(02) TSE Flashcards
just read
not infectious to other species (injected directly to hamsters and mice…)
(Scrapie)
- Sheep with particular PrP protein genotypes at what three codons affect susceptibility to scrapie?
- What strain is mainly tested for in US?
- At codon there is an increased susceptibility to scrapie with what genotype?
- 136, 154, 171
- 171
- QQ (QR and RR are more resistant)
(Q = glutamine, R = arginine)
(Scrapie Pathogenesis)
- Infectious prions are ingestsed and cross mucosa where?
- Prions accumulate where?
- Spread to CNS via what?
- tonsils, Peyer’s patches (and other sites?)
- in macrophages in lymph nodes (or other lymphoid tissues)
- via retrograde transport in nerves (or may also circulate to brain via lymph and blood)
following the spread following oral exposure
5 months - in small intestine and large
10 months - more widspread - more detectable in intestines - in some of the ganglia and a little in spinal cord
as it progresses get more involvement of nerves and CNS
at 17 months - travels into CNS - when clinical signs first become apparent
The prions can cause intracellular aggregates in neurons and glial cells - it’s these oligomers that are cytotoxic - cause damage - eventually result in classical spongiform appearance of the brain
aggregates can also be exported and become extracellular plaque deposits in the brain tissue
sheep brain with scrapie - see lots of infected neurons and glial cells
(Scrapie Diagnosis)
- Post morten hisopathology of brain (spongiform encephalopathy) and IHC demonstration of PrPsc in what three tissues?
- 3rd eyelid biopsy with IHC for PrPsc
- ELISA – not currently approved
- brain, retropharyngeal lymph node, tonsil
(Chronic Wasting Disease)
(Chronic Wasting Disease)
(Clinical Features)
- occurs in what age?
- usually what though?
- what sex?
- seasonality?
- how long is the clinical duration?
- How long in incubation period?
- 17 months to >15 years
- 3-5 years
- either
- not really
- days to >1year, usually months
- minimum ~17 months, max unknown
(CWD: Mode of Transmission)
(Chronic Wasting Disease)
(Pathologic Changes)
- Gross post mortem lesions include what and what?
- Do other tissues (including brain) show gross lesions?
- Tissues with most CWD infectivity include what four?
- cachexia and often aspiration pneumonia
- usually not
- lymph nodes, tonsils, spleen, eyes, and CNS
(Chronic Wasting Disease)
(Lymphoid tissues)
- few or no detectable changes
- PrPsc demonstrabtable before or after neuropathy is detectable?
(Neuropathology)
- earliest lesions occur where?
- IHC detection of PRPsc is diagnostic even without substantial spongiform change
- Characterstic spongiform encephalopathy consists of vacuolar change in what and what? along with what and what?
- lesions notably lack inflammatory cell infiltrates
- before (tonsils and retropharyngeal lymph nodes)
- in parasympathetic vagal nucles (at the obex)
- astrocytes and neurons; demyelination and astrocytosis
(CWD)
these are the retropharyngeal lymph nodes
this is the dorsal side of the brain
he then talked about these for a spell - look around 19:00 to find his explanation
note the lack of inflammation
(Dianostic Tests for CWD)
(Histopathology)
- characteristic what in the brain?
- IHC for PrPsc in what three things?
- ELISA on what only?
- spongiform degeneration
(the real confirmatory test in the IHC)
- affected brain regions (obex), lymph nodes, or tonsil (biopsy may be used for antemortem diagnosis)
- medial retropharyngeal lymph node only (approximately 90% sensitivity) - not really used so much
big deal in UK for a decade or so
tbis shows the public health concern associated with it
this is similar to what he was showing us in Scrapie and CWD - highest levels in brain and spinal cord - lesser in tonsils and lymph node spleen bone marrow, less in liver heart bones, very little in muscle and milk
you still wouldn’t want to eat meat from an infected animal
people who got vCJD were probably exposed to other parts of carcass
- How is BSE diagnosis performed?
- IHC for PrPsc on brain stem at obex
(no other tests are currently approved)
