IMMUNOPATHOGENESIS

1. Multiple Sclerosis,pathogenesis
M. MAHDY

2. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)

3. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)
• Pathophysiology of MS symptoms

4. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)
• Pathophysiology of MS symptoms
• Enigmatic aspects of pathogenesis

5. WE SHOULD CATCH UPTHESE POINTS
• Pathogenesis of MS (IMMUNO-PATHOGENESIS)
• Pathophysiology of MS symptoms
• Enigmatic aspects of pathogenesis
• Remyelination

6. Senior must help
junior

7. LIFE OFT

8. T cell activation

9. Step 1
• Reactivation ofT cells
T cell
+
APC
CD 4
CD8

10. Step 2
• T cell adhesion
VLA4
Vasc.
Endoth.
M
M
P

11. Step 3
• Crossing BBB BRAINTISSUE

12. Step 4
• CNS reactivation

13. Step 5
• T cell differentiation

15. Step 6
• Oligodendrocyte death and demyelination

16. Step 5
• Oligodendrocyte death and demyelination

17. Step 5
• Oligodendrocyte death and demyelination
CD8

18. Step 5
• Oligodendrocyte death and demyelination
CD8
OLG
apoptosis

19. Step 7
• Axonal damage

20. • Axonal damage
B Cell

21. • Axonal damage
B Cell
Plasma
cell

22. • Axonal damage
B Cell
Plasma
cell
comp

23. • Axonal damage
B Cell
Plasma
cell
comp
macrophage

24. • Axonal damage
B Cell
Plasma
cell
comp
macrophage
Axonaldamage

27. Extravasation
astrocytes BRAIN
TISSUE
MY E L I N
oligodendrocyte
B cell
Rolling Adhesion
a4 Integrin
VCAM
B L O O D F L O W
LUMEN OF
VENULE
B A S A L L A M I N A
Circulation
ActivatedT cell
Proteases
Antigen presenting cell
(Astrocyte or Microglial cell)
Activated
microglia/macro
phages
T CELL
REACTIVATI
ON
Activated
Macrophage
Autoantibodies
Complement
IL-1, IL-12,
chemokines
Cytokines and
chemokines
Proteases
TNF-a
O2
•-
NO•
AXONAL
DAMAGE
MS Disease Pathology

28. Pathogenesis of remyelination
• Cytokine wash

29. Pathogenesis of remyelination
• Cytokine wash
• Resolved conduction block

30. Pathogenesis of remyelination
• Cytokine wash
• Resolved conduction block
• Rearrangement of Na channels at
nodes of ranvier &naked axons

31. Pathophysiology of symptoms
Uthoff’sL’hermitteparathesiafatigue

32. Fatigue
• Fast trains of impulses cannot be
transmitted by partially
demyelinated axons
Parathesia
• partially demyelinated axons can
discharge spontaneously

33. L’hermitte
• Increased mechanical sensitivity
Uhthoff’s
• Increased temp sensitivity,
reduction of safety factor in
partially demyelinated axons and
decreased synaptic transmission

34. Paroxysmal symptoms
• Ephaptic transmission

35. Enigmatic aspects
• Areas of demyelination can be clinically
silent.
• Areas without demyelination can produce
symptoms
• Discrepancy between :
• anatomical correlation of symptoms
and signs analysis and radiological findings