Brainscape's Knowledge GenomeTM

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


See full index

Stage 2: Inflammation > Pathology of Type 1 Diabetes > Flashcards

Pathology of Type 1 Diabetes Flashcards

1
Q

Can you biopsy a live pancreas?

A

No

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

What do the islets look like in a pancreas of someone who had chronic T1D?

A
  • Scar tissue
  • Pseudoatrophic islets
  • Devoid of beta cells
  • Retaining alpha (glucagon) and gamma (somatostatin) cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe immune cells in the islets in T1D

A
  • Immune cell infiltration of the islets occurs = insulitis

- T cells, B cells, macrophages

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

What is CD3?

A

A marker associated with T cells

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

Why is T1D autoimmune?

A

1) Evidence of loss of immunological tolerance to self
2) Passive transfer of disease by immune effectors e.g. T cells, antibodies
3) Clinical responsiveness to immune suppression or to re-establishment of tolerance
4) Genetic predisposition

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

Describe use of islet cell autoantibodies in T1D?

A
  • Important diagnostic tool
  • Useful for predicting future disease (can be detected up to 25 years before onset but mostly in children)
  • Can measure at least one islet cell autoantibody in 99.9% of T1D patients
  • Not pathogenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe mother to child transfer of T1D?

A
  • Babies of T1D mothers are not born with diabetes
  • Therefore islet cell autoantibodies are not pathogenic bc they are transferred but the child is not born with beta cell damage/dysfunction
  • Mum T1D 4% risk, dad 6-8% risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is evidence that T cells cause diabetes?

A
  • If someone with T/B cell leukaemia without islet autoantibodies/T1DT1D gets a bone marrow transplant from someone with T1D they get T1D with autoantibodies
  • This rarely happens anymore bc use progenitor cells in transplant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What do residual C-peptide levels reflect?

A

The remaining beta cell mass

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

Describe cyclosporin in T1D

A
  • It stops T cells from proliferating (from T lymphocyte therefore action of T helper and T killer cels)
  • Increases the length of ‘honeymoon period’
  • Associated with unacceptable malignancy and OI rate so not used
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What genes are affected in T1D?

A
  • Mainly HLA class I and II involved in presenting peptides

- Affects immune system

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

What is the action of helper T (CD4) cells in T1D?

A

Th1/Th17 cells release IFN-gamma and IL-17 (pro-inflammatory) in response to islet antigens (proinsulin and IA-2) which are toxic to islet cells

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

What is the action of cytotoxic T (CD8) cells in T1D?

A
  • CD8 cells release IFN-gamma which kills islet cells
  • CD8 cells are targeted to kill beta cells in patients with T1D through recognition of a glucose-regulated preproinsulin epitope
  • As insulin is increased (beta cells working too hard), CD8 cells do more killing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe Treg cells in T1D

A
  • Treg generally releases IL-10 (immunosuppressive)
  • Only find these cells in 25% of patients and they tend to develop T1D later and have better glucose control
  • If clone and expand these cells can stop harmful activities of T cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe Decreased CD25+ Treg cell function in T1D

A
  • Resistance to regulation of Th17 cells (associated with resistance to suppression)
  • Linked to poor function of Treg cells (cells die) due to poor IL-2 signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the autoantigen specific immune imbalance in T1D

A
  • More CD8 and Th1/17 than Treg
  • May have cells in circulation but not activated
  • This balance could be corrected with therapies (more Treg, less killer T cells and less activated Th cells i.e. Th1/17)
17
Q

Describe % of beta cells in T1D

A
  • At diagnosis have 10-30% of beta cells, not enough to have euglycaemia
  • Can control diabetes much more easily with 30% beta cells
18
Q

What is the aim of treatment in recent onset diabetes?

A
  • Trying to preserve honeymoon stage
  • Stop autoimmunity, induce immunoregulation and restore/preserve beta cells
  • Improve glucose control
19
Q

What is the aim of treatment in established diabetes?

A

Prevent, arrest and reverse complications

20
Q

What would be the aim of treatment in patients pre-diabetes or at risk of T1D?

A

Prevent/stop autoimmunity and preserve beta cells

21
Q

Describe autologous haematopoeitic stem cell transplantation for T1D

A
  • Like restarting system

- Risk of neutropenic fever and sepsis

22
Q

What is the goal in T1D treatment?

A

Restoration of immunological tolerance to beta cells

23
Q

What type of autoimmune disease in T1D?

A

Cell specific

24
Q

What happens in T1D?

A
  • No insulin = no dampening effect of glucagon
  • Uncontrolled protein breakdown
  • Gluconeogenesis occurs despite high blood glucose bc liver responds to insulin not high blood glucose
  • Uncontrolled increase production of KB (bc KB produce a bit of insulin but not in T1D)
  • Hyperglycaemia and DKA
25
Q

What occurs in targeted immunosuppression in T1D?

A

1) Block T cell signalling with anti-CD3 antibody and CTLA-4-Ig - binds to all T cells, preferentially affects activated cells
2) Remove key APCs via anti-CD20 antibody leading to pan B cell depletion
3) Block effector cytokines via anti-IL-17 antibody which blocks cytokine signalling

26
Q

Which Mab is anti-CD20 and what is its effect?

A

Rituximab

  • B lymphocyte depletion
  • Preservation of beta cell function
  • Antibody-dependent cytotoxicity leading to B cell clearance (transient effect)
27
Q

How can Treg treatment be used in T1D?

A
  • Can isolate and genetically modify Tregs to make them more sensitive to IL-2, expand with IL-2 and re-infuse them (adoptive cell therapy)
  • Can give low dose IL-2 therapy to boost Tregs
28
Q

Describe antigen specific immunotherapy

A
  • Principle = immunisation of peptide in saline
  • Peptides presented by iDCs
  • Tolerance inducing
  • Effective in allergy
  • Allergen is taken up by resting APCs, it may anergise cells or if you give more cellsW, it can switch to promote Treg cells
  • Present self-peptides in the context of tolerance
  • On going ASI trials in ND-T1D
29
Q

What are the benefits of antigen specific immunotherapy?

A
  • Slower beta cell destruction
  • Lower insulin use
  • Better control
  • No serious adverse events
30
Q

What is T1D caused by?

A
  • T cells - Th1/17, Tc and dysfunctional Tregs

- NOT islet cell autoantibodies but islet cell autoantibodies are highly predictive of disease

31
Q

Are there several checkpoints available in T1D for intervention?

A

Yes

Stage 2: Inflammation (39 decks)

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