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Prions and other strange pathogens Flashcards

1
Q

What did the arrival of Europeans in the Carribean in 1492 lead to?

A

Largest human population replacement in the past 13,000 years
1492- 61 million people
1650- 6 million people

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2
Q

Why was there such a loss in population when the Europeans arrived in the Carribean?

A

Diseases carried by Europeans, plus war, enslavement and famine. Led to
Near-cessation of farming and reduction in fire use.
Regeneration of >50 million hectares of forest, woody savanna
and grassland.
Carbon uptake by vegetation and soils estimated at 5–40 Pg within around 100 years

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3
Q

What process should kill a new host?

A

MHC incompatibility

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4
Q

What is the Tazmanian Devils- Devil facial tumour disease (DFTD)?

A

Schwann cell

Endangering the species

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5
Q

What is the dogs- canine transmissible veneral tumour (CTVT)?

A

From a dog

Roughly 11,000 yrs BP

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6
Q

What is the hamsters- reticulum cell sarcoma?

A

Transmissible by contact, material left of cage mesh and even by mosquitoes

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7
Q

How many women in the US get cancer each year while they’re pregnant?

A

3,500

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8
Q

What are some examples of cancers that have been passed from mother to foetus?

A

Melanoma
Acute leukaemia
Carcinoma

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9
Q

What are mimiviruses?

A

Have genes encoding repair enzymes, correct replication errors, produce mRNA transcripts from genes and translate those mRNAs into proteins

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10
Q

What is considered the hallmark of living things?

A

Informational genes

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11
Q

What do virusoids depend on?

A

Helper viruses which encapsulate them

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12
Q

What is Hepatitis B delta antigen encoded by?

A

A virusoid

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13
Q

What is the smallest genome for animal-infective pathogen?

A

Roughly 1700 nucleotides

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14
Q

What is the structure of virusoids?

A

Negative sense, single stranded, closed circular RNA

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15
Q

What are viroids?

A

Plant pathogens

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16
Q

What is the structure of viroids?

A 
RNA genome
smallest known- 220 nucleotides of RNA
Single stranded, covalent circle
Extensive intra-molecular pairing 
No protein encoded
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17
Q

Are helper virus needed for replication in viroids?

A

No

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18
Q

What makes both strand in viroids?

A

A DNA directed RNA polymerase

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19
Q

What activity do both viroids and virusoids do?

A

Ribozyme activity

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20
Q

What are examples of diseases of protein misfolding?

A

Alpha-synuclein – in Parkinson’s diseease
Beta-amyloid – in Alzheimer’s disease
Both prion-like.
Transmissible protein aggregation/misfolding -

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21
Q

What are prions?

A

Pathogen appears to be comprised of protein only

No genetic nucleotide material involved

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22
Q

What do prions cause?

A

The transmissible spongiform encephalopathies (TSEs)

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23
Q

What is the shape of prions?

A

Prions are aberrantly or misfolded forms of normal cellular proteins

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24
Q

What do prions contradict?

A

‘central dogma of molecular biology’

25
where is scrapie found?
in sheep and goats
26
where is Bovine Spongiform Encephalopathy (BSE) found?
in cattle - mad cow disease
27
what was the first prion disease described in humans and shown to be transmissible?
Kuru (in Papua New Guinea)
28
what are the Creutzfeldt-Jakob disease (CJD) varieties?
- iatrogenic (iCJD) - variant CJD (vCJD or nvCJD) - derived from BSE - familial CJD (fCJD) - sporadic CJD (sCJD)
29
is human CJD derived from scrapie of sheep?
No
30
when was the Kuru epidemic originated?
around 1900 from a single individual thought to have spontaneously developed some form of CJD
31
what did the endocanibalistic funeral practices consisted of?
relatives consumed the bodies of the deceased to return the life force
32
where there any gender differences in the prevalence of Kuru?
8/9 times more prevalent in women and children than in men
33
why was Kuru more prevalent in women and children?
because they ate the rest of the body, including the brain, and took the task of cleaning relatives after death - may have had open sores and cuts
34
can humans get nvCJD from scrapie of sheep
not directly
35
how does cattle get BSE?
from sheep scrapie
36
how can humans get nvCJD?
from BSE
37
what is amyloid?
insoluble fibrous protein aggregates sharing specific traits
38
what is characteristic of CJD?
vacuolation of the neural tissue - amyloid accumulation
39
what does the intracellular process thought to cause?
the production and accumulation of improperly folded PrP protein
40
to what is the transmissible trio protein resistant?
is highly resistant to digestion proteinases (proteinase K)
41
what is PrPc?
normal cellular prion protein
42
what is PrPSc?
abnormal prion/scrapie protein
43
what evidence is there that supports the protein-only hypothesis?
- no virus particles, bacteria, fungi associated with prion diseases - no nucleic acid has been conclusively associated with infectivity- agent is resistant to ultraviolet radiation - no immune response to infection - PrPSc experimentally transmitted between one species and another results in PrPSc with the amino-acid sequence of the recipient species - replication of the initial infectious agent does not occur
44
what other evidence is there for the protein-only hypothesis?
- familial prion disease occurs in families with a mutation in the PrPc gene - mice with PrPc mutations develop prion disease despite conditions where transmission is prevented - animals lacking PrPc do not contract prion disease gene if infected - infectious prions can be formed de novo from purified non-infectious components, in the absence of gene-coding nucleic acids
45
how do we get nvCJD?
injections, surgery, transfusions, needles or electrodes, dentistry
46
how does nvCJD spread?
- oral - very quickly proliferates in tonsils | - enterocytes - M cells and dendritic cells required for/enhance dissemination to the CNS
47
where can prions propagate?
in the lymphoreticular system (spleen, lymph, nodes, tonsils, appendix, and other gut-associated lymphoid tissues)
48
what can the propagation of prions lead to?
neuroinvasion
49
what age group is more susceptible to nvCJD?
females - 20-24 | males - 25-29
50
what is the genetic susceptibility in humans?
- M129 - methionine at position 129 - early onset Kuru - heterozygotes amongst long term survivors of Kuru - V129 resistant to nvCJD
51
what are the prevention measures for nvCJD?
- cattle for consumption killed young -27 months - limitation on which parts of an animals can enter food chain - sterilisation procedures improved - blood products - policy changes
52
what are prions quite resistant to?
denaturation by proteinases, heat, radiation and formalin
53
how can prions be denatured?
at 134ºC for 18 mins in a pressurised steam autoclave
54
can denatured prions be renatured?
yes- to an infective status under certain artificial conditions
55
what does the WHO recommends?
1. immersion in 1N NaOH and heating at 121ºC for 30 mins; clean; rinse in water; and then subject to routine sterilisation 2. immersion in 1N NaOH or sodium hypochlorite for 1h; transfer instrument to water; heat for 1h; clean; and hen subject to routine sterilisation 3. immerse in 1N NaOH or sodium hypochlorite for 1h; remove and rinse in water, then heat to 121ºC or even 134ºC autoclave for 1h; clean; and then subject to routine sterilisation
56
to what is scrapie infectious?
not directly to humans | infectious to cattle and hence to humans (causing nvCJD)
57
what are prions?
abnormal versions of a normal protein
58
how do prions spread?
by transforming normal proteins with which they come into contact into abnormal versions
59
where can this occur?
in the brains of parkinson's disease

Infection and Immunity (20 decks)

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