Neuro-immunology Flashcards

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1
Q

What are the functions of Oligodendrocytes?

A

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

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2
Q

What are the functions of Microglia?

A

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

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3
Q

What are the functions of Astroglia?

A

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

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4
Q

Why is the brain highly vascularized?

A

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

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5
Q

What happens when the blood brain barrier fails?

A

Neuro-inflammation exists.

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6
Q

What is the defect in multiple sclerosis (MS)?

A

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.

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7
Q

How does immune cell trafficking work?

A

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.

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8
Q

Which cells are auto-reactive in MS?

A

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

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9
Q

Which cells are affected in MS and in what way?

A

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.

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10
Q

What does Ocrelizumab do?

A

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

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11
Q

What does Cladribine do?

A

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

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12
Q

Wat does Natalizumab do?

A

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.

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13
Q

What is the choroid plexus?

A

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

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14
Q

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

A

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.

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15
Q

What are the meninges?

A

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

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16
Q

What defects are there in the meninges of MS patients?

A

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.

17
Q

What is the defect in Alzheimer’s disease?

A

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.

18
Q

Why does the amyloid accumulation in AD happen?

A

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.

19
Q

Which cells infiltrate the hippocampal and cortical regions in AD?

A

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.