MS and Neuroimmunology

Question 1

Describe the three different types of MS

Answer 1

1. relapse remitting (RRMS): disability –> no symptoms –> cycles –> disability progresses (no longer recover) with varying levels of symptoms
2. 2o progressive (SPMS): 50% of patients develop SPMS –> symptoms get worse with time
3. 1o progressive (PPMS): never recover - increasing disability over time

Question 2

What does MS mean?

Answer 2

multiple lesions

Question 3

Why do most MS patients have more lesions than expected?

Answer 3

most lesions do not occur in regions that would cause disability

Question 4

What does LFB stain for?

Answer 4

myelin

Question 5

What are the three types of MS lesions?

Answer 5

1. active - high immune cell infiltration, fuzzy border
2. chronic active - fewer immune cells
3. inactive - much fewer immune cells

Question 6

What cell types are found in active plaques?

Answer 6

T cells and macrophages

Question 7

What self-Ag is assumed to cause MS?

Answer 7

probably a myelin Ag such as MBP, considering myelin gets attacked

Question 8

Describe how immune cells in MS overcome the BBB?

Answer 8

immune cells exit the blood via the endothelial basemement memb –> MMPs degrade the parenchymal basement membrane –> immune cells enter the brain

Question 9

Can you regenerate myelin? Neurons?

Answer 9

myelin - yes
neurons - no

Question 10

In MS what is believed to be the primary contributor to progression of diability?

Answer 10

continous loss of axons and neurons

Question 11

Describe the difference in brains of those with RRMS and SPMS

Answer 11

RRMS - moslty focal demyelination
SPMS - mostly corticol demylenination + demyleination in deep grey matter

Question 12

What is the EAE mice model? How is it induced?

Answer 12

EAE = mouse model for MS
induction: inject MBP + adjuvant

Question 13

What is parabiosis?

Answer 13

• fusing one mouse to another –> blood sharing between the mice
• where are the immune cells going
• young mice can rejuvinate old mice

Question 14

What markers can you use to differentiate a monocyte from a MF?

Answer 14

monocyte: Iba1 -
MF: Iba1 +

Question 15

Describe how we make Cre Lox mice

Answer 15

mate a Cre mouse with a floxed mouse

Cre contains the promoter specific to the cell type of interest, LoxP contains target gene and eGFP

Question 16

What is the purpose of Cre-Lox model?

Answer 16

coniditonal KO –> removes gene in cell of choice

affects the cells and their progeny because its in the genome

Question 17

How does cre-lox work?

Answer 17

cells with active cre recombinate - original gene function is disrupted, a reporter gene is transcribed instead

Question 18

What is a downside with tranditional cre-lox models

Answer 18

Cre is present always, including devlopment –> could be fatal

Question 19

Describe inducible Cre Lox

Answer 19

add tamoxifen to activate cre –> an do this in an adult animal

Question 20

What happens if we inhibit the function of microglia in EAE model? What does this implicate?

Answer 20

no MS

• no reactivation of T cells?
• don’t allow passage of BBB?
• T cells tell microglia to be toxic?

Question 21

How does the drug fingolimod affect MS progression?

Answer 21

• fewer relapses
• reduced secondary onset

Question 22

Describe the inside-out vs outside-in model of MS

Answer 22

inside out: cytodegeneration in CNS –> autoimmunity
outside in: autoimmunity –> cytodegeneration in CNS

Question 23

What cells can myelinate axons?

Answer 23

oligiodendrocytes

Question 24

Describe MS progression in patients that remyelinate

Answer 24

have less disability

Question 25

what is a histological feature of those who remyelinate?

Answer 25

shadow plaque - intermediate shading

Question 26

describe oligiodendrocyte basic biology

Answer 26

• oligiodendrocytes need survival factos
• they spontaenously differntiate and even produce myelin proteins
• they spontaenously myelinate - even dead axons

Question 27

why does remyelination fail?

Answer 27

many inhibitors of remyelination, many of which are found in MS lesions