Chapter 16.2: Complement Slides Flashcards
What is the complement system?
A system of enzymes and proteins that function in both the innate and adaptive branches that is part of the humoral immune response.
What connects the complement system to the function of the adaptive immune response?
The use of antibodies.
What does complement activation result in?
Lysis of the foreign cell.
What does the complement system indirectly trigger?
Inflammation and fever.
What are the three ways complement can be activated?
The classical pathway
The alternative pathway
The Lectin pathway
Which two pathways are part of the innate immune system?
The Alternative pathway
The Mannan-binding lectin (MBL) pathway
Which pathway is part of the adaptive immune system and why?
The Classical pathway because it is initiated by antigen-antibody complexes.
Where do all three pathways converge?
The point of a C3 convertase.
What is the classical pathway initiated by?
The binding of antibody to antigen.
What does the binding of the antibody cause?
Binding of IgM or IgG causes a conformational change in the Fc region of the immunoglobulin molecule.
What does the change of the Fc region allow for?
It allows for C1q to bind to the antibody which then undergoes a conformational change.
What does the conformation change to C1q cause?
Causes sequential binding and activation of the serine proteases C1r and C1s, which creates the C1qrs or C1s.
What does C1s do?
It rapidly cleaves C4 and C2 leading to the formation of C4b2a, also known as the C3 convertase.
What does the C3 convertase do?
Cleaves C3 leading to the formation of C4b2a3b complex which is the C5 convertase.
What does the insertion of C5b do?
Leads to the addition of the components C6, C7, and C8 (recruited and not cleaved) which forms an anchor for C9.
What is C8 and what does it do?
It is a strong anchor for the complex and facilitates the addition of multiple C9 molecules.
What does C9 do?
It forms a pore in the membrane.
What are all these components called?
The membrane attack complex (MAC).
What is the alternative pathway initiated by?
It is initiated by cell surface constituents that are recognized as foreign (LPS).
What is the most abundant serum complement component?
C3, which can be cleaved even in health.
What is the first step of the alternative pathway?
C3 binds to the microbial surface and becomes slightly more stable.
How is the stable C3 convertase created in the alternative pathway?
Factor B is cleaved by Factor D, creating Bb.
Bb along with Factor P bind to C3b and fully stabilize the complex on the surface of the pathogen, creating the C3 convertase.
What are lectins?
Proteins that bind to specific carbohydrates.
What initiates the Mannan-Binding lectin pathway?
Initiated by the binding of mannan-binding lectin (MBL) to mannose containing residues of glycoproteins on certain microbes.
What does the binding of MBL do?
It activates mannose-binding protein-associated serine protease.
What does the mannose-binding protein-associated serine protease do?
Cleaves C4 and C2 to create C3 convertase.
What does C3b function as?
An opsonin, which enhances phagocytosis.
What do C3a, C4a, and C5a serve as?
Powerful anaphylatoxins, which stimulate mast cells to release histamine and TNF-alpha.
This increases vascuale permeability.
What do C3a and C5a also act as?
Chemotactic factors that help recruit neutrophils and macrophages.
