Lec4 Complement Flashcards Preview

Immunology > Lec4 Complement > Flashcards

Flashcards in Lec4 Complement Deck (26):
1

Where are complement proteins produced primarily?

Liver

2

3 major functions of complement

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

3

Mannose binding lectin activation

- lectin is a pattern recognition receptor for mannose
- binds mannose on pathogens and initiates complement activation

4

Classical activation

- cross-linkeed antibody is attached to antigen
- initiates complement activation

5

Alternative pathway activation

- spontaneous breakdown of C3 in serum causes low level activation of complement on pathogen surface
- dominant pathway after initiation

6

What does C3 convertase do?

cleaves C3 --> C3a and C3b

7

What is the central amplification step of complement?

C3 --> C3b repeatedly by C3 convertase
get lots of C3b molecules deposited on surface

8

What 2 factors involved in complement amplification?

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

9

What are 2 anaphylatoxins?

C3a
C5a

10

What are 4 inhibitors of complement

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

11

What 3 regulators inhibit C3 convertase

- Factor H/I
- Decay Accelerating Factor
- Membrane cofactor protein

12

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

- most commonly C9 deficient
- predisposes to fulminant meningitis [neisserial infection]

13

Effect of C3 deficiency [in humans, mice]

- uncommon in humans
- associated with pyogenic infections
- in mice leads to T and B cell dysfunction

14

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

- Factor I, membrane cofactor protein, factor H
- degrades C3b so don't get amplification of signal
- instead get iC3b that is an opsinin

15

C1q inhibitor deficiency [cause, effect]

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

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

16

What deficiency associated with hereditary angioedema?

C1q inhibitor deficiency

17

C1q inhibitor [C1qINH] [function/mech]

regulate complement by:
- blocking classical pathway initiation

18

What is C1q?

protein involved in early stage of classical pathway initiation

19

C1q deficiency [disease associated, mech]

- systemic lupus erythematosis
- normal immune complexes cannot be cleared in absence of C1q
- immune complexes then deposited in tissue

20

Factor H deficiency [effect, 2 diseases]

- 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

Factor H [Function/mech]

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

DAF or CD59 Deficiency [cause, disease]

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

How does HIV subvert complement?

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

24

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

- uses CR2 [CD21] for envelope glycoprotein
- preferentially infects B cells

25

How does group A streptococci subvert complement?

- have M protein that binds factor H and augments it
- prevent local complement activation
- expresses peptidase that inhibits C5a

26

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

- CH50 blood test
- tells you total amount complement proteins but may still have abnormality in just C3 or C4 etc