Complement System

Question 1

Classical Pathway

Answer 1

1. IgM and/or IgG must be bound to pathogen
2. Two heads of C1q bind to IgM/ IgG
3. hydroxylated stalk of C1q when bound causes conformational change that activates C1r
4. C1r, a zymogen, auto-cleaves itself to become active and then cleaves C1s to become active
5. C1s cleaves C4 that is bound to bacteria to C4b
6. C4b binds to C2, the bound C2 then gets cleaved to become C2a, resulting in C4b2a

NB: C4b2a is C3 convertase that converts C3 to C3b

7. C4b2a cleaves C3 to C3b which is powerful opsoninant
8. C4b2a3b is C5 convertase

Question 2

Alternative Pathway

Answer 2

1. C3b that is bound to pathogen recruits Factor B
2. C3bB gets cleaved and activated by Factor D to form C3bBb

NB: C3bBb is C3 convertase

3. C3bBb cleaves C3 to C3b which is potent opsonant
4. C3bBb can combine with C3b to from C3bBb3b
   NB: C3bBb3b is C5 converstase

Question 3

Mannose Binding Lectin

Answer 3

1. Mannose Binding Lectin binds to mannose end of bacterial protein
2. MBL recruits Mannose associate serine protease (MASP) MASP1, MASP2
3. MASP1, MASP2 cleave C4 to C4b and the uses parts of classical pathway to make C4b2a and C4b2a3b

Question 4

Formation of MAC attack

Answer 4

C4b2a3b from classical pathway or
C3bBb3b from alternative pathway cleave C5 to C5b
C5b associates with C6, C7 to form C5b67
C5b67 creates binding site for C8 to form C5b678
C5b678 binds C9 to form
C5b6789

Question 5

Function of MAC attack

Answer 5

C5b6789 creates pore in bacteria membrane

this creates a lesion that causes osmotic lysis

Question 6

Three major contributions of complement system

Answer 6

1. Opsonization of pathogen via IgG and C3b
   leading to greater phagocytosis
2. Formation of C5b6789 MAC attack leading to osmotic lysis
3. Formation of chemotaxins and anaphilotoxins to increase blood flow and increase vascular permeability, increase smooth muscle contraction

Question 7

Types and strength of chemotaxins produced by complement

Answer 7

C5a > C3a > C4a

Question 8

Soluble Inhibitors of Classical Pathway

Answer 8

C1 inhibitor causes dissociation of C1q from C1r and C1s

C4 binding protein: C4BP binds to C4 displacing C2a.
C4BP is cofactor for Factor I which destroys free C4b

Question 9

Soluble Inhibitors of Alternative Pathway

Answer 9

Factor H binds to C3b to displace Bb

Factor I can then destroy C3b

Question 10

Membrane Associated Regulators

Answer 10

Membrane Cofactor protein: breaks down C3 convertase

CD59 inhibits MAC attack

Question 11

C3b Receptor

Answer 11

C3b-CRI
Found on macrophages and neutrophils
RBCs pick up free Antibody/ Antigen Complex + C3b
RBCs clear excess immune complex and deposit them in the spleen to get rid of them

Question 12

Fc Delta RI

Answer 12

Found on Macrophages and APCs

Only binds to Ig when Ig is bound to antigen

Question 13

Fc epsilon R

Answer 13

Found on mast cell and binds to IgE

IgE does not have to be bound to antigen