Complement System p1 (classical pathway) Flashcards
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
Complement
Is complement a heat-labile or heat-stable substance?
Heat-labile
Who gave the term “complement”?
Paul Erlich
Who was awarded a Noble Prize for elucidating the nature of complement?
Jules Bordet
Effect of complement activation:
Activation of immune system
Opsonization (C3b, C4b, C5b)
Lysis of foreign cells and immune complexes
What is the effect of chronic complement activation?
Leads to inflammation and tissue damage
Where are acute phase reactants produced?
Hepatocytes
The two most common acute phase reactant in the body
C-reactive protein
Serum amyloid A
Who signals the production of acute phase reactants in the hepatocytes?
Cytokines
What is the response time of the production of acute phase reactants?
12-24 hours
Where are most plasma complement protein synthesized?\
Liver
All plasma complement protein are synthesized in the liver except:
C1
Where is C1 produced?
Epithelial cells and Factor D (made in adipose tissue)
Plasma complement protein are released in inactive precursor called:
Zymogens
In what ways can the complement system be activated?
Classical pathway
Alternative pathway
Lectin pathway
This is an antibody-independent pathway which plays a major role as a natural defense system
Classical pathway
Aka properdin system
Alternative pathway
Stabilized C3 convertase of the alternative pathway
Properdin
This pathway’s major constituent is mannose binding lectin (MBL)
Lectin pathway
What triggers the proteins in the classical pathway?
Antigen-antibody combination
Where is mannose found?
Cell walls
Outer coating of the bacteria, viruses, and protozoa
How many proteins are involved in the classical pathway?
9
Which immunoglobulin is the most efficient in the activation of the classical pathway?
IgM
Can the IgG activate the classical pathway?
Yes
IgGs capable of activating the classical pathway?
IgG 1, 2, 3
Most efficient IgG for the complement fixation
IgG 3
Meaning of MAC
Membrane Attack Complex
What protein is always involved in the recognition stage of the classical pathway?
C1
In the classical pathway, after the C1 has been fixed, what proteins are next to be activated?
C4, C2, C3
What is the C4, C2, C3 known as?
Activation unit
What is the last stage of the classical pathway?
Formation of the MAC
What should happen in order to produce the mechanism of lysis?
C5 protein up to C9 should match to its respective complements
What is the end product of the classical pathway?
Lysis of the foreign cells
What are the subunits that consists the recognition unit in classical pathway?
C1q, C1r, C1s
What is the complex of the recognition stage in the classical pathway made up of?
One C1q
Two C1r
Two C1s
Which subunits in the recognition stage of the classical pathway generate enzyme activity to begin the cascade?
C1r, C1s
Composed of six strands that form six globular heads with a collagen like tail portion
C1q
This protein recognizes the FC region of two adjacent antibody molecules
Binds to the Fc portion of the antibody
C1q
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
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
Where does the binding of the C1q to the FC region occur?
Ch2 region for IgG
Ch3 region for IgM
What are the two adjacent antibody molecule in the classical pathway?
IgG and IgM
What is the end product of the activation unit of the classical pathway?
Formation of C5 convertase
What is the second most abundant complement protein?
C4
This protein cleaves by C1s to form C4a and C4b
C4
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
What are the proteins mainly involved in the activation unit of the classical pathway?
C4 C2
Next component to be activated after C4 in the activation unit of the classical pathway
C2
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
When combined with C4b in the presence of magnesium ions C2 is cleaved by C1s to form:
C2a and C2b
C2a binds to C4b to form:
C3 convertase
Aka C3 convertase
C4b2a
What is the half life of C4b2a?
15 seconds to 3 minutes
If binding does occur, C3 is cleaved in to two parts:
C3a
C3b
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
What are the functions of C3b?
Formation of MAC
Acts as an opsonin which enhances phagocytosis
What new enzyme is created if C3b is bound within 40 nm of the C4b2a?
C5 convertase
Where is the MHC III gene found?
Short hand of the chromosome 6
Where is the MHC III gene found?
Short hand of the chromosome 6
How close should C2 be to be bound to C1s?
60nm
How close should the C4 be to be bound to C1s?
40 nm
How close should the C4 be to be bound to C1s?
40 nm
Aka C5 convertase
C4b2a3b
What is the. Response time of CRP?
6-8 hours
What is the response time of Serum Amyloid-A?
24 hours
A small peptide which causes the increase vascular permeability
Anaphylatoxins
What happens when there is an increase in vascular permeability?
Contraction of smooth muscle and release of histamine from the basophils and mast cells
What are the proteins involved in the increase vascular permeability?
C3a
C4a
C5a
What is the beginning of the MAC?
Cleaving of C5 into C5a and C5b by C5 convertase
What should happen to achieve lysis?
Binding in the c5 and c9
What happens when no binding of c6 occurs to the C5b?
Inactivated
Trimolecular complex that has a high affinity for lipid constituents of the cell membrane
C5b67
They interact with the cell membrane to form a small hole in the membrane
C7
C8
This protein is inserted into the lipid bilayer of the cell membrane
C8
What constitutes as the complete lysis of the cell?
Binding of C9 to C5b678
