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PARA438 > L8 complement system > Flashcards

L8 complement system Flashcards

1
Q

what kind of response is the complement?

A

innate humoral response

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2
Q

bordet’s experiment: non-immunized serum with bacteria = …

A

no effect

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3
Q

bordet’s experiment: immunized serum with bacteria = …

A

lysis

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4
Q

immunized serum + heat + bacterium = ….

A

no effect

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5
Q

immunized serum + heat + non-immunized serum + bacterium = …

A

lysis

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6
Q

what kind of proteins is the complement system compromised of?

A

soluble plasma proteins and membrane-bound proteins

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7
Q

what cells are complement proteins synthesized by?

A
  1. hepatocytes (liver cells), main producers
  2. fibroblasts
  3. epithelial cells
  4. monocytes
  5. macrophages
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8
Q

what are the seven functional categories of complement components?

A
  1. initiators
  2. enzymatic inhibitors
  3. phagocytosis-enhancing components/opsonins
  4. inflammatory mediators
  5. membrane attack proteins
  6. complement receptors
  7. regulatory complement components
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9
Q

what do initiators do?

A

initiate complement reactions,
bind to soluble or membrane-bound molecules,
binds to their ligand causing conformational changes = activation

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10
Q

what are enzymatic mediators, and what do they do?

A

cleave proteins (most enzymatic mediators are proteolytic enzymes) to activate = zymogens

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11
Q

what do opsonins do?

A

enhance phagocytosis through binding to the complement receptors on the surface of phagocytic cells

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12
Q

what do inflammatory mediators do?

A

they are smaller cleavage products, and bind to receptors on endothelial cells of blood vessels increasing capillary diameter. they also bind to receptors and attract other cells (chemotaxis)

ex. C3a and C5a

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13
Q

what do membrane attack proteins do?

A

form the membrane attack complex (MAC). they insert themselves in the membranes of microorganisms to punch holes leading to lysis. they can also form on the surface of infected cells

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14
Q

what are complement receptors, and what are the effects of binding to these receptors?

A

abbreviated as “CR”, bind to complement proteins and signal specific cell functions. they can enhance phagocytosis, cell activation, induce degranulation, chemotaxis, and clearance of immune complexes

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15
Q

what do regulatory complement components do?

A

prevent unintended complement-mediated damage of host cells
ex. factor 1 degrade complement components to prevent deposition of components

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16
Q

what are the 3 major pathways of complement activation?

A
  1. classical pathway
  2. lectin pathway
  3. alternative pathway
17
Q

what are the 3 major steps in the pathways of complement activation?

A
  1. initiation
  2. amplification
  3. termination
18
Q

what do all three pathways lead to?

A

all converge to generation of the C3 and C5 convertases

19
Q

what do convertases do?

A

convert C3 and C5 to their active forms

20
Q

what are the steps in the classical pathway?

A
  1. C1q binds antigen-bound antibody. C1r activates auto-catalytically and activates the second C1r; both activate C1s
  2. C1s cleaves C4 and C2. Cleaving C4 exposes the binding site for C2. C4 binds the surface near C1 and C2 binds C4, forming C3 convertase
  3. C3 convertase hydrolyzes many C3 molecules. some combine with C3 convertase to form C5 convertase
  4. the c3b component of C5 convertase binds C5, permitting C4b2a to cleave C5
  5. C5b binds C6, initiating the formation of the MAC
21
Q

how does the lectin pathway work?

A

instead of antibodies, the lectin pathway is initiated through the binding of lectins (MBL, ficolins)

22
Q

how is C3 convertase produced in the lectin pathway?

A
  1. activated MASP-2 associated with MBL or ficolin cleaves C4 to C4a and C4b, which binds to the microbial surface
  2. C4b then binds to C2, which is cleaved by MASP-2, to C2a and C2b, forming the C4b2a complex = C3 convertase
23
Q

how is C5 convertase created?

A

C3b binds to C4b2a

24
Q

what is the alternative pathway?

A
  1. C3b is deposited by classical or lectin pathway C3 convertase
  2. C3b binds factor B
  3. bound factor B is cleaved by plasma protease factor D into Ba and Bb
  4. C3bBb complex is a C3 convertase, cleaving many C3 molecules to C3a and C3b
25
Q

what are the C3 convertase of each pathway?

A

classical : C4b2a
alternative: C3bBb
lectin: C4b2a

26
Q

what are the C5 convertases of each pathway?

A

classical: C4b2a3b
alternative: C3bBb3b
lectin: C4b2a3b

PARA438 (14 decks)

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