Micro Winter 6 Prion, Demyelinaating Disease & Hiv

Front 1

what is a protein that becomes pathogenic when there is a conformational change

Back 1

prion

**aka slow virus. in sheeps called scrapie- did NOT transmit to humans. thought it had a really long latent period

Front 2

what is transmissible (subacute) spongiform encephalopathies

Back 2

neurodegeerative- scrapie, mad cow, CJD. caused by PRIONS

**the brian is killed and NO immune response is elicited

**transmissible, prolonged incubatino (not spread with casual contact)

**NOT associated with bacteriam parasite, fungus, virus or other infectious agent- prions are the infectious agent

Front 3

what happened to sheep with slow virus infection

Back 3

it was a prion disease that made the sheep eat its wool, we would then kill and eat the sheep but NO HUMAN disease!

Front 4

spongiform alterations are seen in the brain when, what causes them

Back 4

prion disease- TSE, transmissible spongoform encephalitis (ex scrapie, mad cow CJD)

caused by abnormal protein called prion

Front 5

what are the 4 diseases caused by prions

Back 5

1. Kuru
2. CJD
3. Gerstmann-Sträussler-Scheinker disease
4. Fatal familial insomnia

Front 6

whats kuru

Back 6

Prion disease from eating dead relatives

**ataxia, dementia, chorea
**fatal in 3-15 months
*widespread neuronal loss in the brain with amyloid plaques
**neurodegeneration- tremors, loss of voluntary mm, death

Front 7

a diease that means " trembling due to fear or cold"

Back 7

Kuru, prion disease when you are a cannible

**neurodegenerative- loose voluntary mm, cant swallow, get tremors

**overall neuronal mass in brain and amyloid deposits

Front 8

who did NOT get Kuru

Back 8

infants

**incubation was 4-30 years and death in 4-15 months

Front 9

what was the major cause of death in the papa new guinea tribe

Back 9

kuru, now its almost extinct

• Severe ataxia, dementia, choreiform movements
• Uniformly fatal in 3-15 months
• Brain - widespread neuronal loss with amyloid plaques evident
• Fore tribe of Papua New Guinea
• Named for their word for trembling due to fear or cold
• Neurodegenerative disease tremors progressive to loss of voluntary movement and death
• Was the major cause of death when tribe was first discovered (now disappeared)
• Affected all ages other than infants
• Incubation period range 4-30 years
• Spread by cannibalistic consumption/rituals for dead relatives during mourning period

Front 10

what is Creutzfeldt-Jakob disease (classic form

Back 10

*cerebral proin disease that changes fast
*affects old ppl
*dementia, ataxia, seizure (simliar to Kuru)
*incubation 15-20 months
*get it through corneal transplants, neurosurgery, pitutary derived growth hormone

Front 11

waht is the most common cause of CJD, tell me about it

Back 11

SPORADIC!

incubation is 15-20 months (wont linger for YEARS as was seen in kuru)
*pititary derived Growth Hormone can cause infection- can get from tissue transplants.
*can also get it from neurosurgery

Front 12

what are the inherited prion diseases

Back 12

Gerstmann-Sträussler-Scheinker disease

Fatal familial insomnia

Front 13

do prions have DNA or RNA?

are prions easy to get rid of?

do they elicit an immune response

Back 13

NONE! infectious protein (misfolded)

NOPE!, its SUPER hard to inactivate a prion-

no immune response is elicited with infection of a prion "The patient’s brain is destroyed in a matter of 60 days without febrile response, leukocytosis, or humoral immune response"

Front 14

what is the known component of the normal protein that has changed shape and gone nuts (prion) that is infectious

Back 14

PrPSc- proteinaceous particles

PrPC- normal
PrPSc- prion

A simple change in shape converts the normal protein into a pathologic prion.

Front 15

wahts proteinaceous particles (PrPSc)

Back 15

the infectious agent of a prion

PrPC- normal
PrPSc- prion

A simple change in shape converts the normal protein into a pathologic prion.

Front 16

what should you be afraid of
PrPC-
PrPSc-

Back 16

PrPC- normal
PrPSc- prion

Front 17

how can we ensure we are not passing along a prion disease during neurosurgery

Back 17

autoclave it like nuts!!! 1N NaOH and extended autoclaving at 131

*super hard to kill a prion
*PrPSc is infectous after a misfolding
**no DNA or RNA

Front 18

what can you tell me about prion propagation

Back 18

it only takes one bad apple to spoil the whole bunch

**one misfolded PrPSc will cause PrPC to become PrPSc

**keep in mind its a spontaneous midfolding that causes PrPC --> PrPSc

**this all happens POST TRANSLATIONALY

Front 19

in what stage of protion formation does a protein (PrPC) misfold to become a prion (PrPSc)

Back 19

post translational

**recall, one bad apple will ruin the whole bunch so we will have 1 spontaneous misfold that will cause more to misfold

Front 20

tell me about how a and b change in metabolic processing of PrPC, how is PrPSc formed

Back 20

decreased a helix
increased b sheet

**PrPSc is made slowley and will accumulate even though the levels of PrPC mRNA stay the same

Front 21

T or F

in prion disease there is MORE accumulation of PrPSc in the brain as the levels of PrPC mRNA increase

Back 21

False

levels of PrPCmRNA remain unchanged but PrPSc accumulates (PrPC is being degraded much faster!!!!)

Front 22

what is the mech of disease causd by prions

Back 22

not sure, but PrPSc is the ONLY specific molecule for these encephalopathies

Fx of PrPC is not known

Front 23

how do prion diseases manifest

Back 23

1. spongiform degeneration of brain
2. astrocytic gliosos
3. sometimes get amyloid plaque formatino (Kuru)
4. no detectable immune response to infection- pts brain killed in 2 months: no fever, leukocytosis or AB

5. PrPSc- suggests prion is NOT due to inhibition of normal PrP but is caused by accumulation of PrPSc that interfers with something

Front 24

is prion disease casued by abnormal fx of PrPC or increase accumulation of PrPSc

Back 24

accumulation of PrPSc

Front 25

how is a prion disease dx

Back 25

1. old ppl who are getting neurodegenerative disease
2. if you can detect PrPSc AB
3. test for genetic predisposition via PCR- Genetic screens are of no value for sporadic or infectious disease diagnosis, the PrPC gene sequence will be entirely normal

Front 26

should we do genetic screens on everyone to determine their risk for prion disease

Back 26

nope, most cases are sporadic

Genetic screens are of no value for sporadic or infectious disease diagnosis, the PrPC gene sequence will be entirely normal

Front 27

what ist he treatment for prion disease

Back 27

none, its fatal

supportive

**investigation of cmpds that destabalize b sheet (recall we had a decrease in a helix and increase in b sheet)

Front 28

what are the 3 forms of CDJ (and other prion diseases)

Back 28

1. Inherited- point mutation that destabalizes PrPC

2. Sporadic- COMMON, stable occurence. gene sequence is normal in thsee pts. horizontal transfer of prions from infected animal or spontaneous converstion of PrPC to PrPSc

3. infectious- direct inoculation with PrPSc from medical procedure- corneal transplant, graft, neurosurgery

Front 29

what is the new variant CJD (vCJD)

Back 29

younger pts (classis is ppl in 70's)

get core amyloid like depositions with an intense halo of spongiform degeneration

**really small dose required, can be in transfusions
*cases have been confirmed

Front 30

what does our 15 yp pt with a halo of spongiform degeneration with a core of amyloid have

Back 30

new variant CJD

**cases have been confirmed

Front 31

what is the hypothesis of vCDJ

Back 31

first recall vCJD is in younger ppl adn has a core of amyloid with a halo of spongiform degeneration

thought to have come from BSE (mad cow) and transmitted to humans, caused by feeding meat bone meal to livestock

Front 32

what is meat bone meal

Back 32

its dead cow that is then fed to other cows- can be why BSE (mad cow) spread to humans

Transmission of BSE was by oral consumption of prions - hypothesis is that BSE prions have been passed to humans causing the appearance of vCJD

Front 33

can restrictinos on transfusions prevent prion disease

Back 33

yep! prions are transmissible by blood so restrict blood from great britan where there was lots of BSE

Front 34

what is the general trend in the frequency of Kuru and BSE

Back 34

Kuru, steady decline. recall it can have like a 20 year incubation so we stopped the cannibalism but it may still be dormant in some of the older folks

BSE- spike in the 80 but now its declinig as well (change MBM practive)

Front 35

can we quantify BSE in cattle that ppl eat

Back 35

not yet, we are developing it now but we dont really know much about the progression of the disease

Front 36

how can we best control prion disease

Back 36

1. destroy infected animals- and dont feed them to other animals!

2. bann MBM feeding, and dont feed animals other dead animals

3. dont eat the brain and lymph tissue of animals

Front 37

do we know the risk of prion disease in elk and deer

Back 37

The threat to human health posed by a prion disease emerging in certain game animals such as deer and elk, chronic wasting disease, is unknown at present.

Front 38

what is the estimate for the incubatino period of vCDJ

Back 38

50 eyars!!!!! wow, we will be seeing it for a while still

But, others posit the existence of asymptomatic vCJD “carriers” with surveys of tissue samples from hospital patients (tonsils and appendices) suggesting the ultimate level of vCJD could be high and that blood transfusions from an unknown number asymptomatic donors might perpetuate the epidemic even though dietary sources were eliminated years ago.

Front 39

what is the future of vCJD

Back 39

unclear, imcubation can be like 50 years perhaps

But, others posit the existence of asymptomatic vCJD “carriers” with surveys of tissue samples from hospital patients (tonsils and appendices) suggesting the ultimate level of vCJD could be high and that blood transfusions from an unknown number asymptomatic donors might perpetuate the epidemic even though dietary sources were eliminated years ago.