Immunology of Endocrine Disease

Question 1

In which gender are the majority of autoimmune diseases more common?

Answer 1

• Women

Question 2

What is immune tolerance?

Answer 2

Unresponsiveness to an antigen that is triggered by previous exposure to that antigen

Question 3

What are antigens that induce tolerance called?

Answer 3

• Tolerogens

Question 4

What are the two forms of self tolerance?

Answer 4

• Central (negative selection - eliminate immune cells that respond to cell antigens)
• Peripheral (T regs that ensure self attacking lymphocytes that escape central tolerance can’t cause immune responses)

Question 5

Where do central and peripheral tolerance occur?

Answer 5

• Central: primary lymphoid tissue

- Peripheral: outside of primary lymphoid tissue

Question 6

What is molecular mimicry?

Answer 6

• Structural similarities between self and bacterial antigens
• Immune system may attack self antigens due to similarity to invading organisms antigens

Question 7

What is epitope spreading?

Answer 7

The broadening of an autoimmune response after the breakdown of tolerance

• Local tissue damage accelerates due to the resulting inflammation

Question 8

What are some risk factors for autoimmune disease?

Answer 8

• Genetics (alleles on the MHC)
• Hormones (males vs females)
• Infections (mimicry / co-stimulation)
• Drugs
• UV radiation (modifications of antigens / receptors)

Question 9

How are autoimmune diseases treated?

Answer 9

1. Suppression of damaging immune response (specificity and toxicity an issue)
2. Replacement of function of damaged organ (hormone replacement etc.)

Question 10

What are the cell types of the islets of the pancreas? Functions?

Answer 10

1. Beta cells: insulin
2. Alpha cells: glucagon
3. Delta cells: somatostatin
4. Pancreatic polypeptide cells: pancreatic polypeptide

Question 11

What are some risk factors for type 1 diabetes?

Answer 11

• Genetics (HLA factors)

- Viral infection (coxsackie B, mumps)

Question 12

What are the most likely causes of hyperthyroidism?

Answer 12

Graves thyroiditis
Functioning adenoma
Toxic nodular goitre
Exogenous thyroid hormone (rare)
Ectopic secretion by ectopic thyroid tissue or tumours

Question 13

Describe the pathophysiology of Graves thyrotoxicosis

Answer 13

• long-acting thyroid stimulator (LATS) antibodies in the serum stimulate the function and growth of follicular epithelium in the thyroid

Question 14

What is cretinism? Risk factors?

Answer 14

• Congenital hypothyroidism
• Endemic in areas with low iodine diets
• Sporadic cases usually due to congenital absence of thyroid tissue / enzyme defects

Question 15

What is the most common cause of hypothyroidism in adults? How does the disease tend to progress?

Answer 15

• Hashimotos thyroiditis
• In the early stages of the disease damage to the thyroid follicles may lead to release of thyroglobulin causing a transient phase of thyrotoxicosis. Followed by atrophy and fibrosis of the gland

Question 16

What are the targets of the two most common autoantibodies detected in Hashimotos thyroiditis?

Answer 16

one reacting with thyroid peroxidase

the other reacting with thyroglobulin

Question 17

What are Autoimmune polyendocrine syndromes?

Answer 17

A diverse group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance.

Question 18

What is Autoimmune Polyendocrine Syndrome Type 1 (APS-1)?

Answer 18

rare autosomal recessive disease caused by mutations in the autoimmune regulator gene (AIRE)

• Loss of negative selection

Question 19

What are some symptoms / signs of APS-1?

Answer 19

• Chronic mucocutaneous candidiasis (chronic infections with Candida that are limited to mucosal surfaces)
• Hypoparathyroidism
• Primary adrenal insufficiency (Addison’s disease)
• Enamel hypoplasia
• Enteropathy with chronic diarrhea or constipation.
• Primary ovarian insufficiency

Question 20

What is Autoimmune Polyendocrine Syndrome Type 2 (APS-2)? Which gender does it predominantly affect?

Answer 20

• Impairment of multiple endocrine glands due to loss of immune tolerance
• It is heterogeneous and has not been linked to one gene. HLA mutation usually implicated
• Much more common in women

Question 21

What are the characteristic signs / symptoms of Autoimmune Polyendocrine Syndrome Type 2 (APS-2)?

Answer 21

At least 2 of the following:

• Type 1 diabetes
• Autoimmune thyroid disease
• Addison’s disease

Other conditions may develop

Question 22

What is X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX)?

Answer 22

An extremely rare inherited syndrome characterized by:

• Early-onset type 1 diabetes
• Autoimmune enteropathy with intractable diarrhoea and malabsorption
• Dermatitis

Question 23

What are some other conditions that can develop from X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX)?

Answer 23

• Kidney disease (membranous glomerulonephritis or interstitial nephritis)
• Autoimmune thyroid disease
• Alopecia
• Various autoimmune cytopenias
• Hepatitis
• Exocrine pancreatitis.

Question 24

What is the prognosis for X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX)? What are the treatment options?

Answer 24

• Usually fatal within the first few years of life if untreated
• allogeneic bone marrow transplantation can cure the disease