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Question asked by: romyschulten - 2 years ago

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Maak een oefenexamen van de volgende tekst: MS
- Blood brain barrier disruption
- Immune cell infiltration (monocytes, T-cells and B-cells)
- Demyelination
- MBP: myelin basic protein
- PLP: proteolipid protein
Active Wm lesion
- Myelin loss
- Massive infiltration of monocytes and accumulation of foamy macrophages (main
immune cell in lesions)
- T-cells and B-cells predominantly in the meninges and perivascular space
- Most therapies target the memory B cells
- Hypertrophic astrocytes
Chronic active WM lesion
- Hypocellular lesion center (often depletion of oligodendrocytes)
- Accumulation of immune cells at lesion border
- Hypertrophic astrocytes
Glial scar
- Consist of (reactive) astrocytes
- Targeted ablation of reactive astrocytes worsens clinical signs of EAE mice
- Astrocytes
- Produce glial scar (inhibit infiltration)
- Inhibit oligodendrocyte maturation
- Act immune cells
- Some evidence they can be present antigens thereby activating T and B cells
- Produce cytokines and chemokines
Preactive lesion
- No demyelination, no immune infiltration, activated microglia (due to oligodendrocyte
stress)
Immune cell infiltration
- Increase expression of adhesion molecules (VCAM1, ICAM1)
- Loss of tight junction (Claudin 3,5, Occludin)
- Disruption of the basement membrane
Lesion classification
- Whit matter
- Preactive: no demyelination, no immune infiltration, activated microglia (due
to oligodendrocyte sterss)
- Active: demyelination + immune cell infiltration
- Chronic active: demyelination, immune cells at border
- Chronic inactive: demyelination, no immune cells, glial scar
- Grey matter
- Type 1: mixed white & grey matter
- Type 2: intracortical
- Type 3: extend from the surface inwards
- Type 4: whole width of cortex, does not reach into the white matter
MS classification
- RRMS: relapse remitting MS highest prevalence
- SPMS: secondary progressive MS progression after 10-15 years
- PPMS: primary progressive MS 10-20% of cases
- Outside-in model:
- Primary demyelination in which myelin is destroyed leading to need axons
and neuronal degeneration
- Inside-out model:
- Neurodegeneration as a primary event leads to empty myelin sheaths that
degenerate as a secondary event
Molecular mimicry
- Strong similarity in the structure of foreign and self-peptides allowing T and B cells
become autoreactive
- MHC class II recognised peptide
MBP: myelin basic protein
- EBV: Epstein-Barr virus 90% of individuals worldwide
- The prevalence of MS is only 0,03% worldwide
- Prevalence of EBV among MS is not 100%
Models for MS
- EAE: experimental autoimmune encephalomyelitis
- Induced by injected MOG peptide and activating immune system
- Autoreactive T cells (CD4)
- Paralysis
- No wide spread demyelination
- Cuprizone
- Cuprizonde added to food
- Toxic compound that targets oligodendrocytes
- No clear clinical sign
- Severe demyelination

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