to membrane of pathogens

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12
Q

what is the first component of the classical pathway

A

C1q

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13
Q

what is C1q

A

hexavalent
base - collagen like triple helices
stalk - triple helices
globular heads

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14
Q

what do the globular heads of C1q do

A

bind Fc of IgG or IgM

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15
Q

what is the classical pathway activated by

A

IgG r IgM

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16
Q

what binds C1q

A

C1r or C1s

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17
Q

what do C1r and C1s become

A

proteolytic enzymes

lead to C4 and C2 cleaved and C3 cnvretase formed

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18
Q

proteolytically active C1 cleaves what

A

C4 into C4a and C4b - bind to mem of pathogen and recruit C2

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19
Q

what forms C3 converts

A

C4b2a

20
Q

what is MBL

A

mannose binding lectin

21
Q

what is the caacteristics of MBL

A

bouquet like C1q

bind sugar mols found in repeating arrays on microbial surfaces

22
Q

are there antibodies involved in lectin pathway

A

no only in classical

23
Q

what is the lectin pathway

A

MBL-MASP-2 complex bind C4

C2 comes along and for C3 convertase

C3 cleaved and C3b fragments bind to surface

24
Q

whats the alternative pathway

A

also prod C3 convertase but uses diff proteins

25
Q

what is the alternative pathway actitved by

A

many types of microorganisms - bacteria, yeast, trypanosomes

26
Q

when can the alternative pathway function

A

immediately
before Ab response
hence first line defenceagaisnt systemic infection

27
Q

what initiates alternative pathway

A

form and action of soluble C3 convertase iC3b

28
Q

how does C3 become iC3b

A

spontaneous hydrolysis of thioester bond and factor B binding

29
Q

how is C3b which covalently bonds to pathogen surface made from iC3b

A

cleavage of factor B by factor D

a c3 convertase some of C3b fromed

30
Q

what si the makeup of C3 conertase fro alternative pathway

A

C3bBb

31
Q

what does C3b cleave

A

C5 to C5b and C5a

32
Q

what does C5b do

A

bids to surface micro organisms

33
Q

four other proteins C6, C7, C8 and C9 form

A

membrane attack complex which forms funnel shaped hole in cell mem

34
Q

what is opsonisation

A

coating of micro organisms by antibody or complement components

35
Q

what receptors d phagocytes have

A

C3b receptors

36
Q

what are the anaphylatoxins

A

C3a and C5a

37
Q

what does C3a do as an anaphylatoxin

A

binds to receptors on mast cells
histamine release
increase vasc perm
recruit other components of inflam response to infection site

38
Q

what do anaphlatoxins act directly on

A

blood vessels increasing blood flow and vasc perm

39
Q

what does C5a trigger

A

phagocyte chemotaxis

40
Q

what does C5a bind to

A

C5a receptors on phagocytes
phagocyte migrates up concentration gradient of C5a to infection site
phagocyte becomes stickier
phagocyte stop moving

41
Q

what controls the classical pathway

A

C1 inhibitor
Decay accreting factor
complement receptor 1

42
Q

what controls the alternative pathway

A

Factor I
Factor H
CR1

43
Q

what can some micro organisms do

A

avoid effects of complement

44
Q

what else does complement do

A

removing immune complexes

45
Q

deficiencies in classical pathway components assc with

A

immune complex autoimmune diseases

46
Q

how does complement rid of Ic

A

IC bind to RBC and phagocytes via complement receptor and eliminate