Lecture 20: CIS - Basic Complement System Flashcards

1
Q

Alternate Complement Pathway

A
  • autoactivation (1% of total C3 per hour = C3a and C3b)
  • C3b binds Factor B, which is cleaved by Factor D

C3 convertase: C3bBb –> cleaves additional C3 moles

  • Properdin: stabilizes C3bBb during process

C5 convertase: C3bC3bBb –> cleave C5

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2
Q

MAC Formation and Bacteria Lysis

A
  • C5bC6C7 bind to membrane via C7
  • C8 binds to complex and INSERTS into membrane
  • C9 binds to complex and polymerizes (1-16 molecules)
  • pore formed in membrane
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3
Q

Classical Complement Pathway

A
  • Ab-mediated (1 IgM or 2 IgG)
  • C1q binds to Ag-Ab complexes (Fc portions) and activates C1r/C1s (serine proteases)
  • C1r activates C1s, which activates C4 and C2

C3 convertase = C4bC2a

C5 convertase = C4bC2aC3b

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4
Q

Lectin Complement Pathway

A
  • Mannose Binding Lectin binds to terminal mannose on glycolipids and glycoproteins (similar to C1q)
  • zymogens MASP1 and MASP2 activate –> initiate downstream cascade similar to C1r and C1s

C3 convertase = C4bC2a

C5 convertase = C4bC2aC3b

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5
Q

What does the C1 inhibitor do?

A
  • inactivates C1r and C1s, MASP-1 and MASP-2
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6
Q

What does the Decay-Accelerating Factor (DAF) do?

A
  • destabilizes C3/C5 convertases of CP and AP
  • blocks C4b:C2 interaction
  • enhances dissociation of C4bC2a
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7
Q

What does Membrane Cofactor Protein (MCP) do?

A
  • cofactor for Factor 1-mediated cleavage of C3b and C4b

- involved with Factor 1 to cleave C3b and C4b, and prevent them from forming active convertases

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8
Q

What does Complement Receptor Type-1 (CR1) do?

A
  • decay accelerating activity as well as cofactor activity Factor 1-mediated cleavage of C3b and C4b
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9
Q

What does MAC Inhibitory Complex (CD59) do?

A
  • blocks C9 association w/C5b-8 to prevent C5b-9 formation on cells
  • also vitronectin and clusterin
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10
Q

What immune cells do C3a and C5a affect?

A

C3a –> mast cell/basophil –> vasoactive substances

C5a –> monocyte/macrophage –> IL-1/IL-6, prostaglandins, ROS/NOS

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11
Q

Glomerulonephritis and Complement

A
  • most glomerular diseases IMMUNOLOGIC in origin
  • deposition of immune complexes/Abs binding to Ags in kidney
  • MAC activates mesangial/epithelial cells –> release proteases; C5a attracts neutrophils
  • ROS/inflammatory cytokine production by attracted inflammatory cells and proteases both play a role in glomerulonephritis
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12
Q

Vasculitis and Complement

A
  • vessel inflammation –> immune-complex deposition or direct Ab interaction (usually immune-mediated mech)
  • immune complexes deposited on vessel walls, causing vasculitis through classical complement pathway
  • seen in patients with hepatitis B/C and SLE (LUPUS)
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13
Q

Hereditary Angioedema (HAE)

A
  • very rare, potentially life-threatening genetic condition
  • edema (hands, feet, THROAT), intense abdominal pain, nausea, vomiting
  • SWELLING OF AIRWAY/THROAT = Asphyxiation
  • defect in gene controlling C1 inhibitor (inactivate enzymes that are NOT part of complement cascade)
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14
Q

What is HAE also known as?

A

C1 Inhibitory Deficiency

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15
Q

What does C1-INH do?

A
  • C1 Inhibitor
  • inactivates enzymes that are not part of complement cascade
  • inactivates plasma kallikrein, which helps produce bradykinin (causes of swelling)
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16
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH) and Complement

A
  • failure to regulate formation of MAC
  • somatic mutation = glycosylphosphatidylinositol deficiency
  • lack GPI anchor proteins DAF (CD55) and CD59, which normally protect RBCs from action of complement
  • intravascular hemolysis is caused by increased susceptibility of RBCs to complement