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Immunuology > Complement > Flashcards

Complement Flashcards

1
Q

what is complement?

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

what does complement mediate?

A

wide range of functions

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3
Q

what does complement involve?

A

enzymes cascade

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4
Q

Describe enzyme cascades.

A
  • all components circulate as inactive precursors
  • comes into contact with appropriate stimulus
  • one product of one reaction acts as an enzyme for next reaction and so on
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5
Q

what can the compliment system be triggered by?

A

3 pathways:

  • Classical pathway
  • Lectin pathway
  • alternative pathway
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6
Q

What do the 3 pathways have in common?

A

result in proteolytic cleavage

of C3 to C3b (large fragment) and C3a (small)

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7
Q

what is compliment effective at doing?

A

Getting rid of bacterial infection

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8
Q

what is the central protein of the complement system?

A

C3

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9
Q

what does deficient in C3 lead to?

A

recurrent bacterial infections

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10
Q

where is C3b deposited to in all 3 pathways?

A

surface of micro-organism and marks it out for destruction (lysis/ opsonisation)

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11
Q

How does C3b attach to the microorganisms surface?

A
  • C3 comes into close proximity to the membrane of the pathogen
    -thioester bond between Cys and Glu on alpha chain is cleaved
    -Thioester bond becomes exposed and unstable
    Nucleophilic attack by electrons on OH and -NH2 groups
    -covalent bond is formed
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12
Q

what is the first component of the classical pathway?

A

C1q

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13
Q

Describe the structure of C1q.

A

-hexavalent
-“Bunch of tulips” arrangement of 18 polypeptides
-6 collagenous base and arm(stalk) regions
connected to 6 globular heads

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14
Q

what is the classical pathway activated by?

A

IgG and IgM

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15
Q

How does IgG activate the classical pathway?

A
  • 2 IgG molecules are adjacent and in close proximity (control measure to prevent innpaorpriate activation)
  • C1q binds 2 of the 6 globular head regions to the IgG molecules
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16
Q

what is different about IgM?

A

only one molecule but C1q only binds when it goes through a conformational change

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17
Q

what binds to C1q (CP)?

A

C1r and C1s (2 each)

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18
Q

what do C1r and C1s become (CP)?

A

proteolytic enzymes

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19
Q

what is cleaved by C1r and C1s (CP)?

A

C4 and C2

20
Q

what is formed by classic pathway?

A 
C3 convertase (C4bC2a)
-cleaves  C3 into active products
21
Q

what does proteolyally active C1s cleave C4 into?

A

C4a and C4b

22
Q

what does C4b bind to and what does it recruit?

A

microbial surface and recruits C2 protein

23
Q

what else can active C1s enzymes cleave?

A

C2 into C2a and C2b

24
Q

what is the first component of the lectin pathway?

A

Mannose binding lectin

25
Q

what is the structure of mannose binding lectin reminiscent of?

A

C1q

26
Q

what does mannose binding lectin bind?

A

Binds sugars molecules found in repeating arrays on microbial surfaces

27
Q

Describe lectin pathway activation.

A
  • MBL and MASP-2 together act on C4 and C2 (same classical pathways)
  • A C3 covertase is formed
  • C3 is cleaved
  • C3b fragments bind to surface
28
Q

what is different between the classic pathway and the lectin pathway?

A

Same outcome from classic pathway- difference is the lectin pathway does not need an antibody i.e its part of the innate system

29
Q

what does the alternative pathway produce?

A

C3 convertase but uses different proteins

30
Q

what is the alternative pathway directly activated by?

A

Many types of micro-organism e.g.. bacteria, yeasts , trypanosomes

31
Q

how quickly does the alternative pathway function and what does this mean?

A

immediately i.e. before Ab response and hence first major line of defence against systemic infection

32
Q

Describe the alternative pathway.

A
  • C3
  • spontaneous of hydrolysis of thioester bond
  • iC3 produced
  • factor b binds
  • cleavage of factor B by factor D
  • C3 converts , some of the C3b formed attach covalently to pathogen surface
  • C3b attached to pathogen surface binds factor B(cleaves Bb and Ba)
  • stable C3 convertase formed (C3b, Bb, P)
  • More C3b becomes attached to pathogen surface
33
Q

In the alternative pathway, what does C3b attached to pathogen surface bind?

A

factor B

34
Q

Describe the lysis process.

A
  • C3b cleaves C5 to C5b(large) and C5a (small)
  • C5b binds to surface of micro-organism
  • four other proteins (C6, C7, C8 and C9) bind
  • membrane attack complex (MAC) formed
  • forms funnel-shaped hole in cell membrane
35
Q

what is opsonisation?

A

Coating of micro-organisms by antibody or complement components

36
Q

what do phagocytes have receptors for?

A

C3b

37
Q

what effect does opsonisation have?

A

makes phagocytosis more efficient

38
Q

Describe anaphylaxis.

A
  • C3a and C5a are known as anaphylatoxins
  • C3a –> binds to receptors on mast cells
  • histamine release
  • increased vascular permability
  • recruitment of other components of inflammatory response to infection site
39
Q

what does anaphylatoxins act directly on?

A

local blood vessels, increasing blood flow and vascular permeability

40
Q

Describe chemotaxis.

A

-C5a also triggers phagocyte chemotaxis
-C5a binds to C5a receptors on phagocytes:
A) Phagocyte migrates up concentration gradient of C5a to infection site
B) Phagocyte becomes stickier
-Phagocytes stop moving and move through
endothelium towards infection in underlying tissues

41
Q

Describe neutrophil transmigration to site of infection in tissues.

A
  • rolling and tethering
  • adherence
  • rolling arrest
  • transmigration
  • migration into underlying tissues moving towards higher concentrations of C5a
42
Q

what is the classical pathway controlled by?

A
  • C1 inhibitor
  • Decay accelerating factor (DAF)
  • Complement receptor 1 (CR1)
43
Q

what is the alternative pathway controlled by?

A
  • Factor I
  • Factor H
  • CR1
44
Q

What can some micro-organisms do?

A

avoid effects of complement

45
Q

what is complement also important in removing?

A

Immune complexes (IC)

46
Q

What are deficiencies in classical pathway components usually associated with?

A 
immune complex
(autoimmune) diseases
47
Q

Describe the process of complement removing immune complexes.

A
  • IC bind to RBC and phagocytes via complement receptors

- elimination of IC

Immunuology (10 decks)

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