Prions Disease

What are the FIVE normal functions of PrP c?

including protection against apoptotic and oxidative stress

cellular uptake or binding of copper ions

transmembrane signaling

formation and maintenance of synapses

adhesion to the extracellular matrix

T/F Prions are self -replicating glycoprotein

True

___- Normal, soluble, proteinase-susceptible, rich in alpha helical structure

____ - Abnormal, insoluble, proteinase-resistant, rich in beta helical structure

PrP c

PrP Sc

What are prions devoid of?

Nucleic acid (RNA or DNA)

T/F Prions induce immune response

False, does not

Prions are ____ to many methods of chemical and physical inactivation

Resistant

Prions have high _____ and they can infect where? (7)

Infectivity

Central nervous system (Brain, spinal cord), Eye, dorsal root ganglia, pituitary gland, pineal gland, dura mater

How does meat and bone meal get infected by TSE?

"Infectivity" enters via gut

What are the steps of TSE Pathogenesis (5)

Infectivity" enters via gut

"Colonizes" the lymphoreticular tissue

Depending species: move to other LR tissue: LN, spleen, possibly bone marrow

"Replication" likely in follicular dendritic cells, B-lymphocytes, possible other cells

Then to CNS: massive terminal "replication"

TSEs share pathologic features and infectious mechanisms, how do they do this? (4)

Similar amyloid plaques

Similar distribution in tissues and organs

Similar protein misfolding

Similar grey matter lesions in the brainstem, including neuronal vacuolation, other forms of neuronal degeneration, astrocytosis, and a vacuolar or spongy alteration called status spongiosis

T/F Research has shown interspecies transmission is inefficient, but much is still unknown

True

What are the TWO forms of bovine spongiform encephalopathy?

Classical- transferred horizontally between cattle

Atypical- not transferred horizontally between cattle

Which BSE is non transmissible between cattle?

BSE atypical

Which BSE is transmissible between other species including ?humans

Classical

T/F CWD and Scrapie transmissible

True

How is Scrape and Chronic Wasting Disease spread?

horizontally spread

What are the THREE disease that can be transmissible by feeding prion infected feed?

Transmissible Mink Encephalopathy (TME)

Feline spongiform encephalopathy

Exotic ungulate encephalopathy in exotic ungulates

What are the TWO forms of genetic prion diseases that are seen in humans?

Gerstmann-Straussler-Scheinker syndrome: Familial-germ line mutation in PrPgene

Fatal familial insomnia: Familial-germ line mutation in PrP gene

What are the THREE types of acquired prions diseases in humans?

Iatrogenic Creutzfeldt-Jakob disease (iCJD)

Kuru

Variant CJD (vCJD)

T/F Reducing deaths in one year due to autoaccidents in the United States by 0.5% =prevention of all cases of vCJD globally

True

T/F Mad Cow disease is a true foodborne disease

True

Disease susceptibility is regulated by the ___ ____ sequence of the host's prion protein

amino acid

What is the host prion protein?

PRNP

With Scrapie, Signs or effects of the disease usually appear __ to ___ ____ after the animal is infected but may take longer to appear.

2 to 5 years

With scrapie, ____ usually live 1 to 6 months after the onset of clinical signs and in some cases longer, but death is inevitable.

Sheep

What breed of sheep is most likely to get Scrapie?

black faced sheep (suffok)

What are the clinical signs of scrapie? (sorry)

Early signs include subtle changes in behavior or temperament.

These changes may befollowed by scratching and rubbing against fixed objects, apparently to relieve itching.

loss of coordination, weight loss despite retention of appetite, biting of feet and limbs, lip smacking, and gait abnormalities, including high-stepping of the forelegs, hopping like a rabbit, and swaying of the back end.

What is the shortened version of the clinical signs?

Behavioral changes, tremor (especially of the head and neck), pruritus, and locomotor incoordination, which progresses to recumbency and death

With polymorphisms in prion protein sequence in sheep, USDA-APHIS policy recognizes the importance of codon ___ and the potential importance of codon __ in the transmission of scrapie in the United States

(he said this is important, dont shoot the messenger)

171

136

just read this

The gene that encodes the normal prion protein has polymorphisms at codons 136,154, and 171 that influence the ability of the prion cellular protein structure to begeometrically altered by the PrP scrapie template when the animal is exposed to it.At this time, no such polymorphisms have been identified for goats. All goats, therefore, must be assumed to be susceptible

What are the NINE places where abnormal prion proteins (PrP scrapie) may be found?

nervous system, the spleen, lymph nodes, placenta, intestine, blood, pancreas, ovary, and liver

T/F Historically, white-faced sheep have accounted for the majority of known scrapie-infected sheep in the United States, but current surveillance now does not monitor specific breeds, all breeds are tested at the same frequency to ensure no positive flocks are missed.

False, black faced

What is the best tissue for the TSE?

a portion of the brainstem

How can you diagnose Scrapie? (2)

Immunohistochemistry

H&E and Immunohistochemistry

How do you fix Immunohistochemistry for diagnosis of Scrapie?

Formalin fixed

___ ___ ____ was first recognized in the late 1960s in mule deer at a wildlife research facility in northern Colorado

Chronic wasting disease

What animals are susceptible to CWD? (8)

Mule deer

White-tailed deer

North American elk or wapiti

Moose, and any associated subspecies and hybrid

Black tailed deer

Red deer

Reindeer

Sika deer

What are the SIX ways that CWD is transmitted?

Body secretions (Saliva,Urine)

Reproductive (Semen, Vaginal/uterine/placental)

Feces

CNS tissues

Mucosal sites

Antler velvet

T/F CWD is predominantly a disease seen in white tail deer

true

What are the high risk tissues of CWD? (just read)

The head (including brain, tonsils, eyes and any lymph nodes)• Spinal cord/backbone; spleen; skull plate with attached antlers(if visible brain or spinal cord tissue is present); cape (if visiblebrain or spinal cord tissue is present)• Upper canine teeth (if root structure or other soft tissue ispresent) any object or article containing visible brain or spinalcord tissue; unfinished taxidermy mounts

CWD- Disease features:

Chronic and progressive ____ ____ as seen with other TSEs

___% fatality rate

____ progressive

Emaciated to wasting state in some cases

May see unusual behavior

May see no clinical signs

vacuolar degeneration

100

Slowly

T/F if you are a hunter is it okay to handle the high risk tissue

False, do not do that

What are the FIVE ways to diagnose CWD?

◦ IHC and ELISA: Dorsal motor nucleus of vagus required for IHC/(immunohistochemistry) and ELISA testing

Captive deer: Obex, both medial retropharyngeal lymph nodes, and skin

Wild deer: Medial Retropharyngeal lymph nodes and skin

Histology: Microscopic examination shows spongiform change in neuropil and neuronal perikarya

Western blot

What is the MAIN way that they diagnose CWD in wild deer?

What about captive deer?

Captive deer: Obex, both medial retropharyngeal lymph nodes, and skin

Wild deer: Medial Retropharyngeal lymphnodes and skin

What are the clinical signs for BSE?

Non-ambulatory

Incoordination

Generalized wasting and loss of body mass despite a good appetite

Unusual aggression toward cattle and humans

What is the incubation of BSE?

4-6 years

When does the onset of clinical signs for BSE?

2 weeks to 6 months

What is part of the brain is removed to test for BSE?

Obex and associated brainstem

Which form of BSE has most of the cases in Canada and outbreak in the UK and what is in linked to in humans?

Typical" BSE strain (C-type)

vCJD in humans

"Atypical" BSE strain is a distinct strain of prion disease.

What are the TWO types designated due to molecular weight after protease degradation and Western blot?

H- and L-type

T/F CWD ELISA testing is not a food safety test

True

Only one ___ of infectious material could spread BSE*

gram

What is the FDA rule for prevention of BSE?

Prohibit the use of certain cattle origin materials in the food or feed of all animals

What type of cattle are banned from slaughter?

All non-ambulatory cattle

he skipped alot of sh*t at the end go and read or not