Complement system Flashcards
What does the activation of the complement pathway involved?
Sequential proteolytic cleavage of substrates that results in a cascade reaction
what are the 4 main functions of the complement system?
- lyse target cells
- promote phagocytosis 3. induce inflammatory response
- clear immune complexes
activation of the classical complement pathway requires one or more:
antibody-antigen complexes
What is the alternative complement pathway involved in?
Innate immunity and can function in the absence of antibody
What triggers the alternative pathway ?
A range of microbial molecules as well as nonpathogenic molecules
What initiates the alternative pathway?
spontaneous hydrolysis of C3
-C3b then deposits on the microbial surface
Which protein is key in maintaining the activation of the alternative pathway by stabilization?
Properdin
- stabilizes C3bBb
- also called factor P
What is the lectin pathway involved in ?
Innate immunity
-does not depend on the presence of antibody
What activates the lectin pathway?
Interaction of mannose binding lectin with mannose residues on glycoproteins/carbohydrates that are expressed by certain microorganisms
what are the 2 MBL associated proteases generally found on the surface of microbes?
MASP-1 and MASP-2
What is the role of MASP 1 and MASP 2
bind MBL on the microbe to form a complex that is able to cleave C4 and C2
Where can the complement system be regulated?
Before AND after the assembly of C3 convertase
-very important to regulate it so that only the appropriate targets are being attacked
What is C1 inhibitor and what does it do?
Induces dissociation and inhibition of C1r2s2 from C1q
is a serine protease inhibitor
affects the classical and lectin pathways
What is Decay Accelerating Factor (DAF)
Accelerates the dissociation of C4b2a and C3bBb (both the C3 convertases)
What is CR1 (CD55)
a membrane bound regulator of the complement pathway
Block formation of and accelerated dissociation of the C3 convertases by binding C4b and C3b
What is the role of Protectin ?
Binds C5b678 on host cells to prevent the binding of C9 and the formation of the MAC
What are 5 ways to turn off the complement pathway?
- Dissociation of C1 components
- Decay accelerating activity (DAF) for C3 convertases
- Factor I cofactor activity (CR1)
- degrades C3b and C4b` - Inhibition of lysis/MAC (protectin)
- Cleavage of anaphylatoxins by carboxypeptidases
What is the role of anaphylatoxins?
To attract leukocytes to the site of inflammation as well as to increase permeability in the vasculature
What are the 3 anaphylatoxins?
C3a, C4a, C5a
What are the special roles of C3a and C5a?
chemotactic for granulocytes and monocytes
Also cause platelet aggregation
Opsonization of microbes is achieved by?
C3b, C3bi, C4b
What is the role of RBC in the complement pathway?
CR1 on RBC interacts with C3b and carries small soluble complexes to the liver or spleen to be eliminated by phagocytes
CR1, 2, 3, and 4 are?
Receptors that bind complement components and their breakdown parts
What does CR1 bind and where is it expressed?
Binds: C3b, C4b, C1q, iC3b
Found on: RBC, neutrophils, monocytes, macrophages, eosinophils, FDCs, B cells, and some T cells
What does CR2 bind and where is it expressed?
aka Epstein-Barr virus receptor
Binds: C3d, C3dg (products of factor I cofactor activity)
Found on: B cells and FDCs
What does CR3 bind and where is it expressed?
Binds: iC3b and factor H
Found on: monocytes, macrophages, neutrophils, NK cells, eosinophils, FDCs, T cells
What does CR4 bind and where is it expressed?
Binds: iC3b
Found on: monocytes, macrophages, neutrophils, NK cells, T cells
What is the consequence of a breakdown int he clearance mechanism for complement?
some of the immune complexes deposit in the kidneys
-sometimes can occur post strep throat
