What is complement fixation?
The act of C3b sticking to a pathogen
What are the three different complement cascades?
- classical pathway
- lectin pathway
- alternative pathway
What 3 affecter functions does the complement cascade lead to?
- inflammation
- lysis
- opsonization
What initiates the classical pathway?
antibody binding to the surface of a pathogen
What is the MAC
it is the Membrane Attack Complex, formed by C6,C7,C8 and C9 where they come together and punches holes in the cell membrane to form pores
What is the role of C3a and C5a?
C3a and C5a bind C3aR and C5aR respectively and stimulate the release of proinflammatory mediators they are also known as anaphylatoxins
How does C3a and C5a cause inflammation?
- they increase the permeability of the blood vessels
- this allows fluids leakage of blood vessels for immunoglobulins and complement proteins
- also allows for the migration of macrophages and etc to increase
What is opsonization?
basically is the coating of microbes to increase phagocytosis
What is an important receptor in this complement pathway and why?
CR1. it regulates C3 breakdown and enhances phagocytosis
How does opsonization occur?
complement activation leads to deposition of C3b that bind to CR1 and then endocytosis occurs by the macrophages and create the phagosome and then the lysosome fuses with the phagosome to form the phagolysosome
What is MBL and what is it common on?
MBL: in plasma forms complexes with protease zymogens MASP-1 (Mannose - binding protein - Associated Serine Protease) Mannose is common on microbial glycans like Gram + and -, mycobacteria, yeast and some viruse
What is MBL monomer made up of?
- collagen region
- a helical neck region
- carbohydrate-r
(C1r, C1q ,C1s)
What are ficolin monomers?
resemble MBLs, possess fibrinogen-like domains
What is the start of the lectin pathway?
MBL binds to the mannose on the pathogen, causing the conformational change in MASP-1 that cleabes MASP-2 which then activates MASP-2
What starts the alternative pathway?
the spontaneous hydrolysis of C3
What are the 3 C3 convertases?
C4a2b, C3H20, C4bBb
How does C3 attack pathogens while sparing host tissues?
when C3 is cleaved, the thioester bond is exposed and it either attacked by water or attacked by R-OH or R-NH2 that is found on host or pathogen cells. In host cells C3 is stopped but on pathogen cells it is not.
How does Factor H and I counter-act the effect?
Factor H: binds to the C3b on cells (prefers host cells since they have sialic acid on them). Once bound, it prevents factor B from binding. Factor I uses Factor H as a cofactor and cleaves C3b making it iC3b (inactive)
What is the Decay-acceleration factor (DAF)?
it is a compliment control protein that binds to the C3b component of C3bBb causing it to dissociate
What is the Membrane cofactor protein (MCP)?
it is a compliment control protein that has the same role as DAF, but when it binds to C3b it makes it susceptible to cleavage by factor I
What is the order of the pathways of compliment?
First to act: alternative
Second to act: Lectin
Third to act: classical
What is the same in the three pathways?
cleavage of C3 to C3a and C3b covalently bound to surface components of pathogen
What is the end result of these pathways?
- recruitment of inflammatory cells
- opsonization of pathogens, facilitating uptake and killing by phagocytes
- perforation of pathogen cell membranes
What are the two phases
first phase: humoral
second phase: cellular
