Neuroinflammation

Question 1

What is the three signals needed for a dedritic cell to stimulate a t-cell?

Answer 1

1- MHCII-antigen-TCR
2- costimulation contact mediated: B7:CD28
3. costimulation cytokine mediated

Question 2

Name three things that differs with the brain immunology compared to the periphery

Answer 2

• BBB
• Location: in a non-elastic skull (edema)
• lack of lymphatic drainage
• completely different set of immune cells

Question 3

Are Leucocytes found in the brain of healthy induviduals?

Answer 3

They are found in the CSF but not in the brain parenchyma

Question 4

Are macrophages found in the brain of healthy induviduals?

Answer 4

Yes, in the brain parenchyma as well as in blood vasculature in the brain

Question 5

Name two cell types in the brain that does not exist in the periphery and have immunological functions in the brain

Answer 5

Microglia

Astrocytes

Question 6

What functions do microglia have in the physiological brain (non-pathological)

Answer 6

have functions in neuronal development and neuronal plasticity. Are a phagocyte

Question 7

What functions do microglia have in the pathological brain?

Answer 7

In the pathological brain the microglia undergo microgliosis:

• phagocytosis
• secretion of cytokines/chemokines
• express PRRs
• morphological changes

Question 8

What functions do astrocytes have in the physiological brain (non-pathological)

Answer 8

• blood brain barrier
• provide neurons with glucose
• recycle neurotransmitters

Question 9

What functions do astrocytes have in the pathological brain?

Answer 9

it undergoes astrogliosis:

• phagocytosis
• secrete cytokines/chemokines
• Express PRRs
• morphological changes: hypertrophic (increased size)

Question 10

What is the relation between astrocytes and microglia in the pathological brain?

Answer 10

They can activate and inhibit eachother

Question 11

Name consequences of chronic neuroinflammation.

Answer 11

• disruption of the BBB
• neuronal cell death
• secretion of cytokines/chemokines
• secretion of oxidative stress factors
• dysfunctional glia cells

Question 12

Why does the immune system react to e.g. alpha synuclein and Amyloid beta in PD and AD, they are self antigens?

Answer 12

they have gained structures that are not native:

• conformational changes
• aggregation
• post-translational modifications

Question 13

How do alpha synuclein/amyloid beta activate microglia and astrocytes in PD/AD?

Answer 13

alpha-synuclein and amyloid-beta aggregates bind to PRRs on astrocytes and microglia (alpha synuclein is secreted from dead cells)