4) Multiple Sclerosis

Question 1

What is the average age of onset?

Answer 1

30 to 40 years

Question 2

Ethnicity is a factor in susceptibility. What ethnicity is most at risk and what occurs when a person moves to a new area?

Answer 2

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.

Question 3

What is the ratio of women to men who are affected by MS?

Answer 3

3:1

Question 4

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?

Answer 4

5% or 20 to 40 times more likely

Question 5

What are the 3 theories of MS development

Answer 5

Infectious theory
Molecular Mimicry
Autoimmune disease

Question 6

What are the three antigen presenting cells?

Answer 6

Macrophages, monocytes and dendritic cells

Question 7

Antigen-presenting cells work as blood filters and once they grab a protein that looks similar to myelin, what occurs?

Answer 7

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.

Question 8

What is MS on a molecular level?

Answer 8

It is the over activation of proliferation of inflammatory TH-1 cells activated by foreign product.

Question 9

There is an imbalance of between the TH1 and TH2 cells in the blood in what amounts?

Answer 9

More TH-1 cells in comparison to TH-2 cells

Question 10

What type of cell are TH-2 cells?

Answer 10

Anti-inflammatory

Question 11

What does immune deviation mean in relation to MS?

Answer 11

There are more pro-inflammatory TH-1 cells then there are anti-inflammatory TH-2 cells that never restores itself.

Question 12

What predominant inflammatory mediators do active TH-1 cells release?

Answer 12

Tumor necrosis factor alpha (TNF-a)
Interleukin 12 (IL-1)
Interferon gamma (IFN-g)

Question 13

What do the mediators of inflammation do?

Answer 13

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

Question 14

Mediators of inflammation from original activated TH-1 cell not only activate more TH-1 cells but also cause what to occur?

Answer 14

Cause the up regulation of adhesion molecules on the surface of the endothelial lining of blood brain barrier.

Question 15

Mediators of inflammation cause lining of blood brain barrier to be sticky causing what to stick?

Answer 15

TH-1 molecules which create more adhesion molecules and inflammatory mediators.

Question 16

What are Metalloproteases activated by?

Answer 16

Mediators of inflammation

Question 17

Mediators of inflammation cause three main things. What are they?

Answer 17

Proliferation of more TH-1
Up regulation of adhesion molecules
Up regulation of Metalloproteases in blood brain barrier

Question 18

What do proteases do to blood brain barrier?

Answer 18

They loosen up blood brain barrier, allowing TCells to pass into the central nervous system and CSF

Question 19

Do the TH-1 cells directly cause myelin damage?

Answer 19

No! They’re an immune cell.

Question 20

What actually causes damage once TH-1 cells enter the central nervous system?

Answer 20

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

Question 21

What are the cells that create myelin in the central nervous system that would be attacked by antibodies IGG.

Answer 21

Oligodendrocytes

Schwann cells create myelin in peripheral

Question 22

What occurs when the myelin is attacked by the IGG antibodies

Answer 22

The myelin is eaten away and electrical impulses dissipate as they run along through the wholes, therefore can’t get full effect of signal

Question 23

What are the two clinical diagnostics for MS?

Answer 23

Cerebrospinal Fluid examination (Oligoclonal IgG)
Brain MRI (Brain atrophy: size, location and number of lesion)

Question 24

What are the MS- induced symptoms?

Answer 24

Fatigue & Weakness
Bladder control
Neuropathic pain
Cognitivedefects
Optic neuritis
Sexual dysfunction 
Ataxia

Question 25

What is the features needed for diagnosis of MS?

Answer 25

Two attacks that lasted greater then 24 hours separated by 30 days

Question 26

What are the four types of MS?

Answer 26

Primary Progressive MS (males: get attack never recover)
Relapsing-Remitting MS
Secondary Progressive MS (move from relapsing remitting to never changing)
Progressive Relapsing MS (one symptom always recovers (relapsing and remitting) and another is now always)

Question 27

Clinically isolated syndrome is determined by what, indicating you will probably get it.

Answer 27

1 attack that lasted greater than 24 hours EVEN with a +/- ve MRI that doesn’t fulfill McDonald criteria in regard to dissemination in time and/or space.

Question 28

What do immunomodulatory agents do?

Answer 28

Reduce immune response by repressing TH-1 cell production.