Neuroimmunogly

Question 1

What did injected dyes not staining the brain mean for its structure?

Answer 1

Injected dyes do not stain the brain, indicating a barrier.

Question 2

What is the function of the blood-brain barrier?

Answer 2

Protects the brain parenchyma from blood-borne agents and allows selective transport of nutrients.

Question 3

What historical view was held regarding the blood-brain barrier?

Answer 3

It was considered an absolute immune privilege, a physiological wall.

Question 4

What is the current view of the blood-brain barrier?

Answer 4

It communicates flexibility and movement across blood-brain interfaces.

Question 5

What are the components of the blood-brain border?

Answer 5

• Microvascular endothelial cells lining the cerebral capillaries
• Protects the brain from blood-borne agents
• Significant barrier to drugs and exogenous compounds

Question 6

What forms the blood-cerebrospinal fluid barrier?

Answer 6

Epithelial cells of the choroid plexus.

Question 7

What is the role of the avascular arachnoid epithelium?

Answer 7

It has a relatively minor contribution to the brain’s barriers. Avascilar and low surface area

Question 8

What are the three immunological niches in the brain?

Answer 8

• Meninges
• Choroid plexus
• Perivascular spaces

Question 9

How does brain function relate to the immune system?

Answer 9

Brain function is dependent on immune system integrity.

Question 10

What role does the choroid plexus play?

Answer 10

It is an immunological gateway.

Question 11

What is the function of the meninges?

Answer 11

Site of immune surveillance, B cell development, and negative selection.

Question 12

What is the role of the skull bone marrow?

Answer 12

Potential reservoir of immune cells that can migrate to the CNS.

Question 13

What is the neurovascular unit (NVU)?

Answer 13

BB is mostly composed of endothelial cells forming limits of blood vessels, more cell types involved.

Question 14

What is the significance of tight junctions in the BBB?

Answer 14

They are critical for border integrity and are 50x-100x tighter than junctions in peripheral capillaries.

Question 15

Who identified microglia and what are their roles?

Answer 15

Identified by Pio del Rio-Hortega; they are resident macrophages of the CNS involved in phagocytosis and interaction with other brain cells.

Question 16

Microglia phagocytose _____ in pathological conditions

Answer 16

Neuronal debris

Question 17

Where do microglia originate from?

Answer 17

From a pool of macrophages produced during primitive haemopoiesis in the yolk sac.

Question 18

In mice at what gestational fay do microglia more to the neuroepithelium

Answer 18

8.5

Question 19

In humans microglial precursors migrate to brain primordium at what gestational weeks

Answer 19

4.5-5.5 weeks

Question 20

What markers can identify microglia?

Answer 20

• Pu.116
• IBA1
• P2YR12
• TMEM119
• CSF1R

Question 21

Development and maintence of microglia is dependent on what?

Answer 21

Development and maintenance dependent on colony stimulating factor receptor CSF1R, and its ligands IL34 produced by neurones and CSF1 (oligodendrocytes and astrocytes) and TGF-beta.

Question 22

Microglia are hard to detect, what omics can be used

Answer 22

Transcriptomics

Question 23

What is the role of TGF-beta in microglia?

Answer 23

It is involved in the maturation and adult phenotype of microglia.

Question 24

How are microglia and CNS macrophages different

Answer 24

Follow two different pathways
Microglia are throughout the brain
CNS-associated macrophages are in immunological niches

Question 25

What characterizes microglia in health

Answer 25

* Facilitate tissue repair * Survey the microenvironment * Synaptic remodelling * Clear toxic protein aggregates and debris * Secrete anti-inflammatory cytokines *Homeostasis

Question 26

Microglia are tissue-resident macorphages within the brain p_______

Answer 26

parenchyma

Question 27

True or False: Alzheimer's disease is associated with sustained immune activation in the CNS.

Answer 27

True

Question 28

What is the relationship between microglia and Alzheimer's disease?

Answer 28

Microglia can phagocytose protein aggregates and are implicated in inflammation that may potentiate neuronal loss.

Question 29

What is the role of the inflammasome in Alzheimer's disease?

Answer 29

Cellular stimuli lead to caspase-1 activation and IL-1beta production, linked to inflammation and apoptosis.

Question 30

What are dark microglia?

Answer 30

More electron dense than typical microglia, associated with altered ER and mitochondrial structure, and higher expression of TREM2.

Question 31

What characterizes multiple sclerosis (MS)?

Answer 31

* Chronic inflammatory condition of the CNS * Demyelination * Neuroinflammation * Neuronal injury

Question 32

What is the role of microglia during the acute phase of MS?

Answer 32

Contribute to autoimmune targeting of the myelin sheath.

Question 33

What can microglia secrete to aid in repair?

Answer 33

* Platelet-derived growth factor-α (PDGFA) * Insulin-like growth factor 1 (IGF1) * TGF superfamily members * Vascular endothelial growth factors (VEGFs)

Question 34

What is glioblastoma (GBM)?

Answer 34

A highly malignant brain tumour that is poorly responsive to immunotherapy.

Question 35

What are tumor-associated macrophages (TAMs)?

Answer 35

The most abundant population of immune cells in glioblastoma, making up half of total live cells in the tumor mass.

Question 36

What predicts poor treatment response in glioblastoma?

Answer 36

High TAM cell counts.

Question 37

Microglia respond to _AMPs

Answer 37

BAMPs (brain associated molecular patterns)

Question 38

Microglia can detect neuronal firing through detecting release of purines like A___/A___ via P___ and P_____ receptors

Answer 38

Microglia can detect neuronal firing through detecting release of purines like ADP/ATP ect via P2X and P2Y receptors (marker of microglial cells). So, microglia can sense and dampen hyperexcitable neurones.

Question 39

What are two marker receptors of microglia?

Answer 39

P2X and P2Y

Question 40

Microglia can convert ATP into what? What does it suppress?

Answer 40

Adenosine, neuronal activity

Question 41

Massive changes in K+ in neuronal firing are detected by what microglial potassium channels

Answer 41

THIK-1

Question 42

Is GABA sensed by microglia

Answer 42

Yes

Question 43

Examples of microglial states

Answer 43

Damaged associated microglia (DAMs) and interferon-response microglia (IRMs)