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MID Exam 3 > Exam 3 - Prions-Pox > Flashcards

Exam 3 - Prions-Pox Flashcards

1
Q

Prions

Prion Dz alter ego

A

Transmissible Spongiform Encephalopathy
TSE
Kristian’s favorite infx’ous dz!!!!

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2
Q

Prions

Normal protein

A

PrPc

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3
Q

Prions

Pathogenic isoform

A

PrPSc

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4
Q

Prions

PrPc fxn

A 
unknown!
possibly:
-neuron devel
-cell signal transduction
-copper metabolism
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5
Q

Prions

PrPc location

A
  • primarily neurons
  • also muscle and lymph
  • anchored to cell membrane
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6
Q

Prions

PrPSc location

A

intracellularly

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7
Q

Prions

PrPSc arrangement

A

1) Beta pleated sheets
2) rods, fibrils
3) amyloid plaques
4) heterogeneous tertiary structure

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8
Q

Prions

What’s their kryptonite?

A
  • few things!
  • Proteinase K
  • denaturing agents
  • organic solvents
  • detergents
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9
Q

Prions

PrPc genetics

A
  • PRNP gene on ch20
  • polymorphism at codon 129
  • Met/Met homozygous increases risk of PrPSc
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10
Q

Prions

path

A
  • intracellular accumulation of PrPSc
  • spongiform vacuolation
  • amyloid plaque formation
  • neuron loss
  • microglial activation, astrocyte proliferation
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11
Q

Prions

immune response

A
  • none!
  • no nucleic acids, no antigens
  • no inflammation
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12
Q

Prions

transmiss

A
  • consumption of neural tissue

- iatrogenic (neurosurg, transplants)

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13
Q

Prions

3 types of human dz

A
  • familial
  • sporadic
  • acquired
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14
Q

Prions

familial dz

A

-autosomal dominant
-PRNP mutation to PrPSc
-fCJD most common (codon 200)
-fCJD earlier onset, longer course
than spontaneous
-Gerstmann-Straussler-Scheinker
-Fatal familial insomnia (MY FAVEY!!!!)

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15
Q

Prions

Sporadic CJD

A
  • 85% of prion dz
  • random PRNP mutation
  • mean onset 60yo
  • death in 4-5 mo
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16
Q

Prions

sCJD clinical

A

-fatigue, sleep d/o, bx change,
visual change, ataxia, aphasia,
motor deficits, mycoclonus, dementia

17
Q

Prions

Acquired types

A
  • ingestion (Kuru, vCJD)

- iatrogenic

18
Q

Prions

Iatrogenic prevention

A
  • steam autoclave over 121 C

- NaOH, Cl, guanadine thiocyanide

19
Q

Prions

Kuru

A
  • Papua New Guinea
  • ritualistic cannibalism
  • women/children
  • cerebellar involvement
  • 4-40 yr incubation
  • 2mo-2yr death
20
Q

Prions

vCJD

A
  • acquired from cow brain
  • primary mutation is BSE
  • mean onset 28yo
  • prominent psych/bx change, dyesthesias
  • delayed neuro change vs. sCJD
  • Met/Met homozygous at codon 129
  • pulvinar sign in post. thalamus
21
Q

Prions

non-transmissible dz

A
  • Scrapie (sheep)

- Chronic Wasting Dz (deer/elk)

22
Q

Prions

BSE

A

-moooooo
-UK 1985
-WA State 2003 (when Kristian was
in high school!!!

23
Q

Prions

Prion Dz dx

A

-PrPSc in tissue (brain tissue)
-lymph tissue for vCJD
-cerebrospinal fluid analysis: 14-3-3 protein
(14-3-3 ddx w/ stroke)
-pulvinar sign in vCJD

24
Q

Prions

Prion Dz tx

A
  • bleeeeeak!
  • chlorpromazine (antipsychotic)
  • quinacrine (experimental)
25
Q

Poxviruses

morphology

A
  • brick shaped
  • surface tubules, microfilaments
  • dsDNA
26
Q

Pox

path

A
  • entry by fusing w/ outer cell membrane
  • early and late gene expression
  • muture virion
  • wrapped virion (on Golgi)
  • fusion with plasma mem, release
27
Q

Pox
Smallpox
epi

A
  • last known infx’n Somalia 1977
  • humans are only reservoir
  • aerosol, highly contagious
  • can be trasmitted in lab, clinic
28
Q

Pox

Smallpox path

A
  • invades alveolar tissue
  • replicates in lymph nodes
  • brief asx viremia
29
Q

Pox

Smallpox clin/sx

A
  • prodrome (malaise, high fever)
  • rash on face, hands (papules->pustules) after 3 days
  • rash may also be on mucous membranes
  • lesions all at same stg of devel, crust at day 5
  • infx’ous lesions until scabs fall off
  • deep scarring
  • > 30% mortality
30
Q

Pox

Smallpox types

A
  • variola major (90% of cases)
  • variola minor (more mild)
  • flat/malignant (95% mortality)
  • hemorrhagic (rare, 100% fatal)
  • variola sine eruptione (non-infx’ous reinfection)
31
Q

Pox

Smallpox vaccine

A

-live vaccinia (cowpox)
-successful vacc produces lesion at site
-risk of innoculation, eczema, dissemination (HIV),
myopericarditis

32
Q

Pox

Cowpox

A
  • “vaccinia”
  • rodent reservoir
  • tramiss’d by titties or kitties
  • pustular lesions at site of innoculation
  • used for vaccines, DNA delivery
33
Q

Pox

Buffalopox

A
  • Asian buffalo
  • Russia, near East, Italy, Egypt
  • udderly vesicular
  • don’t touch that udder!
34
Q

Pox

Monkeypox

A
  • Africa
  • rodent (prairie dog!) reservoir, human/monkey incidental hosts
  • 12 day incubation
  • similar lesions to smallpox but w/ lymphadenopathy
  • resp sx
  • less communicable than smallpox
  • 15% fatal
  • protection from smallpox vaccine
35
Q

Pox

Molluscum

A
  • benign, self-limited papular eruption (2-6 mm)
  • children, STI, immunocompromised
  • face, trunk, extremities, genitals
  • 14-50 day incubation
  • cryotherapy
36
Q

Pox

Orf

A
  • sheep, goats, Europe, New Zealand
  • stop fondling the livestock
  • reddish nodules ->pustules->ulceration
  • self heal 3-6 wks

MID Exam 3 (13 decks)

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