L23- Neuroimmunology Flashcards

(36 cards)

1
Q

What are 4 positive aspects of the blood brain barrier

A

 BBB impermeability to some substances – experiments with water soluble dyes late 19th century

 Prolonged survival of tissues when grafted into the CNS, compared to other sites (i.e. skin grafts)

 Lack of a cell-mediated response to instilled antigens

 Lack of a route to the lymph nodes for the antigen-presenting cells that reside in the parenchyma and perivascular spaces of the healthy CNS

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2
Q

What is the choroid plexus?

A

Choroid plexus are modified ependymal cells that produces CSF. It acts as a diffusion barrier between blood and CSF and it is home to various immune cells. It is a key point of entry for peripheral immune cells into the CSF space.

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3
Q

How do immune cells cross into the choroid plexus?

A

Infiltrating immune cells first migrate from the blood across the fenestrated endothelium into the stromal space. They then move along the basolateral surface of the choroid plexus epithelium, from where they gain passage across the epithelium into the CSF-filled ventricles.

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4
Q

Name a Parenchymal microglial cell?

A

Brain resident macrophages

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5
Q

What do the parenchymal microglial macrophages do?

A

Functions as immune sentinels and contributes for the maintenance of brain homeostasis

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6
Q

Define microgliosis

A

Microgliosis is an intense reaction of CNS microglia to pathogenic insults. One of the characteristic features of microgliosis is an increase in the number of activated microglia at the site of lesion. Microgliosis occur without blood cell infiltration – proliferative capacity.

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7
Q

Where do these parenchymal microglial macrophages arise from?

A

Enters brain very early in the embryogenic phase - derived from yolksac precursors

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8
Q

Where would you find (Kolmer’s) Epiplexus cells?

A

Innate immune cells located in the choroid plexus of the brain ventricles.

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9
Q

What do Kolmer’s Epiplexus cells do?

A

Function includes phagocytosis, antigen presentation, iron accumulation and NO production. Express markers of macrophages, dendritic cells and microglia.

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10
Q

What role do meningeal, perivascular and ventricular macrophages perform?

A

Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis. … Meningeal (MM) and perivascular macrophages (PVM) constitute major populations of resident macrophages in the CNS that can be distinguished from microglial cells.

Derived from blood-borne monocytes (population homeostasis).

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11
Q

Neutrophils and other granulocytes are absent from the healthy CNS. So what immune cells protect the CNS?

A

The CNS, which consists of the brain and spinal cord, is continuously monitored by resident microglia and blood-borne immune cells such as macrophages, dendritic cells and T cells to detect for damaging agents that would disrupt homeostasis and optimal functioning of these vital organ.

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12
Q

Explain how the brain vasculature is different?

A

 Cerebrospinal fluid (CSF) surrounds the brain and spinal cord - Blood–cerebrospinal fluid barrier (BCSFB)

 Blood – Modified capillary endothelium - Blood-brain barrier (BBB)

 Interstitial fluid - surrounds cells and parenchyma Glymphatic system and/or neurovascular unit (ependymal cells and pia-glial membranes) and/or choroid plexus

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13
Q

Where can you find the cerebrospinal fluid?

A

Cerebrospinal fluid (CSF) surrounds the brain and spinal cord, both internally and externally.

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14
Q

What cells produce cerebrospinal fluid?

A

CSF is mainly produced by the choroid plexuses (ependymal cells) - highly vascularised tissues located within each ventricle of the brain

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15
Q

Where does reabsorption of CSF occur?

A

Reabsorption of CSF into blood occurs at arachnoid villi (continuous with the lymphatics in the nasal mucosa – into regional cervical lymph nodes)

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16
Q

What is the ratio of immune cells of healthy CSF?

A

The immune cell content of healthy CSF is estimated to consist of approximately 90% T cells, 5% B cells, 5% monocytes and <1% dendritic cell

17
Q

What is the important role of T cells in CSF?

A

T cells constitutively monitor the CNS by trafficking through CSF.

The T cell appears to be the leader of the immune cells in the CSF. T cells have a controlling effect on all other immune cells in the CSF. When T cells are present other cells are in check. Without T cells these cells become inflammatory and produce multiple cytokines that interfere with brain function.

18
Q

What is the ratio of WBC of normal CSF found in babies and in adults?

A

Normal CSF may contain up to;

5 WBCs per mm^3 in adults and
20 WBCs per mm^3 in newborns

19
Q

Do you find antibodies and complement in the CFS?

A

Antibodies and complement are normally absent

20
Q

What colour is healthy CSF

A

Clear and colourless

21
Q

Cerebrospinal fluid cytology is performed to check…?

A

Cytology, culture, glucose and protein levels

22
Q

What is the importance of the blood brain barrier?

A

Strictly controls the movement of solutes across the CNS vasculature. See Q1 for added benefits

23
Q

Describe the blood brain barrier

A

Direct membrane-membrane contact between endothelial cells - Tight and adherens junctions seal capillary endothelium. Contains glia limitans perivascularis and pericytes.

24
Q

Where would you find glia limitans perivascularis?

A

The glia limitans perivascularis abuts the perivascular space surrounding the parenchymal blood vessels and functions as a supportive constituent of the blood–brain barrier. In contrast, the non-parenchymal blood vessels present in the subarachnoid space are not covered by the glia limitans.

25
What is the role of pericytes for BBB?
Pericytes aids in the regulation of transcellular barrier and maintenance of vessel function. Pericytes regulate capillary blood flow, the clearance and phagocytosis of cellular debris, and the permeability of the blood–brain barrier. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signalling.
26
Where does passage of cells across BBB occur?
Passage of cells across the BBB occurs primarily at the post-capillary venules
27
Describe what happens when cells move across post-capillary venules.
Endothelial expression of P- and Eselectins (rolling) > Leucocyte activation (LFA-1 and VLA-4 > Leucocyte adhesion to endothelial cells (ICAM-1) (arrest)
28
When does passage through glia limitans occur?
Passage through glia limitans most likely during infections, ischemia or inflammatory diseases
29
What disrupts the BBB?
 Vasogenic agents – Histamine, thrombin, proinflammatory cytokines (TNF-α, IL-1β, IL-6, vascular endothelial growth factor -VEGF)  Infectious agents – bacteria, bacterial toxins, viruses, parasites and fungal pathogens
30
How can viruses cross the BBB?
Viruses can cross the endothelial barrier as (1) cell-free virus, (2) associated to infected leukocytes, (3) induce BBB breakdown, (4) induce downregulation of TJP expression and/or cell death (5). After entry into the brain flaviviruses may infect the astrocytes (6), microglia (7), pericytes (8) and neurons (9)
31
What causes transmissible spongiform encephalopathies?
Prions
32
What are prions?
Proteinaceous infectious particle (prions) - infectious, misfolded proteins that cause disease and lack instructional nucleic acid
33
What diseases are caused by prions?
Kuru, Creutzfeldt–Jakob disease, variant Creutzfeldt–Jakob disease, Gerstmann–Sträussler– Scheinker disease and fatal familial insomnia  Scrapie (sheep), bovine spongiform encephalopathy, chronic wasting disease (dears)
34
Explain how prions cause TSE? (Transmissible spongiform encephalopathies)
 Oral route > innate phagocytic immune cells > lymphatic tissues (M cells) > disease-associated prion protein (PrPSc ) replicates in follicular dendritic cells (B follicles) > neuroinvasion from the intestine  Neuronal loss, vacuolation and astrocyte and microglia activation  Affect brain structure, creating microscopic holes and hence a ‘spongy’ texture
35
What is the innate immune response to TSE?
Innate immune response – proteosomal degradation, but also necessary for infection
36
What is the adaptive immune response to TSE?
* Absence of anti- PrP in the course of TSE infection * T cell-independent B cell activation is impaired due to the high resistance of prions to protease digestion - refolding renders the PrP Sc isoform extremely resistant to proteolysis * (in theory) T cells that recognise PrP Sc will be identified as self-reactive and will be deleted (identical primary amino acid sequence of PrP Sc and PrPc )