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Essential Neuroscience > Neuroinflammation and HIV- and COVID-19-Associated CNS Injury > Flashcards

Neuroinflammation and HIV- and COVID-19-Associated CNS Injury Flashcards

1
Q

In neuroinflammation, microglial activation is an early sign that precedes ______

A

neuronal cell death

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2
Q

______ has been linked to pathology and disease progression several neurodegenerative disorders

(e.g. Alzheimer’s Parkinson’s, HIV-associated neurocognitive disorders, Huntington’s, MS, ALS, stroke, etc.)

A

Microglial activation

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3
Q

_____ are the resident macrophages of the CNS

A

Microglia

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4
Q
  • Membrane-bound off-signal
  • Constitutively expressed and involved in myeloid suppression
A

CD47

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5
Q
  • Membrane-bound off-signal
  • Inhibits cytokine release
A

CD22 & CXCL1

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6
Q
  • Membrane-bound off-signal
  • Inhibits myeloid activity
  • May be important in maintaining immune suppression in the CNS
A

CD200

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7
Q
  • Soluble neuronal off-signal
  • Anti-inflammatory cytokine
  • Constitutively expressed in the brain
A

TGF-β

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8
Q

What neurotransmitters can act as off signals for microglia? (3)

A
  • Norepinephrine
  • Glutamate
  • ATP
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9
Q

What neurotrophins can act as off signals for microglia? (3)

A
  1. NGF
  2. BDGF
  3. NT-3
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10
Q

____ suppresses antigen presentation capacity by downregulation of MHCII and co-stimulatory molecules of microglia

A

IL-10

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11
Q

Resting microglia tends to look more _____ while activated microglia tends to look more _____.

A
  • Dendritic
  • Ameboid
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12
Q

“On” signals for microglia are present in _____

A

stressed or impaired neurons

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13
Q
  • Membrane bound on signal
  • Ligation promotes phagocytosis of apoptotic neurons and reduces inflammation
A

TREM-2

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14
Q
  • Soluble on signal
  • Induce microglia migration (in vitro)
A
  • CCL21
  • CXCL10
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15
Q
  • Soluble on-signal
  • Deemonstrated to be released in its active form from apoptotic neuronal cell cultures
  • Mediates release of TNFα, IL-6, and IL-1β in “microglia” cultures
A

Matrix metaloproteinase-3 (MMP-3)

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16
Q

Do purines (ATP, UTP) act as microglial on or off signals?

A

On

17
Q

Why is the CNS considered “immune privileged”?

A
  • Able to tolerate the introduction of antigen without eliciting an inflammatory immune response
  • Largely attributed to the blood-brain-barrier
  • CNS produces anti-inflammatory factors
18
Q

What is ADEM?

A
  • Acute disseminated encephalomyelitis
  • Brief, widespread inflammatory attack in the brain and spinal cord resulting in demyelination
  • Immune-mediated (infection, vaccine)
19
Q

What are the symptoms of ADEM? (5)

A
  1. Sometimes misdiagnosed as MS
  2. Rapid onset fever, fatigue, headache, vomitting/nausea
  3. Blindness
  4. Difficulty walking/coordination
  5. Impaired consciousness (sometimes coma)
20
Q

What are some potential treatment options for ADEM? (3)

A
  1. Suppress inflammation (IV steroids and oral steroids)
  2. Plasmapheresis
  3. IVIg
21
Q

In MS, ___ and ___ produce inflammatory demyelination of the CNS.

A

CD4 and CD8 T-cells

22
Q

What is the function of MHC I?

A
  • Binds peptides made from degradation of cytosolic proteins and presents them to CD8+ T cells
  • Peptides from normal proteins will not activate CD8+ T cells
  • Forgein proteins will activated CD8+ T cells
23
Q

What is the function of MHC II?

A
  • Binds peptides generated from degradation of extracellular proteins
  • Extracellular proteins are endocytosed, digested, and presented to CD4+ T cells
24
Q

What cells act as “sentinels at the gate” of the CNS parenchyma?

A

CNS-associated macrophages

25
Q

What CNS-associated cells act as APCs?

A
  • Macrophages
  • Dendrtic cells
26
Q

_____ is inflammation of blood vessel walls in the brain or spine

A

CNS vasculitis

27
Q

What are the symptoms of CNS vasculitis?

A

Symptoms reflect the area of the brain that is effected

  1. Severe, long-lasting headaches
  2. Strokes or TIAs
  3. Forgetfulness/confusion
  4. Weakness
  5. Problems with eyesight
  6. Seizures
  7. Encephalopathy
  8. Sensation abnormalities
28
Q

What are some potential treatments for CNS vasculitis?

A
  • High dose steroids (prednisone) in combination with cyclophosphamide (to decreased the immune system’s response to autoimmune diseases)
  • Treatment of primary illness of there is one
29
Q

What are the 3 levels of HIV-associated neurocognitive disorders? (HAND)

A
  1. HIV-associated dementia (HIV-D)
  2. Mild neurocognitive disorder (MND)
  3. Asymptomatic neurocognitive impairment (ANI)
30
Q

True or false. HAND can be assessed by a single test.

A

False. No single test confirms a diagnosis. Must be combination of neuropsychological testing, CSF analysis, and neuroimaging

31
Q

What is HIVE?

A
  • HIV encephalitis
  • Pathological correlate of HIV-D
  • Diffuse brain atrophy
  • Hyperintense lesions in the periventricular white matter
32
Q

What are some histopatholoical hallmarks of HIV? (3)

A
  1. Nodular lesions with multinucleated giant cells
  2. Perivascular cuffs
  3. Activated microglia
33
Q

What is HIV p24?

A
  • Component of HIV capsid
  • Indicates productive HIV infection
34
Q

____ is expressed by 8-10% of monocytes and increases susceptibility to HIV infection - entry and replication

A

CD16

35
Q

What is CD163?

A
  • High affinity receptor for hemoglobin-haptoglobin complex
  • Periphery: present on majority of monocytes and distinct macrophage populations
  • Brain: not normally expressed by microglia, but are present on perivascular macrophages.
36
Q

What stress-related immunological transcripts are decreased in HIV or HIVE?

A
  1. Heat-shock proteins
  2. Factors related to attenuating inflammation
  3. Functional factors (SOD and iNOS)
37
Q

What stress-related immunological transcripts are upregulated in HIV or HIVE?

A

Proinflammatory factors:

  1. IL1B
  2. IL6
  3. Serpin peptidase inhibitor
  4. Primary TNFa receptor
38
Q

What microglia-derived neurotrophic factors are downregulated in HIV infections? (4)

A
  1. Brain-derived neurotrophic factor (BDNF)
  2. Glial cell-derived neurotrophic factor (GDNF)
  3. Ciliary neurotrophic factor (CNTF)
  4. Nerve growth factor-B (NGFB)
39
Q

What microglia-derived neurotrophic factors are upregulated in HIV infections? (2)

A
  1. Neurotrophin-3 (NTF3): survival, differentiation of new and existing neurons
  2. Fibroblast growth factor-2 (FGF2): may be involved in survival of specific neuron populations

Essential Neuroscience (10 decks)

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