Multiple Sclerosis Flashcards
What is multiple sclerosis
Chronic autoimmune disease of cns - attack own body
Can you see ms
Destruction of myelin sheath around neurons - lesions can be seen by mri
What happens during ms
Nerves cannot properly mass along signals
Sclerosis = scar tissue
Range of symptoms ms
Pain, fatigue, tingling, impaired gait (pattern of walking), vision problems, ladder problems, dizziness, cognitive and mood problems - paralysis
Describe Ms and immune system - gen
Trigger unknown
Inflammation causes increased recruitment of other immune cells (vasodilation)
Describe Ms and immune system - lymphocytes
Lymphocytes cross blood brain barrier and auto reactive cd4+ T cells (ones that passed through development) re encounter their specific autoantigen presented by mhc2 on macrophages (microfilm present self peptides)
Describe Ms and immune system - demyelination
Auto reactive T cells, B cells and innate immune cells lead to demyelination - antigen = myelin sheath
Describe Ms and immune system - tregs
Greg’s can regulate the inflammation for a bit - can come back tho, chance they regulate
So kinda comes in waves
Name the 4 types of Ms
Relapsing remitting
Primary progressive
Progressive relapsing
Secondary progressive
= depends on patient
which is most common Ms
~85% of patients suffer from relapsing remitting ms - experience periods when symptoms get better - remission followed by attacks - relapses
Describe relapsing remitting Ms
Episodes of relapses - attacks which may or may not leave permanent disability followed by periods of remission
Doesn’t go back to baseline = can mean there is permanent disability
Describe primary progressive Ms
Steady increase in disability with no relapse or remissions
Describe progressive relapsing Ms
Steady increase in disability with subsequent relapses and no remissions
Describe secondary progressive Ms
Initial relapsing remitting Ms that begins to steadily increase in disability without periods of remission
Name steps to diagnosis Ms
MRI = see lesions in brain
Vision, coordination, sense of balance
Spinal tap
Blood test
Evoked potential testes
Why spinal tap to diagnose Ms
Collecting cerebral fluid to determine how much inflammation in cns - see if pro inflammatory cytokines or antibodies
Why blood test to diagnose Ms
To rule out other diseases that might have similar symptoms
Why evoked potential test to diagnose ms
Electrical signals used to measure how quickly and accurately nervous system responds = to light, touch or sound
Describe Ms treatments timeline generally
Treatments target parts of immune system
1993-1004 = ifnB and corticosteroids
2013 = oral dimethyl fumarate
Describe ifnB therapy and corticosteroids used to treat ms generally
Reduces relapses by 30%
Weekly injection
Describe potential mechanism of ifnB therapy
Control of secretion of pro and anti inflammatory cytokines
Reducing ability of lymphocytes to cross bbb
Affecting apc function
May inhibit some T cell differentiation and increase T cell death - apoptosis
Describe corticosteroid therapy
Immunosuppressant —> reduces inflammation caused by pro inflammatory cytokines, increase induction of apoptosis in lymphocytes, reduces migration of leukocytes to brain
Generally wha do medicines given for this disease do
Decrease function of immune cells = immunosupressed, vulnerable to infections
Various components of immune system targeted by these Ms therapies - can lead to immunosupression
Describe dimethyl fumarate therapy in Ms - generally
Reduce relapses by 50%
Oral pills
More recent therapy - approved for Ms in 2013
Fewer side effects
Describe dimethyl fumarate therapy in Ms - potential mechanism
Anti inflammatory effectors - can suppress production of pro inflammatory cytokines
Stimulate tregs
Induce changes in maturation, availability and antigen presentation capacity of apcs
Name generally what other therapies for Ms target
mAbs
= target monocytes, lymphocytes, prevent transmigration across bbb, result in depletion of T cells, target B cells
Etc =
All lead to immunosuppression
What contributes to Ms progression
Many factors
Genetics - link between Ms and Hla genes
Pathogens, micro biome, smoking, bmi, lipids, lipoproteins, physical activity, diet, diabetes, hypertension
