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22 spring: immunology > Test 1: lecture 5 complement > Flashcards

Test 1: lecture 5 complement Flashcards

1
Q

___is an immune defense system that recognizes pathogens and altered cells and facilitates their elimination

A

Complement

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2
Q

complement system is involved in ___ immunity

A

innate (first line of defense)

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3
Q

complement system are a set of soluble proteins excreted by the ___ as ___

A

liver

zymogens (inactive/proenzymes)

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4
Q

C3 is a central component of complement found in ___ and activated by ___

A

serum

protein cleavage

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5
Q

C3 when cleaved turns into ___

A

C3a and C3b

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6
Q

C3a acts as a ____

A

anaphylatoxin (recruits other immune cells)

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7
Q

C3b will form a covalent bond to pathogen via ___

A

thioester

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8
Q

how does C3b bind to surface

A

thioester reaction (S-C=O)

csy→gly→glu→Gln

cyst attached to a Gln and form a bond that is highly reactive to nucleophile (has electrons it wants to share)= amino group of a protein (NH2), hydroxyl group (OH), water

attacked by R-OH or R-NH2 will bind to surface of pathogen

if attacked by H20 will be inactivated/soluable

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9
Q

what happens to C3b thioester bond when attacked by ROH or RNH2?

A

C3b will bind to pathogen surface

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10
Q

what happens to thioester bond of C3b when it binds with H20

A

will be inactivated/soulable

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11
Q

___ converts C3 → C3b

A

convertase

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12
Q

MBL

A

mannose binding lectin

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13
Q

what are the two zymogen proteases on the MBL?

A

mannose binding lectin

2 serine protease zymogens= MASP-1 and MASP-2

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14
Q

lectin- a protein or domain binds to ___

A

carbohydrates (carbohydrate recognition domains CRD)

mannose binding lectin (MBL

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15
Q

lectin pathway will activate ___

A

binds to carbs,

MASP-1 will activate itself and then activate MASP-2

MASP2 will convert C4 → C4a and C4b

C4b will bind to pathogen

lectin will convert C2 → C2b and C2a

C2a binds to C4b → convertase for C3

these two will convert C3 → C3a and C3b

C3b will bind to pathogen

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16
Q

what convertase is used for C3

A
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17
Q

lectin pathway generates the C3 convertase ___

A

C4bC2a

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18
Q

lectin pathway simple

A

MASP-2 activated

C4 → C4b binds

C2 → C2a binds

C4bC2a converts C3→ C3a and C3b

C3b binds

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19
Q

alternative pathway

A

C3 binds with H20 but doesnt break apart → iC3

inactive factor B binds to iC3

activated Factor D will bind and activate factor B → Bb and Ba creating iC3Bb

iC3Bb is a convertase (free floating) for C3

will convert C3 into C3a and C3b

20
Q

in the alternative pathway, ___ is a free floating convertase for C3

21
Q

how is alternative pathway activated?

A

thioester bond inside C3 will be hydrolyzed by water forming iC3

22
Q

key between lectin and alternative pathway

A

lectin needs to bind to carb on pathogen surface to start process

where alternative just happens and it creates C3b that may or may not bind to near by pathogens (does not need to know pathogen is there, just constantly testing the plasma)

23
Q

___ is a system to constantly probe for pathogens

A

alternative pathway

doesn’t need to bind to pathogen to start pathway- just happens

attack first, regulate later

24
Q

amplification step of complement system

A
  • Surface-bound C3b binds factors B then to factor D
  • Forms C3 convertase C3bBb

•Amplification loop – each newly bound C3b can make another convertase by binding to its own B and D

•Fixes C3b on the pathogen surface which will eventually trigger complement effector mechanisms

25
Q

what binds to C3b in the amplification step

A

inactive B will bind to create C3bB

then active D binds and actives B → Ba and Bb

creates C3bBb which is a convertase for C3

26
Q

•Both the classical and lectin pathways also activate the alternative pathway convertase through ___

27
Q

•alternative pathway components, like ___, will be activated by the classical and lectin pathways.

A

Factor B or Factor D

28
Q

three types of C3 convertases

A

C4bC2a → classical and lectin in first step

C3bBb → used by alternative, classical and lectin during the amplification step

iC3Bb→ used by alternative pathway in first step

29
Q

what C3 convertases are used by the lectin and classical pathway

A
  • C4bC2a (pathogen surface) activates the cascade
  • C3bBb (pathogen surface) amplifies the response
30
Q

what C3 convertases are used to the alternative pathway

A
  • iC3Bb (soluble) activates the cascade
  • C3bBb (pathogen surface) amplifies the response
31
Q

effector function of phagocytosis of the complement system

A

C3b binds to bacteria

C3b is recongnized by CR1 receptors on phagocytic cells

CR1 binds to C3b and eats cell

then forms vesicle and breaks down pathogen

32
Q

•Pathogens opsonized by C3b are bound by phagocytic cells expressing ___

A

Complement Receptor 1 (CR1)

33
Q

C3b bond pathogen attached to CR1 on phagocytic cells will be endocytosed and killed when ___ fuse with phagosomes

34
Q

C___ does not have thioester domain

35
Q

how to activate C5 in the alternative pathway

A

step 1 of forming Membrane Attack Complex

C3bBb will cleave C3→ C3b and C3a

C3b will bind to C3bBb instead of pathogen surface creating C3b2Bb

C3b2Bb will convert C5 → C5a and C5a

36
Q

how to activate C5 in the classical/lectin pathway

A

C4bC2a binds with a molecule of C3b

C4bC2aC3b will convert C5→ C5a and C5b

37
Q

how to form MAC

A

1st step = C5 activation

C3b2Bb(alternative pathway) or C4bC2aC3b (classical/lectin) will convert C5→ C5a and C5b

C5b binds with C6 and C7

C5bC6C7 binds to membrane and then binds to C8

this will cause binding and polymerization of C9 which will form a pore (MAC → membrane attack complex)

38
Q

how does C5b form a pore?

A

C5b binds with C6 and C7

C5bC6C7 binds to membrane and then binds to C8

this will cause binding and polymerization of C9 which will form a pore (MAC → membrane attack complex)

39
Q

MAC form ___ in the membrane

40
Q

how does a prevent MAC on self

A

CD59 stops C9 from binding to C5b678

41
Q

what does CD59 do?

A

prevents C9 from binding to MAC and creating a pore

42
Q

what does C3b2Bb do?

A

C5 → C5b and C5a (MAC → making pore)

alternative convertase

43
Q

what does C4bC2aC3b do?

A

converts C5 → C5b and C5a (MAC → making pore)

classical and lectin pathway

44
Q

what does C3a and C5a do?

A

anaphylatoxins

increase the CR1 on phagoctyic cells (will bind to more C3 on pathogens)

cytokine release

degranulation

chemotaxis

MAST cells release histamine → increase vascular permeability

45
Q

what are anaphylotoxins?

A

C3a and C5a that go off and stimulate phagocytic cells to increase there function

46
Q

___ is a much more potent chemoattractant but: ___ levels usually are much higher

A

C5a

C3a

(anaphylatoxin)

47
Q

how does complement pathway work?

22 spring: immunology (23 decks)

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