Hd (04-17-06) Complement I

Front 1

What 2 things do the products of the complement pathway do?

Back 1

1) Facilitate antigen clearance
2) Generate an inflammatory response

Front 2

What are the 3 pathways of complement activation?

Back 2

1) Classical pathway (Ag-Ab complexes)
2) MB-Lectin pathway (Lectin binding to pathogen surfaces)
3) Alternative pathway (Pathogen surfaces)

Front 3

What is the nomenclature used for the classical pathway?

Back 3

C1-C9. Cleaved protein C3 would form C3a and C3b.
*All bound active components are designated with "b".

Front 4

What is the nomenclature used for the alternative pathway?

Back 4

Capital letters, like B or D. Cleaved protein would be Ba and Bb.

Front 5

What nomenclature is used for the MB-Lectin pathway?

Back 5

MASP-1 (Mannan-Binding Lectin Associated Serine Protease-1).

Front 6

What is the initiation step of the classical pathway?

Back 6

Recognition of an Ab-Ag complex by the complement component C1, which binds to the Fc portion of the Ab.

Front 7

How is C1 activated in the typical sense? Which Ab activates it?

Back 7

C1-q-r-s binding to Ab-Ag complex requires C1q to bind simultaneously to 2 Fc portions of IgM. The pentameric nature of IgM allows a single molecule of Ag-bound IgM to activate C1.

Front 8

What are the 2 additional ways that C1 can be activated?

Back 8

1) C1 can bind directly to certain microbial, pathogenic surfaces.
2) C1 can bind to C-reactive protein, which can then bind to bacterial polysaccharides.

Front 9

What occurs following C1 activation?

Back 9

C1r is activated and cleaves off a portion of C1s, leaving a newly activated C1-q-r-s complex that will cleave C4.
C4b is now reactive and binds to C2.
Then C1s will come around and cleave C2, forming the C4bC2b complex, which will finally cleave C3 into C3b and C3a.

Front 10

Why is C3 convertase (C4bC2b complex) a point of major amplification?

Back 10

One C4bC2b complex can cleave up to 1,000 C3 molecules.

Front 11

What 2 things do the products of the complement pathway do?

Back 11

1) Facilitate antigen clearance
2) Generate an inflammatory response

Front 12

What are the 3 pathways of complement activation?

Back 12

1) Classical pathway (Ag-Ab complexes)
2) MB-Lectin pathway (Lectin binding to pathogen surfaces)
3) Alternative pathway (Pathogen surfaces)

Front 13

What is the nomenclature used for the classical pathway?

Back 13

C1-C9. Cleaved protein C3 would form C3a and C3b.
*All bound active components are designated with "b".

Front 14

What is the nomenclature used for the alternative pathway?

Back 14

Capital letters, like B or D. Cleaved protein would be Ba and Bb.

Front 15

What nomenclature is used for the MB-Lectin pathway?

Back 15

MASP-1 (Mannan-Binding Lectin Associated Serine Protease-1).

Front 16

What is the initiation step of the classical pathway?

Back 16

Recognition of an Ab-Ag complex by the complement component C1, which binds to the Fc portion of the Ab.

Front 17

How is C1 activated in the typical sense? Which Ab activates it?

Back 17

C1-q-r-s binding to Ab-Ag complex requires C1q to bind simultaneously to 2 Fc portions. The pentameric nature of IgM allows a single molecule of Ag-bound IgM to activate C1.

Front 18

What are the 2 additional ways that C1 can be activated?

Back 18

1) Direct binding to certain microbial surfaces.
2) Binding to C-reactive protein.

Front 19

What occurs following C1 activation?

Back 19

C1r then activates and cleaves off a portion of C1s, leaving a newly activated C1-q-r-s complex that will cleave C4.
C4b is now reactive and binds to C2.
Then C1s will come around and cleave C2, forming the C4bC2b complex, which will finally cleave C3 into C3b and C3a.

Front 20

Why is C3 convertase (C4bC2b complex) a point of major amplification?

Back 20

One C4bC2b complex can cleave up to 1,000 C3 molecules.

Front 21

What is the function of C3b?

Back 21

It is a powerful opsonin and enhances the uptake of antigens by phagocytes.

Front 22

What is the function of C3a?

Back 22

C3a remains soluble and has local inflammatory effects.

Front 23

What is the function of the C4bC2bC3b (C5 convertase) complex?

Back 23

Cleaves C5 to C5b and C5a.
C5a is a soluble inflammatory mediator and C5b complexes with additional complement components.

Front 24

What is the function of C5b?

Back 24

Initiates the final phase of complement activation, forming the Membrane Attack Complex (MAC).

Front 25

What is the initial activation step of the MB(Mannan Binding)-Lectin Pathway?

Back 25

Mannan Binding Lectin(MBL)-MASP-1-MASP-2 complex, (which is homologous to C1q) binds to mannose and other carbohydrates found on surface pathogens.
When MBL binds to pathogen, MASP-1 and MASP-2 are activated, which cleave C4 and C2, generating C4bC2b (C3 convertase).
*The remainder of this pathway is the same as the classical.

Front 26

What is the host advantage of the MB-Lectin pathway?

Back 26

Activation of complement directly by pathogens, without having to go through Ab binding.

Front 27

What is the initial activation step in the alternative pathway?

Back 27

Slow, spontaneous hydrolysis of C3 in plasma.

Front 28

What will hydrolyzed C3 (of the alternative complement pathway) bind and cleave to?

Back 28

Factor B --> C3(H2O)Bb, which is a C3 convertase.

Front 29

What is the role of C3 convertase?

Back 29

Cleave C3 into C3b (and C3a).

Front 30

What is the fate of activated C3b?

Back 30

It will degrade unless bound favorably to a pathogenic surface.

Front 31

What will occur if C3b binds favorably to a pathogenic surface?

Back 31

C3b will bind to Factor B --> C3bB.

Front 32

What is the purpose of Factor D?

Back 32

Cleaves Factor B to form bound C3bBb.

Front 33

What is the purpose of Factor P?

Back 33

Stabilizes C3bBb and stimulates it to act as a C3 convertase, analogous to C4bC2b in the classical pathway.

Front 34

How is C5 convertase formed in the next step?

Back 34

Another C3b molecule binds to C3bBb to form C3b-C3b-Bb, a C5 convertase.
This will cleave C5 to C5b and C5a.

Front 35

What occurs following the cleavage of C5?

Back 35

This is the point where the alternative and classical pathways converge and form the MAC complex.

Front 36

How does the classical pathway feed into the alternative pathway?

Back 36

C3b generated in the classical pathway can enter the alternative pathway by interacting with Factors B and D.

Front 37

How is the activation of the alternative pathway an amplification system?

Back 37

Alternative pathway can enhance both C3 convertase activity and MAC formation. (C3 convertase can cleave up to 1,000 C3's.)

Front 38

What are the 4 consequences of Complement Activation?

Back 38

1) Cell lysis and viral neutralization.
2) Opsonization.
3) Clearance of Immune Complexes.
4) Inflammation.

Front 39

Describe cell lysis and viral neutralization by complement activation.

Back 39

MAC complex drills a hole in bacterial and viral membranes. Viral particles can also be coated by complement and neutralized, preventing it from host cell attachment.

Front 40

Describe opsonization by complement activation.

Back 40

Neutrophils and macrophages carry receptors for C3b. Any antigen coated with C3b will be easily phagocytosed.
C5a will stimulate phagocytic cells to ingest C3b coated antigens.

Front 41

Describe the inflammatory response by complement activation.

Back 41

C5a gradients recruit leukocytes to the site of antigenic challenge (chemotaxis).
C3a, C4a, C5a fragments (anaphylatoxins) bind to mast cell and basophil receptors, triggering degranulation of histamine. This will increase vascular permeability and extravasation of Ig and complement molecules.

Front 42

What is the CR2 receptor and what is its function?

Back 42

It is a C3 complement receptor that when bound, will activate the B-cell response, enhancing antigen uptake and presentation. This optimizes the adaptive immune response.