4) Multiple Sclerosis Flashcards
What is the average age of onset?
30 to 40 years
Ethnicity is a factor in susceptibility. What ethnicity is most at risk and what occurs when a person moves to a new area?
Northern Europeans and North Americans.
If a person moves to one of these areas before the age of 15, the take on the susceptibility risk of the region.
What is the ratio of women to men who are affected by MS?
3:1
If one identical twin has MS the other twins has a 31% increased risk of developing it. What is the percentage when you have a first degree relative even though MS is not a hereditary disease?
5% or 20 to 40 times more likely
What are the 3 theories of MS development
Infectious theory
Molecular Mimicry
Autoimmune disease
What are the three antigen presenting cells?
Macrophages, monocytes and dendritic cells
Antigen-presenting cells work as blood filters and once they grab a protein that looks similar to myelin, what occurs?
It presents it to a naive Helper T-cell, allowing T-cells to differentiate in to an inflammatory TH-1 cell which drives the autoimmune inflammatory response.
What is MS on a molecular level?
It is the over activation of proliferation of inflammatory TH-1 cells activated by foreign product.
There is an imbalance of between the TH1 and TH2 cells in the blood in what amounts?
More TH-1 cells in comparison to TH-2 cells
What type of cell are TH-2 cells?
Anti-inflammatory
What does immune deviation mean in relation to MS?
There are more pro-inflammatory TH-1 cells then there are anti-inflammatory TH-2 cells that never restores itself.
What predominant inflammatory mediators do active TH-1 cells release?
Tumor necrosis factor alpha (TNF-a) Interleukin 12 (IL-1) Interferon gamma (IFN-g)
What do the mediators of inflammation do?
They induce positive feedback of proliferation to make more TH-1 cells active, all because of 1 type of foreign protein that looks like myelin cells
Mediators of inflammation from original activated TH-1 cell not only activate more TH-1 cells but also cause what to occur?
Cause the up regulation of adhesion molecules on the surface of the endothelial lining of blood brain barrier.
Mediators of inflammation cause lining of blood brain barrier to be sticky causing what to stick?
TH-1 molecules which create more adhesion molecules and inflammatory mediators.
What are Metalloproteases activated by?
Mediators of inflammation
Mediators of inflammation cause three main things. What are they?
Proliferation of more TH-1
Up regulation of adhesion molecules
Up regulation of Metalloproteases in blood brain barrier
What do proteases do to blood brain barrier?
They loosen up blood brain barrier, allowing TCells to pass into the central nervous system and CSF
Do the TH-1 cells directly cause myelin damage?
No! They’re an immune cell.
What actually causes damage once TH-1 cells enter the central nervous system?
They become reactivated in central nervous system on recognition of the myelin proteins (which look like the protein that entered before). Activate macrophages that eat away myelin coating nerves, also activate B-lymphocytes in to antibodies which are also phagocytes
What are the cells that create myelin in the central nervous system that would be attacked by antibodies IGG.
Oligodendrocytes
Schwann cells create myelin in peripheral
What occurs when the myelin is attacked by the IGG antibodies
The myelin is eaten away and electrical impulses dissipate as they run along through the wholes, therefore can’t get full effect of signal
What are the two clinical diagnostics for MS?
Cerebrospinal Fluid examination (Oligoclonal IgG) Brain MRI (Brain atrophy: size, location and number of lesion)
What are the MS- induced symptoms?
Fatigue & Weakness Bladder control Neuropathic pain Cognitivedefects Optic neuritis Sexual dysfunction Ataxia
