Brain Flashcards
name the 3 characteristics of the neuro-immune system
- healthy humans have 150.000 T lymphocytes in the CSF
- T cells patrol the CSF or PVS for pathogens
- memory CD4+ T cells return to the blood stream via lymphatic vessels in the meningeal spaces and the deep cervical lymph nodes
what is the definition of meningitis?
inflammation of the meninges
what is the definition of cerebritis?
inflammation of brain tissue (encephalitis)
what is sepsis?
proliferation of bacteria in the bloodstream
name 3 bacterial inflammations affecting the CNS
- tuberculosis
- syphilis
- lyme disease
name 3 viral inflammations affecting the CNS
- herpes simplex type 1
- rabies
- poliomyelitis
what is the CNS?
everything inside the skull and spine but also the optic nerve
what is the definition of immune privilege?
the permissiveness and proneness of a tissue or anatomical site to develop and sustain immune activity
how does a T cell move from lumen to CNS?
blood-brain barrier –> perivascular space –> glia limitans
what is the natural habitat of CNS T cells?
the perivascular space, reactivation in PVS is needed to enter parenchyma
how is inflammation controlled in the brain?
- 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
name the 4 major CNS cell types
- neurons
- astrocytes
- oligodendrocytes
- microglia
name 4 exogenous causes of chronic inflammation in the CNS
- herpes simplex virus
- measles virus
- cytomegalovirus (CMV)
- Theiler’s Murine encephalomyelitis virus (TVEM)
which lymphocytes infiltrate the CNS during early, middle and late chronic inflammation?
early; macrophages
middle; expansion of T and B cells
late; mainly CD8 T cells
what is and which cells play a role in neuromyelitis optica?
demyelination of the optic nerve and the spinal cord, AQP4 and MOG specific IgG
MCMV (animal model for human CMV)
- macrophages infiltrate CNS first
- CD8+ T cells persist in brain
- CD8 IFNy induce chronic microglia activation
what is natalizumab and what side effects does it have?
treatment for MS, humanized anti-a4 integrin antibody (VLA-4); blocks entry of lymphocytes to CNS
side effects; reactivation of JC virus and PML
name 3 differences between streptococcus pneumoniae and neisseria meningitidis
- S; gram-positive diplococcus vs. N; gram-negative
- 100% nasopharyngeal carriers vs. 5-15%
- sinusitis, otitis media vs. Waterhouse-Friderichsen syndrome
name 7 initial clinical features of acute bacterial meningitis
- headache
- nausea
- photophobia
- fever
- neck stiffness
- altered mental status
- petechia
name treatments for bacterial meningitis
- antibiotics in combination with dexamethasone
- vaccinations
what is the definition of encephalitis?
acute inflammation of the brain parenchyma
name 6 symptoms of viral encephalitis
- fever
- headache
- behavioral changes
- altered level of consciousness
- focal neurologic deficits
- seizures
name 2 routes of viral entry into the CNS
- hematogenous (entero/arbovirus)
- migration via peripheral nerves (herpes/rabies virus)
name 2 mechanisms of neurovirulence
- cytopathic effect = direct death of virus-infected neurons
- immune response; antiviral immune responses and exacerbated immune response due to viral infection of microglia
name 3 pathological hallmarks of MS
- CNS inflammation; influx of peripheral immune cells
- demyelination; loss of myelin sheet
- neurodegeneration; loss of axons, synapses and neurons
describe the EAE model
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)
describe the CMI model
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
describe the pathogenesis in early relapsing-remitting MS
autoreactive T cells activated in the lymph nodes and cross inflamed endothelium, and get reactivated in PVS leading to white matter demyelination
describe the pathogenesis in advanced, progressive MS
white matter lesions contains CD4+ Trm cells and CD38+ B cells, IgG production breaks microglia tolerance
name the characteristics of MS cortical lesions
- more grey than white matter demyelination
- lesions contain T cell infiltrates and macrophages
- formation of follicle-like structures in meninges
