Interactions of the Endocrine and Immune Systems Flashcards
Three most common autoimmune endocrinopathies?
Graves Disease
Hashimoto’s Disease
Type I Diabetes
What type of autoimmune disease is Hashimoto thyroiditis?
Type II (antibody) Type IV (T cell-mediated)
What does Hashimoto eventually cause?
Progressive thyroid failure as less and less thyroid hormone is produced
What are the antibodies responsible for Hashimoto thyroiditis?
Anti-thyroglobulin
Anti-thyroid peroxidase (anti-TPO)
What are the two proteins whose genes typically mutated in Hashimoto?
CTLA-4
PTPN22
What does CTLA-4 do?
Coreceptor found on T-cells that binds to B7 on antigen presenting cells to deactivate the T-cells
What type of autoimmune disease is Graves Disease?
Type II
What three genes are found to be mutated in Graves Disease?
CTLA-4
PTPN22
HLA-DR3
What is the most common autoantibody found in Graves Disease?
TSI (thyroid stimulating immunoglobulin)
What does TSI do?
Binds the TSH receptor mimicking TSH
What are four causes the exophthalmos in Graves?
T-cell infiltration of retro-orbital space
Inflammation of extraocular muscles
Extracellular matrix components accumulation
Increased number of adipocytes
What is the role of orbital pre-adipocytes in exophthalmos?
They express TSH receptors and trigger the immune response
What is the cause of extracellular matrix component accumulation in Graves?
Activated CD4 helper cells secrete cytokines stimulating fibroblast proliferation
Cells found in the islets of Langerhans:
Beta cells: insulin
Alpha cells: glucagon
Delta cells: somatostatin
PP cells: pancreatic peptide
What type of autoimmune disease is Type I diabetes?
Type IV
What HLA genes are associated with Type I diabetes?
HLA-DR3
HLA-DR4
Which non-HLA gene mutations are associated with Type I diabetes?
CTLA-4
PTPN22
Insulin
How can insulin mutation be associated with Type I diabetes?
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
When activated Th1 cells and CD* CTLs are activated and make their way to the islets cells what pathway do they follow for destruction?
Th1 cells: IFN-y and TNF-> Beta cell injury
CD8 CTL: kill beta cells
What are the islet autoantigens attacked in Type I diabetes?
Insulin
GAD
ICA512
Which autoantigen in T1D is useful as a marker for the disease?
Anti-GAD
Overall net effect of cortisol?
Anti-inflammatory
What is a good diagnostic tool for autoimmune adrenalitis?
Antibodies against enzymes needed in steroid hormone production
Two clinical setting of autoimmune adrenalitis?
- ) APS1/APECED
2. ) APS2
What causes APS1?
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
What is seen in APS1 patients?
Chronic candiasis in skin, teeth and nails
When does APS1 and APS2 present?
APS1: birth (they die young)
APS2: early adulthood
What is seen in patients with APS2?
Adrenal insufficiency
Hashimoto thyroiditis
Type I diabetes
