Immunological processes in MS

Question 1

What are the 5 potential causes of MS?

Answer 1

Inside-out/outside-in hypothesis, genetic risk factors, infectious factors, environment, and lifestyle.

Question 2

What is the inside-out model?

Answer 2

There is cytodegeneration in the CNS which leads to autoimmunity.

Question 3

What is the outside-in model?

Answer 3

There is autoimmunity that leads to cytodegeneration in the CNS.

Question 4

What are the associated infectious factors in MS?

Answer 4

There are similarities with viral-induced demyelination and association with viral infections (EBV, HHV6, measles) but a single virus can’t stand alone as a causal factor of MS.

Question 5

What are the associated non-infectious factors in MS?

Answer 5

Sunlight (melatonin/vitamin D), geographical distribution, diet, delayed/reduced infections: hygiene hypothesis and microbiome.

Question 6

What is EAE and what are the 3 different models?

Answer 6

Experimental autoimmune encephalomyelitis is a model for MS in mice. There is active EAE, where there is immunization with myelin, there is passive transfer EAE where there are T-cells transferred from active EAE animals into naïve animals and there is spontaneous EAE where mice express the receptor of autoreactive T-cells as a transgene.

Question 7

What is the antigen in MS?

Answer 7

Myelin proteins, and mostly proteolipid proteins (PLP) and myelin basic proteins (MBP).

Question 8

Which T-cells are differently expressed in MS?

Answer 8

MS is a Th1 mediated disease, where T-regs are reduced and Th17 mediates tissue damage. The autoreactive (CD4) T-cells recognize myelin proteins, but CD8 cells induce axonal damage and are more present than CD4 T-cells.

Question 9

What is the position of B-cells in MS?

Answer 9

They produce antibodies against oligodendrocytes and produce oligoclonal Ig bands. Ablation of B-cells is beneficial in therapy.

Question 10

What is the position of macrophages in MS?

Answer 10

There are inflammatory (recruited) macrophages in the CNS that migrate over the BBB and phagocytose myelin.

Question 11

What is the position of microglia in MS?

Answer 11

Pro-inflammatory microglia is detrimental and contribute to the destruction of myelin and neurodegeneration in MS, while anti-inflammatory microglia play a role in damage repair and remission.

Question 12

What is the function of lipid mediators?

Answer 12

They mediate inflammation, and when they do not function correctly there will be chronic inflammation.