Immunopharmacology - Multiple Sclerosis Flashcards
Environmental factors of MS? (6)
Far from equator Decreased sun Decreased vitamin D Microbes Least common in rural Migration
2 important factors of MS?
Environmental
Genetic
Causes of MS? (3)
Higher number of immune cells (virus/genetic defect)
Environment
Heredity
Which virus is involved in MS? It infects which cells?
EBV : Esptein-Barr virus
B cells
4 mechanisms that EBV infects B cells?
- Molecular mimicry
- B cell transformation through LMP1 and LMP2A
- B cell trafficking to CNS
- Unknown mechanisms
What is MS?
It results in a progressive decline in ______ and _____ function
What is the target of the immune response?
Autoimmune disease where the immune system attacks myelin
Motor and cognitive function
Myelin basic protein
What is the pathological hallmark in MS?
It contains what? (2)
Lesions (disseminated white matter lesions of the CNS)
- Perivascular inflammation
- Demyelination
Where are demyelinating plaques mostly found in the CNS? Most frequently affected sites are… (4)
Anywhere within white matter
- Optic nerves
- Brainstem
- Cerebellum
- Spinal cord
How does axonal injury occur?
Repeated cycles of demyelination and remyelination
Explain autoimmune-mediated demyelination
Acute inflammatory response of auto-reactive lymphocytes (T cells) and macrophages produce demyelination by the release of pro-inflammatory factors that damage oligodendrocytes and axons
4 subtypes of MS?
Benign
Relapsing-remitting
Primary progressive
Secondary chronic progressive
7 signs/symptoms of MS?
Vision impairment Tingling and numbness of the skin and limbs Weakness and exhaustion Difficulty with walking Memory loss Depression Urinary and bowel problems
4 treatments of relapsing-remitting MS?
Interferon-beta
Glatiramer acetate
Tysabri
Dimethyl Fumarate
2 treatments of secondary progressive MS?
Interferon-Beta
Mitoxantrone
Treatment of primary progressive MS?
none
Treatment of acute relapses of MS?
Corticosteroids
MOA of glucocorticoids?
Inhibition of the expression of pro-inflammatory genes
How is Interferon-Beta administered?
MOA?
Subcutaneous injection
Unclear MOA: reduces inflammation, perhaps promotes apoptotic elimination of auto-reactive immune cells
Glatiramer acetate is found where?
It works as a _____ for the immune system
in myelin basic protein
decoy
Administration of glatiramer does what?
shifts population of T cells from pro-inflammatory Th1 cells to regulatory Th2 cells that suppress the inflammatory response
What type of drug is mitoxantrone?
It suppresses the proliferation of which cells? (3)
Type II topoisomerase inhibitor
T cells, B cells, macrophages
Mitoxantrone enhances ______ _______ function and inhibits ________ function and ______ presentation
T-cell suppressor function
B-cell function
Antibody presentation
Tysabryi is what type of drug against which molecule?
Monoclonal Ab against cellular adhesion molecule alpha4-integrin
MOA of Tysabryi?
Interferes with ability of immune cells to attach to endothelial cells and cross BBB
What type of drug is Fampridine-SR? MOA?
Selective neuronal K+ channel blocker
Closes exposed potassium channels in damaged nerve fibres, enables axon to transmit nerve impulses again
What is the first oral therapeutic approved for the treatment of MS?
Most recent oral therapeutic approved?
Fingolimod (Gilenya) Dimethyl fumarate (Tecfidera)
What type of drug is Fingolimod? MOA?
Sphingosine 1-phosphate receptor modulator
Sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction
MOA of dimethyl fumarate?
Activates Nrf-2, increases expression of mitochondrial and anti-oxidant genes that reduce inflammation and protect oligodendrocytes and neurons
