Prions Flashcards
TSE’s?
Transmissable Spongiform Encephalopathy
What causes TSEs?
Prions (infectious proteins)
TSE disease process
Long incubation period but then rapidly progressive. Usually leads to a fatal dimentia
Pathology shows multifocal spongiform changes
Are there amyloid plaques present in TSE
not usually
Inflammation in TSE (transmissable spongiform enceph)
minimal
Human TSE
- kuru
- creutzfeld-jakob
- Gertsmann Straussler Scheinker disease
- Fatal familial insomnia
- Variant CJD
Animal TSE
Scrapie (seen in sheeps and goats)
Bovine spongiform encephalopathy (BSE)
Chronic Wasting Disease (deer and elk)
Agents that cuase TSEs are resisitant to what
Regular virus treatments which damage nucleic acids.
Prion stands for
Proteinacious infectious particles
Prion protein is highly conserved among humans and animals
KNOW
where is the prion protein encoded>
on a single axon on human chromosome 20
Prion protein is highly expressed where
neurons and lymphocytes
Prion protein final product
a 209 amino acid glycoprotein that is anchored to cell surfaces by a fatty acid
WHat are the two general forms of prions
The physiologic type: PrPc
The patologic type: PrPsc or PrP res
Stands for PrP scrapie or PrP resistant
KNOW PrPc and PrPsc can have identical sequences yet they are different because of what
They way they fold.
PrPsc is unusually stable and only partially degraded by proteases. Aggregates in cell cytoplasm and leads to neuron apoptosis
Remember…you must express PrPc in order to contract disease. ALso remember that there are probably chaperone proteins involved in this process since simly mixing PrPsc and PrPc together doesnt generate scrapie protein
ok
What the fuck is the scrapie disease
- subacute, progressive ataxia of sheep
- first found at one year of age in lymphatics and tissues
- by 2 yrs the brain is infected
First documented human TSE
Kuru
Most common human TSE
Creutzfeld Jakob (CJD)
Three forms of CJD
sporadic- most common
Iatrogenic
Familial
classic CJD quadrad
- Dementia
- Myoclonus
- Ataxia
- Mutism
Sporadic CJD onset age
around 60
Mean survival time for sporadic CJD
only 5-8 mos
Cause of sporadic CJD
pretty much unknown
How do you get iatrogenic CJD
Dural grats
Corneal grafts
HGH
NOT BLOOD TRANSMISSION
Familial CJD inheritance
Auto dominant
age of onset 45-50
survival 2-4 yrs
CJD diagnosis
- CLinical course: rapid dementia and myoclonus
- histology shows spongiform change and no amyloid which rules out alzheimers
- Check CSF to rule out tertiary syphillis
Gertzman Schausler Shanker (sp?) follows what inheritance patterns
AD
What mutation is GSS associated with
codon 102 of PrP
Clinical features of GSS
avg age of onset is 48
mean time to death is 5 years
gait abnormalities and ataxia
dementia is less common
KNOW>..GSS shows amyloid plaques and spongiform changes
ok
FFI inheritance
AD
Clinical features of FFI
- sleep disturbaces
- autonomic dysfunction
histo of FFI
no spongiform changes. just neuronal loss
Variant CJD
NEW!! found in UK in 90’s
the causative agent of CJD is the same as what
The same as BSE (mad cow). So it came from contaminated beef or blood transfusion which is different that the CJD we discussed earlier
One major difference between regular CJD and variant is
Regular affects pretty much only the CNS
Variant = CNS, retina, DG, bone marrow, tonsils, spleen, lymphnodes, appendix, blood
Also:
Age of onset is 29 in variant (compared to 60)
mean survivial is 14 in variant (compared to 5-8)
SEnsory abnormalities , anxiety, depression
ALL INDIVIDUALS WITH vCJD were homozygous for
methionine at position 129 of Prp
Diagnosis of vCJD
prion positive tonsil biopsy
histology shows spongiform changes in basal ganglia…flower appearance
how do you properly sterilize graft equit to protect from iatrogenic CJD
soak in 1 M sodium hydroxide for an hour followed by autoclave at 134 C
