Immunology of Multiple Sclerosis Flashcards
Describe the evidence supporting a role of the immune system in the pathogenesis and clinical course of MS Discuss the interactions between the adaptive and innate immune system in the context of MS pathophysiology Critically evaluate and discuss the relationship between inflammation and neurodegeneration in the context of MS pathogenesis, clinical evolution, and therapeutic needs
Give 3 immunopathological features of multiple sclerosis
1) Perivascular cuffs and intraparenchymal infiltrates of inflammatory cells
2) B cells in perivascular and meningeal locations, where they aggregate or form ectopic lymphoid follicles
3) Myelin-laden macrophages in and around lesions
Which inflammatory cells are most predominant in inflammatory lesions?
Macrophages
Describe macrophages in an active MS plaque
Foamy, containing numerous lipid droplets from myelin breakdown products
Which cells are exclusively infected by EBV?
B cells
In Ascherio & Munch’s 2000 study, what percentage of MS patients tested seropositive for EBV, and what percentage of healthy controls?
100% of MS patients, 90% of controls
In Munger et al’s 2011 study on military personnel, how much higher was the MS risk with an anti-EBNA titer >320 compared to <20?
36x higher
Which interleukin do pro-inflammatory CD4 T helper Th1 cells require for differentiation?
IL-12
Name two homing receptors expressed by pro-inflammatory CD4 T helper Th1 cells
CCR5 and CXCR3
Describe the relationship between IFN-gamma, IL-12, and MS disease activity
Increased clinical activity correlates with increases in IFN-gamma and IL-12 in both the CNS and CSF
Name the mouse model of MS
Experimental autoimmune encephalomyelitis (EAE)
Describe how Th1 cells induce inflammation
Th1 cells release IFN-gamma, inducing MHC class II expression in the CNS. This results in chemokine production which attracts and activates macrophages and monocytes
Which interleukin do pro-inflammatory CD4 T helper Th17 cells require for differentiation into pathogenic cells?
IL-23
Which molecule epigenetically imprints Th17 cells?
RORyT
Name 2 homing receptors expressed by Th17 cells
CCR6 and CCR4
Describe the effect of IL-23 deficiency on mice
It renders them completely resistant to experimental autoimmune encephalomyelitis
Describe the relationship between Th17 cells and MS
Increased numbers of IL-17 producing CCR6 cells are found in the brain lesions of MS patients post-mortem - especially in chronic lesions
Name 3 anti-inflammatory cytokines secretes by CD4 T helper Th2 and T-reg cells
IL-4, IL-5, IL-13
Describe the action of Th2 cells
They slow down or prevent inflammation
Where are CD4 CD25 T-reg cells generated?
The thymus
Name two molecules secreted by CD4 CD25 T-reg cells
IL10 and TGF-beta