Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MEDSCI 708 > Topic 5 > Flashcards

Topic 5 Flashcards

1
Q

What are the major roles that Th17 cells may play?

A

They may serve as a major therapeutic target for inflammatory diseases and they appear to be crucial for the maintenance of gut/immune homeostasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the common points across Th developmental pathways?

A

Master transcriptions factors which are switched on to further enhance differentiation
Signalling transducer and activator of transcription these are transcription factors required for Th development
Autocrine feedback loops which sustain and enhance specific Th responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the cytokine which provides the autocrine feedback loop for Th1 cells?

A

IFN-gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the cytokine which provides the autocrine feedback loop for Th2 cells?

A

IL-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the cytokine which provides the autocrine feedback loop for Th17 cells?

A

IL-21

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the key players in Th1 differentiation?

A

IFN-Gamma and IL-12 begin the differentiation process via the IL-12 receptor to activate T-bet and pSTAT4 leading to the up regulation IL-18R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the key players in Th2 differentiation?

A

IL-4 and IL-12 begin the differentiation process acting through an unknown receptor to activate GATA3 and Pstat5 to upregulate the IL-33R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the key players in Th17 differentiation?

A

TGFBeta and IL-6 or IL-21 can initiate differentiation acting through the IL-23 receptor to activate RORgammat and pSTAT3 leading to the upregulation of IL-1R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the 3 step model for Th17 cell development?

A

Naïve T cells are prompted to enter the Th17 cell pathway through either TGFBeta and IL-6 or TGFBeta and IL-21
This activates RORgammaT and STAT3 leading to IL-17 expression and amplification of the cell population as well expression of IL-23R this allows IL-23 to stabilize the Th17 cell population and induces the expression of the cytokines IL-17A, IL-17F and IL-22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What cells can produce IL-6?

A

DC’s, monocytes, macrophages, mast cells, B cells, subsets of activated T cells, Tumour cells, Tumour cells, fibroblasts, endothelial cells, keratinocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What can induce the expression of IL-6?

A

IL-1, TNF, PDGF, IL-3, GM-CSF, IL-17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does IL-21 influence Th17 cells?

A

It is produced by activated T cells, NK cells but not antigen presenting cells
It is important for the expansion of activated B cells and class switching
It is induced by IL-6 and IL-21
Its expression is dependent on STAT3 alone and it can allow the alternative pathway of Th17 cell differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why is IL-23 essential for Th17 cells?

A

IL-23R is expressed on activated/memory T cell population

Promotes the production of IL-17, IL-1, TNF, IL-6 production by innate immune cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What occurs in the regulatory interplay between Th1, Th2 and Th17 cells?

A

Th1 and Th2 cells can negatively regulate each other and Th17 cells while Th17 cells are not able to negatively regulate any other subtype
This shows how these cells are relatively easy to turn off, possibly reflecting their potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the effect of Il-17 on endothelial cells?

A

This leads to the production of tissue factor, IL-6 and IL-8 leading to inflammation and potentially thrombosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the effect of IL-17 on epithelial cells and fibroblasts?

A

Expression of IL-6, IL-8, CCL20, G-CSF and GM-CSF promoting inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the effect of IL-17 on macrophages or dendritic cells?

A

Expression of IL-1, TNF and IL-6 which can promote inflammation as well as expression of MMPs which can cause cartilage damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the effect of IL-17 on chondrocytes?

A

Expression of nitric oxide which can lead to cartilage damage

19
Q

What is the effect of IL-17 on oesteoblasts?

A

Induction of RANKL which can induce oesteoclasotgenesis leading to bone erosion

20
Q

What is the role of IL-22R in Th17 cell function?

A

This is a heterodimeric receptor which contains IL-22R and IL-10R2, while IL-10R2 is ubiquitously expressed, IL-22 is limited to cells in the pancreas, kidney, colon, small intestine and liver
It is found on endothelial and epithelial cells rather than immune cells and thus allows Th17 cells to communicate with tissues

21
Q

What is the function of IL-21?

A 
B cell differentiation, Ig class switching
Differentiation and cytotoxic program
22
Q

What is the function of IL-22?

A

Production of beta-defensins, epidermal hyperplasia, acute phase reactants

23
Q

What is the function of IL-17A/F?

A

Induction of Cytokines, chemokines, and inflammatory mediators and recruitment of immune cells to the site of inflammation

24
Q

What is the function of CCL20?

A

Recruitment of cells to the site of inflammation

25
Q

What is the role of Th17 cells in host defence?

A

They can allow activation and release of antimicrobial peptides and aid in barrier function

26
Q

How common are Th17 cells relative to other immune cell populations?

A

Only 1% of healthy human CD4+ cells are IL-17 producing though numbers can increase dramatically in pathological environments
A large number of these memory cells have a specificity to fungal antigens

27
Q

What are the consequences of a lack of Th17 cells?

A

Recurrent, persistant infections of the skin, nails, oral and genital mucosae
This has led to the suggestion that Th17 cells are required for the clearance of pathogens which require huge inflammatory responses

28
Q

What is the type of pathogen which Th17 cells may be specialized at dealing with?

A

Those which require a huge inflammatory response as Th17 cells are capable of rapidly inducing inflammation in mucosal tissues

29
Q

How do Commensal bacteria shape T cell resident homeostasis?

A

These bacteria coat epithelial surfaces such as skin, airways, gut and genital mucosa
They contribute to immune surveillance through helping to maintain a balanced population of Th17, Th1 and Treg cells

30
Q

What are the potential consequences of commensal specific memory T cells?

A

They could provide cross-reactive protective responses to pathogens
However they could also contribute to altered barrier integrity and the development of autoimmune inflammatory conditions such as IBD and psoriasis

31
Q

What are the tools which can be used for targeting the IL-17, Th17 pathway?

A

Inhibitors can be used to prevent Th17 cell generation such as inhibitors of RORC, STAT3 and IL-23 antibodies
Il-17 or its receptor may be targeted with antibodies

32
Q

What is halofuginone?

A

This inhibits mouse/human Th17 cell differentiation by activating amino acid starvation response a cytoprotective signalling pathway. It can protect against experimental autoimmune encephalomyelitis

33
Q

What is digoxin?

A

This inhibits ROR-GammaT and thus inhibits murine Th17 cell differentiation without affecting other lineages and leads to reduced severity of EAE mice

34
Q

What is leukaemia inhibitory factor?

A

This can ameliorate EAE by selectively inhibiting pathogenic Th17 differentiation

35
Q

What are the characteristics of terminally differentiated Th17 cells?

A

The memory phenotype is long-lived, resistant to apoptosis and with a high capacity for expansion, they ensure maintenance of a constant repertoire of memory Th17 cells for a human life time despite finite life of individual effector cells and reduced thymus function
They can mediate or promote long term-antitumour immunity
Show plasticity and can be transdifferentiated into Th1and Th2 under specific conditions
Manipulation of Th17 apoptosis and survival may be of therapeutic interest

36
Q

How do Th17 cells have plasticity?

A

CD4 cells can de or re differentiate with deletion of master regulators allowing phenotypic change through it is possible that differentiation may vary between in vivo and in vitro experiments
It is possible that a partial rather than complete polarisation of a phenotype may be the norm in vivo

37
Q

What change in differentiation is induced by GATA3?

A

Allows Th2 cells to produce IFN-gamma

38
Q

What change in differentiation is induced by a reduction of FOXP3?

A

Reduction of this in Tregs results in a Th2 phenotype

39
Q

What is the role of Th17 cells in cancer?

A

They are a sign of a positive prognosis, particularly for patients with advanced disease

40
Q

What evidence shows that Th17 cells are required for disease in a mouse model of colitis?

A

In Dextran Sodium sulfate model mice it was found that the symptoms of disease as well as the expression of IL-6, TNF-alpha, IL-17, IL-17F, MCP-1 and RORgammaT were all reduced in IL-21 knockout mice

41
Q

What is Psoriasis?

A

Affects approximately 2% of the population and has a complex aetiology which likely contains a genetic component which could be activated by various environmental and infectious triggers

42
Q

What is the role of IL-17 in Psoriasis?

A

It acts on keratinocytes to produce innate defense proteins and chemokines that promote inflammation. These effects are amplified through TNF

43
Q

What are the anti-IL-17 agents currently being trialled for Psoriasis?

A

Brodalumab which targets IL-17R with 82% of patients on highest doses which achieves over 75% from baseline
PASI 75= is the current gold standard and 62% of patients achieved a PASI 100 (complete clearance)

44
Q

What is the effect of a high salt diet on development of EAE?

A

High salt diets seem to boost the induction and activation of Th17 cells

MEDSCI 708 (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions