L6 Pathology Prion disease Flashcards

1
Q

how is the post mortem examination carried out

A

high risk
dedicated equipment
full protective gear: visor, double gloves, safety boots

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2
Q

what findings lead to protein only hypothesis

A

no viral particles detectable
no significant inflammatory or immunological reactions of the host
deposition of an abnormal protein, often in form of plaques

infectivity is associated with the protein deposits
damage to nucleic acids does not inactivate infectivity
extraction of the protein fraction abolishes infectivity

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3
Q

what is Prusiner 1982 hypothesis

A

the plaque protein is the infectious agent

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4
Q

what is the Weissmann 1985 hypothesis

A

the normal non-infectious protein PrP^c is encoded by the host (cellular form of PrP)and mainly expressed on neurons

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5
Q

what is the protein only hypothesis

A

the infectious prion protein has the same amino acid composition, but is resistant to proteases and tend to ploymerise

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6
Q

what are thermodynamic assumptions

A

there is conversion prevented by energy barrier between PrP^c and PrP^sc
or there is equilbrium

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7
Q

what happens in seeding and

A

if there is an excessive production of this misfolded form, you have a seed formation and that recruits further seeds built up to an infection seed then fragments into infectious seed or amyloid

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8
Q

what is not essential in template directed refolding

A

amyloid not essential for replication

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9
Q

what is the definition of prion

A

Agent of transmissible spongiform encephalopathy (TSE), with unconventional properties.
The term does not have structural implications other than that a protein is an essential component

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10
Q

what is the definition of PrP^c/PrP^sen

A

The naturally occurring form of the mature Prnp gene product. Its presence in a given
cell type is necessary, but not sufficient, for replication of the prion

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11
Q

what is the definition of PrP^sc or PrP^res

A

Abnormal’ form of the mature Prnp gene product. Partly resistant to digestion by
proteinase K.
Believed to differ from PrPC conformationally. Often considered to be the transmissible agent or
prion.

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12
Q

how many amino acids are in the PrP isoforms

A

209

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13
Q

what is the primary translation product and how many anchors needed for the glycosilation

A

primary gene product with the signal peptides

3 gpi

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14
Q

what happens in a mature PrP

A

primary translation/gene product matures and the signal peptide is taken off

the cellular formis protease sensitibe- breaks down into fragemnts

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15
Q

what happens in PrP^sc

A

the abnormal form with misfolded proteins with same primary structure and no other amino acids is now partially resistant to proteases - can be used as detection

prp-res for resistant

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16
Q

what is the corollary to the protein only hypothesis

A

Prnp knockout mice are resistant to scrapie
presence of abnormally folded protein, leads to the production of more abnormally folded protein

take awaysubstrat eshould be no more product

  • this was experimentded in 1991 - generated mice
17
Q

name a sporadic form of prion disease

A

Creutzfeldt-Jakob Disease

18
Q

name hereditary forms

A

Familial CJD and Gerstmann-Sträussler-Scheinker-Syndrome

– Fatal familial insomnia

19
Q

name transmitted forms

A
Kuru (ritual cannibalism in New Guinea)
– Medical procedures (Iatrogenic CJD)
• contaminated growth hormone
• Dura mater graXs, cornea graps
• Surgical instruments, EEG electrodes
– Variant CJD (BSE epidemics
20
Q

how many polymorphism does prion gene have

21
Q

what is seen microscopically in CJD

A
neuronal loss
spongiosis
gliosis
Fine spongiform changes in the cortex, and synaptic PrP
Macrovacuoles, coarse PrP
Cortical ribbon, perineuronal net
22
Q

what gss phenotype forms plaques in PRNP gene

A

P1OL

P1O5L

23
Q

what can form in prp deposition patterns

24
Q

where are vCJD prions detectable in BSE

A

detectable in the lymphore;cular system (e.g. tonsils, appendix),
thought to precede CNS
invasion
within the follicular dendritic cells there’s abnormal prion patients who acquire BSE

25
how many glycosilation trees does the prp gene production have
none, 1 or 2
26
where is the distribution of abnormal PrP in human tissues in body of variant
``` brain eyes sympathetic ganglia tonsil lymph nodes spinal cord spleen adrenal rectum ```
27
what is the clinical feature or kuru
progressive cerebellar ataxia
28
what does kuru resemble
iatrogenic CJD caused by peripheral administration of contaminated growth hormone
29
how can prion diseases transmit through medical procedures
More than 200 cases of Creutzfeldt-Jakob disease (CJD) have resulted from treatment with human cadaveric pituitary-derived growth hormone contaminated with prions • Approximately 200 cases of CJD resulted from the transmission through dura mater grafts • Electrodes, cornea grafts, surgical instruments • Blood transfusion
30
who did studies on kuru to primates
The agent was previously thought to be a slow virus • But it had rather unusual biological proper;es. • Transmission studies were carried out in primates (Gajdusek, Gibbs, Alpers 1967) • The findings led to the proposi;on of the protein only hypothesis (Griffith 1967)
31
in what ways can the disease be iatrogenic
``` vCJD blood transfusion gonadotroph hormone corneal grafts neuro-surgical instruments dural grafts growth hormone ```