1. Belle Huffman Biology 430 Dr. Spilatro
Multiple Sclerosis
Belle Huffman
Biology 430
Dr. Spilatro

2. Multiple Sclerosis Disabling disease of the central nervous system.
The immune system attacks the myelin sheaths.
which are protective coatings around nerve fibers.
These help to promote efficient transmission of a nerve impulse along the axons in the CNS.

3. Autoimmune disease1 the prefix “auto” means “self”
No specific antigen has yet been identified in MS.
Instead the immune system is attacking structures and cells to the CNS. 
— means that the immune system is reacting against normally-occurring antigens in the body

4. Epidemiology
More than 2.3 million people are affected with MS worldwide.1
More than two to three times as many women.1
Relative Risk: 15.7-DQB1, 5.2-DRB5 and 8.3-DRB12

5. Risk Factors HLA-DRB1*1501 gene highly expressed2
Environmental factors3
Exposure to the Epstein-Barr virus3
Low levels of vitamin D3
Smoking3

6. Triggers5
Stress
Smoking
Heat
Medications
Fatigue

7. Classic symptoms1 6 Walking Difficulties Numbness or Tingling Weakness
Vision Problems
Cognitive Changes
Pain
Less Common Symptoms
Speech Problems
Swallowing Problems
Tremors
Seizures
Breathing Problems
Headaches
Hearing Loss

8. Secondary Symptoms These occur from primary problems
Example: Bladder dysfunction causes UTI
Tertiary Symptoms
“Trickle down” effects of the disease
Example: No longer walk or drive, you may not be able to have your normal job

9. 4 Types of MS1 Clinically Isolated Syndrome (CIS)
Relapsing-remitting MS (RRMS)
Primary progressive MS (PPMS)
Secondary progressive MS (SPMS)

10. Will focus on Relapsing-remitting MS (RRMS)1
85% of people with MS have RRMS.
Clear distinct attacks with remissions.
Active vs. Non Active.
Worsening vs. Not Worsening.

11. Normal vs. MS Nerve Cells413
Image of normal nerve cells vs nerve in multiple sclerosis. Talk about how the T cells of the immune system (possible B cells) are what attacks the myelin sheath causes nerve impulses to be slowed or halted and produces the symptoms of MS. 12

12. Myelin basic protein 7 MBP7 Molecular mimicry 7
T cells confusing MBP with viruses

13. There are different Pathways leading to Ms4
There are different Pathways leading to Ms

14. T cell entrance through the blood brain barrier

15. Antibody production against Myelin Sheaths

16. Cytokine production

17. Cytokine Administration
Targets-DC
Inhibits autoantigen presentation
T cell migration
Th17 cell differentiation
I am going to talk about each of these and how they are going to interact with the pathway show above
Table 19-3 in book

18. Targeting of Autoreactive T cells and B cells
Targets CD52
T cell depletion and B cell depletion

19. Extravasation Target CD49d Disruptions of T cell trafficking
Target a4b1 and a4b7 integrin
Disruptions of leukocyte extravasation

20. References 1.
2. Alcina A, Abad-Grau MdM, Fedetz M, Izquierdo G, Lucas M, et al. (2012) Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations. PLoS ONE 7(1): e doi: /journal.pone
3.O’Gorman, Cullen, Robyn Lucas, and Bruce Taylor. “Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms.” International Journal of Molecular Sciences 13.9 (2012): 11718–11752. PMC. Web. 20 Nov 4. 5.
6. "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI: /wjm/  ISSN   Public Domain.
7.  Tejada-Simon, Maria (2003). "Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosi". Annals of Neurology. 53 (2): 189–97. 8.
9. K. Kakalacheva et al. / Biochimica et Biophysica Acta 1812 (2011) 132–140
10. M. Severa et al. / Cytokine & Growth Factor Reviews 26 (2015) 229–239
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