Neuroinflammation and HIV- and COVID-19-Associated CNS Injury Flashcards
In neuroinflammation, microglial activation is an early sign that precedes ______
neuronal cell death
______ 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.)
Microglial activation
_____ are the resident macrophages of the CNS
Microglia
- Membrane-bound off-signal
- Constitutively expressed and involved in myeloid suppression
CD47
- Membrane-bound off-signal
- Inhibits cytokine release
CD22 & CXCL1
- Membrane-bound off-signal
- Inhibits myeloid activity
- May be important in maintaining immune suppression in the CNS
CD200
- Soluble neuronal off-signal
- Anti-inflammatory cytokine
- Constitutively expressed in the brain
TGF-β
What neurotransmitters can act as off signals for microglia? (3)
- Norepinephrine
- Glutamate
- ATP
What neurotrophins can act as off signals for microglia? (3)
- NGF
- BDGF
- NT-3
____ suppresses antigen presentation capacity by downregulation of MHCII and co-stimulatory molecules of microglia
IL-10
Resting microglia tends to look more _____ while activated microglia tends to look more _____.
- Dendritic
- Ameboid
“On” signals for microglia are present in _____
stressed or impaired neurons
- Membrane bound on signal
- Ligation promotes phagocytosis of apoptotic neurons and reduces inflammation
TREM-2
- Soluble on signal
- Induce microglia migration (in vitro)
- CCL21
- CXCL10
- 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
Matrix metaloproteinase-3 (MMP-3)
Do purines (ATP, UTP) act as microglial on or off signals?
On
Why is the CNS considered “immune privileged”?
- 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
What is ADEM?
- Acute disseminated encephalomyelitis
- Brief, widespread inflammatory attack in the brain and spinal cord resulting in demyelination
- Immune-mediated (infection, vaccine)
What are the symptoms of ADEM? (5)
- Sometimes misdiagnosed as MS
- Rapid onset fever, fatigue, headache, vomitting/nausea
- Blindness
- Difficulty walking/coordination
- Impaired consciousness (sometimes coma)
What are some potential treatment options for ADEM? (3)
- Suppress inflammation (IV steroids and oral steroids)
- Plasmapheresis
- IVIg
In MS, ___ and ___ produce inflammatory demyelination of the CNS.
CD4 and CD8 T-cells
What is the function of MHC I?
- 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
What is the function of MHC II?
- Binds peptides generated from degradation of extracellular proteins
- Extracellular proteins are endocytosed, digested, and presented to CD4+ T cells
What cells act as “sentinels at the gate” of the CNS parenchyma?
CNS-associated macrophages
