Lecture 4 Flashcards
Name the 3 pathways of complement activation
Classical pathway
Lectin pathway
Alternative pathway
What is the end product common to all 3 complement pathways?
Membrane attack complex (MAC).
True or False: IgM is more efficient at initiating the classical pathway than IgG.
TRUE.
Because IgM is a pentamer, it does not require multiple antibodies to activate C1.
Which complement protein is highest in concentration in the blood?
C3.
What is the consequence of an unregulated complement system?
Death.
What is the function of the membrane attack complex (MAC)?
Creates a pore in a cellular membrane, leading to cellular lysis.
Name two mechanisms by which the complement system is regulated.
Substrate modulation
- a complement protein cannot be cleaved by a protease until it first binds to another protein. Prevents unnecesary cleavage.
Fragment binding
- complement molecules are cleaved into two parts. One part (b component) usually quickly covalently binds to a nearby surface. If it does not bind, it is quickly degraded. Limits enzyme cascades to site of infection.
Which complement activation pathway is reliant on the adaptive immune system?
Classical pathway
Requires antibodies for C1 binding.
True or False: The lectin and alternative pathways can be activated without the presence of antibodies.
TRUE
These pathways are considered as part of innate immunity.
True or False: Mannose is commonly found in mammalian cells.
FALSE.
Mannose is typically found in bacteria, fungi, and other pathogenic microbes.
The presence of mannose on a microbe initiates the lectin pathway of complement activation.
How many IgG molecules are required to fix complement?
At least 2, and they must be spaced closely together.
For this reason, approximately 10,000 IgG molecules must be bound to a cell before the complement cascade normally starts.
Can C1 bind to free-floating antibodies in the blood stream?
No.
C1 can only bind to antibodies that have been bound to an antigen.
What is the function of C3 convertase in the complement cascade?
Splits C3 into C3a and C3b.
C3a - causes increased vascular permeability and is chemotactic.
C3b - opsonization. Also binds with C3 convertase to create C5 convertase.
Which complement molecule is responsible for opsonization of pathogens for later recognition by phagocytic cells?
C3b
What is the general effect of complement activation on nearby vasculature?
Vasodilation
Increased vascular permeability
What is the effect of calcium chelation on the complement system?
Inactivation.
C1 is a large complex of proteins held together by calcium. Chelating calcium effectively inactivates C1.
What is the effect of Heparin on the complement system?
No effect.
Heparin is a thrombin antagonist. If added to serum, it will inactivate clotting factors, but will not affect complement.
How might one inactivate complement in serum?
Calcium chelation (ex: EDTA)
-inactivates complement and clotting factors.
Heat to 56 degrees Celcius for 30 minutes
-inactivates complement but preserves antibodies.
Describe the process occuring here.
Two IgG molecules are bound to a membrane. C1 has cross-linked the two IgGs, causing a conformational change in C1 to expose its active site.
C5 convertase cleaves C5 into C5a and C5b. What are the major functions of C5a?
Phagocyte chemotaxis
Mast cell degranulation
Neutrophil activation
What is the function of mannose-binding lectin (MBL)?
Binds to mannose molecules present on pathogen surfaces.
Functionally similary to C1. Initiates the lectin pathway of complement activation.
What is meant by the term “terminal pathway” in terms of the complement cascade?
The end pathway common to all 3 complement activation pathways that results in formation of the MAC.
Once C5 is cleaved, the terminal pathway is initiated.
What molecule is pictured here?
Membrane attack complex (MAC).
How is the alternative pathway activated?
C3 in the plasma slowly degrades into C3a and C3b on a regular basis. If C3b binds to a microbial surface, Factor B will bind, creating a C3 convertase (different molecule, but same action as in the other 2 pathways).
This results in more C3 cleavage and activation of the complement system.
How is the alternative pathway regulated?
C3 in the plasma slowly degrades into C3a and C3b on a regular basis.
Mammalian cells contain sialic acid, which binds factor H. If C3b binds to a mammalian cell, it is quickly destroyed by factors H and I.
Bacterial cells lack sialic acid. If C3b binds, the complement system is quickly activated.
In general, what are the four biological consequences of complement activation?
Cell lysis
Vasodilation / Increased vascular permeability
Chemotaxis
Opsonization
What process is pictured here?
C1 binding to IgM.
Note that only 1 IgM molecule is needed for C1 to bind.
Where are complement molecules produced?
Liver
