Brain

Question 1

name the 3 characteristics of the neuro-immune system

Answer 1

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

Question 2

what is the definition of meningitis?

Answer 2

inflammation of the meninges

Question 3

what is the definition of cerebritis?

Answer 3

inflammation of brain tissue (encephalitis)

Question 4

what is sepsis?

Answer 4

proliferation of bacteria in the bloodstream

Question 5

name 3 bacterial inflammations affecting the CNS

Answer 5

1. tuberculosis
2. syphilis
3. lyme disease

Question 6

name 3 viral inflammations affecting the CNS

Answer 6

1. herpes simplex type 1
2. rabies
3. poliomyelitis

Question 7

what is the CNS?

Answer 7

everything inside the skull and spine but also the optic nerve

Question 8

what is the definition of immune privilege?

Answer 8

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

Question 9

how does a T cell move from lumen to CNS?

Answer 9

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

Question 10

what is the natural habitat of CNS T cells?

Answer 10

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

Question 11

how is inflammation controlled in the brain?

Answer 11

• 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

Question 12

name the 4 major CNS cell types

Answer 12

1. neurons
2. astrocytes
3. oligodendrocytes
4. microglia

Question 13

name 4 exogenous causes of chronic inflammation in the CNS

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

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

Question 16

MCMV (animal model for human CMV)

Answer 16

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

Question 17

what is natalizumab and what side effects does it have?

Answer 17

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

Question 18

name 3 differences between streptococcus pneumoniae and neisseria meningitidis

Answer 18

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

Question 19

name 7 initial clinical features of acute bacterial meningitis

Answer 19

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

Question 20

name treatments for bacterial meningitis

Answer 20

1. antibiotics in combination with dexamethasone
2. vaccinations

Question 21

what is the definition of encephalitis?

Answer 21

acute inflammation of the brain parenchyma

Question 22

name 6 symptoms of viral encephalitis

Answer 22

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

Question 23

name 2 routes of viral entry into the CNS

Answer 23

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

Question 24

name 2 mechanisms of neurovirulence

Answer 24

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

Question 25

name 3 pathological hallmarks of MS

Answer 25

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

Question 26

describe the EAE model

Answer 26

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)

Question 27

describe the CMI model

Answer 27

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

Question 28

describe the pathogenesis in early relapsing-remitting MS

Answer 28

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

Question 29

describe the pathogenesis in advanced, progressive MS

Answer 29

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

Question 30

name the characteristics of MS cortical lesions

Answer 30

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