Brainscape's Knowledge GenomeTM

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


See full index

TMS exam > 5 - effect of enterovirus on diabetes > Flashcards

5 - effect of enterovirus on diabetes Flashcards

1
Q

4 Ts of diabetes

A

toilet
thinner
thirsty
tired

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

how many adults have diabetes

A

422 million

diabetes in on the rise

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

cost of diabetes to NHS

A

uses 10% of NHS budget

costs NHS £22 million a day

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

which diabetes usually has a childood diagnosis

A

Type 1

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

what can a blood test via the arm tell you about diabetes

A

presence of genetic variants, autoantibodies, C-peptide, immune cell subsets, cytokine response, biomarkers (methylated DNA)

gives information about metabolic state of individual and progression of disease

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

what does a blood test from the arm NOT tell you about diabetes

A

the cause/causes of the disease (ETIOLOGY)

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

how can you find the etiology of diabetes

A

tissue biopsy from the pancreas

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

role of immunostaining in testing patients with/without diabetes

A

stain the islets of langerhans to detect for insulin and glucagon production

in T1 diabetes glucagon will remain but there will be barely any insulin
- shows selective elimination of beta cells

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

immune infiltration of the islets of langerhans

A

in diabetes immune cells infiltrate the islets in a non-uniform manner

some regions are more targeted than others
e.g. lots of CD8+ T cells and CD20

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

importance of presence of CD8+ T cells

A

increase in number in filtrate as insulin concentration decreases
therefore principal mediators of insulin cell death

CD20 flow in afterwards in parallel with CD8

immune cells go away after all beta cells have gone

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

why is there often a delay in diabetes diagnosis

A

markers are not present until most beta cells have been destroyed and it is too late

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

outline the association between enterovirus and type 1 diabetes mellitus

A

infection with enterovirus may alter immune system increasing susceptibility to diabetes by triggering autoimmunity

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

Detection of VP1 in individual islet cells in a child with

recent-onset type 1 diabetes

A

Look in islets of people with T1 diabetes
Cells stain positive for the virus –> suggests that islet cells are susceptible to the virus (can be infected)
If the cells become infected, may be a mechanism by which their functionality could be altered

Viral VP1 was very rarely detected in the islets of children
without type 1 diabetes

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

detection of viral VP1 in the islets of children

without type 1 diabetes

A

very rarely detected

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

Histological evidence that there may be viral infection in beta cells

A

results of children tested for the virus :

72 have T1 diabetes –> 44 of which have lots of viral protein present in the islets

50 children dont have diabetes –> only 3 had small amounts of viral protein in the islets

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

evidence that VP1 immunopositivity is restricted solely to beta-cells within the islets

A

islets were stained to show insulin and viral proteins

viral proteins are not found in glucagon producing cells

17
Q

which parts of the cell might become activated in virally-infected cells?

A

Protein kinase R (PKR)
MDa 5
RIG-1
TLRs

18
Q

role of protein kinase in viral infection

A

viral response protein
involved in mediation of translational arrest in virally infected cells
(cell switches off protein synthesis to try and dampen down the virus taking over therefore stops virus replicating)

19
Q

role of Mda 5 in viral infection in patients with diabetes

A

acts as a viral sensor
recognises single stranded (ss) RNA

expressed at a higher frequency in diabetics

20
Q

Expression of protein kinase R in islets immunopositive for VP1

A

greater expression (up-regulated) in virally infected islets

21
Q

mechanism of PKR

A

phosphorylates a key factor in the protein synthesis pathway (an initiation factor known as eIFalpha)

this inactivates the pathway and halts protein translation

Therefore any proteins that are rapidly turned over will be continue to be broken down by the cells but not replaced/re-synthesised –> become lost from cells

22
Q

what is Mcl-1

A

anti-apoptotic protein

powerful regulator of apoptosis
abundantly expressed in beta cells in islets

23
Q

Mcl-1 expression in virally infected cells

A

Mcl-1 is selectively depleted from islet cells expressing VP1

e.g. Mcl-1 is present in neighbouring un-infected cells but absent from those expressing VP1

24
Q

effects of virally infected cells not having Mcl-1

A

cells expressing VP1 die because they do not have the anti-apoptotic protein (Mcl-1)

virally infected cells are therefore sensitive to pro-apoptotic stimuli

25
Q

process of ssRNA production by enterovirus

A

enterovirus lifecycle
dsRNA intermediate during replication
cells detect dsRNA as foreign

26
Q

could dsRNA be used as a marker of or means to monitor infection

A

dsRNA sense by mda5

positive and negative RNA in double stranded formation was found present in muscle of mice with chronic inflammatory myopathy (CIM)
(Tam et al 1999)

dsRNA is also detectable in islet beta cells with T1 diabetes –> shows they are virally infected
dsRNA not present in alpha cells with T1 diabetes

27
Q

Mda 5 expression in non-diabetic controls

A

Mda 5 is present
present mainly in alpha cells
not much Mda 5 in beta cells in controls

28
Q

is diabetes an infectious disease

A

no

29
Q

main feature of T1 diabetes

A

autoimmune

30
Q

which two cell types mainly mediate decrease of beta cells

A

CD8+ T cells

CD20+ T cells

31
Q

effects resulting from persistent viral infection

A

evasion of normal immune mechanisms so virus isn’t fully cleared
some beta cells remain +ve for viral RNA and do not produce viral capsid protein allowing virus to hide genomically

therefore virus persists in the genomic form in the beta cells as RNA

32
Q

what triggers beta cell death

A

environmental agents acting in the context of an already susceptible genetic background

33
Q

immune cell destruction of beta cells

A

autoimmune
recognise beta cells as foreign
many immune cells work together
immune cell count decreases to 0 after beta cells have died

34
Q

beta cell autoantigens

A

released from beta cells after damage

processed and presented to helper T cells by APCs

35
Q

role of macrophages in beta cell destruction

A

antigen presenting cells
first cells to infiltrate islets
release IL-2 to activate CD4+ T cells
produce ROS

36
Q

role of cytokines in beta cell destruction

A

bind to receptors on beta cells to activate MAP-kinases and T factors

signalling cascades initiated (NFkB and STAT-1)

results in functional impairment and endoplasmic reticulum stress

apoptosis

37
Q

what activates CD8+ T cells

A

IL-2 produced by Th1 cells

TMS exam (22 decks)

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