6.4 immunology of demyelinating disorders

Question 1

MS

Answer 1

1. Autoimmune, inflammatory disease affecting myelin sheaths in the CNS, loss of oligodendrocytes; astrogliosis
2. Relapsing/remitting or progressive disease
3. Etiology – unknown
   - -> Disease develops in genetically susceptible individuals exposed to environmental triggers

Question 2

evidence that MS is autoimmune

Answer 2

1. Auto-reactive T lymphocytes
2. Autoantibodies
3. Genetic associations
   (MHC, Other)
4. Response to immunotherapies

Question 3

role of infection in developing MS

Answer 3

1. happens in genetically susceptible individuals that have had a viral infection
2. Infectious agents: (Persistent viral infections)
3. Mechanisms of tolerance abrogation (Molecular mimicry Bystander activation)

Question 4

genetic association with MS

Answer 4

1. Association with HLA-DR-B1, DQ-A1 and DQ-A2
2. Other: MHC class I (HLA-A3; HLA-B7)
   IL receptor genes (IL-2R; IL-7R)

Question 5

MS: steps for pathogenesis

Answer 5

1. Myelin peptides inserted in the cleft of HLA I and II (dendritic cells) –> 2. Dendritic cells migrate to local lymph nodes –> 4. T lymphocytes test displayed peptides –> 5. T lymphocytes that bind are activated –> 6. Activated T lymphocytes cross blood brain barrier –> now Autoantibodies against myelin antigens

Question 6

what does the presence of oligoclonal bands in CSF mean?

Answer 6

Oligoclonal bands represent the presence of monoclonal antibodies produced by intrathecal B cells

Question 7

there are 8 treatment modalities for MS. see if you can name them.

Answer 7

1.Inhibit inflammation – corticosteroids; plasma exchange
2. Interfere with adhesion molecules – IFN-β; natalizumab
3. Skew response to Th2 and interfere with HLA presentation of MBP peptides-glatinamir acetate
4. Suppress the immune response-mitoxantrone
Investigational treatments:
5. Decrease inflammation – statins
6. Decrease T cell activity – monoclonal antibody against CD25
7. Decrease B cells – monoclonal antibody against CD20
8. Decrease T cells-monoclonal antibody against CD52

Question 8

what are some symptoms for Guillain-Barré? and what is it? what symptoms precede it?

Answer 8

1. Acute demyelinating polyneuropathy
2. Ascending motor weakness
3. Areflexia
4. Some sensory deficit
5. Usually preceded by flu-like symptoms
6. Associated with viral and bacterial infections

Question 9

Immunopathology for Guillain-Barre:

Answer 9

1. Viral or bacterial infection: (Campylobacter jejuni, Cross reactivity/molecular mimicry)
2. Antigens (Schwann cell myelin (glycolipids; glycosphingolipids), Neuronal cell membrane (gangliosides), Myelin associated proteins)

Question 10

activation of immune process in G-B:

Answer 10

1. Myelin proteins phagocytized by macrophages – peptides prepared –>
2. CD4+ T cells recognize peptides displayed by APC (HLA II molecules) –>
3. Activated T cells mature into TH1, TH2 or TH17 lymphocytes –>
4. CD8+ T cells, B cells and/or inflammatory cells recruited and activated

Question 11

what causes damage in G-B?

Answer 11

1. Macrophages, lymphocytes infiltrate nerve –>
2. Peripheral nerves demyelinated –>
3. Muscle action potentials blocked