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Module 2 > Humanised mice for the study of chronic viral infections > Flashcards

Humanised mice for the study of chronic viral infections Flashcards

1
Q

Why are HBV; HCV and HIV difficult to study?

A

narrow species tropism- only humans and chimpanzees

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2
Q

What is a surrogate model for HBV infection?

A

woodchuck hep B virus

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3
Q

What is the problem with cell culture systems?

A

limited to highly adapted viral genomes and don’t fully recapitulate viral pathogenesis

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4
Q

What is the success of xenografting dependent on ?

A

the inability for the host to reject the foreign cells

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5
Q

What is the immunodeficiency in Nude mice?

A

athymic- no T cells

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6
Q

What is the immunodeficiency with IL2gR-deficiency?

A

NK cell and DC deficiency

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7
Q

Which cells express CD47?

A

majority of health cells

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8
Q

what is the function of CD47?

A

interacts with SIRPa on macrophages triggering a don’t eat me signal

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9
Q

Why are NOD mice very useful xenorecipients?

A

have a SIRPa allele very similar to human SIRPa therefore mouse macrophages recognise human cells as self

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10
Q

What happens when the IL2 gamma chain is knocked out?

A

results in deficiencies in multiple subsets of cell and inability to respond to lots of cytokines– unable to mount an immune reposnse

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11
Q

What are human peripheral blood lymphocyte mice?

A

mice where PBMCs have been intraperitoneally injected into the mouse- allowing you to test human immune cell responses for a short period

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12
Q

What is the problem with human peripheral blood lymphocyte mice?

A

will get host vs graft as human T cells will attack mouse

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13
Q

How do you create human immune system mice?

A

take haematopoietic stem cells from the foetal liver and inject them into an irradiated mouse, which then develops a human immune system educated by mouse antigens

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14
Q

What is a human bone marrow/liver/thymus mice?

A

a mouse that develops multi-lineage haematpoiesis as well as organised lymphoid tissues of human origin

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15
Q

What happens to HIV in HIS mice?

A

accumulate mutations in CD8 T cell epitopes Env and Nef to evade T cells

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16
Q

What is a problem with HIS mice?

A

have a suboptimal humoral rresponse

17
Q

How can humoral immunity in HIS mie be improved?

A

cytokines and growth factors

18
Q

what happens when cytokine are supplemented to HIS mice?

A

get a change in Th1/Th2 balance- increased Th2 cells

19
Q

What are MISTRG mice?

A

Rag2 deficient, IL2gR deficient mice with human versions of IL3; GM-CSF and thrombopoietin that have completely functional NK cells

20
Q

What is the probem with injecting human IL-12 into a mouse?

A

the immune response kills the mouse after around 4 weeks

21
Q

How is a human liver-chimeric mouse created?

A

a highly immunodeficient mouse lacking T, B and NK cells with liver injury is injected into the spleen with human hepatocytes creating a model for HBV and HCV

22
Q

Why does there need to be liver injury in the immunodeficient mouse?

A

to give the human hepatocytes a survival advantage

23
Q

What can be used as a marker of engraftment with human liver-chimeric mice?

A

albumin

24
Q

What has to be given to enable engraftment in the mouse with fetal liver?

A

oncostatin M

25
Q

What can the pathogenesis; adaptive immunity adn vaccinations be testing on mice with HBV/HCV?

A

create a human immune system mouse first then reconstitute the liver

26
Q

What is the result of HBV infection on human NK cell infiltration into the liver?

A

HBV doubles the numbers of NK cells infiltrating hte liver

27
Q

What is the new frontier in humanised mouse models?

A

replacing the use of primary cells in creating humanised models with induced pluripotent SCs

28
Q

Which cytokines is the common gamma chain part of hte receptors for?

A

IL2; IL4; IL7: IL9; IL15 nad IL21

29
Q

What is the problem with the HIS model?

A

cells are educated on the murine thymus- lacks some human-specific factors needed to fully mimic all aspects of human T cell development and are H2 restricted (mouse MHC)

30
Q

What is a disadvantage of hte BLT model?

A

development of a wasting GVHD-like syndrome following long-term engraftment

31
Q

Why is the BLT model mainly used for studying HIV?

A

BLT has a higher level of human mucosal engraftment allowing hte vaginal and rectal transmission of HIV to be studied

32
Q

What mediates the entry of HCV into the cell?

A

claudin-1

Module 2 (38 decks)

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