Prions

Question 1

TSE’s?

Answer 1

Transmissable Spongiform Encephalopathy

Question 2

What causes TSEs?

Answer 2

Prions (infectious proteins)

Question 3

TSE disease process

Answer 3

Long incubation period but then rapidly progressive. Usually leads to a fatal dimentia
Pathology shows multifocal spongiform changes

Question 4

Are there amyloid plaques present in TSE

Answer 4

not usually

Question 5

Inflammation in TSE (transmissable spongiform enceph)

Answer 5

minimal

Question 6

Human TSE

Answer 6

• kuru
• creutzfeld-jakob
• Gertsmann Straussler Scheinker disease
• Fatal familial insomnia
• Variant CJD

Question 7

Animal TSE

Answer 7

Scrapie (seen in sheeps and goats)
Bovine spongiform encephalopathy (BSE)
Chronic Wasting Disease (deer and elk)

Question 8

Agents that cuase TSEs are resisitant to what

Answer 8

Regular virus treatments which damage nucleic acids.

Question 9

Prion stands for

Answer 9

Proteinacious infectious particles

Question 10

Prion protein is highly conserved among humans and animals

Answer 10

KNOW

Question 11

where is the prion protein encoded>

Answer 11

on a single axon on human chromosome 20

Question 12

Prion protein is highly expressed where

Answer 12

neurons and lymphocytes

Question 13

Prion protein final product

Answer 13

a 209 amino acid glycoprotein that is anchored to cell surfaces by a fatty acid

Question 14

WHat are the two general forms of prions

Answer 14

The physiologic type: PrPc

The patologic type: PrPsc or PrP res
Stands for PrP scrapie or PrP resistant

Question 15

KNOW PrPc and PrPsc can have identical sequences yet they are different because of what

Answer 15

They way they fold.

PrPsc is unusually stable and only partially degraded by proteases. Aggregates in cell cytoplasm and leads to neuron apoptosis

Question 16

Remember…you must express PrPc in order to contract disease. ALso remember that there are probably chaperone proteins involved in this process since simly mixing PrPsc and PrPc together doesnt generate scrapie protein

Answer 16

ok

Question 17

What the fuck is the scrapie disease

Answer 17

• subacute, progressive ataxia of sheep
• first found at one year of age in lymphatics and tissues
• by 2 yrs the brain is infected

Question 18

First documented human TSE

Answer 18

Kuru

Question 19

Most common human TSE

Answer 19

Creutzfeld Jakob (CJD)

Question 20

Three forms of CJD

Answer 20

sporadic- most common
Iatrogenic
Familial

Question 21

classic CJD quadrad

Answer 21

• Dementia
• Myoclonus
• Ataxia
• Mutism

Question 22

Sporadic CJD onset age

Answer 22

around 60

Question 23

Mean survival time for sporadic CJD

Answer 23

only 5-8 mos

Question 24

Cause of sporadic CJD

Answer 24

pretty much unknown

Question 25

How do you get iatrogenic CJD

Answer 25

Dural grats Corneal grafts HGH NOT BLOOD TRANSMISSION

Question 26

Familial CJD inheritance

Answer 26

Auto dominant age of onset 45-50 survival 2-4 yrs

Question 27

CJD diagnosis

Answer 27

- CLinical course: rapid dementia and myoclonus - histology shows spongiform change and no amyloid which rules out alzheimers - Check CSF to rule out tertiary syphillis

Question 28

Gertzman Schausler Shanker (sp?) follows what inheritance patterns

Answer 28

AD

Question 29

What mutation is GSS associated with

Answer 29

codon 102 of PrP

Question 30

Clinical features of GSS

Answer 30

avg age of onset is 48 mean time to death is 5 years gait abnormalities and ataxia dementia is less common

Question 31

KNOW>..GSS shows amyloid plaques and spongiform changes

Answer 31

ok

Question 32

FFI inheritance

Answer 32

AD

Question 33

Clinical features of FFI

Answer 33

- sleep disturbaces | - autonomic dysfunction

Question 34

histo of FFI

Answer 34

no spongiform changes. just neuronal loss

Question 35

Variant CJD

Answer 35

NEW!! found in UK in 90's

Question 36

the causative agent of CJD is the same as what

Answer 36

The same as BSE (mad cow). So it came from contaminated beef or blood transfusion which is different that the CJD we discussed earlier

Question 37

One major difference between regular CJD and variant is

Answer 37

Regular affects pretty much only the CNS Variant = CNS, retina, DG, bone marrow, tonsils, spleen, lymphnodes, appendix, blood Also: Age of onset is 29 in variant (compared to 60) mean survivial is 14 in variant (compared to 5-8) SEnsory abnormalities , anxiety, depression

Question 38

ALL INDIVIDUALS WITH vCJD were homozygous for

Answer 38

methionine at position 129 of Prp

Question 39

Diagnosis of vCJD

Answer 39

prion positive tonsil biopsy | histology shows spongiform changes in basal ganglia...flower appearance

Question 40

how do you properly sterilize graft equit to protect from iatrogenic CJD

Answer 40

soak in 1 M sodium hydroxide for an hour followed by autoclave at 134 C