Complement System Flashcards
Complement
complex system of proteins that interact to kill invading microbes. Trigger inflammation and regulate immunity.
What initiates the classical complement pathway?
when 1 IgM or 2 IgG molecules bind to antigenic surface
What initiates the alternative pathway
triggered by the presence of bacterial PAMPs. FH and FI destroy C3b and stop the pathway, preventing the continuous activation of complement and production of the MAc
C3 Convertase
when C3b binds to bacteria, FB and FD form C3 convertase to activate more C3 and kill the bacterial cells. Very unstable. Amplification step because it is stabilized by FP to kill as many cells as possible
What does the terminal sequence operate?
tubular complex of poly-C9 that causes cell lysis
Why does complement have to be regulated
so healthy cells are not attacked/prevent autoimmunity
Basic mechanism of complement inhibition
- C1 inhibitor inhibits activation of classical pathway
- other inhibitors block C3 and C5 convertases
- CD55 protects healthy cell membranes
- vitronectin, clusterin, and CD59 inhibit amplification pathway
Opsonization
bacterial coated by antibodies and/or complement bind to neutrophil receptors and are readily ingested
Complement Proteins Labelling
labeled numerically with the prefix C or designated as factors by letters of the alphabet
Where are complement proteins found?
free in serum or cell-surface receptors
What is the most common complement protein in serum?
C3
Which complement proteins are made in the liver?
C3, C6, C8, and FB
Which complement proteins are made by macrophages?
C2, C3, C4, C5, FB, FD, FP, and FI
What is C1q produced by?
Mast cells
Alternate Pathway
innate pathway that accounts for most complement activated
Lectin Pathway
innate pathway triggered by mannose on microbial surfaces. They activate MBL associated serine protease (MASP). This activates C4
Classical Pathway
triggered by antibody binding and hence part of the adaptive response. Triggered when 1 IgM or 2 IgG bind to an antigenic surface
Pathways triggered by bacterial PAMPs
alternative and lectin pathways
What do all three pathways activate?
C3, which in turn initiates the amplification pathway and generates the terminal complement complex
Is alternative C3 convertase stable?
no, so Factor P binds to the complex and it forms a stable C3bBbP complex
Substrate Modulation
Constraint- FD can act on FB only after it has bound to C3b but not before. This regulates several reactions in the complement pathways. It ensures that the activities of enzymes such as FD are confined to the correct molecules
Activated C3b
binds covalently to microbial surfaces and will not come off. Potent opsonin. Triggers the terminal pathway and inactivated by FH and FI
Terminal Pathway
triggered by the activation of C3b. Components come together to trigger C9 polymerization. Poly-C9 forms a tubular complex that inserts into a target cell membrane. The target then undergoes osmotic lysis
C3a target
eosinophils
C5a target
neutrophils, eosinophils, macrophages
Canine C3 Deficiency
Occurs in Brittany Spaniels as a result of a mutation in the C3 gene. Results in increased susceptibility to disease, most notably bacterial pneumonia. Inherited as an autosomal recessive condition
Factor H Deficiency in Pigs
Uncontrolled activation of the alternate pathway results. Massive amounts of C3 are deposited in the kidneys. Renal failure results
Type 1 Phagocytosis
mediated by antibodies through CD32
Type 2 Phagocytosis
mediated by complement through CD35
What stops the alternative pathway?
factor H
