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I&I WC1 > Organ-specific immunity: BRAIN > Flashcards

Organ-specific immunity: BRAIN Flashcards

This deck contains the lectures" "Inflammation of the CNS", "Immune privilege; blood-brain barrier", and "Innate and adaptive immune responses in the brain"

1
Q

How many T lymphocytes patrol the CSF or perivascular space for pathogens in healthy individuals?

A

150 000

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2
Q

How do memory CD4 T cells return to the blood stream?

A

Via lymphatic vessels in the meningeal spaces and the deep cervical lymph nodes

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3
Q

Which parts of the brain play a role in the neuro-immune system?

A
  • CSF
  • Blood-CSF barrier
  • Dural lymphatic vessels
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4
Q

What are the types of inflammation that can occur in the brain? (3)

A
  • Bacterial
  • Viral
  • Parasitic
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5
Q

Name examples of bacterial agents involved in neonate brain inflammation (4)

A
  • E.coli
  • Listeria
  • Staphylococci
  • Pneumococci
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6
Q

Name examples of bacterial agents involved in adult brain inflammation (4)

A
  • Pneumococci
  • Meningococci
  • N. meningitidis
  • Staphylococci
  • H. influenzae
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7
Q

What is meningitis?

A

Inflammation of the meninges

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8
Q

Why do you die from meningitis?

A

Swelling due to adema

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9
Q

What is cerebritis?

A

Inflammation of brain tissue (“encephalitis”)

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10
Q

What causes brain abscesses? (3)

A
  • Endocarditis
  • Lung infections
  • Abdominal infections
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11
Q

What is a severe complication of meningococcus meningitis?

A

Waterhouse-Friedrichsen syndrome (sepsis)

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12
Q

What are specific inflammations affecting the CNS? (4)

A
  • Tuberculosis
  • Sarcoidosis
  • Neuro-lues (Syphilis stage 3)
  • Lyme disease
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13
Q

What happens when tabes dorsalis occurs during syphilis?

A

Demyelination of sensory neurons afferent to the spinal cord

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14
Q

Name three examples of viral inflammation in the brain

A
  • Herpes simplex type 1
  • Rabies
  • Poliomyelitis
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15
Q

What are the five viral entry routes into the brain?

A
  • Via PNS
  • Via bloodvessel
  • Via olfactory epithelium
  • Via microglia
  • Infection of BMVECs
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16
Q

In which group of patients are parasitic brain inflammations prevalent?

A

Immunodeficient patients (transplantation; AIDS)

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17
Q

What are the two types of vasculitis?

A
  • Systemic
  • Primary granulomatous
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18
Q

Name three demyelinating diseases

A
  • Multiple sclerosis
  • Acute demyelinating encephalomyelitis (ADEM)
  • Progressive myelo-encephalopathy (PML)
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19
Q

What is the role of macrophages during MS?

A

Destroying myelin sheets

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20
Q

What is a MS plaque?

A

Spot of demyelination

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21
Q

What is the CNS?

A

Everything inside the skull and spine, but also the optic nerve

22
Q

What is the definition of immune privilege?

A

The permissiveness and proneness of a tissue or anatomical site to develop and sustain immune activity

23
Q

What are immune privileged sites?

A
  • Brain
  • Eyes
  • Placenta + fetus
  • Testicles
24
Q

Why are the placenta and fetus immune privileged sites?

A

If not, you would generate an immune response against your own child

25
Q

What are the three main questions when considering immune privilege?

A
  • Tolerance of the CNS for foreign bodies
  • Migration of antigens within the CNS to SLOs
  • Migration of lymphocytes
26
Q

What are the mechanisms by which tumors avoid immune recognition? (5)

A
  • Low immunogenicity
  • Tumor treated as self-antigen
  • Antigenic modulation
  • Tumor-induced immune suppression
  • Tumor induced privileged site
27
Q

How does a tumor induce a privileged site?

A

By secreting factors creating a physical barrier to the immune system

28
Q

Which structure secludes the CNS?

A

Blood-brain barrier

29
Q

What is the blood-brain barrier?

A

Unique composition of specialized endothelial cells and ascessory cells

30
Q

Name unique features of the endothelial cells of the blood-brain barrier (3)

A
  • Very tight junctions between the endothelial cells –> prevents spontaneous passing of large cells or molecules
  • Active pumps (pump in- AND out of the CNS)
  • Large amounts of pericytes
31
Q

What do pericytes secrete? (2)

A
  • Pro- and anti-inflammatory mediators
  • Growth factors
32
Q

Where do you end up if you pass the endothelial layer of the bb-barrier? What is this structure?

A

Perivascular space. Small fluid-filled structures that surround blood vessels in the brain

33
Q

What is the most immunogenic site of the CNS?

A

Perivascular space

34
Q

Why are the dual sinuses the ideal spot to be if you want immune surveillance in your brain?

A

This is the spot where blood and waste (molecules/potential antigens) are ultimately drained from your brain

35
Q

Why is it convenient to have mesenchymal structure in the PVS?

A

They form a framework for resident and surveilling leukocytes to be maintained and stored, waiting for antigens to appear.

36
Q

What is the natural habitat of CNS T-cells? What do they express to regulate immune responses in the brain?

A

Perivascular space. Express inhibitory factors

37
Q

What is an extra control step for lymphocytes in the brain?

A

Reactivation in PVS –> Mandatory step to enter the brain parenchyma

38
Q

What are the differences/similarities between perivascular macrophages and microglia? (4)

A
  • Phagocyte active (both)
  • Activated by IFN-y vs requires multiple cytokines for activation
  • Specialized vs moderate APC
  • Many vs. few co-stimulatory molecules
39
Q

Why does the brain parenchyma not inflame or elicit immune responses? (2)

A
  • The innate immune cells/microglia are much less able to elicit inflammation vs. perivascular macrophages
  • Extremely high expression of anti-inflammatory mediators in the brain parenchyma
40
Q

Example of an anti-inflammatory molecule expressed in the brain parenchyma

A

CD200

41
Q

Summary: what are the reasons why your brain does not get inflamed easily? (3)

A
  • Very controlled entry of cells
  • Compartmentalized, immunogenic region in CNS
  • Parenchyma is loaded with anti-inflammatory mediators
42
Q

What are the routes a T cell can take to enter the PVS? (2)

A
  • Meningal vasculature
  • Choroid plexus
43
Q

Which cells appear at the site of initial antigenic challenge and stay there for the remainder of the life of a mouse?

A

Resident memory T cells

44
Q

What is the function of CD69?

A

Functional agonist of all kinds of molecules that promote tissue egress

45
Q

How does the inflamed endothelium control diapedesis of activated immune cells? (4)

A
  • Tethering/Adhere to endothelial wall
  • Rolling
  • Activation
  • Arrest
  • Diapedesis
46
Q

In which direction do leukocytes role across the endothelium?

A

Rolling into opposite direction of the blood flow

47
Q

Which lymph nodes are involved in CNS drainage? (mouse)

A
  • Superficial cervicals
  • Deep cervicals
  • Lumbar
48
Q

Summary: What factors contribute to the CNS being an immune privileged site? (5)

A
  • Limited capacity of parenchymal APCs
  • Anti-inflammatory signals in the CNS parenchyma
  • Strictly compartimentalized CNS lymphocyte presence
  • Seclusion of CNS behind a blood brain barrier
  • Requirement of T cell re-activation after crossing the BBB
49
Q

What are the major cell types of the CNS? (3)

A
  • Neurons
  • Macroglia - astrocytes/oligodendrocytes
  • Microglia
50
Q
A

I&I WC1 (25 decks)

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