L4 - The immunology of multiple sclerosis Flashcards Preview

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Flashcards in L4 - The immunology of multiple sclerosis Deck (19):
1

What is progression of the average person with MS?

severe fatigue and lethargy

numbness in left foot

3 years later pain behind left eye

inflamed optic nerve

Commences on B-interferon therapy

Left leg starts to drag at 40 - slowly starts to weaken

GRADUAL progession of paraplegia or hemiplegia

2

The pain in MS runs through...

unmyelinated neurons

peripheral nerve myelin is produced by different cells to the CNS

optic nerve is part of the CNS

3

the periventricular, subcortical U-fibre and posterior fossa lesions are all...

high intensity areas of inflammation

4

true or false

There is lots of variability in MS genetic patients in terms of severity, relapses and progression

true

5

What are the risk factors for MS?

20-30 fold increase if caucasian or have an effected sibbling

2-3 fold incraese if female or carrier of HLA-DR15 allele of the MCH class 2 molecule presenting antigens

2 fold increase if low Vit D levels

7 fold increase if high latitude of residence

1.3 increase if smoker or obese female

6

What are the lesions in MS?

Occur only in the CNS

Transverse Myelitis/optic Neuritis are examples

7

True or false

lesions for MS are in the perihperal nervous system

False

8

How can we study MS lesion evolution?

Gadolinium enhancing lesion - inject contrast, show the breakdown of BBB

Look for CD68+ve macrophages (could be disguised as a brain tumour)

Look for perivascular T and B cells

9

Myelin is made by oligodendrocytes - how is it damaged? T cells or B cells

T cells or potentially B cells

If B cells are killed MS imrpoves

If T cells are made to not leave the lymph nodes also good

But if we kill both = very toxic

10

Is the inflammation cause or consequence of MS?

If lymphocytes are maintained in lympoid organs (like with Fingolimod drug), MS is improved even though it isnt immunosuppressive

So traffic of T cells into the brain is important - if stoppedMS will improve

Alemtuzumab in hu CD52mice resultsed in depletion of lymphocytes in peripheral blood and lymphoid organs - has a MASSIVE effect on MS relapse rates

11

What are the identified risks from clinical trials with MS?

infusion associated reactions

serious infections

Autoimmune conditions

Nephropathies

12

true or false

When you put the inflammation cause to the test and specifically kill t cells, MS is improved

false

so could be B cells...

13

Could the inflammation just be a response to the oligodendrocyte/myelin death?

This is the 'inside-out' hypothesis

the immune response just being a response to the primary pathology in the oligendendrocyte

Could be something here - killing a field of oligodendrocytes to start with

14

Are lesional axons lost?

Yes

when you kill axon - protein blows up initp end bulb

15

The immunology of MS and its drugs treatments show us that....

we really don't know whats going on

16

The Big Question: What is the most likely reason for disability progression?

Cumulative axon injury by acute and chronic inflammation in and around lesions involving macrophages, T cells and B cells

This is bad because no regeneration in the CNS

17

true or false

MS is an autoimmune disease

False

It MAY be but we don't know

origin of the acute MS lesion is uncertain

18

true or false

Drugs that reduce MS lesions and relapses work on lymphocytes and macrophages

true

19

What is the strongest genetic risk factor for MS?

HLADR15 carriage

(also caucasians, women, low vit D)