Advanced molecular immunology and cell biology (AM_470656)
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Lecture 9. The immune system in the brain (neuro-immunology) (AM_470656)
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Advanced molecular immunology and cell biology (AM_470656)
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Vrije Universiteit Amsterdam (VU)
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The Immune System
Information on immune cells in the CNS, multiple sclerosis as an example, immune cell filtration through the blood-brain barrier, and immunotherapy in multiple sclerosis.
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Vrije Universiteit Amsterdam (VU)
Biomedical Sciences
Advanced molecular immunology and cell biology (AM_470656)
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Molecular Cell Biology and Immunology
Lecture 9. Neuro-immunology
INDEX
1. Cells of the CNS ........................................................................................................................................................................................... 1
2. Multiple sclerosis as typical neuro-immunological disease and pathology .................................................................................................. 1
2.1. Diagnosis ............................................................................................................................................................................................ 1
2.2. Clinical course ..................................................................................................................................................................................... 1
2.3. Risk factors ......................................................................................................................................................................................... 2
3. Which immune cells play a role................................................................................................................................................................... 2
3.1. Trigger in MS ...................................................................................................................................................................................... 2
3.2. Pathological events in MS ................................................................................................................................................................... 3
3.3. What happens to the myelin? ............................................................................................................................................................. 3
3.4. Lesion formation ................................................................................................................................................................................ 3
3.5. T cells ................................................................................................................................................................................................. 4
3.6. B cells ................................................................................................................................................................................................. 4
3.7. Macrophages and microglia ................................................................................................................................................................ 5
4. How do they reach the brain – brain barriers – basis for therapy ................................................................................................................ 5
4.1. Immune cell infiltration – BBB ............................................................................................................................................................ 5
4.2. Choroid plexus .................................................................................................................................................................................... 6
5. Immunotherapy in MS ................................................................................................................................................................................ 6
5.1. Natulizimab ........................................................................................................................................................................................ 6
5.2. Fingolimod.......................................................................................................................................................................................... 6
6. Progressive MS ........................................................................................................................................................................................... 6
, 1. CELLS OF THE CNS
We have neurons and glia cells (microglia, astrocytes). The neurons are 30% of the cells of the brain, there is a large group under
the name glia cells, they are the ‘glue’ for the neurons. However, glia cells have been recognized for their roles in homeostasis
and disease.
Microglia cells: resident brin macrophages: present antigens, help neural plasticity and they secrete substances.
Astrocytes are the most important cells of the nervous system, they are between the blood vessels and neurons.
Oligodendrocytes: form the myelin that covers the axons, needed for the conductions of the action potential.
2. MULTIPLE SCLEROSIS AS TYPICAL NEURO-IMMUNOLOGICAL DISEASE AND PATHOLOGY
A very heterogenous disease in the symptoms, it affects many young people (between 20 and 50 years). It mostly affects young
adults, 3 times more women than men → there is a hormonal component in disease. It affects 1 in every 1.000 people; the global
distribution is mostly in the northern and southern part of the equator (not the centre).
It has been known for a long time that it affects the brain and spinal cord: it’s an autoimmune disease that affects the CNS.
Immune cells recognize a number of brain antigens as foreign and start an immune response. Jean-Martin Charcot described the
features of MS first.
→ In the brain there are lesions.
There is inflammation in the brain, that subsides and leaves scars in the brain that can be seen, there are multiple scars = multiple
sclerosis.
2.1. DIAGNOSIS
The diagnosis can be via. (cursive = additions)
MRI: if a patient has clinical symptoms and they make an MRI, they can see a
patten of white spots in the brain area close to the ventricles, the lesions.
o Depending on the location of the lesions, the patient will have a
different phenotype of the illness: if there is a lesion in the vision
region you will have problems will vision, etc. → This makes it
difficult to diagnose because there are many different symptoms
that can occur.
o The lesions come and go, this also gives the clinical patter very diverse.
When you see the white spots you can add a marker for leaky vessels and you can see the immune cells in the brain.
To see metabolic changes, you can do PET staining with a molecule to see tissues that are metabolically active (the cost
is high and the methods are invasive)
2.2. CLINICAL COURSE
On the image, the arrows are the symptoms that come and go.
The 1st stage of MS has a spiky patter. The patter of relapsing-
remitting: there are clinical symptoms during a time period
and then it can go away. It can last for up to 15 years.
At a certain stage they go to a progressive stage that can be:
o Secondary progression
o There are other patients that start with a very
progressive stage of the disease. They are usually
the mild, the timespan of the disease is 10 years
(sorter) before they become wheelchair bound.
Characteristic of this stage:
o In the more progressive stage of the disease, the
inflammation subsides.
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