Complement Flashcards

1
Q

what is compliment?

A

a very complex system of about 50 different proteins found either in serum or as receptors on white cells

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2
Q

in an enzyme cascade all components circulate as ? . when in contact with an appropriate stimulus what happens?

A

inactive precursors

precursor turns into active proteolytic enzyme. which cleaves another precursor into a proteolytic enzyme etc.etc.

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3
Q

name the 3 pathways that result in compliment activation

A

classical pathway
lectin pathway
alternative pathway

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4
Q

the three pathways that activate compliment result in what?

A

the formation of an enzymatic activity capable of cleaving C3 (the central component of complement) to become C3a and C3b

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5
Q

what are the 4 things that C3b can do?

A
  • Feed back into the alternative pathway
  • Result in opsonisation of things like bacterial targets
  • Cause solubilisation (removal) of immune complexes
  • Cleave the next precursor in the complement cascade C5 -> C5b and C5a
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6
Q

what does C3a do?

A

is involved in anaphylaxis

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7
Q

what does C5a do?

A

involved in chemotaxis

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8
Q

what does C5b do?

A

In associated with the target membrane of the cell that triggered compliment comes together with the late components C6-9 which results in lysis of the cell

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9
Q

understand this overview of compliment

A
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10
Q

complement is particularly important in what?

A

controlling bacterial infections

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11
Q

a deficiency in the central protein C3 of the complement system results in what?

A

recurrent bacterial infections

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12
Q

once C3 is cleaved to C3b and C3a. C3b is deposited onto the surface microorganisms and marks it for destruction by what 2 things?

A

lysis
opsonisation

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13
Q

explain how C3b is deposited onto the membrane of the pathogen

A

when C3 is cleaved, C3 a leaves exposing a thioester bond on C3b which makes it unstable and subject to nucleophilic attack by -OH and -NH2 groups on the pathogen membrane. following nucleophilic attack a covalent bond forms anchoring C3b to the pathogen membrane

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14
Q

what is the difference between the classical, lectin and alternative pathway that activate complement?

A

The classical pathway required that the microorganism that is activating complement has been recognises first by immunoglobulins
Whereas the lectin and alternative pathway are directly activated by the microorganism, no need for immunoglobulin involvement.

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15
Q

how are the classical and lectin pathway similar?

A

Classical and lectin pathway are similar as they result in the same C3 convertase which will act on C3. the alternative pathway creates a different C3 convertase

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16
Q

what is the first component of the classical pathway

A

C1q

17
Q

the classical pathway is activated by what?

A

IgG and IgM

18
Q

the classical pathway
IgG/M molecules bound to ? surface. ? globular heads bind to ? region of IgG/M. Once multiple globular heads are bound the activation of complement proceeds
? and ? then bind to ? and become proteolytic enzymes which cleaves ? into ? which leaves and ? which attaches to antigenic surface
? is cleaved into ? and ?, ? associates with ? forming ?

A

antigenic
C1q
Fc
C1r
C1s
C1q
C4
C4a
C4b
C2
C2a
C2b
C2a
C4b
C3 convertase

19
Q

does the classical pathway involve immunoglobulins?

A

yes

20
Q

does the lectin pathway involve immunoglobulins?

A

no

21
Q

does the alternative pathway involve immunoglobulins?

A

no

22
Q

what is the first component of the lectin pathway?

A

mannose binding lectin

23
Q

the first component of the lectin pathway MBL - mannose binding lectin binds to what?

A

sugar molecules in repeating arrays on microbial surfaces (interacts directly with the surface of the microbe)

24
Q

lectin pathway activation
- ? binds to ? on microbial surface
- ? then binds enabling it to cleave ? and ?
- ? and ? form and bind creating ?
- ? cleaves ? to ? and ?
- ? associates with membrane of bacterial cell

A

MBL
sugar molecules
MASP-2
C4
C2
C4b
C2a
C3 convertase
C3 convertase
C3
C3b
C3a
C3b

25
Q

outcomes from complement activation: lysis
- ? attached to microbe membrane cleaves ? to ? and ?
- ? binds to the surface of the microorganism
- Four other proteins (????) bind and form ?
- This is a funnel shaped hole in the membrane which allows soluble molecules to flow in and out
Lots of these result in lysis of the cell

A

C3b
C5
C5b
C5a
C5b
C6,7,8,9
the membrane attack complex MAC

26
Q

what is opsonisation?

A

The coating of microorganisms by antibody or complement components which make them more susceptible to phagocytosis. As phagocytes have specific receptors for C3b

27
Q

C3a and C5a are known as what?

A

anaphylatoxins

28
Q

anaphylaxis is mediated by what?

A

C3a

29
Q

Anaphylaxis
? binds to receptors on ?. This triggers them to release ?. This causes an increase in ? so other components of the ? response can be recruited to the infection site.
In addition anaphylatoxins act directly on ?, increasing ? and ?

A

3a
mast cells
histamine
vascular permeability
inflammatory
local blood vessels
blood flow
vascular permeability

30
Q

chemotaxis is mediated by what?

A

C5a

31
Q

how does C5a trigger phagocyte chemotaxis?

A

phagocyte (neutrophil) migrate up a concentration gradient of C5a in the blood, gradually get slower and stop, move through endothelium towards the site of infection in the tissues. phagocytosis then occurs

32
Q

how is the classic pathway controlled? 3

A

C1 inhibitor
decay accelerating factor DAF
complement receptor 1 CR1

33
Q

how is the alternative pathway controlled?

A

factor I
factor H
complement receptor 1 CR1

34
Q

deficiencies in classical pathway components are usually associated with which disease?

A

immune complex (autoimmune) disease

35
Q

what is an immune complex?

A

complex between antigen and antibody molecules that clump together.

36
Q

how are immune complexes eliminated?

A

bind to RBC and phagocytes via complement receptors which help to eliminate them