Lec4 Complement

Question 1

Where are complement proteins produced primarily?

Answer 1

Liver

Question 2

3 major functions of complement

Answer 2

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

Question 3

Mannose binding lectin activation

Answer 3

• lectin is a pattern recognition receptor for mannose

- binds mannose on pathogens and initiates complement activation

Question 4

Classical activation

Answer 4

• cross-linkeed antibody is attached to antigen

- initiates complement activation

Question 5

Alternative pathway activation

Answer 5

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

Question 6

What does C3 convertase do?

Answer 6

cleaves C3 –> C3a and C3b

Question 7

What is the central amplification step of complement?

Answer 7

C3 –> C3b repeatedly by C3 convertase

get lots of C3b molecules deposited on surface

Question 8

What 2 factors involved in complement amplification?

Answer 8

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

Question 9

What are 2 anaphylatoxins?

Answer 9

C3a

C5a

Question 10

What are 4 inhibitors of complement

Answer 10

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

Question 11

What 3 regulators inhibit C3 convertase

Answer 11

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

Question 12

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

Answer 12

• most commonly C9 deficient

- predisposes to fulminant meningitis [neisserial infection]

Question 13

Effect of C3 deficiency [in humans, mice]

Answer 13

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

Question 14

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

Answer 14

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

Question 15

C1q inhibitor deficiency [cause, effect]

Answer 15

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

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

Question 16

What deficiency associated with hereditary angioedema?

Answer 16

C1q inhibitor deficiency

Question 17

C1q inhibitor [C1qINH] [function/mech]

Answer 17

regulate complement by:

- blocking classical pathway initiation

Question 18

What is C1q?

Answer 18

protein involved in early stage of classical pathway initiation

Question 19

C1q deficiency [disease associated, mech]

Answer 19

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

Question 20

Factor H deficiency [effect, 2 diseases]

Answer 20

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

Question 21

Factor H [Function/mech]

Answer 21

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]

Question 22

DAF or CD59 Deficiency [cause, disease]

Answer 22

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

Question 23

How does HIV subvert complement?

Answer 23

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

Question 24

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

Answer 24

• uses CR2 [CD21] for envelope glycoprotein

- preferentially infects B cells

Question 25

How does group A streptococci subvert complement?

Answer 25

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

Question 26

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

Answer 26

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