Complement System p1 (classical pathway) Flashcards

1
Q

A complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanism against foreign cells

A

Complement

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2
Q

Is complement a heat-labile or heat-stable substance?

A

Heat-labile

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3
Q

Who gave the term “complement”?

A

Paul Erlich

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4
Q

Who was awarded a Noble Prize for elucidating the nature of complement?

A

Jules Bordet

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5
Q

Effect of complement activation:

A

Activation of immune system
Opsonization (C3b, C4b, C5b)
Lysis of foreign cells and immune complexes

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6
Q

What is the effect of chronic complement activation?

A

Leads to inflammation and tissue damage

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7
Q

Where are acute phase reactants produced?

A

Hepatocytes

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8
Q

The two most common acute phase reactant in the body

A

C-reactive protein
Serum amyloid A

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9
Q

Who signals the production of acute phase reactants in the hepatocytes?

A

Cytokines

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10
Q

What is the response time of the production of acute phase reactants?

A

12-24 hours

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11
Q

Where are most plasma complement protein synthesized?\

A

Liver

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12
Q

All plasma complement protein are synthesized in the liver except:

A

C1

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13
Q

Where is C1 produced?

A

Epithelial cells and Factor D (made in adipose tissue)

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14
Q

Plasma complement protein are released in inactive precursor called:

A

Zymogens

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15
Q

In what ways can the complement system be activated?

A

Classical pathway
Alternative pathway
Lectin pathway

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16
Q

This is an antibody-independent pathway which plays a major role as a natural defense system

A

Classical pathway

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17
Q

Aka properdin system

A

Alternative pathway

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18
Q

Stabilized C3 convertase of the alternative pathway

A

Properdin

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19
Q

This pathway’s major constituent is mannose binding lectin (MBL)

A

Lectin pathway

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20
Q

What triggers the proteins in the classical pathway?

A

Antigen-antibody combination

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21
Q

Where is mannose found?

A

Cell walls
Outer coating of the bacteria, viruses, and protozoa

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22
Q

How many proteins are involved in the classical pathway?

A

9

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23
Q

Which immunoglobulin is the most efficient in the activation of the classical pathway?

A

IgM

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24
Q

Can the IgG activate the classical pathway?

A

Yes

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25
IgGs capable of activating the classical pathway?
IgG 1, 2, 3
26
Most efficient IgG for the complement fixation
IgG 3
27
Meaning of MAC
Membrane Attack Complex
28
What protein is always involved in the recognition stage of the classical pathway?
C1
29
In the classical pathway, after the C1 has been fixed, what proteins are next to be activated?
C4, C2, C3
30
What is the C4, C2, C3 known as?
Activation unit
31
What is the last stage of the classical pathway?
Formation of the MAC
32
What should happen in order to produce the mechanism of lysis?
C5 protein up to C9 should match to its respective complements
33
What is the end product of the classical pathway?
Lysis of the foreign cells
34
What are the subunits that consists the recognition unit in classical pathway?
C1q, C1r, C1s
35
What is the complex of the recognition stage in the classical pathway made up of?
One C1q Two C1r Two C1s
36
Which subunits in the recognition stage of the classical pathway generate enzyme activity to begin the cascade?
C1r, C1s
37
Composed of six strands that form six globular heads with a collagen like tail portion
C1q
38
This protein recognizes the FC region of two adjacent antibody molecules Binds to the Fc portion of the antibody
C1q
39
What should be the conditions for the C1q to initiate the classical pathway?
At least two of the globular heads of C1q must be bound
40
Process of the recognition stage of the classical pathway
Fc region is bonded with C1q Activation of C1r Cleaves the thioester bond of C1s Activates C1s End of recognition stage
41
Where does the binding of the C1q to the FC region occur?
Ch2 region for IgG Ch3 region for IgM
42
What are the two adjacent antibody molecule in the classical pathway?
IgG and IgM
43
What is the end product of the activation unit of the classical pathway?
Formation of C5 convertase
44
What is the second most abundant complement protein?
C4
45
This protein cleaves by C1s to form C4a and C4b
C4
46
What will form if there is a delay in the binding of the C4b to protein which resulted in the reaction with water molecules?
iC4b
47
What are the proteins mainly involved in the activation unit of the classical pathway?
C4 C2
48
Next component to be activated after C4 in the activation unit of the classical pathway
C2
49
This is closely associated with the gene for factor B (alternative pathway) on chromosome 6 in the major histocompatibility complex (MHC class III)
C2 gene
50
When combined with C4b in the presence of magnesium ions C2 is cleaved by C1s to form:
C2a and C2b
51
C2a binds to C4b to form:
C3 convertase
52
Aka C3 convertase
C4b2a
53
What is the half life of C4b2a?
15 seconds to 3 minutes
54
If binding does occur, C3 is cleaved in to two parts:
C3a C3b
55
What is the most significant step in the entire process of complement activation of the classical pathway?
Cleavage of C3 component to form C3a and C3b
56
What are the functions of C3b?
Formation of MAC Acts as an opsonin which enhances phagocytosis
57
What new enzyme is created if C3b is bound within 40 nm of the C4b2a?
C5 convertase
58
Where is the MHC III gene found?
Short hand of the chromosome 6
58
Where is the MHC III gene found?
Short hand of the chromosome 6
59
How close should C2 be to be bound to C1s?
60nm
60
How close should the C4 be to be bound to C1s?
40 nm
60
How close should the C4 be to be bound to C1s?
40 nm
61
Aka C5 convertase
C4b2a3b
62
What is the. Response time of CRP?
6-8 hours
63
What is the response time of Serum Amyloid-A?
24 hours
64
A small peptide which causes the increase vascular permeability
Anaphylatoxins
65
What happens when there is an increase in vascular permeability?
Contraction of smooth muscle and release of histamine from the basophils and mast cells
66
What are the proteins involved in the increase vascular permeability?
C3a C4a C5a
67
What is the beginning of the MAC?
Cleaving of C5 into C5a and C5b by C5 convertase
68
What should happen to achieve lysis?
Binding in the c5 and c9
69
What happens when no binding of c6 occurs to the C5b?
Inactivated
70
Trimolecular complex that has a high affinity for lipid constituents of the cell membrane
C5b67
71
They interact with the cell membrane to form a small hole in the membrane
C7 C8
72
This protein is inserted into the lipid bilayer of the cell membrane
C8
73
What constitutes as the complete lysis of the cell?
Binding of C9 to C5b678