Final Exam Flashcards

1
Q

Prions are made of _______.

A

Proteins

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2
Q

Viroids only infect _______.

A

Plants

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3
Q

Prions cause _____.

A

TSEs. Transmissible spongiform encephalopathies.

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4
Q

(T/F) Prions invoke immune responses like viruses.

A

False

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5
Q

We discussed 5 kinds of human prion diseases. List them.

A

Kuru, CJD, vCJD, GSS, and FFI

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6
Q

We discussed 4 animal prion diseases. List them.

A

Scrapie, BSE, FSE, and CWD

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7
Q

Where did Kuru originate?

A

In the South Fore people.

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8
Q

South Fore people practiced _________, a likely cause for the emergence of Kuru.

A

Endocannabalism

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9
Q

Kuru was originally known as _______ sickness.

A

Laughing

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10
Q

In the 1950s, _______ traveled to New Guinea to study Kuru.

A

Gadjusek

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11
Q

Gadjusek was the first to say that Kuru is _________.

A

Transmissible

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12
Q

What are the 3 stages of Kuru infection?

A

Ambulant, Sedentary, and Terminal

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13
Q

What is the length of the incubation period for Kuru?

A

Very long incubation period

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14
Q

_______ initiated research on Kuru, CJD, and Scrapie in 1972, later winning a Nobel prize for isolating a single infectious particle he named “prion”

A

Pruisner

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15
Q

Prion stands for?

A

Proteinaceous infectious particle (PrP)

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16
Q

What are the 2 forms of a prion?

A

PrPc (normal cellular protein) and PrPres (mutated)

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17
Q

In 1994, _______ used a yeast protein called ____ as a model organism for prion work, helping Pruisner’s work to be accepted.

A

Wickner, Ure2P

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18
Q

(T/F) Prions are not very resistant to routine inactivation methods.

A

False

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19
Q

PrP is encoded by the ______ gene.

A

PRNP

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20
Q

How does PrPres destroy neurons in the brain?

A

By accumulating into clumps

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21
Q

The misfolded protein structure of a prion has a high content of _____ _____.

A

Beta sheets

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22
Q

How are more proteins misfolded after initial infection with a prion?

A

The misfolded protein molecule catalyzes the misfiling of other proteins

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23
Q

PrPc may bind to ______ and be shuttled into lysosomes where it is degraded.

A

Copper

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24
Q

Prions infect which 4 regions of the brain?

A

Cerebrum, cerebellum, thalamus, and spinal cord

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25
Q

What are the 3 ways TSEs can arise?

A

Infectious, sporadic, and inherited.

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26
Q

Which TSEs are inherited?

A

CJD, GSS, and FFI

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27
Q

Which TSEs are infectious?

A

vCJD, Kuru, and CJD acquired via iatrogenic infection

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28
Q

Which TSEs are sporadic?

A

Sporadic (normal) CJD

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29
Q

How do eaten prions travel from the stomach to the brain?

A

Via splanchnic or vagus nerves present in the abdominal region

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30
Q

(T/F) The infectious dose of a prion is unknown.

A

True

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31
Q

(T/F) Prions are known not to exist in the blood.

A

False.

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32
Q

Which form of CJD (vCJD vs. sporadic CJD) has a longer incubation period?

A

Sporadic CJD

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33
Q

What is the average age at death for vCJD patients?

A

28

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34
Q

What is the average age at death for sporadic CJD patients?

A

68

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35
Q

How does one make a definite diagnosis of vCJD?

A

Prion-positive immunostaining of biopsy material from tonsils, spleen, or lymph nodes

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36
Q

How can one make a definitive diagnosis of vCJD post-mortem?

A

Western blot analysis of brain tissue

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37
Q

Genetic studies are conducted to determine if a patient suspected of having vCJD is (homozygous/heterozygous) for _________ at codon ____.

A

Homozygous
Methionine
129

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38
Q

Upon autopsy, slices of brain contain _______ similar to a sponge after TSE infection.

A

Vacuoles

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39
Q

The PRNP gene exists at codons _____ and ____.

A

129 and 219

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40
Q

(T/F) Mutations in the PRNP gene result in spontaneous formation of PrPres.

A

True

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41
Q

Transmissibility of TSEs among same species is (easy/impossible). Explain why.

A

Easy. High degree of homology in prion protein

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42
Q

What is the likely origin of BSE?

A

Likely came from scrapie infected sheep, disease spread to cattle by eating contaminated bone meal derived from sheep offal

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43
Q

What is the likely origin of vCJD in humans?

A

Ingestion of beef contaminated with BSE agent.

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44
Q

______ ______ disease affects deer.

A

Chronic Wasting

45
Q

Where do deer contract CWD?

A

From the environment. Environment serves as a stable reservoir for CWD prions (i.e. eating contaminated wheat grass)

46
Q

What is the expression to prevent hunters from potentially spreading CWD to humans?

A

“No skull no backbone”

47
Q

(T/F) There is no potential for CWD to transmiss to humans.

A

False.

48
Q

Which species were used in early experimental CWD studies?

A

Squirrel monkeys and cynomolgus macaques.

49
Q

Describe a plant viroid’s genome.

A

ssRNA covalently closed in a circular loop. High degree of internal base pairing

50
Q

Plant viroids are (enveloped/naked)

A

Naked

51
Q

Where do plant viroids replicate?

A

In the nucleus or chloroplast

52
Q

Viroids replicate via a ______ _______ model.

A

Rolling circle

53
Q

What is a good way to remember how viroids replicate?

A

Toilet paper

54
Q

What kind of polymerase do plant viroids use?

A

RNA-dependent RNA polymerase

55
Q

The only known human disease known to be caused by a viroid is _______.

A

Hepatitis D

56
Q

Hepatitis D was originally ascribed to a defective virus called the ______ _____.

A

Delta agent

57
Q

For Hepatitis D to occur, there must be simultaneous infection of a cell with both the _______ __ virus and the _______ __ viroid.

A

Hepatitis B virus,

Hepatitis D viroid

58
Q

When Timothy Brown was diagnosed with both HIV and acute myeloid leukemia, he underwent a procedure known as _________ ____ _____ _________.

A

Hematopoietic stem cell transplantation

59
Q

Doctors selected a (homozygous/heterozygous) _______-_____ for Timothy Brown

A

Homozygous CCR5-Δ32

60
Q

Timothy Brown suffered from _____-_____-_____ disease and __________, both complications of transplant operations.

A

Graft-versus-host disease

Leukoencephalopathy

61
Q

The _____-_____-_____ disease that Timothy Brown suffered from may have eliminated the HIV virus from his system.

A

Graft-versus-host disease

62
Q

Define gene therapy.

A

Experimental treatment that involves introduction of genes into a person’s cells to REPLACE or COMPENSATE for defective genes that cause disease or medical problems

63
Q

Genes can be delivered to cells via vectors such as _______ or ______.

A

Viruses or plasmids

64
Q

In 1999, gene therapy experienced its first setback. _________ was one of 2 individuals where were administered 300 times the normal gene therapy virus vector dose.

A

Gelsinger

65
Q

Gelsinger died as a result of ____-__ accumulation after gene therapy in 1999.

A

IL-6

66
Q

In 2003, gene therapy experienced another major setback. 2 children developed ________ and died after retroviral gene therapy treatment for __-____.

A

Leukemia

X-SCID

67
Q

In 2003, one of the boys who developed leukemia also experienced another phenomenon that caused uncontrolled cell division of his white blood cells. Why did this occur?

A

The modified retrovirus integrated into his genome into a gene regulating the normal cell cycle

68
Q

Why is the size of the gene limited in gene delivery by viruses?

A

The patient may mount an immune response to viruses that are too large.

69
Q

Viruses engineered for gene therapy must be ____ ____ specific.

A

Cell type

70
Q

There are 4 hallmarks of a good gene delivery system. Describe them.

A
  1. Target the appropriate host cell
  2. Integrate the correct gene into the cell’s chromosomal DNA
  3. Transcribe and translate the gene of interest so that the gene product can
    function properly
  4. Cause no toxic or harmful effects
71
Q

There are 2 methods used to target genes of interest in patent’s cells using viruses. Name them.

A

In vivo gene therapy

Ex vivo gene therapy

72
Q

How does in vivo gene therapy work?

A

The patent’s body is directly infused or injected with the modified gene therapy viral vector.

73
Q

(T/F) In vivo gene therapy is a scalable technique

A

True

74
Q

How does ex vivo gene therapy work?

A

Patient’s cells are removed, grown in culture, infected with viral vector to introduce gene of interest, then infused back into patients

75
Q

(T/F) Ex vivo gene therapy is a scalable technique.

A

False

76
Q

Why is ex vivo gene therapy not a scalable technique?

A

Very expensive, requires highly specialized equipment that is not commonplace in hospitals.

77
Q

Retroviruses (can/cannot) integrate into the cell’s genetic material.

A

Can

78
Q

Adenoviruses (can/cannot) integrate into the cell’s genetic material.

A

Cannot

79
Q

Adeno-associated viruses (can/cannot) integrate into the cell’s genetic material.

A

Can

80
Q

Herpes Simplex Viruses (can/cannot) integrate into the cell’s genetic material.

A

Cannot

81
Q

Vaccinia or poxviruses (can/cannot) integrate into the cell’s genetic material.

A

Cannot

82
Q

Why is viral gene delivery preferred over plasmid gene delivery?

A

Plasmid delivery of genes is much less efficient

83
Q

Cells can remove defective gene products via 3 kinds of molecules. Name them.

A

siRNAs, ribozymes, and antisense RNAs

84
Q

Define xenotransplantation

A

Any procedure that involves the use of live cells, tissues, and
organs from a non-human source that are transplanted into humans or used for clinical Ex vivo perfusion

85
Q

(T/F) Xenotransplantation includes transplantation of animal products such as pig insulin or pig heart valves.

A

False. Xenotransplantation does not include non-living animal products.

86
Q

In 1960, _______ and _______ studied immune tolerance and rejection in animals and humans.

A

Medawar and Burnet

87
Q

Medawar and Burnet’s research spearheaded ______ ______ development of immunosuppressive treatments to prevent organ rejection.

A

Tissue typing

88
Q

________ was approved by the FDA in 1983 as an immunosuppressant.

A

Cyclosporin

89
Q

What drives the development of xenotransplantation?

A

Shortage of human organ donors

90
Q

Describe the HIV Organ Policy Equity (HOPE) program.

A

HIV infected individuals can donate organs to other HIV infected individuals

91
Q

The majority of the illicit trade of organs is for which organ?

A

Kidneys

92
Q

Why are pigs used for xenotransplantation as opposed to monkeys or apes? Describe 5 reasons.

A
  1. Pig organs are similar in size and physiology
  2. Pigs are readily available, can be bred easily
  3. Short gestation period
  4. Can be raised in a pathogen free environment
  5. Can be genetically modified to minimize rejection, making a more “human” pig
93
Q

What are the 3 kinds of rejection?

A

Hyperacute, acute vascular, and chronic

94
Q

In hyper acute rejection, the organ is dead within _________.

A

Minutes to hours

95
Q

In acute vascular rejection, the organ is dead _________ after transplant.

A

Days to weeks

96
Q

In chronic rejection, the organ dies __________ after transplant as a result of ________.

A

Months to years after transplant as a result of multiple acute rejections

97
Q

1 solution to the problem of organ rejection is the creation of _______ ________ pigs.

A

Gene knockout

98
Q

In gene knockout pigs, which gene is knocked out?

A

Alpha 1,3 galactose

99
Q

1 solution to the problem of organ rejection is via continuous intravenous injection of ____________.

A

Alpha 1,3 galactose (natural or synthetic)

100
Q

How is continuously injecting alpha 1,3 galactose into an organ transplant recipient a solution to organ rejection?

A

Sequesters antibodies

101
Q

1 solution to the problem of organ rejection involves the insertion of _______ _____ __,__ ____________ __ _________ gene and ______ ________ _______ ___ gene into pig genomes

A

Human alpha 1,2 fucsyltransferase H transferase gene

Human complement inhibitor CD59 (hCD59) gene

102
Q

What is the purpose of inserting human genes into a pig genome in organ transplantation research?

A

To make pig tissues look more like human tissues

103
Q

Define xenozoonosis

A

A disease transmitted from an animal to human recipient after transplantation of an animal organ

104
Q

In 2000, it was discovered that pigs harbor ______ __________ ________ _______ in their genomes.

A

Porcine endogenous retrovirus sequence

105
Q

(T/F) Unlike HERVs, which can be activated into virus, PERVs are defective and cannot be activated into virus.

A

False.

106
Q

There are 2 methods by which we can inactivate PERVs. Name them.

A

Usage of RNAi

Usage of CRIPR-Cas9

107
Q

________virus reactivation is one of the most common infectious complications in immunosuppressed individuals

A

Herpesvirus

108
Q

In 2004, an organ donor with _______ donated her organs to others. The recipients of the organs then contracted this disease.

A

Rabies