Complement Flashcards
List 4 ways in which complement works for host defense. Briefly describe the outcomes of each mechanism
What are the goals of complement?
- Generate MEMBRANE ATTACK COMPLEX
- Induce & enhance INFLAMMATION
- Promote OPSONIZATION
- Enhance REMOVAL OF IMMUNE COMPLEX
- Help ACTIVATE B CELLS
How are membrane attack complexes generated?
Through the complement pathway
C5b + C6 + C7 + C8 + C9n = MAC
What is the complement activation fragments in inflammation influence on endothelial cells?
On endothelial cells, C5a and C3a have the ability to directly act on endothelium to increase permeability.
All 3 peptides ➔ stimulate release of histamine by binding to mast cells ➔ release of mast cell/basophil products incr. vascular permeability ➔ allow plasma flow from interstitium & makes it easier for blood-borne phagocytic cells to pass into the tissue
State which complement activation fragments acts in the complement during inflammatory response.
Complement activation fragements that act during inflammatory responses are C5a, C3a and C4a.
List the complement activation fragments responsible for inflammation in decreasing order of efficiency.
C5a > C3a > C4a (efficiency anaphylatic agent)
What is the complement activation fragments in inflammation influence on endothelial cells?
On endothelial cells C5a and C3a have the ability to directly act on endothelium to increase permeability.
What is the complement activation fragments in inflammation influence on mast cells?
All three peptides stimulate release of histamine and other vasoactive products by binding to receptors on mast cells (and basophils). Release of these mast cell/basophil products also leads to increased vascular permeability which allow plasma to flow from interstitium and makes it easier for blood-borne phagoccytic cells to pass into the tissue.
What is the complement activation fragments in inflammation influence on phagocytic cells?
C5a, C3a and C4a have chemotactic activity, resulting in an influx of neutrophils, macrophages and monocytes into the area. Neutrophils and macrophages are key cell types involved in inflammation, thus increasing their # enhances inflammation.
Neutrophils “called in” to the site of inflammatory stimulus can be activated by C5a, C3a and possibly C4a.
Explain the role of complement in opsonization and the removal of immune complexes.
- Deposition of fragments C3b, C4b and iC3b marks that surface for removal by phagocytic cells bearing receptors that are specific for these fragements.
- Bacteria flagged with C3b, iC3b or C4b
- Phagocytic cells tht r equipped with these complement receptors include neutrophils, macrophages and monocytes - C3b interchelates into Ab-Ag (IC) lattices, keeping immune complexes soluble
- RBCs carry these IC to the liver and spleen for removal
What are the opsonins in opsonization in complement?
C3b, iC3b, C4b, or Ab (IgG or IgA)
Explain how complement is regulated.
Complement pathways are inhibited by specific proteins that circulate in the blood and by cell surface anchored inhibitors.
Fluid phase inhibitors - C1 inhibitor & Factor H
- FH dissociates the alternative pathway C3 convertase and serves as a cofactor for Factor I cleavage of C3b
What is the consequence of dysregulation of the complement system?
Complement activation must be controlled to avoid unintended destruction of homologous cells,
inappropriate stimulation of an inflammatory response and the depletion of complement which would leave the host vulnerable to invading pathogens.
What are the receptors important for the regulation of complement?
CR1, CR3, C3aR, CRIg
How are B cells activated in complement?
CR2 increases B cell sensitivity to Ag coated with C3d
1. BCRs & CR2 cluster together
2. B cell activation signal greatly increases
