Midterm 2 - Lecture 12

Question 1

What are transmissible spongiform encephalopathies?

Answer 1

• a family of diseases of humans and animals characterized by spongy degeneration of the brain with severe and fatal neurological signs and symptoms

Question 2

3 TSE theories

Answer 2

1) Virus: a virus with unusual biochemical and biophysical characteristics
2) Prion: an exclusively produced host protein which becomes protease resistant
3) Virino: a host derived protein coat (PrPc) and a small non-coding regulatory nucleic acid

Question 3

What theory is the most accepted theory of TSE?

Answer 3

Prion Theory
- a group of diseases causes by the same type of infectious agent: prion

Question 4

How is TSE currently defined?

Answer 4

• defined by the transmission and involvement of neurodegeneration by abnormal form of a prion protein

Question 5

What do the plaques formed by TSE resemble?

Answer 5

• Alzheimer’s disease
• Parkinson’s disease
• Huntington’s disease

Question 6

What is PrPTSE resistant to?

Answer 6

• Highly resistant: proteases, sunlight, heat, normal sterilization processes

Question 7

Is there a detectable immune response for PrPTSE?

Answer 7

• at present no
• only rapid test for brain samples

Question 8

Function of PrPc?

Answer 8

1) Neurons: adhesion and signaling
- growth factor of synapses
- pro and anti apoptosis
- copper binding in presynaptic membrane and during oxidative stress

2) Neural and hematopoietic stem cells
- increases cell proliferation in neuron rich regions
- targets stem cells to appropriate area for differentiation

3) T cells: activation

4) Other leukocytes
- modulates phagocytosis
- enhances leukocyte homing to inflammation
- expressed on monocyte/lymphocyte lineages

Question 9

Where do prions replicate and increase infectivity?

Answer 9

• in the ileum and other lymphoid rich tissue
• these are antigen presenting cells (dendritic cells, M cells and macrophages) and tissue stromal cells
• compliment receptors on dendritic cells up uptake prions
• B and T cell uptake help transport to other areas of the body

Question 10

How do prions get transported from lymphoid system to the nervous system?

Answer 10

• autonomic nervous system (sympathetic nervous system) innervates lymphoid tissue

Question 11

What is TSE characterized by?

Answer 11

• prolonged incubation (months to years)
• progressive neurological illness: 100% mortality
• presence of scrapie associated fibrils: neural PcPTSE plaques
• brain: vacuolation, astrocytosis
• rare to no inflammatory and immune response in the brain

Question 12

Examples of Animal TSE

Answer 12

1. Bovine Spongiform Encephalopathy (‘mad cow disease’)
2. Scrapie (sheep)
3. Chronic Wasting Disease (wild ruminants)
4. Mink Spongiform Encephalopathy
5. Feline Spongiform Encephalopathy

Question 13

What caused Mad Cow Disease?

Answer 13

• improper rendering of cattle products (reduce costs); removal of solvent extraction that included steam-heat treatment

Question 14

What are the 2 theories of BSE transmission?

Answer 14

1. Cattle fed rendered sheep products
2. A cow underwent spontaneous PrPc mutation and was rendered then fed back to cattle

Question 15

Does maternal transmission of BSE to calves occur?

Answer 15

• uncommon
• unsure if this is true transmission these calves or genetic susceptibility for acquiring BSE from contaminated feed source

Question 16

Scrapie

Answer 16

• domestic and wild sheep and goat disease
• higher in black-faced sheep
• vertically transmitted from mother to fetus: placenta and amniotic fluids