Immune Mechanisms of Diabetes Flashcards by Deleted Deleted

What do we see when insulin is being normally metabolised and there’s appropriate glucose uptake by cells?

A. High levels of insulin, glucose, and FFA in serum

B. low levels of M2 Macrophages

C. High serum IL-1B and Low serum IL-1Ra

D. Low serum IL-1B and High serum IL-1Ra

Low serum IL-1B and High serum IL-1Ra

We should also see*
- high levels of M2 Macrophages*
- low serum levels of insulin, glucose, and FFAs*

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Which of the following do we see in obese patients with T2DM?

A. Increase of lipolysis in adipose tissue

B. Increase macrophage accumulation in adipose tissue

C. Increase glucose and TAG production in liver

D. Inflammation in the liver

E. All of the above

All of the above

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Obesity is an inflammatory state, that doesn’t cause an increase in the number of adipocytes, but rather increases the size and number of lipids inside of them. This increases the stress on adipocytes and we see secretion of what cytokines that perpetuate an inflammatory response onto the endothelium?

TNF-a

IL-1B

IL-6

This homes neutophils, macrophages and other immune cells

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In “Lean” adipose tissue we see Treg cells, Th2 secreting cytokines to keep Treg active, iNKT, eosinophils, and M2 Macrophages. These all help providean environment in an antiinflammatory state. What cytokines predominate?

IL-4

IL-13

IL-10

(adiponectin-not a cytokine)

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Which of the following cytokines is secreted by M1 Macrophages and is the big bad in terms of causing an acute inflammatory response, has a role in adipose inflammation, and insulin resistance?

A. IL-1

B. IL-13

C. IL-21

D. IL-6

IL-6

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Which of the following is not stimulated by the release of IL-6 from M1 macrophages as seen in T2DM patients?

A. Liver produces acute phase proteins like c-reactive protein

B. Increase lipolysis and AMPK generation

C. Increase risk of cancer and rheumatiod arthritis

D. Increase GLP-1 production in intestines and pancreas

E. All of the above occurs

F. None of the above occurs

All of the above occurs

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FFAs like palmitate, are released from stressed adipocytes and seen at high levels in the serum. The binding of FFA to what TLR stimulates recruitment of M1 macrophages, and proinflammatory cytokine production that overtime lead to sustained Beta cell dysfunction?

A. TLR2

B. TLR3

C. TLR4

D. TLR6

TLR4

- overtime the cytokines cause an inflammatory state that causes sustained Beta cell dysfunction

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In normal weight insulin sensitive people we have a majority of M2 Macrophages, Treg cells, and Th2 response shut it down cytokines IL-4, 10, and 13. However, in an obese insuline resistant we change the above profile and instead have a majority of what?

Cytokines:

Igs:

T cell response type:

TNF-a

IFN-y

IgG2c

Th1 response

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T/F: Insulin resistance is related to Beta cell dysfunction because the more insulin resistance the more Beta cell dysfunction you get

True

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T1DM is a true autoimmune disease that is a Type IV hypersensitivity. Which of the following is true of this disease?

A. Beta cell destruction is mediated by CD4 T cells

B. Beta cell destruction is mediated by CD8 T cells

C. Beta cell destruction is mediated by NK cells

D. Alpha cell destruction is mediated by CD8 T cells

Beta cell destruction is mediated by CD8 T cells

this results in insulin deficiency

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T1DM has strong Class II HLA associations (Chromosome 6). Which of the following are found in about 90% of individuals?

A. HLA DR3/DR4

B. HLA DR5/DR6

C. HLA DQ2/DQ8

D. HLA DR2/DR6

HLA DQ2/DQ8

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T1DM has strong Class II HLA associations (Chromosome 6). Which of the following are most commonly diagnostic in children prior to age 5?

A. HLA DR3/DR4

B. HLA DR5/DR6

C. HLA DQ2/DQ8

D. HLA DR2/DR6

HLA DR3/DR4

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Understand and be able to talk through this chart

Again

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Which of the following are correctly paired and under Th1 responses related to T1DM? (select all that apply)

A. IL-4; activates B lymphocytes to produce islet cell auto-Abs and anti-GAD Abs

B. IFN-y; activates Macrophages with release of IL-1 and TNF-a

C. IL-2; activates autoAg specific CD8 T cells

D. None of the above

B. IFN-y; activates Macrophages with release of IL-1 and TNF-a

C. IL-2; activates autoAg specific CD8 T cells

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Which of the following are correctly paired and under Th2 mediated responses in T1DM?

A. IL-4; activates B lymphocytes to produce islet cell auto-Abs and anti-GAD Abs

B. IFN-y; activates Macrophages with release of IL-1 and TNF-a

C. IL-2; activates autoAg specific CD8 T cells

D. None of the above

A. IL-4; activates B lymphocytes to produce islet cell auto-Abs and anti-GAD Abs

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Which of the following cytokines gets released from Th1 and induces the activation of Auto-antigen specific cytotoxic T cells?

A. IFN-y

B. IL-4

C. IL-2

D. IL-1 and TNF-a

IL-2

Which of the following leads to destruction of beta cells and thus decreased insulin secretion as seen in T1DM patients?

A. IL-4; activates B lymphocytes to produce islet cell auto-Abs and anti-GAD Abs

B. IFN-y; activates Macrophages with release of IL-1 and TNF-a

C. IL-2; activates autoAg specific CD8 T cells

D. All of the above

E. None of the above

All of the above

IL-4; activates B lymphocytes to produce islet cell auto-Abs and anti-GAD Abs

IFN-y; activates Macrophages with release of IL-1 and TNF-a

IL-2; activates autoAg specific CD8 T cells

There are around 20 genes associated with T1DM, however, what are the 4 big ones?

HLA Class II

Insuline gene

AIRE

CTLA-4 (ligand of Treg cells)

Which of the following HLAs is a halotype that is found to be protective against T1DM?

A. HLA DR3/DR4

B. HLA DR5/DR6

C. HLA DQ2/DQ8

D. HLA DR2/DR6

HLA DR2/DR6

found on short arm of HLA complex (actually all of the relevant ones for T1DM are)

All of the following are Non-HLA genes involved in autoimmunity and relevant for T1DM. Which of them is also implicated in RA, T1DM, and thyroid immune disease, as it regulates T cell selection and activation?

A. PTPN22 (tyrosine phosphatase)

B. CTLA-4

C. AIRE

D. FoxP3

E> FAS

PTPN22 (tyrosine phosphatase)

All of the following are Non-HLA genes involved in autoimmunity and relevant for T1DM. Which of them would lead to an impaired inhibitory checkpoint and regulatory T cell function?

A. PTPN22 (tyrosine phosphatase)

B. CTLA-4

C. AIRE

D. FoxP3

E. FAS

CTLA-4

All of the following are Non-HLA genes involved in autoimmunity and relevant for T1DM. Which of them is involved in immune dysregulation, polyendocrinopathy, and enteropathy, because it leads to deficiency in Treg cells?

A. PTPN22 (tyrosine phosphatase)

B. CTLA-4

C. AIRE

D. FoxP3

E. FAS

FoxP3

All of the following are Non-HLA genes involved in autoimmunity and relevant for T1DM. Which of them is associated with diabetes, adrenal and parathyroid issues, because it reduces expression of peripheral tissue Ags in the thymus leading to defective elimination of self reactive T cells?

A. PTPN22 (tyrosine phosphatase)

B. CTLA-4

C. AIRE

D. FoxP3

E. FAS

AIRE

All of the following are Non-HLA genes involved in autoimmunity and relevant for T1DM. Which of them is involved with splenomegaly, lymphadenopathy and adrenals, because it leads to defective apoptosis of self-reactive T and B cells in the periphery?

A. PTPN22 (tyrosine phosphatase)

B. CTLA-4

C. AIRE

D. FoxP3

E. FAS

FAS

Errors in the insulin gene lead to reduction in tolerance to insulin and insulin precursors due to low presentation. This gene found on Chromosome 11 IDDM2, is susceptible to VNTR in its promotor region. The number of repeats is indicative of the impact it will have on insulin production and is categorized in a class based on the number of repeats. Which class is associted with lower insulin mRNA synthesis? A. Class I: 26-63 repeats B. Class II: 80 repeats C. Class III: 141-209 repeats

Class I: 26-63 repeats

T/F: The CTLA-4 gene is found on chromosome 2

True

T/F: A defect in CTLA-4 expression on Treg cells and activated T cells decreases the ability to control and down-regulate the immune response, which is absolutely necessary to maintain tolerance

True

What 3 chemicals cause direct destruction of Beta cells?

N-nitroso compounds Alloxan Compounds in smoked meats

Prenatal factors that increase likilihood of T1DM, include genetic factors and HLA genotype. There are also postnatal factors, what are they? Hint: Think milk, vitamins, and infections

Decrease breastfeeding Increased cow's milk exposure Decrease Vitamin D intake Obesity Decrease in childhood infections Viral Infections

Viruses may lead to destruction of Beta cells via what two major mechanisms?

Direct cytotoxicity Molecular mimicry

What viruses are implicated in T1DM via molecular mimicry\>

Mumps Rubella Cytomegalovirus Enterovirus Retrovirus MR. CER

Islet cell Auto-Ab production is found in everyone with T1DM. THese ICAs and are even found months to years in advance of metabolic changes, and thus can be used to predict the course of the disease. Presence of what 3 ICAs can confirm diagnosis?

1. Glutamic Acid Decarboxylase (GAD65) 2. Insulinoma Ag-2 (IA-2, tyrosine phosphatase) 3. Insulin auto-Ab (IAA)

Look at this one

Maybe a question based on what should present over time, or what is seen before X