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Winter course I > Brain > Flashcards

Brain Flashcards

1
Q

name the 3 characteristics of the neuro-immune system

A
  1. healthy humans have 150.000 T lymphocytes in the CSF
  2. T cells patrol the CSF or PVS for pathogens
  3. memory CD4+ T cells return to the blood stream via lymphatic vessels in the meningeal spaces and the deep cervical lymph nodes
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2
Q

what is the definition of meningitis?

A

inflammation of the meninges

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3
Q

what is the definition of cerebritis?

A

inflammation of brain tissue (encephalitis)

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4
Q

what is sepsis?

A

proliferation of bacteria in the bloodstream

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5
Q

name 3 bacterial inflammations affecting the CNS

A
  1. tuberculosis
  2. syphilis
  3. lyme disease
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6
Q

name 3 viral inflammations affecting the CNS

A
  1. herpes simplex type 1
  2. rabies
  3. poliomyelitis
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7
Q

what is the CNS?

A

everything inside the skull and spine but also the optic nerve

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8
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

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9
Q

how does a T cell move from lumen to CNS?

A

blood-brain barrier –> perivascular space –> glia limitans

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10
Q

what is the natural habitat of CNS T cells?

A

the perivascular space, reactivation in PVS is needed to enter parenchyma

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11
Q

how is inflammation controlled in the brain?

A
  • limited capacity of parenchymal APCs to provide effective activation
  • high levels of anti-inflammatory molecules (CD200)
  • requirement of T cell re-activation after crossing the BBB
  • entry of inflammatory cells is tightly regulated by BBB
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12
Q

name the 4 major CNS cell types

A
  1. neurons
  2. astrocytes
  3. oligodendrocytes
  4. microglia
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13
Q

name 4 exogenous causes of chronic inflammation in the CNS

A
  1. herpes simplex virus
  2. measles virus
  3. cytomegalovirus (CMV)
  4. Theiler’s Murine encephalomyelitis virus (TVEM)
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14
Q

which lymphocytes infiltrate the CNS during early, middle and late chronic inflammation?

A

early; macrophages
middle; expansion of T and B cells
late; mainly CD8 T cells

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15
Q

what is and which cells play a role in neuromyelitis optica?

A

demyelination of the optic nerve and the spinal cord, AQP4 and MOG specific IgG

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16
Q

MCMV (animal model for human CMV)

A
  • macrophages infiltrate CNS first
  • CD8+ T cells persist in brain
  • CD8 IFNy induce chronic microglia activation
17
Q

what is natalizumab and what side effects does it have?

A

treatment for MS, humanized anti-a4 integrin antibody (VLA-4); blocks entry of lymphocytes to CNS
side effects; reactivation of JC virus and PML

18
Q

name 3 differences between streptococcus pneumoniae and neisseria meningitidis

A
  1. S; gram-positive diplococcus vs. N; gram-negative
  2. 100% nasopharyngeal carriers vs. 5-15%
  3. sinusitis, otitis media vs. Waterhouse-Friderichsen syndrome
19
Q

name 7 initial clinical features of acute bacterial meningitis

A
  1. headache
  2. nausea
  3. photophobia
  4. fever
  5. neck stiffness
  6. altered mental status
  7. petechia
20
Q

name treatments for bacterial meningitis

A
  1. antibiotics in combination with dexamethasone
  2. vaccinations
21
Q

what is the definition of encephalitis?

A

acute inflammation of the brain parenchyma

22
Q

name 6 symptoms of viral encephalitis

A
  1. fever
  2. headache
  3. behavioral changes
  4. altered level of consciousness
  5. focal neurologic deficits
  6. seizures
23
Q

name 2 routes of viral entry into the CNS

A
  1. hematogenous (entero/arbovirus)
  2. migration via peripheral nerves (herpes/rabies virus)
24
Q

name 2 mechanisms of neurovirulence

A
  1. cytopathic effect = direct death of virus-infected neurons
  2. immune response; antiviral immune responses and exacerbated immune response due to viral infection of microglia
25
Q

name 3 pathological hallmarks of MS

A
  1. CNS inflammation; influx of peripheral immune cells
  2. demyelination; loss of myelin sheet
  3. neurodegeneration; loss of axons, synapses and neurons
26
Q

describe the EAE model

A

experimental autoimmune encephalomyelitis; model for inflammatory white matter lesions in relapsing-remitting MS –> intra-axonal Ca2+ upregulation through a leaky membrane drives focal axonal degeneration (FAD)

27
Q

describe the CMI model

A

chronic meningeal inflammation; model to study meningeal inflammation and cortical pathology in progressive MS –> meningeal inflammation induces cortical neurodegeneration in MS cortex through activation of cortical microglia

28
Q

describe the pathogenesis in early relapsing-remitting MS

A

autoreactive T cells activated in the lymph nodes and cross inflamed endothelium, and get reactivated in PVS leading to white matter demyelination

29
Q

describe the pathogenesis in advanced, progressive MS

A

white matter lesions contains CD4+ Trm cells and CD38+ B cells, IgG production breaks microglia tolerance

30
Q

name the characteristics of MS cortical lesions

A
  1. more grey than white matter demyelination
  2. lesions contain T cell infiltrates and macrophages
  3. formation of follicle-like structures in meninges

Winter course I (15 decks)

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