Neuro-immunology

Question 1

What are the functions of Oligodendrocytes?

Answer 1

Oligodendrocytes are responsible for the myelination of multiple axons and ensure conduction (node of Ranviers).

Question 2

What are the functions of Microglia?

Answer 2

Microglia are macrophage like cells and are responsible for phagocytosis, programmed cell death, neuronal plasticity and synaptic pruning.

Question 3

What are the functions of Astroglia?

Answer 3

Astroglia (star shaped cells) are responsible for the structure of the CNS, buffering, producing growth factors and the integrity of the blood-brain barrier.

Question 4

Why is the brain highly vascularized?

Answer 4

This is essential for brain homeostasis. It also actively transports nutrients and hinders drug delivery.

Question 5

What happens when the blood brain barrier fails?

Answer 5

Neuro-inflammation exists.

Question 6

What is the defect in multiple sclerosis (MS)?

Answer 6

In MS there is an impaired BBB function, which will lead to inflamed endothelial and immune cell infiltration across the blood-brain barrier. The immune cells will react to myelin proteins that leads to demyelination and gliosis (the activation of astrocytes and microglia). In the end this will lead to neurodegeneration and cognitive impairment.

Question 7

How does immune cell trafficking work?

Answer 7

Immune cell trafficking is a multistep process. The cells will start tethering, where they have very light attachment to the epithelial, and they will start rolling to slow down. Then there will be a strong adhesion and the cells flatten out over the endothelial cells. The endothelial cells will pull the leukocyte towards them and the immune cells find a weaker spot to get through. This can be in between the cells or through the cells.

Question 8

Which cells are auto-reactive in MS?

Answer 8

Auto-reactive (CD4) T cells recognise the myeline proteins.

Question 9

Which cells are affected in MS and in what way?

Answer 9

MS is a Th1/Th17 mediated disease and the functional activity of Tregs is reduced in MS patients. The CD8 T cells will undergo clonal expansion within the CNS and promote vascular permeability and transect axons. macrophages also migrate over the BBB and phagocytose myelin.

Question 10

What does Ocrelizumab do?

Answer 10

Ocrelizumab is an anti-B cell activator and limits B- cell activation.

Question 11

What does Cladribine do?

Answer 11

Cladribine limits proliferation of T-cells and B-cells.

Question 12

Wat does Natalizumab do?

Answer 12

The most successful treatment for MS is Natalizumab, which separates leukocytes in the bloodstream and so prevents crossing of the BBB into the CNS. It targets the a4-integrin-containing adhesion molecules (VCAM-1) required for migration.

Question 13

What is the choroid plexus?

Answer 13

The choroid plexus forms the blood-Cerebrospinal fluid barrier and is responsible for the CSF secretion. It contains neurotrophic factors and thus provides neuroprotection.

Question 14

What impairments are there in the choroid plexus of MS patients?

Answer 14

In MS patients the choroid plexus has an impaired epithelial barrier function, a loss of neuroprotective function, epithelial inflammation and T-cell accumulation and activation.

Question 15

What are the meninges?

Answer 15

The meninges are the vessels that cover the cortex of the CNS.

Question 16

What defects are there in the meninges of MS patients?

Answer 16

In MS there is accumulation of B-cells in the meninges and locally activation of microglia cells which will lead to neurodegeneration.
The meninges play a dominant role in the progression of the disease.

Question 17

What is the defect in Alzheimer’s disease?

Answer 17

In Alzheimer’s there is also BBB failure and there are extracellular amyloid-beta deposits present. There is also Tau hyperphosphorylation which leads to microtubule destabilization and Tau oligomer formation (neurofibrillary tangles/NFTs). There’s also a profound neuro-immune response.

Question 18

Why does the amyloid accumulation in AD happen?

Answer 18

The amyloid accumulation is due to the mis cleavage of the amyloid precursor protein. This will from sticky Aβ proteins which will stick together and form extracellular plaques.
This will lead to microglia activation which will produce inflammatory cytokines and neurotoxic factors that will also lead to neurodegeneration. This phenotype of microglia cells are called disease associates microglia cells.

Question 19

Which cells infiltrate the hippocampal and cortical regions in AD?

Answer 19

In Alzheimer’s disease T cells infiltrate in the hippocampal and cortical regions. There are high amounts of CD4+ T cells in the PBMCs and CD3+ T cells in the hippocampus.