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(OMS1) GIGU Exam > Lecture 17: Immune Mechanisms of Diabetes > Flashcards

Lecture 17: Immune Mechanisms of Diabetes Flashcards

1
Q

Which ethnicities are at higher risk of developing Type II DIabetes?

A

African Americans
Hispanics
Native Americans

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2
Q

Genetics seems to work in an ____ fashion regarding Type II Diabetes.

A

Additive fashion

e.g. higher with both T2D parents and monozygotic twin

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3
Q

In an non-inflammatory state, what type of immune cells are more common?

A 
Treg
Th2
iNKT cells
M2 Macrophages
Eosinophils
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4
Q

What causes quiescent transition to inflammatory state?

What cytokines/cells play a role in inducing the inflammatory state?

A

stressed adipocytes (hyeprtrophy) > more adipocyte dysfunction > activating the endothelium

Activated endothelium releases: 
Th1 cells
M1 Macrophages
CD8+ T cells
B cells
Dendritic Cells
Mast Cells
Neutrophils
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5
Q

In an inflammatory state, what cytokines are released by dysfunctional adipocytes that damage the organs (leading to its resistance to insulin)?

A

TNF-α
IL-1β
IL-6

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6
Q

How does IL-6 play a role in the development of Type II diabetes?

A

Role in inducing adipose dysfunction leading to insulin resistance (how this happens is still unclear)
-released from M1 macrophages and activated adipocytes

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7
Q

How does long chain FFA palmitate play a role in the induction of adipose inflammation?

A

Palmitate binds to TLR-4 on activated adipocytes >
release of pro-inflammatory cytokine/chemokine production > M1 recruitment > chronic inflammation >
β cell dysfunction

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8
Q

In an obesity insulin resistance state, what cytokines are effectively shut down?

A

IL-4
IL-10
IL-13

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9
Q

Genetics seems to work in a ____ fashion regarding Type I Diabetes.

A

Multiplicative function

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10
Q

What autoimmune disease are type I diabetics at a greater risk for?

A

Celiac Disease

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11
Q

What genes can play have an important factor in developing Type I Diabetes?

A

HLA
INS-insulin gene
AIRE
CTLA-4

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12
Q

What are the high risk HLA class II alleles regarding type I diabetes?

A

DQ2/DQ8
DR3/DR4

*lack Asp57

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13
Q

What HLA class II haplotype confers protection against type I dabetes?

A

DR2/DQ6

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14
Q

What is the function of AIRE expression?

A

Presentation of insulin in thymus to developing T cells

-very imp to prevent T1D

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15
Q

Individuals with two class __ alleles have an increased risk to develop T1D.

A

2 Class I alleles

  • lower insulin mRNA synthesis –> reduction in tolerance to insulin
  • 26 to 63 repeats
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16
Q

What is the function of CTLA-4?

A

Regulates expression of Tregs and can down regulate immune response

17
Q

Describe the correlation between breastfeeding and T1D.

A

Decreased breast feeding may lead to increase chance of developing T1D

18
Q

Describe the correlation between exposure to cow’s milk and T1D.

A

Early exposure to cow’s milk can increase change of developing T1D

  • less insulin compared to breast milk
  • huge genetic variations in cow milk proteins
19
Q

Describe the correlation between Vitamin D and T1D.

A

Decreased Vit D intake may lead to increase chance of developing T1D

20
Q

What viruses can be implicated in the development of T1D?

A 
Mumps
Rubella
Cytomegalovirus
Enteroviruses
Retroviruses
21
Q

What chemicals can be implicated in the development of T1D?

A

Pesticides
N-nitroso compounds
Alloxan
Smoked meat/foods

22
Q

After autoantigens are presented and processed to APCs, what happens?

A
  1. TH1 lymphocytes are activated releasing IFNγ and IL-2

2. Th2 lymphocytes are activated and release IL-4

23
Q

What does IFNγ activate?

A

M1 Macrophages

-releases IL-1 and TNF-α

24
Q

What does IL-2 activate?

A

Specific CD8+ cells

25
Q

What does IL-4 activate?

A

B lymphocytes to produce islet cell autoantibodies

26
Q

What type of autoantibodies are detected in individuals with T1D?

A

Islet cell autoantibodies

  • Glutamic Acid Decarboxylase (GAD65)
  • Insulinoma Antigen-2 (IA-2)
  • Insulin autoantibodies (IAA)

*2 or more of these autoantibodies are highly predictive of T1D

27
Q

How can T1D change Treg function?

A

Treg become unstable and lose Foxp3 expression

-produce inflammatory cytokines IFN-γ and IL-17

28
Q

What is a therapeutic solution to mitigate loss of Tregs?

A

Soluble CTLA-4

(OMS1) GIGU Exam (40 decks)

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