Lecture 6 - Identifying Host Factors Flashcards

1
Q

How is virulence considered?

A

In the context of the host

As a relative term

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2
Q
How can host determinants be found?
1)
2)
3)
4)
A

1) Introduce immune or susceptible antibodies or cells into host animal
2) Deplete host factors with antibodies
3) Deplete host factors using knockout mice
4) Deplete host factors with a transgene

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3
Q

How to identify a host determinant
1)
2)
3)

A

1) Alter a mouse in a certain way (factor depletion using antibodies, etc)
2) Infect altered mouse, normal mouse with pathogen
3) Observe LD50, ID50, bacterial growth, pathology, transmission, etc

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4
Q

What is iNTS?

A

Invasive non-typhoidal salmonellosis

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5
Q

Evolution of invasive non-typhoidal salmonellosis
1)
2)

A

1) Salmonella enterica var. typhimurium was the leading cause of bacterimia in HIV+ patients in Malawi
2) Moved from infecting HIV+ to HIV- individuals

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6
Q

Causative agent of invasive non-typhoidal salmonellosis

A

Salmonella enterica var. typhimurium

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7
Q

Deficiencies predisposing to more severe salmonella infections

A

Deficiencies in IL-12, CD4

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8
Q

Invasive non-typhoidal salmonellosis mortality rate in children

A

45%

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9
Q

Difficulties in making a vaccine against Salmonella enterica var typhimurium (or treatment)
1)
2)
3)

A

1) Intracellular bacteria (vaccine immunity is normally antibody-mediated)
2) CD4+ T cells needed for a robust immune response - many patients are HIV+, therefore have little to no CD4+ T cells
3) Difficult to get antimicrobials into host cells

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10
Q

Cytokine that can control S typhimurium infection

A

IFNg

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11
Q

Issues with iNTS murine model

A

Lethal infection in mice within two to three days. Human infection lasts several weeks

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12
Q

Type of mice used in iNTS murine model

A

C57B6 mice

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13
Q

Solution to poor iNTS murine model

A

Use an attenuated strain of S. typhimurium that is less virulent in mice.
New strain controlled by mice within around 2 weeks

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14
Q

S. typhimurium experiment to determine controlling immune response
1)
2)
3)

A

1) Gather C57B6 mice with various immune deficiencies
2) Innoculate with a set amount of S typhimurium
3) Observe different courses of disease

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15
Q
Immunodeficiencies of C57B6 mice used in S typhimurium experiment
1)
2)
3)
4)
A

1) Deficient in IFNg, lymphocytes (RAG2 deficient). Very susceptible
2) Deficient in CD4+, CD8+ T cells. Susceptible (died)
3) Deficient in CD4+ T cells (chronic infection)
4) Mice lacking B cells, CD8+ T cells, MHC I, CD1. Course of disease is same as wild type mice

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16
Q

Information from S typhimurium study in mice
1)
2)
3)

A

1) No control in mice lacking IFNg and lymphocytes
2) Chronic infection in mice lacking CD4+ T cells (mimics HIV)
3) Exacerbated chronic infection in mice lacking both CD4+ and CD8+ T cells

17
Q

Which enzyme degrades DNA to siRNA?

A

DICER

18
Q

What is 2-dimensional gel electrophoresis?

A

Proteins are separated by weight along the Y-axis, and separated by charge along the X-axis

19
Q

How can siRNA be used to find host determinants?

A

Made complementary to gene of interest, inserted into host cells to observe effect of suppressing gene of interest

20
Q

What are genome-wide association studies?

A

1) Take genomes from a group of people - uninfected, infected, severely infected
2) Compare genomes to see if any genes, SNPs, correlate with disease severity