The second speaker of this two-part seminar series by the Department of Neurology was by professor Zipp. She immediately started talking about the model disease in her field, namely multiple sclerosis. She showed that on an MRI image there are two differently colored parts associated with MS, one showing the inflammatory pathology of MS because of a too permissive blood-brain barrier, the other showing the degenerative pathology of the shrinking parenchyma.
What happens in MS is the following. Firstly a specific kind of T-cell that specifically targets the central nervous system (CNS) targets an antigen in the CNS. Then they transmigrate the blood-brain barrier. When they enter the CNS they attack the myelin of the nerves’ axons. But there is not only a process of demyelination. Bare neurons are also attacked. This was shown by showing that in the cortex you get swollen meninges. Because the cortex is unmyelinated, the bare neurons can also be attacked. In this process the T-17 helper cells play a very large role.
Figure 1: Overview of the inflammation process in MS
Over time MS happens in a peculiar way. It has periodic relapses and remissions. In 40% of the cases it eventually loses this profile, leading to a continuous increase of disabilities. But in the other 60% the relapses eventually stop. It is not yet sure if this is the case because of neuron repair or because the neurons of this population is for some reason more durable than the other 40%.
Next she showed some of her experimental data. First she showed that the processes of dendritic cells play a role in the blood-brain barrier, acting like a kind of gatekeeper specifically keeping the T-17 helper cells out of the CNS. Also, through a transgenic cell staining it was seen that the T-17 cells directly attack the myelin without recruiting other cells.
Next she introduced three novel concepts in her field.
Firstly, she explained the process called counterbalancing. The microglia, a type of cells in the CNS, can carry and transport the T-17 helper cells inside of their protrusions. This is done to migrate the cells. It can end in 2 ways, either the engulfed cells die due to apoptosis or they escape. This process can be used by the T-17 cells to move through the CNS to harder to reach places. A specific compound called wortmannin has been found that blocks this process. This process is not specific to T-17 cells. In essence, this process is the microglia trying to phagocytize the cells, but it is doing more harm than good.
Secondly, it was seen that in mice there is no demyelination during a relapse, maybe explaining the two different populations.
Finally, the process of neuroprotection was explained. It has been seen that repair of damage was seen in patients. Another kind of T-cell, the Th-2 cells, is able to increase the axonal regeneration. The neurons of MS patients possess Interleukin 4 receptors. This compound reduces the severity of the MS by inducing axonic growth.
I found this last fact to be especially amazing, since an interleukin, a compound exclusively related to the immune system, is apparently able to interact with the nervous system. This suggests that the usual view of the human body as a set of different systems can be very wrong. Because of this, interdisciplinary work such as the work of professor Zipp should be appreciated way more, because these innovations will really improve health care a whole lot.