Test 2: Complement System Flashcards
Functions of complement system?
- lysis of target cell
- opsonization
- activation of inflammatory response
- clearance of immune complexes
Classical Pathway different than Alternative or Lectin because…
Classical is the only one that is antibody dependent
Initiation of Classical Pathway
C1q binds to Fc region of Ab/Ag complex
What Ab typically starts the classical pathway and why?
IgM because of its large size–pentamer
Formation of classical recognition unit
Attachment of C1q activates C1r (two of them) then C1s–>C1qrs
Formation of classical activation unit
- Recognition unit splits C4 then C2–>C4b2a
- this unit will split C3–>C4b2a3b=C5 convertase
What is the major component of the complement system?
C3
Formation of Membrane Attack Complex
C5 convertase splits C5–>C5b
-this attracts 67and 8–>C5b678 which will attract polymerized C9= C5b6789
What are the 2 major mechanisms of the MAC?
- Direct destruction of cell wall; creates pores/holes in cell
- Indirect: MAC changes lipid structure of antigen which disrupts the osmolarity–>lysis
Stimulants of Alternative pathway?
bacterial cell wall components, fungi, viruses, parasites, immune complexes, RBCs, and polymers
Major difference between classical and alternative pathways?
Recognition unit…No C1, C2, or C4
Initiation of Alternative pathway?
C3 spontaneously hydrolyzes–>C3b fragment will attach to foreign surface
Components of alternative pathway
C3b, Factor B, Factor D and Properdin
continuation of alternative pathway after C3b?
Factor B binds to C3b and is cleaved by Factor D–>C3bBb=C3 convertase
-Properdin binds and stabilizes C3 convertase and hydrolyzes more C3–>C3bBbC3b–>activation of C5 convertase–>MAC
Mannose Binding Lectin (MBL) pathway difference with classical?
Recognition unit is different: MBL+ MASP1 MASP2 and MASP3
What binds C1r2s2 so that it dissociates from C1q?
C1 inhibitor
What blocks association of C4b and C2a?
C4b-binding protein, complement receptor type I, or membrane cofactor protein (MCP)
What cleaves inhibitor bound C4b?
Factor I, makes them ineffective
In alternative pathway, what prevents binding of C3b and Factor B?
CR1, MCP, or factor H
What cleaves inhibitor bound C3b?
Factor I, makes it ineffective
What dissociates C3 convertase?
C4bBP, CR1, factor H, and DAF
What prevents insertion of MAC into membrane?
S protein
What prevents assembly of poly-C9 and blocks formation of MAC?
HRF and MIRL
Importance of CR1 receptor?
mediates transport of immune complexes to liver/spleen to clean the circulation
