MS and Neuroimmunology Flashcards
Describe the three different types of MS
- relapse remitting (RRMS): disability –> no symptoms –> cycles –> disability progresses (no longer recover) with varying levels of symptoms
- 2o progressive (SPMS): 50% of patients develop SPMS –> symptoms get worse with time
- 1o progressive (PPMS): never recover - increasing disability over time
What does MS mean?
multiple lesions
Why do most MS patients have more lesions than expected?
most lesions do not occur in regions that would cause disability
What does LFB stain for?
myelin
What are the three types of MS lesions?
- active - high immune cell infiltration, fuzzy border
- chronic active - fewer immune cells
- inactive - much fewer immune cells
What cell types are found in active plaques?
T cells and macrophages
What self-Ag is assumed to cause MS?
probably a myelin Ag such as MBP, considering myelin gets attacked
Describe how immune cells in MS overcome the BBB?
immune cells exit the blood via the endothelial basemement memb –> MMPs degrade the parenchymal basement membrane –> immune cells enter the brain
Can you regenerate myelin? Neurons?
myelin - yes
neurons - no
In MS what is believed to be the primary contributor to progression of diability?
continous loss of axons and neurons
Describe the difference in brains of those with RRMS and SPMS
RRMS - moslty focal demyelination
SPMS - mostly corticol demylenination + demyleination in deep grey matter
What is the EAE mice model? How is it induced?
EAE = mouse model for MS
induction: inject MBP + adjuvant
What is parabiosis?
- fusing one mouse to another –> blood sharing between the mice
- where are the immune cells going
- young mice can rejuvinate old mice
What markers can you use to differentiate a monocyte from a MF?
monocyte: Iba1 -
MF: Iba1 +
Describe how we make Cre Lox mice
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
What is the purpose of Cre-Lox model?
coniditonal KO –> removes gene in cell of choice
affects the cells and their progeny because its in the genome
How does cre-lox work?
cells with active cre recombinate - original gene function is disrupted, a reporter gene is transcribed instead
What is a downside with tranditional cre-lox models
Cre is present always, including devlopment –> could be fatal
Describe inducible Cre Lox
add tamoxifen to activate cre –> an do this in an adult animal
What happens if we inhibit the function of microglia in EAE model? What does this implicate?
no MS
- no reactivation of T cells?
- don’t allow passage of BBB?
- T cells tell microglia to be toxic?
How does the drug fingolimod affect MS progression?
- fewer relapses
- reduced secondary onset
Describe the inside-out vs outside-in model of MS
inside out: cytodegeneration in CNS –> autoimmunity
outside in: autoimmunity –> cytodegeneration in CNS
What cells can myelinate axons?
oligiodendrocytes
Describe MS progression in patients that remyelinate
have less disability
what is a histological feature of those who remyelinate?
shadow plaque - intermediate shading
describe oligiodendrocyte basic biology
- oligiodendrocytes need survival factos
- they spontaenously differntiate and even produce myelin proteins
- they spontaenously myelinate - even dead axons
why does remyelination fail?
many inhibitors of remyelination, many of which are found in MS lesions
