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

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.

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

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

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

Triggers5 Stress Smoking Heat Medications Fatigue

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

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

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

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.

Normal vs. MS Nerve Cells4 13 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

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

There are different Pathways leading to Ms 4 There are different Pathways leading to Ms

T cell entrance through the blood brain barrier

Antibody production against Myelin Sheaths

Cytokine production

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

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

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

References 1. https://rarediseases.info.nih.gov/diseases/10255/multiple-sclerosis 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): e29819. doi:10.1371/journal.pone.0029819 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. 2017. 4. https://www.nature.com/articles/nri1108 5. https://health.clevelandclinic.org/2015/04/avoid-8-common-triggers-to-make-your-life-with-ms-easier/ 6. "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.008. ISSN 2002-4436. 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. https://www.drugs.com/condition/multiple-sclerosis.html?category_id=284&include_rx=true&include_otc=true&show_off_label=true&submitted=true 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 11. https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=349 12. https://biologydictionary.net/myelin-sheath/ 13. https://www.thenakedscientists.com/forum/index.php?topic=6663.0