Lecture 18 Immunology of Endocrine Diseases

Question 1

Define immunological tolerance

Answer 1

unresponsiveness to an antigen that is induced by previous exposure to that antigen.

Question 2

Tolerance to self antigens is called

Answer 2

Self-tolerance

Question 3

What happens to antigen-specific receptors that bind to self molecules to avoid autoimmune disease

Answer 3

self-reactive molecules must be either eliminated or downregulated so that the immune system is made specifically tolerant to self-antigens.

Question 4

Define Central Tolerance

Answer 4

Self-tolerance induced in immature self-reactive lymphocytes.
The thymus plays an important role in eliminating T cells with high affinity to self antigens. Bone marrow is important in B cell tolerance

Question 5

Define Peripheral Tolerance

Answer 5

Mature lymphocytes that recognise self-antigens in peripheral tissues become incapable of activation by re-exposure or die by apoptosis

Question 6

Name an important mechanism for induction of peripheral tolerance and how is it maintained

Answer 6

Co-stimulation or second signals
Tregs maintain peripheral tolerance by suppressing the activation of lymphocytes specific for self or other antigens
1.	Anergy (functional unresponsiveness)
2.	Treg suppression
3.	Deletion (cell death)

Question 7

How can peripheral intolerance be bypassed

Answer 7

inflammation or tissue damage is present due to the increased activity of proteolytic enzymes which can cause intra- and extracellular proteins to be broken down, leading to high concentrations of peptides (cryptic epitopes) being presented to responsive T cells.
• The structures of self-peptides may be altered by viruses, free radicals or ionising radiation, thus bypassing previously established tolerance

Question 8

What is the HLA association of Addison disease and Hashimoto thyroiditis

Answer 8

DR3

Question 9

What is the HLA association of insulin dependent DM

Answer 9

DR4

Question 10

What are the causes of autoimmune disease

Answer 10

Environmental factors
Infections - co stimulation, molecular mimicry
Drugs
UV radiation

Question 11

What is Molecular Mimicry

Answer 11

• Structural similarity between self-proteins and microbial antigens may trigger an autoimmune response

Question 12

List aetiologies of type 1 diabetes

Answer 12

Autoimmune destruction
Association with certain HlA types
Viral infections- Coxsackie B, Mums

Question 13

Complications in large blood vessels in diabetes

Answer 13

MI
Stroke
Ischaemic limbs

Question 14

Complications in small blood vessels in diabetes

Answer 14

Retinopathy
Nephropathy
Neuropathy

Question 15

Complications in pregnancy in diabetes

Answer 15

Preeclamptic toxaemia
Large babies
Neonatal hypoglycaemia

Question 16

What is the most common cause of Grave’s Disease

Answer 16

Lon-acting thyroid stimulating immunoglobulin that mimics the action of TSH

Question 17

What are the features of Grave;s

Answer 17

Exopthalmos
Pretibial Myxodema
Finger clubbing

Question 18

Why does Grave’s Disease cause exopthalmos

Answer 18

Infiltration of the orbital tissues by fat, mucopolysaccharides and lymphocytes and may be due to an additional autoantibody reacting with these tissues

Question 19

What is called when hypothyroidism is present in neonates and what are the consequences

Answer 19

Cretinism

Physical growth and mental development are impaired, sometimes irreversibly

Question 20

Can an individual with Hashimoto’s develop thyrotoxicosis? If so why

Answer 20

Yes, damage to the thyroid follicles may lead to release of thyroglobulin causing a transient phase of thyrotoxicosis

Question 21

Describe histological features of Hashimoto’s disease

Answer 21

Eosinophilic granular cytoplasm due to proliferation of mitochondria (Askanazy cells, Hürthle cells or oncocytes)
Fibrosis

Question 22

What autoantibodies can be detected in Hashimoto’s

Answer 22

Thyroid peroxidase

Thyroglobulin

Question 23

What is Autoimmune Polyendocrine Syndromes

Answer 23

Functional impairment of multiple endocrine glands due to loss of immune tolerance

Question 24

Name the manifestation of APS-1

Answer 24

Addison’s

Hypoparathyroidism

Question 25

Name manifestation of APS-2

Answer 25

Addison’s
Auto-immune thyroid disease
Type 1 diabetes

Question 26

Clinical features of APS-1

Answer 26

• Chronic mucocutaneous candidiasis
• Hypoparathyroidism
• Primary adrenal insufficiency (Addison’s disease)
• Enamel hypoplasia
• Enteropathy with chronic diarrhoea or constipation.
• Primary ovarian insufficiency

Question 27

Which APS is more common APS-1 or APS-2

Answer 27

APS-2

Question 28

What are other manifestations for APS-2

Answer 28

• Celiac disease
• Alopecia, vitiligo
• Primary ovarian insufficiency
• Pernicious anemia

Question 29

What is IPEX

Answer 29

X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy
– Early-onset type 1 diabetes
– Autoimmune enteropathy with intractable diarrhea and malabsorption
– Dermatitis that may be eczematiform, ichthyosiform, or psoriasiform

Question 30

What are clinical manifestation of IPEX

Answer 30

Eosinophilia and elevated IgE
Kidney disease
–	Autoimmune thyroid disease
–	Alopecia
–	Various autoimmune cytopenias
–	Hepatitis
–	Exocrine pancreatitis.