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What are the three complement pathways?
- Classical
- Lectin-binding
- Alternative
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Is complement part of the innate or acquired immunity?
Innate
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What is required to activate the classical pathway?
Antibody
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What is required to activate the Lectin-binding pathway?
- Mannose binding lecting (MBL)
- or Mannose binding protein (MBP)
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What is require to activate the alternative pathway?
Pathogen surface
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What is the convergence point for all three complement pathways?
C3 convertase
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What organ produces MBL? How?
Liver, Macrophage cytokine activation
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What binds to the antibody to initiate the Classical pathway?
C1
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What binds to the MBL or MBP to initiate the Lectin-binding pathway?
MASP
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What occurs to initiate the alternative pathway?
- C3 is automatically cleaved to C3b so it will bind to the pathogen and then bind B.
- B will then be cleaved by Factor D to become the C3bBb C3 convertase.
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What cleaves factor B in the Alternative pathway?
Factor D
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Name the three C3 convertases associated with the three complement pathways
- 1) Classical: C4b2b
- 2) Lectin: C4b2b
- 3) Alternative: C3bBb
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What are the four goals of the complement pathways?
- 1) Lysis
- 2) Opsonization
- 3) Inflammation
- 4) Clear immune complexes
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What fragments perform Lysis?
C5b-9
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What fragments perform opsonization?
C3b and C4b
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What fragments perform inflammation?
C3a, C5a, C4a
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What fragments perform immunity clearing?
C3b
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What is Opsonization?
Catalyzed phagocytosis (C3b, C4b)
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What are three main opsonin receptors?
CR1, CR3, CR4
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How are immune complexes cleared?
- 1) Binding of C3b
- 2) RBC binding
- 3) RBC degradation in spleen or RBC phagocytosis by Macrophages
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Which is a more potent inflammatory complement factor, C3a, C4a or C5a?
C5a
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What is formed to lyse cells?
MAC
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What forms the MAC complex?
C5b, 6,7,8,9
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What happens if there is a deficiency in the C1 inhibitor?
Excess swelling b/c of active C3a and C5a which are anaphylatoxins and induce inflammation
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What occurs with excess DAF and D59 synthesis on RBCs? What binds at those locations?
- excess complement
- D59 = MAC complex location
- DAF = C3/C5 convertase location
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What is a prominent disease if the classical pathway is deficient?
LUPUS
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What diseases are common with MAC deficiency (C5b, 6, 7, 8, 9)?
Meningitis and Gonorrhea
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