Exam 3 - Prions-Pox

Question 1

Prions

Prion Dz alter ego

Answer 1

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

Question 2

Prions

Normal protein

Answer 2

PrPc

Question 3

Prions

Pathogenic isoform

Answer 3

PrPSc

Question 4

Prions

PrPc fxn

Answer 4

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

Question 5

Prions

PrPc location

Answer 5

• primarily neurons
• also muscle and lymph
• anchored to cell membrane

Question 6

Prions

PrPSc location

Answer 6

intracellularly

Question 7

Prions

PrPSc arrangement

Answer 7

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

Question 8

Prions

What’s their kryptonite?

Answer 8

• few things!
• Proteinase K
• denaturing agents
• organic solvents
• detergents

Question 9

Prions

PrPc genetics

Answer 9

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

Question 10

Prions

path

Answer 10

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

Question 11

Prions

immune response

Answer 11

• none!
• no nucleic acids, no antigens
• no inflammation

Question 12

Prions

transmiss

Answer 12

• consumption of neural tissue

- iatrogenic (neurosurg, transplants)

Question 13

Prions

3 types of human dz

Answer 13

• familial
• sporadic
• acquired

Question 14

Prions

familial dz

Answer 14

-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!!!!)

Question 15

Prions

Sporadic CJD

Answer 15

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

Question 16

Prions

sCJD clinical

Answer 16

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

Question 17

Prions

Acquired types

Answer 17

• ingestion (Kuru, vCJD)

- iatrogenic

Question 18

Prions

Iatrogenic prevention

Answer 18

• steam autoclave over 121 C

- NaOH, Cl, guanadine thiocyanide

Question 19

Prions

Kuru

Answer 19

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

Question 20

Prions

vCJD

Answer 20

• 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

Question 21

Prions

non-transmissible dz

Answer 21

• Scrapie (sheep)

- Chronic Wasting Dz (deer/elk)

Question 22

Prions

BSE

Answer 22

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

Question 23

Prions

Prion Dz dx

Answer 23

-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

Question 24

Prions

Prion Dz tx

Answer 24

• bleeeeeak!
• chlorpromazine (antipsychotic)
• quinacrine (experimental)

Question 25

Poxviruses | morphology

Answer 25

- brick shaped - surface tubules, microfilaments - dsDNA

Question 26

Pox | path

Answer 26

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

Question 27

Pox Smallpox epi

Answer 27

- last known infx'n Somalia 1977 - humans are only reservoir - aerosol, highly contagious - can be trasmitted in lab, clinic

Question 28

Pox | Smallpox path

Answer 28

- invades alveolar tissue - replicates in lymph nodes - brief asx viremia

Question 29

Pox | Smallpox clin/sx

Answer 29

- 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

Question 30

Pox | Smallpox types

Answer 30

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

Question 31

Pox | Smallpox vaccine

Answer 31

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

Question 32

Pox | Cowpox

Answer 32

- "vaccinia" - rodent reservoir - tramiss'd by titties or kitties - pustular lesions at site of innoculation - used for vaccines, DNA delivery

Question 33

Pox | Buffalopox

Answer 33

- Asian buffalo - Russia, near East, Italy, Egypt - udderly vesicular - don't touch that udder!

Question 34

Pox | Monkeypox

Answer 34

- 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

Question 35

Pox | Molluscum

Answer 35

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

Question 36

Pox | Orf

Answer 36

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