Immunology of multiple sclerosis Flashcards
What is an experimental autoimmune encephalomyelitis (EAE)?
It is an animal model for multiple sclerosis
What are the 3 required signals for T-cell activation?
- Antigen presentation
- Co-stimulatory signal
- Cytokine secretion from APC to T-cell
What are the evidences for a Th1 cell mediated response in EAE and MS?
- Increase activity of IFNγ and IL-12 in the cerebrospinal fluid (cytokines inducing Th1)
- Induction of EAE by transfer of Th1 cells
Other than Th1, what other T-cell can induce EAE/MS and what cytokines induce it?
Th17 induced by IL-1ß and IL-23
What is GM-CSF and why is it important in EAE?
- It is a protein that acts like a cytokine
- Acts specifically on infiltrating monocytes to amplify the inflammatory response
- Essential for EAE (with knockouts => no EAE)
Does the intestinal bacteria modulate immune response?
Yes, different bacterial species boost Th-cell populations differentially
How does melatonin levels correlate with multiple sclerosis?
- Melatonin levels negatively correlate with multiple sclerosis relapses in humans
- Melatonin treatment ameliorates pathology in a mouse model of multiple sclerosis
What can be said about microglia in multiple sclerosis?
- TGF-β is not critical for microglia survival but is required for the maintenance of the microglia-specific homeostasis
- Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation
What can be said about astrocytes in multiple sclerosis?
Neurotoxic reactive astrocytes are induced by activated microglia
What can be said about oligodendrocytes in multiple sclerosis?
Disease-specific oligodendrocytes lineage cells arise in MS (altered oligodendrocyte heterogeneity)
What can be said on primary neurodegeneration in multiple sclerosis?
- Oligodendrocyte death and reactive microglia are present in early stages
- Subtle focal changes in the white matter weeks before new lesions are formed
