C' Pathways

3 steps of classical pathway

1. Recognition

2. Activation

3. Membrane attack complex

Classical pathway recognition (2)

1. C' protein needs to react with 2 Ab molecules in the Fc receptor (theme of cross-linking)

2. C1q binds Fc receptors of Ab molecules that are bound to a foreign substance. This changes the conformation of C1r to activate C1s

Classical pathway activation (9)

1. Activated C1s cleaves C4

2. Now, Ca and C4b (b stays at the site and a goes away)

3. C4b deposit at Ag site

4. C2 comes along and is cleaved by C1s

5. Now, C4b2a formed (C3 convertase! Can have different components)

6. C3 convertase goes after C3 (most abundant protein) → hydrolyzed → C3a, and C3b

7. C3b added to C3 convertase → now C5 convertase (C4b2a3b)

8. C5 convertase goes after C5, splits them → C5a and C5b

9. C5b inserts into the membrane of Ag/microbe

DRAW OUT?

Classical pathway membrane attack complex (2)(1)

1. 6,7.8,9 add to that to form the membrane attack complex

   1. Complex works the same way in the alternative pathway

2. Angstrom (pore) formed

Lectin (MBL) uses

1. uses mannose/carb

2. Does NOT require Ab

Lectin (MBL) is big in

1. Big in neonates

MASPs

Take on the role of C1r and C1S

(Other components take on the role of C1q)

When mannose/ carb bound, what happens

1. it starts building C3 convertase, which can hydrolyze (cleave)

2. Same format as classical, just no Ab needed like classical

Alternative pathway is good for

Neonates

What is needed for alternative pathway?

No Ab needed

Just Ag and functional c' needed 

3 unique molecules in alternative pathway

properdin (P)

factor B (Bb)

Factor D

Alternative pathway steps (9)

1. C3 can be hydrolyzed by water here, C3b - binds to Ag -the  recipient of factor B (can grab/bind)

2. Factor D cleaves factor B. Factor D is not common in the serum-regulatory mechanism

3. Forms Bb

4. C3bBb is the C3 convertase in this system

5. Properdin comes in to stabilize C3 convertase

6. СЗbВbР → СЗbВbРЗb C5 convertase

7. Initially cleaves C5 into C5a and C5b

8. C5b adds itself to Ag

9. Sticks with 6,7,8,9 that are added → membrane attack complex

DRAW OUT