Neuroinflammation and Neurodegeneration Flashcards
_________________ placed heterotopically in the __________ and into the ___________ of the rabbits survive for prolonged, sometimes indefinite, periods of time.
allogeneic skin grafts, anterior chamber of the eye, brains
What is an allogeneic graft?
graft derived from a different donor of the SAME SPECIES
What is a syngeneic graft?
graft derived from a genetically identical individual (e.g. identical twin)
What is a xenogeneic graft?
graft derived from a DIFFERENT SPECIES
What is an autologous graft?
graft derived from the SAME INDIVIDUAL
What is a heterotopic graft?
graft placed in a NON PHYSIOLOGICAL SITE (e.g. skin transplanted into the brain)
What are some immune privileged sites?
- eye (cornea, anterior chamber, vitreous cavity, subretinal space)
- brain (ventricles and striatum)
- pregnant uterus
- ovary
- testis
- adrenal cortex
- hair follicles
What is the function of the BBB?
create resistance to anything coming from the outside
TRUE or FALSE: the adaptive immune system is the first line of defense
FALSE: innate is first line
TRUE or FALSE: the adaptive immune system is characterized by memory
TRUE
What are the innate immune system cells?
- macrophages
- neutrophils
- NK cells
- mast cells
- basophils
-eosinophils - dendritic cells
- microglia
- astrocytes
What are the adaptive immune system cells?
- T cells
- B cells
- dendritic cells
- microglia
- astrocytes
Is CNS inflammation an innate or adaptive response>?
innate
What happens to the shape of astrocytes when they are activated?
they become narrow (normally wide and flat)
_______________ ______________ is one of the most common and earliest features of nearly all neuroinflammatory disorders.
microglial activation
In vitro assays of microglial function have conclusively demonstrated their ability to acquire _____________ or ____________ functions. (What does this mean?)
neuroprotective; neurotoxic (i.e. microglia are both pro- and anti-inflammatory)
What are the functions of microglia and macrophages within the CNS?
- pruning synapses during development
- work with complement proteins (label synapses that need to be removed)
- monitor neuronal activity/environment
- clean up lesion/dead tissue during pathology
What are microglia functions during CNS injury?
- phagocytosis of synapses
- activate astrocytes
- remyelination
What is the most important step for activating microglia?
priming
TRUE or FALSE: alert state microglia can become pathological
TRUE
___________ ____________ keep microglial in a down-regulated state.
neuron-glial interactions
TRUE or FALSE: younger age promotes alert state of microglia
FALSE: promotion of alert state increases with age
TRUE or FALSE: While M1 microglia are more anti-inflammatory, M2 are more pro-inflammatory
FALSE: M1 is pro, M2 is anti-inflammatory
What is the relationship betwen microglial activation and neuronal degeneration?
bidirectional (see slide 20 diagram)
TRUE or FALSE: thickness of the corpus callosum is increased in MS.
FALSE: decreased
Is MS a neurodegenerative disease?
yes
What are the characteristics of a neurodegenerative disease?
- affect specific parts of functional systems in nervous system
- begin insidiously, after long period of normal function with gradual progression
- CSF shows minimal changes (mild increase in proteins)
- imaging shows either no change or only a volumetric reduction (atrophy)
TRUE or FALSE: HLA genetic mutation is specific to MS
FALSE: connected with immune response in general
TRUE or FALSE: in MS, neuronal degeneration from mitochorndrial injury, oxidative stress, and ionic imbalance will continue even WITHOUT inflammation
TRUE
TRUE or FALSE: MS is a progressive disease
TRUE
Describe the inside-out hypothesis of neurodegeneration in MS.
- WM pathology: demyelination –> axonal degeneration
- GM pathology: axonal degeneration –> demyelination (inside out)
- MS could occur due to one or the other, or both
What is the role of autophagy in neurodegeneration?
triggers inflammation
What is the ER normally responsible for? What does pathology cause?
- normal: synthesis of proteins
- path: misfolded proteins
What are the mechanisms activated in the ER with pathology?
- apoptosis
- inflammation
what are the priming factors fro ER stress in AD? What can these lead to?
- metabolic syndrome
- depression
- aging
- TBI
- infection
- can lead to neuroinflammation
