MULTIPLE SCLEROSIS
MICRB 410 – 001
WHAT IS MS?
• autoimmune disorder  destruction of myelin sheath that protects
nerve cells; mediated by CD4 T cells
myelin basic
protein (MBP)
proteolipid
protein (PLP)
• Etiology is mostly unknown
myelin
oligodendrocyte
glycoprotein (MOG)
• molecular mimicry: MBP  measles, hepatitis B, influenza virus
• can activate myelin-reactive T cells (Steinman, 1996)
• Sclerosis = lesions from deteriorated myelin sheath
MECHANISM OF MS
Image from: Janeway’s Immunobiology, 9th ed.
MECHANISM OF MS
• Inflammation causes T cells express α4:β1 AND
VLA-4
• binds to VCAMs on HEV
• T cells encounter self-antigen presented on
MHC II from microglial cells, the “macrophages”
of the CNS, which act as APCs
Image from: Janeway’s Immunobiology, 9th ed.
2
MECHANISM OF MS
• Site is infiltrated by IL-17 and IFN-γ  activates
myeloid lineage cells
3
• B cells will produce antibodies against MBP, PLP,
and MOG
• Mast cells will be activated
• This results in demyelination
Image from: Janeway’s Immunobiology, 9th ed.
IMMUNOLOGICALLY PRIVILEGED SITES
• Tissue barriers prevent immune cells from
entering/interacting with antigen
• Antigens should induce T cell tolerance
• Self-reactive T cells may not have been
clonally deleted
Image from: www.verywellhealth.com
PREVALENCE OF MS
• Twice as likely in women than men
• 309 cases per 100,000 (as of 2010)
• Average age at symptoms onset: 28.5
yo (Wallin et al., 2019)
• Incidence of disease decreases from
northern latitudes to southern
• Tied to vitamin D production (Munger
et al., 2006)
Image from: Wallin et al., 2019
CLINICAL SIGNS OF MS
• Double-vision, color
distortion, blindness
• Muscle weakness,
difficulty with
balance, paralysis,
paresthesia, speech
impediments
• Difficulty with
concentration,
memory, attention
• Depression
Image from: http://sharpbrains.com/wp-content/uploads/2016/04/MS-around-the-world-prevalence-800x506.jpg
TREATMENTS FOR MS
FINGOLIMOD
NATALIZUMAB
sphingosine-phosphate analog that
causes retention of lymphoid cells in
lymph nodes; prevents cell migration
by preventing recognition of S1P
gradients (Kappos et al., 2010)
a humanized antibody directed against
α4:β1 which blocks adhesive
interactions to endothelial cells
preventing cells from entering tissues
(Miller et al., 2003)
NATALIZUMAB
TREATMENTS FOR MS
There is no cure for MS, only treatments to reduce the severity or number of relapses.
HOWEVER, people with MS can lead long, fulfilling lives with proper treatment.
CITATIONS
Coles, A., Deans, J., & Compston, A. (2004). Campath-1H treatment of multiple sclerosis: Lessons from the bedside for
the bench. Clinical Neurology and Neurosurgery, 106(3), 270–274. https://doi.org/10.1016/j.clineuro.2004.02.013
Kappos, L., Radue, E.-W., O’Connor, P., Polman, C., Hohlfeld, R., Calabresi, P., … Burtin, P. (2010). A Placebo-Controlled
Trial of Oral Fingolimod in Relapsing Multiple Sclerosis. New England Journal of Medicine, 362(5), 387–401. https://doi.org/10.1056/NEJMoa0909494
Miller, D. H., Khan, O. A., Sheremata, W. A., Blumhardt, L. D., Rice, G. P. A., Libonati, M. A., … O’Connor, P. W. (2003). A
Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. New England Journal of Medicine, 348(1), 15–23. https://doi.org/10.1056/NEJMoa020696
Multiple Sclerosis Information Page | National Institute of Neurological Disorders and Stroke. (2019). Retrieved November
27, 2019, from https://www.ninds.nih.gov/Disorders/All-Disorders/Multiple-Sclerosis-Information-Page#disorders-r1
Munger, K. L., Levin, L. I., Hollis, B. W., Howard, N. S., & Ascherio, A. (2006). Serum 25-hydroxyvitamin D levels and risk
of multiple sclerosis. Journal of the American Medical Association, 296(23), 2832–2838. https://doi.org/10.1001/jama.296.23.2832
Steinman, L. (1996). Multiple Sclerosis: A Coordinated Review Immunological Attack against Myelin in the Central
Nervous System. In Cell (Vol. 85). Stanford.
Wallin, M. T., Culpepper, W. J., Campbell, J. D., Nelson, L. M., Langer-Gould, A., Marrie, R. A., … Larocca, N. G. (2019).
The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology, 92(10), E1029–E1040.
https://doi.org/10.1212/WNL.0000000000007035
QUESTIONS?