Speaker: Frauke Zipp
Department: Neurology, Mainz (Germany)
Location: Erasmus MC Rotterdam
Date: February 6, 2017
Author: Teun Huijben
Frauke Zipp is the head of the neuro-immunology research group in the Department of Neurology of the Medical University of Mainz, Germany. The main focus of her research is gaining better understanding of the complex interplay between the immune system and the central nervous system.
Many diseases are caused by problems in the interactions between the immune system and the central nervous system (CNS), examples are: Multiple Sclerosis (MS), Acute Disseminated Encephalomyelitis (ADEM), Meningitis, strokes, migraine and Alzheimers, Parkinsons and Huntington disease. Of all these diseases, MS is the best model disease of this interaction, since it is a chronic inflammation of the central nervous system.
The hypothesis of the cause of MS is an auto-immune respons where T-cells attack the central nervous system during the young adolescence. These CNS-specific T-cells are activated in some way and cross the blood-brain barrier. Arrived in the brain they are re-stimulated by seeing the CNS-antigens and their activation induces a cascade of reactions ultimately resulting in demyelination of axons (figure 1). Myelin is a fatty substance wrapped around axons to increase their electrical conductivity and provides mechanical protection. When this myelin is removed, the axons get damaged and the resulting neural injury will have all sort of effects.
Figure 1: Demyelination of axons in multiple sclerosis. As an effect of the auto-immune attack of T-cells in the brain, the myelin around axons is removed and axon function disrupted. 
How the demyelination is caused by the immune respons is not exactly known. One idea is that the activated lymphocytes enter the CNS and attack oligodendrocytes, cells that produce and maintain the myelin. Another idea is that cytotoxic (Cd8+) and T-helper (Cd4 + and Th17) cells directly attack the axons.
Remarkable is that 40 percent of the patients does not have extreme pathology effect and show a pattern of relapses and remissions. This suggest some repair of the CNS during these remissions. Frauke Zipp and her group are interested in this repair and also in better understanding MS in general to come up with new therapies.
To study MS they use an EAE (Experimental Autoimmune Encephalitis) mouse model that mimics the human disease. Using cultures of these cells it is possible to follow the immune respons of the brain by imaging living cells. This in vivo research led to multiple new concepts.
The first one is counterbalancing the inflammatory response. Microglia cells are the immune cells of the brain that can be best compared with macrophages. They found that microglia cells are able to catch Th17 cells using their long processes and engulf them by phagocytosis. Hereby defending the CNS against the mistaken attack of the immune system. Another concept is the discovery that T-helper-2 cells (Th2) are able to repair the nervous system during periods of remission. They do this by inducing regeneration of axons damaged by the immune system.
Overal, it was a quite difficult seminar to follow given our limited knowledge about the brain and the many medical terms used by Fauke Zipp. However, it is interesting and promising that her research has led to completely new concepts regarding the understanding of multiple sclerosis. And hopefully more research will result in newer and better therapies to defeat this disease.