4.6 Multiple Sclerosis Flashcards
Typical age of onset of MS is…
20-40 years old
What are the four disease courses of MS (names)?
- Primary progressive
- Secondary progressive
- Relapsing remitting
- Progressive relapsing
What is the most common MS disease course?
Relapsing remitting
Describe the progression of relapsing remitting MS
- Sudden increase in disability
- This gets better with time, leading to a period of remission, with disability still worse than pre-spike
- Repeats
Describe the course of primary progressive MS
Linear increase in disease; no relapses
Describe secondary progressive MS
After a period of relapsing remitting MS, moves to linear progression
Describe progressive relapsing MS
Relapse spikes, separated by linear increases in disability.
Specifically, which parts of the peripheral nervous system are affected by MS?
- None
- CNS only
Describe the pathophysiology of MS, and link this to disease process. What causes worsening/remission of the disease?
- Inflammation of CNS leads to release of inflammatory mediators, infiltration of CD8 T cells that kill oligodendrocytes, and B cells whose antibodies bind to myelin
- Leads to demyelination and oligodendrocyte death
- Remyelination (this is our “remission”, so in RR MS it goes back and forth here)
- Eventually, the mechanisms of remyelination may become exhausted (nutrients, growth factors, progenitors etc.), leading to dysfunction, and neuronal death (permanent disability)
List some different symptoms of MS
- Motor: spasms, weakness, balance/coordination issues
- Fatigue
- Vertigo, pins and needles, neuralgia
- Bladder incontinence/constipation
- Memory loss, depression, cognitive difficulties
If someone has an identical twin who has MS, their chance of developing the disease is…
50%
True or false: presence of another autoimmune disease increases MS risk
True :(
What are some environmental factors that can drive MS?
- Smoking
- Sunlight (more sun -> less MS)
- Viral infection
- Diet
What is the role of CD4 T Cells in the pathogenesis of MS?
- Release inflammatory cytokines
- Damaging the blood brain barrier and recruiting neutrophils, monocytes, and macrophages
Which cytokines to CD4 T cells release that are involved in the pathogenesis of MS?
- IL-17 (neutrophil recruitment)
- Interferon Gamma (activates CD8 cells and macrophages)
- Granulocyte-macrophage colony stimulating factor (GM CSF)
What are the subsets of CD4 T cells important for the pathogenesis of MS?
Th1 and Th17
What is the role of CD8 T cells in the pathogenesis of MS?
Cytotoxic to oligodendrocytes
What is the role of B cells in the pathogenesis of MS?
- Produce antibodies that bind to and destroy myelin
- Present antigen to CD4 T Cells
Where is it thought that autoreactive lymphocytes first gain access to the CNS?
Through the choroid plexus
How does closeness to the equator link to risk of MS (this is very cool)?
- Closer to the equator = more sunlight
- More sunlight = lower risk of MS
- Therefore, the closer we get to the equator, the lower the risk of MS
What are some potential reasons why vitamin D might decrease the risk of MS?
- Strengthens immune system
- Influences cytokine expression
- Increase production of immunosuppressive factors in CNS
Which two viruses are most associated with the development of MS?
- Epstein Barr virus
- Herpes Human Virus 6
Name 3 pharamacological treatments for MS prevention, and give a very brief outline of their mechanisms where applicable.
- Beta interferon (alters T cell activity)
- Glatiramer acetate (unknown)
- Dimethyl fumarate (anti inflammatory)
In terms of monoclonal antibodies for MS therapy: as we progress through first/second/third line therapy, what happens to safety and efficacy?
- Safety decreases
- Efficacy increases
What factors allow the CNS to be an “immune privileged” site?
- Blood brain barrier
- Lack of lymphatic drainage
- Limited expression of MHC molecules
What is the role of T regulatory cells in MS?
Loss of regulation of autoreactive B cells and CD8 T cells -> CNS inflammation
In terms of B cells, how might EBV worsen MS?
- Latent memory of infection resides in memory B cells
- Leads to larger autoimmune response within CNS
