Immune Mechs Of Diabetes - 2/5 Shynra

Question 1

Type 2 diabetes is due to what?

Answer 1

Insulin resistance

Question 2

What does lean adipose tissue contain?

Answer 2

Higher proportion of M2/M1 macrophages

high # of Treg cells

Question 3

What does obesity lead to?

Answer 3

Adipocyte necrosis and increase in M1 macrophages

Reduction in Treg, INC in CD4 Th1 and CD8

Question 4

What are the major anti-inflammatory cytokines?

Answer 4

IL-10, 4, 13

Question 5

Patients with Type I Diabetes are prone to what?

Answer 5

Ketoacidosis

Question 6

What kind of disorder is type 1 diabetes?

What associations do they have?

Answer 6

T cell-mediated autoimmunity

HLA

Question 7

T1D development involves genetic and environmental factors such as what?

Answer 7

Birth delivery mode, use of antibiotics, diet

Question 8

What is the concordance rate for T1D in monozygotic twins?

Answer 8

30-50%, meaning environment plays very large role

Question 9

What is the relationship between breast feeding and T1D?

Answer 9

DEC breast feeding leads to INC T1D

Question 10

What leads to mucin synthesis and maintenance of tight junctions?

Answer 10

Prevotella -> Butyrate

Question 11

What leads to mucin degradation, altered permeability and T1D?

Answer 11

Bacteriodes -> propionate, succinate, acetate

Question 12

What can act as a immune modulator and suppressant that is linked with T1D?

Answer 12

Vitamin D

Question 13

What may contribute to protection form T1D?

Answer 13

Exposure to infectious agents during childhood

Question 14

What can kill Beta cells?

Answer 14

Streptozocin and bafilomycin A1 from Streptomyces

Question 15

How may viruses act against Beta cells?

Which viruses in particular?

Answer 15

Direct cytotoxicity
Triggering of autoimmunity by molecular mimicry

Mumps and Rubella

Question 16

There are 18 genes associated with susceptibility to T1D, what are the most significant?

Answer 16

HLA
Insulin gene
AIRE
CTLA-4

Question 17

What chromosome is the HLA region located?

Presentation of insulin Ags for what?

Answer 17

6

CD8 T cells

Question 18

What chromosome is the insulin gene located?

Ag for what?

Answer 18

11

Autoimmune response

Question 19

What chromosome is CTLA-4 gene located on?

Does what?

Answer 19

2

Regulation of autoimmune response

Question 20

What are the high risk HLA alleles in T1D?

Answer 20

DQ2/DQ8 and DR3/DR4

Question 21

Individuals with T1D are often found with what kind of HLA class II molecules?

Answer 21

Lacking Asp57 on the beta chain

Question 22

What haplotypes confer dominant protection to T1D?

Answer 22

DR2/DQ6

Question 23

What is the VTNR polymorphism categorized into?

Answer 23

Classes I, II, and III

Question 24

Which class is most susceptible of the insulin VTNR associated with lower insulin mRNA synthesis?

What are the results?

Answer 24

Class I

Low insulin synthesis, low Ag presentation in the thymus
Failure of deleting self-reactive CD8 T cells

Question 25

What is the insulin gene?

Answer 25

IDDM2

Question 26

What breaks central tolerance?

Answer 26

class I alleles

Question 27

What controls expression of insulin in the thymus?

How does it work?

Answer 27

AIRE

Lower levels of insulin mRNA in the thymus

Question 28

What is a critical factor in the induction of central tolerance against insulin?

Answer 28

AIRE

Question 29

What is the function of CTLA-4?

Answer 29

Suppression of T cell activation and activation of its apoptosis

Question 30

What is CTLA-4 a homologous of?

What does it bind?

Answer 30

CD28

CD80/86 aka B7

Question 31

What does CTLA-4 compete with?
To bind what?

What does CTLA-4 control?

Answer 31

CD28
CD80/86

Peripheral tolerance

Question 32

Failure of T cells to express CTLA-4 results in what?

Answer 32

Aberrant immune responses seen in T1D

Question 33

What are detected in individuals with T1D with increased frequency?

What are the specific types?

Answer 33

Islet Cell Autoantibodies (ICA)

GAD65
IA-2I
IAA

Question 34

What kind of disease is T1D?

What stimulates this type of T cell?

Answer 34

Th1

IL-12

Question 35

What do Th1 cell stimulate?

Effect on islet beta cells?

Answer 35

IFN-gamma

Toxic via IL-1B, TNF-a, and free radical production by macrophages

Question 36

How can susceptibility to T1D be greatly enhanced?

Answer 36

Treg cells fail to prevent activation/expansion

Question 37

What syndrome is associated with loss of Treg and leads to neonatal diabetes?

Answer 37

IPEX

Question 38

What is diabetes mellitus type I a result of?

Answer 38

Loss of Beta cells