Prions- Detection and Control Flashcards
What are the clinical signs of BSE?
Cows with BSE, apprehension then inco-ordination
Motor neurones affected
Clinical signs alone are not sufficient to diagnose a prion disease
How can we diagnose Prion disease and whatmethods are not enough to diagnose?
Clinical signs- NO
Brain plaques/Vacuolation- also found in other rare conditions
Lab tests- Ab, NO, this is because host protein all self reactive T-cells have been depleated before birth, so no Tcell help for B cells and No IgG Ab.
DNA or RNA probes?: PrPSc is a surrogate marker,
Ab staining of brain tissue:
Although prions infections do no generate IgG Ab they can be product experimetally so how do they generate Ab)
Put them in a mouse as this will be foreign for the mouse
Ab not selective for PrPSc but only Sc forms aggregates
Western Blots
What are the 3 different isoforms of thr PrPc molecules?
Note they are not 3 different proteins!!
1: Both sites are glycosylated
2. One of the sites is glycosylated
3. Not glycosylated
All of these can be converted to PrPSc
How to differintiate PrPSc from c?
Protease Sensitivity of PrPᶜ
The sample is split into two: one is left untreated (-), and the other is treated with a protease (+).
Result: After protease treatment, PrPᶜ is completely degraded, meaning it is protease-sensitive.
Protease Resistance of PrPˢᶜ
The sample is again split into untreated (-) and protease-treated (+).
Result: After protease treatment, PrPˢᶜ is only partially degraded, leaving behind a characteristic protease-resistant fragment (~27-30 kDa).
What parts of the brain does CJD vCJD and Kuru affect?
CJD: Cerebrum, Thalamus
vCJD: Cerebellum, Thalamus
Kuru: Cerebellum
Experimentally- if you inject brain tissue from different diseases into mice get diff but highly reproductible patterns in what??
Length of incubation period in inbred mice
Incubation period is due to both replication rate and the time taken to travel to the brain
This test shows that incubation time in scrapies is longer than BSE
and CJD has a longer incubation period that vCJD
Scrapies have longer than vCJD
vCJD and feline songiform enc (FSE) comes from BSE prions as they all have very similar incubation prions
Describe how scrapie transmits?
Scrapie can persist in the environment for at least 16 yrs
Scrapie remains in soil
Scrapie transmitted by ingestion
Describbe how BSE transmits?
No evident of environmental factor
Causitive agent was in the food
Infected Meat and bone Meal (MBM)
MBM- high protein dietry supplement prepared from the slaughterhous scraps/leftovers
MBM increased growth rates and milk yields
So, increased % MBM fed to cattle
Occurs sporadically in cows
Hard to destroy: Prions are resistent to conventianal sterilisation techniques- heat requires 121 C for 1 hours.
What has to happen first for the Prions to enter the CNS?
PrPc is also expressed on non neuronal cells including immune cells)
Prion infection requires replication of prions outside the CNS first
Within folicular dentritic cells
Anther reason that incubation times are long
How to control CJD and Kuru in man?
Kuru: Stop canabalism
vCJD: food chain, blood transfusions, Surgery-sterilise equipment - use new equipement
What are the directed drug discovery stratergies in prion diseases
Lowering PrP gene expression
Promoting PrP degradation
Relocalization of PrPc
Binding and stabilization of PrPc
Blocking PrPc- mediated neurotoxic pathway
How do we control BSE?
Cul
Control diet- ban MBM
How do we control sheep scrapie?
No vaccine or treatment
Resistent to commercial disinfectants
Scrapie is notifiable disease
Cul infected animals
Movement restrictions of flocks
National breeding plans
Selective breeding mutations at codons 136, 154 and 171
VRQ: most susceptible
ARR: most resistent
ARQ: in between
Not popular with farmers
