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42 Cards in this Set

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What 2 things do the products of the complement pathway do?
1) Facilitate antigen clearance
2) Generate an inflammatory response
What are the 3 pathways of complement activation?
1) Classical pathway (Ag-Ab complexes)
2) MB-Lectin pathway (Lectin binding to pathogen surfaces)
3) Alternative pathway (Pathogen surfaces)
What is the nomenclature used for the classical pathway?
C1-C9. Cleaved protein C3 would form C3a and C3b.
*All bound active components are designated with "b".
What is the nomenclature used for the alternative pathway?
Capital letters, like B or D. Cleaved protein would be Ba and Bb.
What nomenclature is used for the MB-Lectin pathway?
MASP-1 (Mannan-Binding Lectin Associated Serine Protease-1).
What is the initiation step of the classical pathway?
Recognition of an Ab-Ag complex by the complement component C1, which binds to the Fc portion of the Ab.
How is C1 activated in the typical sense? Which Ab activates it?
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.
What are the 2 additional ways that C1 can be activated?
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.
What occurs following C1 activation?
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.
Why is C3 convertase (C4bC2b complex) a point of major amplification?
One C4bC2b complex can cleave up to 1,000 C3 molecules.
What 2 things do the products of the complement pathway do?
1) Facilitate antigen clearance
2) Generate an inflammatory response
What are the 3 pathways of complement activation?
1) Classical pathway (Ag-Ab complexes)
2) MB-Lectin pathway (Lectin binding to pathogen surfaces)
3) Alternative pathway (Pathogen surfaces)
What is the nomenclature used for the classical pathway?
C1-C9. Cleaved protein C3 would form C3a and C3b.
*All bound active components are designated with "b".
What is the nomenclature used for the alternative pathway?
Capital letters, like B or D. Cleaved protein would be Ba and Bb.
What nomenclature is used for the MB-Lectin pathway?
MASP-1 (Mannan-Binding Lectin Associated Serine Protease-1).
What is the initiation step of the classical pathway?
Recognition of an Ab-Ag complex by the complement component C1, which binds to the Fc portion of the Ab.
How is C1 activated in the typical sense? Which Ab activates it?
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.
What are the 2 additional ways that C1 can be activated?
1) Direct binding to certain microbial surfaces.
2) Binding to C-reactive protein.
What occurs following C1 activation?
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.
Why is C3 convertase (C4bC2b complex) a point of major amplification?
One C4bC2b complex can cleave up to 1,000 C3 molecules.
What is the function of C3b?
It is a powerful opsonin and enhances the uptake of antigens by phagocytes.
What is the function of C3a?
C3a remains soluble and has local inflammatory effects.
What is the function of the C4bC2bC3b (C5 convertase) complex?
Cleaves C5 to C5b and C5a.
C5a is a soluble inflammatory mediator and C5b complexes with additional complement components.
What is the function of C5b?
Initiates the final phase of complement activation, forming the Membrane Attack Complex (MAC).
What is the initial activation step of the MB(Mannan Binding)-Lectin Pathway?
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.
What is the host advantage of the MB-Lectin pathway?
Activation of complement directly by pathogens, without having to go through Ab binding.
What is the initial activation step in the alternative pathway?
Slow, spontaneous hydrolysis of C3 in plasma.
What will hydrolyzed C3 (of the alternative complement pathway) bind and cleave to?
Factor B --> C3(H2O)Bb, which is a C3 convertase.
What is the role of C3 convertase?
Cleave C3 into C3b (and C3a).
What is the fate of activated C3b?
It will degrade unless bound favorably to a pathogenic surface.
What will occur if C3b binds favorably to a pathogenic surface?
C3b will bind to Factor B --> C3bB.
What is the purpose of Factor D?
Cleaves Factor B to form bound C3bBb.
What is the purpose of Factor P?
Stabilizes C3bBb and stimulates it to act as a C3 convertase, analogous to C4bC2b in the classical pathway.
How is C5 convertase formed in the next step?
Another C3b molecule binds to C3bBb to form C3b-C3b-Bb, a C5 convertase.
This will cleave C5 to C5b and C5a.
What occurs following the cleavage of C5?
This is the point where the alternative and classical pathways converge and form the MAC complex.
How does the classical pathway feed into the alternative pathway?
C3b generated in the classical pathway can enter the alternative pathway by interacting with Factors B and D.
How is the activation of the alternative pathway an amplification system?
Alternative pathway can enhance both C3 convertase activity and MAC formation. (C3 convertase can cleave up to 1,000 C3's.)
What are the 4 consequences of Complement Activation?
1) Cell lysis and viral neutralization.
2) Opsonization.
3) Clearance of Immune Complexes.
4) Inflammation.
Describe cell lysis and viral neutralization by complement activation.
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.
Describe opsonization by complement activation.
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.
Describe the inflammatory response by complement activation.
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.
What is the CR2 receptor and what is its function?
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.