Prions

Question 1

PrP^c

Answer 1

also known as PrP^sen
normal protein found on the membranes of cells
found in tissues, including neurons
alpha helical- predominance of alpha protein sheet
susceptible to protease digestion

Question 2

PrP^SC

Answer 2

infectious prion particles
same amino acid sequence of PrP^c
predominance of beta pleated sheets
resistant to proteases, radiation, boiling, formaldehyde
sensitive to bleach, phenol, iodine
infectivity reduced when autoclaved at 132 for 90 minutes

Question 3

sporadic spongiform encephalopathy

Answer 3

spontaneous misfolding of cellular prion proteins

sporadic creutzfeldt-jakob disease CJD occurs in people 50-70yrs old

Question 4

genetic or familial spongiform encephalopathy

Answer 4

specific mutation within the gene encoding PrP^c
familial CJD
inherited disease

Question 5

infectious (or transmissible/acquired) spongiform encephalopathy

Answer 5

infection acquired as result of feeding meat meal or bone meal, iatrogenically by transplantation of cornea, the use of purified hormones, etc
the exogenous PrP^SC binds to PrP^C, induces conformational change PrP^C to PrP^SC
chain reaction of conversion initiated

Question 6

Characteristic pathology of transmissible spongiform encephalopathies

Answer 6

vacuolization (a spongiform degeneration in the grey matter of a brain)
severe astrocytosis (astroglial hypertrophy and proliferation)
Loss of neurons

Question 7

T/F there is a species barrier

Answer 7

true
infection is easier when the target PrP^C and PrP^SC sequences are the same
rarely, cross species infection can occur

Question 8

Do infectious prions induce inflammatory changes or immune response in the host?

Answer 8

No

Question 9

Scrapie

Answer 9

chronic, fatal, neurodegenerative disease of adult sheep and sometimes goats
they scratch on posts to relieve pruritus

Question 10

transmission of scrapie

Answer 10

sheep- oral route or from superficial wounds when in pastures contaminated by infected placental tissue or body fluids
ewes to lambs- prob postpartum exposure to placenta, bood, birth fluids, and milk
vertical transmission disputed

Question 11

What breeds have high incidence for scrapie

Answer 11

suffolk sheep
cheviot sheep
swaledale sheep
hampshire sheep

Question 12

Susceptibility of scrapie

Answer 12

attributed to single gene: Sip (scrapie incubation period)
sA- short incubation allele
pA- long incubation allele

Question 13

Sheep with what allele of scrapie die sooner?

Answer 13

sAsA or sApA die from intracerebral inoculation before pApA sheep

Question 14

CS of scrapie

Answer 14

earliest sign is intense pruritus
rub against objects, bite flanks (patchy wool loss)
muscle tremors, weaving gait, staring eyes
later signs: hindquarter paralysis, death (6wks-5mths post signs)

Question 15

Diagnosis of scrapie

Answer 15

ante-mortem diagnosis using immunohistochemistry
tonsillar biopsy
third eyelid testing- lymphoid tissue from inside of eyelid

Question 16

histopathology of scrapie

Answer 16

neuronal vacuolation and degeneration of brain tissue
EM demonstration of scrapie associated fibrils

**complete absence of inflammatory, humoral or cell mediated immune response

Question 17

Control of scrapie

Answer 17

reportable
USDA genetics based flock clean up and monitoring plan (sheep with susceptible genotypes are removed)
exposed flocks monitored with the 3rd eyelid test

Question 18

Bovine spongiform encephalopathy

Answer 18

Mad cow, raging cow
etiology: BSE prions
adult cattle, humans, other animals
susceptibility not related to sex, breed, or genotype

Question 19

transmission of BSE

Answer 19

contamination of meat an dbone meal produced from meat and offal from slaughtered and dead sheep
possible vertical

Question 20

CS of BSE

Answer 20

NO pruritus

apprehension, hyperesthesia, incoordination, aggressive behavior, recumbency