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Immunology > Lec4 Complement > Flashcards

Lec4 Complement Flashcards

1
Q

Where are complement proteins produced primarily?

A

Liver

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2
Q

3 major functions of complement

A
  1. innate immunity [pattern recognition receptors, facilitate killing and disposal of pathogens]
  2. waste disposal [clearance immune complexes and apoptotic cells]
  3. bridge innate and adaptive immunity
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3
Q

Mannose binding lectin activation

A
  • lectin is a pattern recognition receptor for mannose

- binds mannose on pathogens and initiates complement activation

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4
Q

Classical activation

A
  • cross-linkeed antibody is attached to antigen

- initiates complement activation

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5
Q

Alternative pathway activation

A
  • spontaneous breakdown of C3 in serum causes low level activation of complement on pathogen surface
  • dominant pathway after initiation
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6
Q

What does C3 convertase do?

A

cleaves C3 –> C3a and C3b

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7
Q

What is the central amplification step of complement?

A

C3 –> C3b repeatedly by C3 convertase

get lots of C3b molecules deposited on surface

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8
Q

What 2 factors involved in complement amplification?

A

factor B and D bind C3b on cell surface [regardless of how it got there] and amplify downstream complement

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9
Q

What are 2 anaphylatoxins?

A

C3a

C5a

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10
Q

What are 4 inhibitors of complement

A
  1. C1q inhibitor
  2. Factor H
  3. Decary accelerating factor [CD55]
  4. CD59 [protectin]
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11
Q

What 3 regulators inhibit C3 convertase

A
  • Factor H/I
  • Decay Accelerating Factor
  • Membrane cofactor protein
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12
Q

MAC protein deficiency [which component most commonly deficient, effect]

A
  • most commonly C9 deficient

- predisposes to fulminant meningitis [neisserial infection]

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13
Q

Effect of C3 deficiency [in humans, mice]

A
  • uncommon in humans
  • associated with pyogenic infections
  • in mice leads to T and B cell dysfunction
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14
Q

What set of 3 cofactors degrades C3b? What is function of resulting product?

A
  • Factor I, membrane cofactor protein, factor H
  • degrades C3b so don’t get amplification of signal
  • instead get iC3b that is an opsinin
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15
Q

C1q inhibitor deficiency [cause, effect]

A

cause: genetic deficiecny [multiple mutations] or autoantibodies [acquired]

effect: hereditary angioedema
- - get swelling without uticaria in skin, mucosal tissue of GI and upper respiratory

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16
Q

What deficiency associated with hereditary angioedema?

A

C1q inhibitor deficiency

17
Q

C1q inhibitor [C1qINH] [function/mech]

A

regulate complement by:

- blocking classical pathway initiation

18
Q

What is C1q?

A

protein involved in early stage of classical pathway initiation

19
Q

C1q deficiency [disease associated, mech]

A
  • systemic lupus erythematosis
  • normal immune complexes cannot be cleared in absence of C1q
  • immune complexes then deposited in tissue
20
Q

Factor H deficiency [effect, 2 diseases]

A
  • local complement activation at exposed basement membranes [because factor H normally protects against this]
  • hemolytic uremic syndrome [kidney disease + intravascular hemolysis]
  • macular degeneration [eye]
21
Q

Factor H [Function/mech]

A

regulate complement by:

  • inactivating C3 and C4 convertases
  • works with factor I and membrane cofactor protein
  • protects from complement activation in exposed basement membrane [kidney, eye]
22
Q

DAF or CD59 Deficiency [cause, disease]

A

cause: mutations that prevents attachment GPI anchor [that is mech of how DAF and CD59 insert into cell surface] in some cells [including RBCs]
- get no DAF or CD59 expression

Disease: paroxysmal nocturnal hemoglobinuria – blood in urine, hemolysis

23
Q

How does HIV subvert complement?

A
  • allows activation and depostion of C3b on surface
  • have regulators to prevent amplification
  • C3b acts as opsinin so allows virus to enter cell
24
Q

How does Epstein Barr subvert complement? What cells does it usually infect?

A
  • uses CR2 [CD21] for envelope glycoprotein

- preferentially infects B cells

25
Q

How does group A streptococci subvert complement?

A
  • have M protein that binds factor H and augments it
  • prevent local complement activation
  • expresses peptidase that inhibits C5a
26
Q

How to measure amount of complement proteins? What does this test tell you?

A
  • CH50 blood test

- tells you total amount complement proteins but may still have abnormality in just C3 or C4 etc

Immunology (17 decks)

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