2-5-16-Immune Mechanisms Of Diabetes (Shnyra) Flashcards Preview

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Flashcards in 2-5-16-Immune Mechanisms Of Diabetes (Shnyra) Deck (41):
1

Obesity leads to adipocyte necrosis and an increase in ___ macrophages. There is also a reduction in Treg cells and an increase in ___ cells

M1

B cells, CD4+ TH1, and CD8+ T cells

2

List some of the pro-inflammatory cytokines involved obesity and insulin resistance

IL-1b, TNF-a, IL-6, CCL2, CCL3, CXCL8

Anti-inflammatory--> IL-10, IL-4, IL-13

3

Type 1 diabetes is a ___-mediated autoimmune disorder

T cell

4

The onset of T1D is associated with infiltration of the islets of langerhans by ___ cells and the infiltrate is termed Insulitis

Mononuclear cells and CD8+ T cells

5

Describe the relationship between breast-feeding and type 1 diabetes incidences

Studies have shown an inverse correlation between a decrease in breast-feeding and an increase in T1d risk

Early exposure to cow milk in life may contribute to T1d

6

Wheat gluten is a potent ___

Diabetogen

Risk of T1D is higher in pts with gluten-sensitive enteropathy

7

Streptozocin and bafilomycin A1 from streptomyces are cytotoxic for ___ cells

Beta

8

List viruses that have been implicated in T1D:

Mumps
Rubella
CMV
Enteroviruses
Retroviruses

9

The __ region (MHC gene on chromosome 6) presents insulin ags. For CD8+ T cells is associated with susceptibility to T1D

HLA

10

The __ gene (chromosome 11) is an ag for the autoimmune response and is associated with susceptibility to T1D

Insulin

11

___ is a regulator of insulin gene expression in the thymus

AIRE

12

The ___ gene (chromosome 2) is a regulator of the autoimmune response that is associated with susceptibility to T1D

CTLA-4

13

In the thymus, insulin ags are presented within ___ MHC

Class II

14

Which HLA alleles are considered "High risk" in T1D?

HLA-DQ2/DQ8 and DR3/DR4

DQ2/DQ8 found in more than 90% of individuals with T1D

DR3/DR4 most common in children diagnosed with T1D prior to age 5

15

HLA class II molecules that lack ___ of the beta chain are often found among individuals with T1D

Asp57

16

HLA class II haplotypes such as ___ confer dominant protection against T1D

DR2/DQ6

17

This tandem repeat is a polymorphism that is categorized into classes I, II, and III associated with the insulin gene

VNTR core repeat sequence (VNTR polymorphism)

18

The susceptible class I alleles of the insulin VNTR are associated with lower __ synthesis resulting in: low ag synthesis --> low ag presentation in the thymus --> failure of deleting self-reactive CD8 T cells

insulin mRNA

19

Regarding the insulin gene, the central tolerance is broken with class ___ alleles

I

20

The absence or a defect in ___ in the medullary thymic epithelial cell can lead to failure of negative selection and AUTOIMMUNITY. It is a critical transcriptional factor regarding insulin

AIRE

21

___ is the susceptibility locus on chromosome 2 associated with T1D.

CTLA-4

22

CTLA-4 encodes a glycoprotein that is a ___ homologue and binds B7 protein (CD80/86)

CD28

23

The function of ___ is suppression of T cell activation and apoptosis

CTLA-4

24

CTLA-4 on a T cell binds ___ on an APC

B7

25

CTLA-4 competes with __ for binding CD80 leading to cell-cycle arrest that prevents expansion of activated T Cells

CD28

26

Failure of T cells to express the __ gene due to a mutation may contribute to aberrant immune responses seen in T1D

CTLA-4

27

___ can be used to treat autoimmune diseases by outcompeting CD28 on T cells for binding CD80/86 on an APC

sCTLA-4

28

The presence of __ abs can be used to predict/diagnose if an individual has T1D

Islet cell

29

The specificities of several identified Islet Cell Abs (ICA) include:

GAD65 (glutamic acid decarboxylase)
IA-2, tyrosine phosphatases
IAA (insulin autoantibodies)

30

The presence of __ distinct antibody specificities is highly predictive of future T1D

2 or more

When combined with HLA typing, autantibody screening is also useful for predicting disease in general populations

31

T1D is a ___-mediated disease

Th1

32

Regarding the pathogenic role of T cells:

T cells are activated in the ___ that drain the pancreas -->

Once activated, islet-specific T cells traffic to the pancreas where they ___ and accumulate resulting in organ-specific inflammation -->

Local APCs capable of presenting ag in the context of Class II MHC molecules secrete ___ which plays an important role in the pathogenesis of T1D -->

These APCs activate ag-specific ___ cells and further stimulates IFN-y -->

IFN-y inhibits ___ cytokine production (IL-4/5/10) and enhance IL-1b, TNF-a, and free radical production by macrophages which are all toxic to islet beta cells

Lymph nodes

Proliferate

IL-12

CD4 T

Th2

33

Asthma is more prevalent in children in T1D than non-diabetic children and the common denominator in cases is the failure of regulatory mechanisms controlled by __ cells

Treg

34

Susceptibility to T1D may be greatly enhance when __ cells fail to prevent activation/expansion of auto-reactive T cells

Treg

35

List cytokines secreted by Treg cells that lead to decreased in CD40, CD80/86, and IL-12

IL-4, IL-10, TGF-b

36

What are the effects of Tregs on B cells and NK cells?

Directly suppress B cell activation

Inhibit proliferation and differentiation of NK cells

37

What are the "CD's" of Treg cells?

CD4+/CD25+

38

The loss of Tregs in IPEX syndrome leads to ____

Neonatal diabetes

39

IPEX (Immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome) is a rare disease linked to the dysfunction of the transcriptional activator ___

FoxP3

40

___ appears to function as the master regulator in the development and function of regulatory T cells

FoxP3

41

Lean adipose tissue contains a greater proportion of ___ macrophages as well as ___ cells

M2/M1

Treg