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Module 3 > Human xenograft models > Flashcards

Human xenograft models Flashcards

1
Q

What does the ability to xenograft cells or tissue depend on?

A

inability of the host to reject foreign cells- no host vs graft

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2
Q

What is compartmental xenografting?

A

engraftment of health cells/tissues of mice with human cells

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3
Q

What type of immunodeficiency do Nude mice have?

A

athymic- no T cell repsonses

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4
Q

What type of immunodeficiency do SCID and Rag1 deficient mice have?

A

no B and T cell maturation

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5
Q

What type of immunodeficiency do IL2gR deficient mice get?

A

NK cell and DC deficiency

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6
Q

How do macrophages recognise RBCs to phagocytose?

A

they slowly lose CD47 which is recognised by SIRPa on macrophages

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7
Q

Which cytokines does IL2 receptor common gamma chain deficiency result in deficiencies in?

A

IL-2; IL-4; IL-7; IL-9; IL15; IL-21 TSLP

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8
Q

What cell types does IL2 gamma chain defiency result in deficiencies of?

A

B cells; T cells; NK cells; DCs

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9
Q

What is the benefit of the BLT model?

A

human T cells are educated on human thymus; superior reconsitituion of GALT; rectal and vaginal tissues with human leucocytes

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10
Q

How is the engraftment of humanised mouse models determined?

A

FACS comapring the number of cells with human vs mouse CD45

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11
Q

How long can human PBL-SCID mice be used for?

A

4-6 weeks due to severe GvHD

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12
Q

What disease are BLT mice particularly used for?

A

HIV- pathogeneesis and treatments

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13
Q

What type of virus is dengue virus?

A

plus strand RNA virus of the flaviviridae family

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14
Q

What is the secondary infection of dengue virus associated with?

A

exacerbation of symptoms- haemorrhagic fever or shock syndrome

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15
Q

Why are humanised mice models useful in dengue virus?

A

other animal models have not been very useful, but humanised mice exhibit key dengue pathogenesis

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16
Q

What is the disease with yellow fever?

A

viral haemorrhagic fever- mortality 15-50%

17
Q

How was the yellow fever vaccine developed?

A

live attenuated Asibi strain by passaging in different animal cells

18
Q

Why are humanised mice models good for yellow fever?

A

there are no animal models of the diseease

19
Q

What happened to the yellow fever virus as it was passaged to become attenuated?

A

it lost virulence but gained immunogenicity

20
Q

What is responsible for the pathogenicity of ywllo fever?

A

envelope

21
Q

How was the importance of hte envelope in yellow fever determined?

A

reverse genetics

22
Q

What is the problem with HIS mice and yellow fever vaccination?

A

do not develop humoral repsonses properly and actually die faster than non-immunised mice exposed to yellow fever

23
Q

Waht type of humanised mouse model does yellow fever vaccination work in?

A

PBL-SCID model: if mice are given PBMCs from an immunised human—lack of immune functionality in the mice is reponsible for lack of immune clearance

24
Q

Waht are the antibody levels like in HIS mice compared with normal human?

A

massively redued

25
Q

How can humoral immunity in huamnised mice models be improved?

A

supplementing non-corss reactive cytokines and growth factors

26
Q

Waht cytokines are essential for B cell differentiation?

A

GM-CSF and IL-4

27
Q

Which type of Th response is favoured in huamnised mice?

A

Th2

28
Q

How cna humanised mice models be used to study T cell plasticity?

A

Th2 bias in humanised mice but if supply IL-12, cells switch to Th1

29
Q

What is seen in NK cells in conventional humanised micemodels?

A

IL2gR deficiency combined with limited cross-reactivity with human factors–impaired nk cells

30
Q

What mouse model displays completely functional NK cells?

A

expression of human IL3; GM-CSf and thrombopoeitin —-MISTRG mice

31
Q

What is important about MISTRG mice?

A

normal myeloid development

32
Q

What mutations are see in FNRG KO-NOD mice?

A

FAH-/-: metabolic liver disease; NOD background- optimal xenograft maintenance; Rag-/-: T and B cell deficiency; IL2gR-/-: NK cell deficiency

33
Q

How much of the mouse liver can be repopulated with human hepatocytes?

A

upto 90%

34
Q

How can the repopulation of hte mouse liver with human cells be measured?

A

human albumin levels

35
Q

What is the function of human liver-chimeric mice?

A

study of human-specific hepatotropic infections

36
Q

What is given to facilitate the engraftment of foetal hepatoblasts in FNRG mice?

A

recombinant human oncostatin M

37
Q

what happens with NK cells upon infection with HBV?

A

NK cells infiltrate the human liver

38
Q

What are some of the laternative approaches to animal models?

A

bio-engineering artificial organs using primary cells and microfluidics

Module 3 (33 decks)

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