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Spring 2022 > BIOL 435 Ch. 5 Part One (The Complement System) > Flashcards

BIOL 435 Ch. 5 Part One (The Complement System) Flashcards

1
Q

complement (C’) system

A
  • group of serum proteins circulating in inactive form

- once activated, multiple possible outcomes

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2
Q

multiple possilbe outcomes (C’ system activated)

A
  • target cell membrance lysis (MAC)
  • chemotaxis
  • opsonization to enhance phagocytosis
  • inflammation
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3
Q

functional categories of C’ proteins

A
  • initiators
  • convertase activators
  • enzymatic mediators
  • opsonins
  • anaphylatoxins
  • membrance attack complex
  • complement receptors
  • regulators
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4
Q

3 pathways in C’ system

A

-classical
-lectin
-alternative
*all generate C3b
>an important, multifunctional C’ protein

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5
Q

classical pathway

A

-IgM or IgG binds to a multivalent Ag
>allows binding of C1q
-C1 finds Fc on adjacent IgG molecules or IgM bound to Ag
*need at least 2 Ab

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6
Q

binding of C1q

A

-begins the process of C’ deposition

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7
Q

C1qr2s2

A

-inititates a cascade of reactions enabling the next reaction in the sequence

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8
Q

C1 binding followed by

A
  • cleavage of C4: C4b bound to pathogen membrane
  • then cleaveage of C2
  • C4b2a
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9
Q

C4b2a

A

-bound to cell surface
=C3 convertase
-cleaves many C3 proteins

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10
Q

C5 convertase

A

=C4b2a3b

  • C3 converts and C3 proteins
  • cleaves C5 protein
  • embedded in membrane
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11
Q

C3a and C5a

A

-anaphylotoxin: promotes inflammation

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12
Q

when C4 is cleaved

A

-a thioester bond is exposed on C4b (or C3b)
>reactive
>binds amino groups on target surface
>bonding must happen quickly
-if no target is present, bond is hydrolyzed and rendered inert
*90% don’t get bound

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13
Q

C3b (+C4b)

A
  • bind microbial surfaces: opsonization
  • attach to Fc of Ab
  • bind Fc receptors on macrophages and RBC and are cleared
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14
Q

Ag

A

-large
-substance that generates an immune response
-a single Ag, may have many BCR specific for it
>only a small part binds to BCR/Ab

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15
Q

epitopes

A

-antegenic determinant
-1 to 6 monosaccharides
-5 to 8 AAs
-small pieces of Ag
-any Ag can have multiple of them
-based on shape or linear sequence
>may ‘change’ when Ag changes shape

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16
Q

C1r

A

-cleaves the other C1r, then cleaves C1s2

>C4 clevage

17
Q

C5b

A
  • embedded in membrane

- begins membrance attack complex (MAC)

18
Q

common components in all 3 pathways

A
  1. *C3b: opsonin
  2. MAC
  3. C3a and C5a: anaphylotoxin
19
Q

Ag/Ab complexes/clusters

A

-bring together all Ag and make them more visible

>more likely to be cleared

20
Q

lectin pathway initated

A

-when soluble proteins recognize microbial CHO antigens

21
Q

lectins

A
  • bind to microbial surfaces
  • serve as docking sites for MBL-associated serine proteases (MASPs)
    ex. MBL
22
Q

MASPs

A

-MBL-associated serine proteases
-cleave C4 and C2 to form the C3 convertase
>subsequent steps are same as the classical pathway (forms C5 convertase)

23
Q

3 ways alternative C’ pathway is initiated

A
  1. Tickover pathway
  2. Properdin-activated pathway
  3. Protease-activated pathway
24
Q

alternative C’ pathway no matter how it starts

A
  • actived C3b binds to membrane of target cell
  • factor B (fB) binds and is cleaved by factor D (fD) =Bb
  • C3bBb=C3 convertase
  • Properdin (fP) stabilizes the C3 convetase
25
Q

tickover pathway-always on

A

-C3 is constantly made and inactivated
1. Spontaneous hydrolysis of C3=C3(H2O)
2. C3(H2O) bind fB
3. fB is cleaved by fD
4. C3(H2O)Bb is a ‘fluid-phase convertase’
>cleaves C3

26
Q

tickover pathway if membrane around

A
  1. Some C3b bind to microbial surface
  2. C3b binds fB
    >cleaved by fD=C3bBb
  3. C3bBb=membrane bound C3 convertase
    >stabilized by Properdin
  4. Another C3b binds
    >C3bBbC3b formed=C5 convertase
27
Q

Properdin pathway

A
  1. Properdin can directly bind to a surface
  2. Can recruit C3b and fB
    >fD recruited, cleaving fB into Bb
  3. C3bPBb=active C3 convertase
  4. Identical to tickover pathway
28
Q

protease-activated pathway

A

-initiation of clotting cascades can stimulate cleave of C’ proteins
>thrombin cleaves C3 and C5
>platelet activation
*strong inflammatory reactions could activate C’ systems

29
Q

platelet activation

A

-releases ATP, calcium ions and serine/theronine kinases

>can stabilize C3b in fluid phase

30
Q

C5 initiates

A

-generation of MAC

31
Q

MAC

A
  • membrane attack complex
  • result of deposition of C5b, C6, C7, C8 and C9 in target cell membrane =pore structure
  • disrupts osmotic integrity, resulting in cell death
32
Q

MAC formation

A
  • C6 embeds
  • C7 embeds
  • C8 all the way through
  • C9 produce massive hole: many of them come together
33
Q

cell ‘fights’ MAC

A
  • endocytosis if only a few

- exocytosis and release them

Spring 2022 (54 decks)

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