Compliment Flashcards
What are the three effects of the products generated by the compliment components
1) Recruit inflammatory cells
2) Opsonize microbial pathogens and immune complexes to make them more recognizable by the immune system
3) Kill microbial pathogens through MAC
The classical pathway is activated by what?
Antigen:antibody complexes
The Lectin pathway is activated by what?
Lectin binding to pathogen surfaces
The Alternative pathway is activated by what?
pathogen surfaces
What component of the classical pathway recognizes the antibody:antigen complex? What is it binding?
C1: binds to the Fc portion of the antibody molecule
Why does C1 not bind to soluble unbound antibody?
The binding of the antibody to antigen induces a conformational change in the antibody constant region. This exposes a site on the Fc portion that can be bound by C1
How many globular heads make up C1?
6
How many globular heads of C1 must be bound to antibody?
At least 2: this means that two Fc portions need to be within close molecular proximity of each other on the antigenic surface
What is the chain of events that occurs within the C1 complex following binding to two or more globular heads?
C1q binds to the Fc regions, C1r undergoes a conformational switch and becomes enzymatically active and cleaves C1s, which after cleavage is enzymatically active as well
Differentiate activation of C1 binding to IgG vs IgM
IgG: monomer, therefore there must be a higher density of IgG on the antigen in order to activate C1
IgM: pentameric, therefore can always activate C1 by itself
Which protein initiates the lectin pathway?
Mannose-binding lectin and ficolins recognize and bind carbohydrates on pathogen surfaces
What does ficolin bind?
oligosaccharides containing acetylated sugars
What does MBL bind?
mannose, fucose and other complex carbohydrates
What are the two serine proteases physically associated with MBL/ficolin that are analogous to C1r and C1s?
MASP-1 and MASP-2
Activated C1qrs or MBL/ficolin activated MASP1 and MASP2 cleave what?
C4 is cleaved into C4a and C4b,
C4b fragments then bind C2
How is C2 cleaved?
C2 is cleaved by C1s (or MASP-1/MASP-2) into C2a and C2b.
C2a combines with the C4b on the cell surface to form the C4b2a complex
What is another name for C4b2a? What is its purpose?
C4b2a is a C3 convertase, capable of cleaving C3 into C3b and C3a. This is a major point of amplification of the pathways, since one C3 convertase can cleave up to 1000 molecules of C3
What is the purpose of producing C3b?
C3b covalently bound to the antigenic surface acts as a powerful opsonin and enhances the uptake of antigenic particle by phagocytes
What is the C5 convertase?
C4b2a3b is the C5 convertase. It produces C5a and C5b.
C5a is a soluble inflammatory mediator, and C5b is a capable of complexing with other components
Describe the MAC
C5b binds to C6 and C7
C8 binds the complex and inserts into the membrane
1-16 molecules of C9 bind to form a pore in the membrane
MAC complexes are more effective at what class of bacteria
Gram negative, because they don’t have much of a cell wall_
What is required for the activation of the alternative pathway?
The activation of the alternative pathway depends on slow hydrolysis of C3, which spontaneously occurs in the plasma
What is the C3 convertase of the alternative pathway?
Hydrolyzed C3 (that occurred spontaneously in the plasma) can bind Factor B, and the resulting C3Bb complex is a C3 convertase that can generate additional molecules of C3b
C3b binds factor B, allowing for cleavage by what? What is formed?
Factor D. This forms C3bBb
