15th Page Flashcards
What is the classical pathway?
specific immune system mechanism that triggers complement activation.
2nd oldest pathway
Classical pathway
main ab-directed mechanism for triggering complement activation
Classical Pathway
Which antibodies activate the classical pathway?
Only IgM and IgG (except IgG4) activate complement.
What are the three main stages of the classical pathway?
- Recognition unit
- Activation unit
- Membrane attack complex (MAC)
What components are involved in the recognition unit?
C1 (particularly C1q)
What does the activation unit consist of
C4, C2, C3
What does the membrane attack complex (MAC) consist of?
C5, C6, C7, C8, and C9.
1st MAC unit
C5
starts pore formation on membrane
C8
polymerizes to cause cell lysis
C9
binds to C5b in MAC
C6
binds to C5bC6 in MAC
C7
initiates membrane attack complex
C5
Key intermediate in all pathway
C3
Most concentrated complement component
C3
Binds to C4b form C3 convertase
C2
Part of the C3 convertase (C4b)
C4
Cleaves c4 and c2
C1s
Activate C1s
C1r
Binds to Fc of IgM and IgG
C1a
Alternative pathway
oldest complement activation pathway
Properdin system
Alternative pathway
Pillemer and his associates in the 1950s.
alternative pathway was described by:
It is antibody-independent
alternative pathway
unique serum proteins involved in the alternative pathway
Factor B and Factor D.
Which components are not used in the alternative pathway?
C1, C2, and C4
Key component of the alternative pathway?
C3, like in the classical pathway.
Conc. of Factor D in plasma?
lowest concentration in plasma at 1 µg/mL.
What does Factor B (Bb) binds?
Alternative pathway
C3b to form C3 convertase.
Factor D cleaves what?
Alternative pathway
Factor B.
Properdin stabilizes what?
Alternative pathway
stabilizes C3 convertase and C5 convertase in the presence of Mg.
What is the lectin (MBL) pathway?
3rd oldest complement activation pathway.
What is a lectin?
A lectin is a protein that binds to carbohydrates.
What does mannose-binding lectin (MBL) bind to?
mannose or related sugars such as N-acetylglucosamine to initiate the pathway.
Where is MBL produced?
liver in acute-phase inflammatory reactions.
What complex does MBL form?
complex with MASP-1 and MASP-2.
What does MBL resembles?
C1a in both structure and function.
What is the function of MASP-1?
help cleaves C4 and C2.
What is the function of MASP-2?
cleaves C4 and C2.
binds to mannose
MBL
What is the function of C1 inhibitor (C1 iNH)?
Dissociates C1r and C1s from C1q.
What does Factor I do?
Cleaves C3b and C4b.
Cofactor with I to inactivate C3b, prevents binding of B to C3b.
Factor H
cofactor with I to inactivate C3b, prevents binding of B to C3b
S protein (vitronectin)
Prevents attachment of the C5B67 complex to cell membrane.
Factor H
The principal soluble regulator of the alternative pathway.
Dissociates C2b or Bb from binding sites, thus preventing formation of C3 convertase.
cofactor with I to inactivate C4b
C4-binding protein
MIRL
Membrane Inhibitor of Reactive Lysis
Prevents insertion of C9 into cell membrane.
Dissociates C2b or Bb from binding sites, thus preventing formation of C3 convertase
It binds C3b and C4b but has the greatest affinity for C3b.
What happens once C3b and C4b are bound to CR1?
degraded by Factor I.
cofactor with I
CR1
Mediates transport of immune complexes, found in the peripheral blood cells
CR1
Where is MCP (CD 46) found?
virtually all epithelial and endothelial cells except erythrocytes.
MCP
most efficient cofactor for Factor I-mediated cleavage of C3b.
How does MCP help control the alternative pathway?
Binding of Factor B to C3b is inhibited.
complement deficiencies associated with lupus-like syndrome and recurrent infections?
C1 (q, r, or s), C2
Most common deficiency.
What is the most severe complement deficiency?
C3
Associated with severe recurrent infections and glomerulonephritis (S. pyogenes).
complement deficiency of glomerulonephritis (S. pyogenes)
C3
severe recurrent infections
C3
complement deficiency for atherosclerosis
C2
most common complement deficiency
C2
Which complement deficiencies are associated with Neisseria infections?
C5 - C8
Also associated with pneumococcal diseases.
What is C1 INH deficiency associated with?
Hereditary angioedema
increased kinin-related proteins
may affect subcutaneous tissues, GI tract, respiratory
Causes swelling due to increased production of kinin-related proteins.
complement deficiency of no known disease association
C9
complement deficiency for neisseria infection
properdin
complement deficiency for pneumococcal dse
C3, 2, 1, 4, properdin
What is PNH?
Paroxysmal Nocturnal Hemoglobinuria
Associated with deficiency of complement regulators.
What does the accumulation of fluids due to complement activation cause?
Edema or swelling
May affect subcutaneous tissues, GI tract, and respiratory tract.
What is PIG-A?
Phosphatidyl Inositol Glycan - A
Will be constantly turned over to be activated until it becomes depleted.
Recurrent pyogenic infection
Factor H & I
C3 will be constantly turn over to be activated until it depletes