L4- Complement Flashcards

(55 cards)

1
Q

When does complement get involved in immune defence?

A

Once APC have sensed antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where is the components of the complement system made?

A

Liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is complement?

A

Complement (C’) system: a collection of >30 heat labile proteins present in blood and other body fluids

•  Augments:

o  opsonization and killing of bacteria [in presence or absence of antibodies]

o  induction of inflammatory responses that help fight infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

In the absence of infection, C’ proteins circulate in an inactive form are called what?

A

Zymogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens once complement is activated?

A

Detection of pathogens or antibody bound to pathogens activates a cascade of proteolysis in which C’ zymogens are activated sequentially, each becoming an active protease which cleaves and activates many molecules of the next zymogen in the pathway – final result is formation of effector C’ components that aid removal of pathogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which C’ is responsible for;

Binding to antigen: antibody complexes and pathogen surfaces

A

C1q

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which C’ is responsible for;

Binding to carbohydrate structures such as mannose or GlcNAc on microbial surfaces

A

MBL
Ficolins
C1q
Properdin (factor P)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which C’ is responsible for;

Activating enzymes

A
C1r
C1s
C2a
Bd
D
MASP-2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which C’ is responsible for;

Membrane-binding proteins and opsonins

A

C4b

C3b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which C’ is responsible for;

Peptide mediators of inflammation

A

C5a
C3a
C4a

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which C’ is responsible for;

Membrane-attack proteins

A
C5b
C6
C7
C8
C9
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which C’ is responsible for;

Complement receptors

A
CR1
CR2
CR3
CR4
CRIg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 3 pathway names of C’ activation?

A

Lectin pathway
Classical pathway
Alternative pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe lectin pathway of C’ activation

A

Lectin pathway is initiated by soluble carbohydrate-­‐binding proteins (mannose-­‐binding lectin and ficolins) that bind to carbohydrate structures on microbial surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe classical pathway of C’ activation

A

Classical pathway is initiated when C’ component C1 (recognition protein C1q associated with proteases C1r and C1s) recognizes a microbial surface or binds to antibodies on microbial services

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe alternative pathway of C’ activation

A

Alternative pathway can be initiated by spontaneous hydrolysis and activation of C’ component C3 , which can then bind to microbial surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

When any pathway interacts with pathogen, a C3 convertase is created which cleaves C’ component C3 to C3a (involved in inflammation) and C3b (the main effector molecule of the C’ system.

T or F?

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

C3a and C5a do what together?

A

Recruit phagocytic cells to site of infection and promote inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does C3b do?

A

Phagocytes with receptors of C3b engulf and destroy the pathogen

(After release from C3a it is bound to the microbial surface)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Completion of the complement cascade ends with the formation of what?

A

Membrane attack complex (MAC) which disrupts cell membrane and causes cell lysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Lectin pathway is triggered by any of four different pattern recognition receptors (PRRs) present in blood and extracellular fluids, that recognize carbohydrate on microbial surface. What are they?

A
  •   Mannose-­‐binding Lectin (MBL)

*   Three ficolins: L-­‐ficolin, M-­‐ficolin, and H-­‐ficolin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

The production of ______ collection increases in acute phase infection?

A

Mannose-­‐binding lectin (MBL);

Individuals deficient in MBL or MASP-­‐2 have more respiratory infections, caused by common extracellular bacteria, during early childhood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which pathway uses soluble receptors that recognize microbial surfaces to activate the complement cascade

A

Lectin pathway

24
Q

Which PRR forms trimeric clusters of carbohydrate-recognition domains and binds with high avidity to its carbohydrates

A

MBL

High avidity to both mannose and funisex residues

25
Which PRR binds oligosaccharides containing acetylated sugars
Ficolins
26
Explain the lectin pathway
*   Recognition of microbial surface carbohydrate structures by MBL or ficolin activates MBL-­‐associated serine protease (MASP-­‐2) , which then cleaves C4 *   C4b binds covalently to microbial surface, then binds C2, which is then cleaved by MASP-­‐2; C2a binds to C4b to form the C3 convertase, C4b2a *   C3 is cleaved, and C3b binds to microbial surfaces as the major opsonin for phagocytosis
27
What is the C3 convertase code?
C4b2a
28
Explain classical pathway
*   C1q is a pathogen sensor *   Binds directly to bacterial surfaces; C-­‐reactive protein; Fc region of antibody (mainly IgM) *   Binding to ligand activates C1s to act on C’ proteins C4 and C2 *   C4 is cleaved to C4a and C4b, which binds covalently to pathogen surface *   Bound C4b binds the serine protease C2a (which has been produced by cleavage of C2 by C1s) *   C4b2a is the classical pathway C3 convertase
29
What happens with unbound C4b?
Unbound C4b is irreversibly inactivated, it cannot move from pathogen surface to nearby host cell surface
30
What is the function of the active form of C1q?
Binds directly to pathogen surface or indirectly to antibody bound to pathogens, thus allowing auto-activation of C1r
31
What is the function of the active form of C1r?
Cleaves C1s to active protease
32
What is the function of the active form of C1s?
Cleaves C4 and C2
33
What is the function of the active form of C4b?
Covalently binds to pathogen and opsonizes it. Binds C2 for cleavage by C1s
34
What is the function of the active form of C4a?
Peptide mediator of inflammation (weak activity)
35
What is the function of the active form of C2a?
Active enzyme of classical pathway C3/C5 convertase. | It cleaves C3 and C5
36
What is the function of the active form of C2b?
Precursor of vasoactive of C2 kinin
37
What is the function of the active form of C3b?
Many molecules of C3b bind to pathogen surface and act as opsonins. Initiates amplification via alternative pathway. Binds C5 for cleavage of C2b
38
What is the function of the active form of C3a?
Peptide mediator of inflammation (intermediate activity)
39
Which pathway is constantly occurring?
The alternative pathway
40
Which pathway is an amplification loop for C3b formation?
The alternative pathway
41
Explain the alternative pathway
*   In the alternative C’ pathway, C3 in plasma is continuously cleaved at low rates to form C3b *   C3b in plasma is unstable and either inactivated by hydrolysis, or forms covalent bonds with cell surfaces thus allowing C’ activation to continue *   Cell-­‐bound C3b can now bind factor B; Bound factor B is cleaved by plasma proteases factor D into Ba and Bb to form; C3bBb is C3 convertase •  Many molecules of C3b can now form on the cell surface
42
What is Properdin?
Properdin is an example of the membrane and plasma proteins which regulate the formation and functon of C3 convertases (Helps to stabilise this complex)
43
What cell makes Properdin?
Neutrophils and is released when neutrophils are activated in the presence of pathogens
44
Why is Properdin necessary?
The alternative pathway C3 convertase, C3bBb, is very short-­‐lived and degrades in the absence of binding by Properdin •  Properdin-­‐deficient patients are particularly susceptible to Neisseria meningitidis infection; also binds to N.gonorrhoeae (Stabiliser of C3bBb complex) pathogens lack complement-regulatory proteins. Binding of Properdin (factor P) stabilises the C3bBb complex
45
What does C3bBb do?
It is a C3 convertase and deposits many molecules of C3b onto the pathogen surface. Opsonization activation of terminal complement components
46
What does C3b protein do in the alternative pathway?
Binds to surface pathogens, binds B for cleavage by D, C3bBb is C3 convertase and C3b2Bb is C5 convertase
47
What does Ba do in the alternative pathway?
Small fragment of Factor B, unknown function
48
What does Bb protein do in the alternative pathway?
Bb is an active enzyme of the C3 convertase C3bBb and C5 convertase C3b2Bb
49
What is the role of Factor D in the alternative pathway?
Plasma serine protease, cleaves B when it is bound to C3b to Ba and Bb.
50
Surface bound C3 convertase deposits large numbers of C3b fragments on pathogen surfaces and generates C5 convertase activity. What happens next?
In the classical and lectin pathways, a C5 convertase is formed by binding of C3b to C4b2a to yield C4b2a3b. *   In the alternative pathway the C5 convertase is formed by the binding of C3b to the C3bBb convertase to form C3b2 Bb *   C5 captured by these C5 convertases is cleaved to C5a and C5b *   C5b intiates assembly of the terminal components of the C’ pathway *   C5a activates phagocytosis – one of the major functions of the C’ pathway
51
Activation of C’ leads to deposition of C3b on microorgansim surface •  C3b can bind the C’ receptor CR1 on the surface of phagocytes but this is not sufficient to trigger phagocytosis. What needs to happen?
Binding of C5 to the C5a receptor now activates the cell to phagocytose organisms bound to CR1
52
The terminal complement components that form the membrane-attack complex are what?
C5a; small peptide mediator of inflammation (high activity) C5b; initiates assembly of the membrane-attack system C6; binds C5b; forms acceptor for C7 C7; Binds C5b6; amphiphilic complex inserts into lipid bilayer C8; Binds C5b67; initiates C9 polymerisation C9n; Polymerizes to C5b678 to form a membrane-spanning channel; lysing cell
53
How many C9 bind to form a pore in the membrane for the terminal complement that form the membrane-attack complex?
10-16
54
What protects the host cells from C’ activation?
C’ regulatory proteins are only expressed on host cells and prevent activation of C’ *   Decay accelerating factor (DAF) displaces Bb from C3b in the alternative pathway and C2a from C4b in the classical and lectin pathways *   CR1 (the receptor for C3b) binds C4b, displacing C2a; also binds C3b, displacing Bb Paroxysmal noctural haemoglobinuria is a disease characterized by C’-­‐mediated lysis of red blood cells that lack cell-­‐surface DAF *   CD59 (aka protec;n) prevents recruitment of C9 by the complex of C5b,C6, C7 and C8 and therefore, prevents forma;on of the membrane aUack complex of the microbial surface *   Paroxysmal noctural haemoglobinuria also develops when red blood cells lack CD59
55
The small fragments of some complement proteins initiate a local inflammatory response. What response is this?
*   The small C’ fragments cause local inflammatory responses by acting directly on local blood vessels, to induce *   Increased blood flow *   Increased vascular permeability *   Increased binding of phagocytes to endothelial cells *   Increased phagocyte activity *   Fluid and protein accumulate and lymphatic drainage is increased, bringing pathogens and their antigenic components to nearby lymph nodes