Interactions of the Endocrine and Immune Systems

Question 1

Three most common autoimmune endocrinopathies?

Answer 1

Graves Disease
Hashimoto’s Disease
Type I Diabetes

Question 2

What type of autoimmune disease is Hashimoto thyroiditis?

Answer 2

Type II (antibody)
Type IV (T cell-mediated)

Question 3

What does Hashimoto eventually cause?

Answer 3

Progressive thyroid failure as less and less thyroid hormone is produced

Question 4

What are the antibodies responsible for Hashimoto thyroiditis?

Answer 4

Anti-thyroglobulin

Anti-thyroid peroxidase (anti-TPO)

Question 5

What are the two proteins whose genes typically mutated in Hashimoto?

Answer 5

CTLA-4

PTPN22

Question 6

What does CTLA-4 do?

Answer 6

Coreceptor found on T-cells that binds to B7 on antigen presenting cells to deactivate the T-cells

Question 7

What type of autoimmune disease is Graves Disease?

Answer 7

Type II

Question 8

What three genes are found to be mutated in Graves Disease?

Answer 8

CTLA-4
PTPN22
HLA-DR3

Question 9

What is the most common autoantibody found in Graves Disease?

Answer 9

TSI (thyroid stimulating immunoglobulin)

Question 10

What does TSI do?

Answer 10

Binds the TSH receptor mimicking TSH

Question 11

What are four causes the exophthalmos in Graves?

Answer 11

T-cell infiltration of retro-orbital space
Inflammation of extraocular muscles
Extracellular matrix components accumulation
Increased number of adipocytes

Question 12

What is the role of orbital pre-adipocytes in exophthalmos?

Answer 12

They express TSH receptors and trigger the immune response

Question 13

What is the cause of extracellular matrix component accumulation in Graves?

Answer 13

Activated CD4 helper cells secrete cytokines stimulating fibroblast proliferation

Question 14

Cells found in the islets of Langerhans:

Answer 14

Beta cells: insulin
Alpha cells: glucagon
Delta cells: somatostatin
PP cells: pancreatic peptide

Question 15

What type of autoimmune disease is Type I diabetes?

Answer 15

Type IV

Question 16

What HLA genes are associated with Type I diabetes?

Answer 16

HLA-DR3

HLA-DR4

Question 17

Which non-HLA gene mutations are associated with Type I diabetes?

Answer 17

CTLA-4
PTPN22
Insulin

Question 18

How can insulin mutation be associated with Type I diabetes?

Answer 18

T-cells are sensitized in the thyroid gland against antigens found on normal insulin, when there is mutated insulin made by beta cells the T-cells will attack it

Question 19

When activated Th1 cells and CD* CTLs are activated and make their way to the islets cells what pathway do they follow for destruction?

Answer 19

Th1 cells: IFN-y and TNF-> Beta cell injury

CD8 CTL: kill beta cells

Question 20

What are the islet autoantigens attacked in Type I diabetes?

Answer 20

Insulin
GAD
ICA512

Question 21

Which autoantigen in T1D is useful as a marker for the disease?

Answer 21

Anti-GAD

Question 22

Overall net effect of cortisol?

Answer 22

Anti-inflammatory

Question 23

What is a good diagnostic tool for autoimmune adrenalitis?

Answer 23

Antibodies against enzymes needed in steroid hormone production

Question 24

Two clinical setting of autoimmune adrenalitis?

Answer 24

1. ) APS1/APECED

2. ) APS2

Question 25

What causes APS1?

Answer 25

Mutation in AIRE gene which encodes a transcription factor in the thymus that is needed to turn on genes needed for tolerization of T-cells; causes T-cells to not be sensitive against multiple proteins

Question 26

What is seen in APS1 patients?

Answer 26

Chronic candiasis in skin, teeth and nails

Question 27

When does APS1 and APS2 present?

Answer 27

APS1: birth (they die young)
APS2: early adulthood

Question 28

What is seen in patients with APS2?

Answer 28

Adrenal insufficiency
Hashimoto thyroiditis
Type I diabetes