Immunology of Endocrine Disease

Question 1

Autoimmune disease

Answer 1

A large group of clinical disorders which are
characterised by tissue or organ damage
mediated through aberrant immunological
mechanisms which are directed against
autoantigens

Question 2

Autoimmune disease is a multifactorial interaction of:

Answer 2

• Genetic factors (susceptibility)
• Environmental factors (aetiology)
• Autoimmune mechanisms (pathogenesis)

Question 3

What interacts to influence autoimmune disease?

Answer 3

• Genetic factors -Immune regulatory factors
• Hormonal factors
• Environmental factors
• ‘Other’ factors

Question 4

What is the pathogenesis behind autoimmune disease?

Answer 4

• Antibody mediated
• Cell mediated
• Complement mediated
• Phagocytes, cytokines, NK cells etc. etc.
• Combinations of the above

Question 5

What is the proposed sequence of events behind autoimmune disease?

Answer 5

• Initiating event + genetic susceptibility
• Breakdown of self-tolerance
• Autoreactivity
• Humoral+/- cellular
• Tissue damage

Question 6

Give examples of organ specific diseases.

Answer 6

• Hashimoto’s thyroiditis
• Primary myxoedema
• Thyrotoxicosis
• Pernicious anaemia
• Addison’s disease
• Juvenile diabetes

Question 7

Give examples on non-organ specific diseases.

Answer 7

• Dermatomyositis
• SLE
• Scleroderma
• Rheumatoid arthritsis

Question 8

What role does HLA play in autoimmunity?

Answer 8

• Receptors for aetiological agents
• Influence on tolerance induction or positive selection of particular T cell clones
• Molecular cross-reactivity/ molecular mimicry

Question 9

What can autoimmune reactions on the thyroid result in?

Answer 9

• Grave’s disease
• Myxoedema
• Hashimoto’s

Question 10

What can autoimmune reactions on the pancreas result in?

Answer 10

T1DM

Question 11

What can autoimmune reactions on the steroid cell result in?

Answer 11

Gonadal insufficiency

Question 12

What are primary autoantibodies?

Answer 12

Pathological agents

Question 13

What are secondary autoantibodies?

Answer 13

Non-pathogenic, disease markers

Question 14

What are the potential (known) autoantigens in autoimmune thyroid disease?

Answer 14

• TSHr
• Thyroglobulin
• Peroxidase
• Other

Question 15

What is the autoimmune mechanism of Grave’s disease?

Answer 15

Humoral

Question 16

Describe the autoimmunity involved in Grave’s disease.

Answer 16

• HLA-B8, DR3
• Class II HLA on thyroid cell surface
• TSHr growth & metabolism antibodies
• Autoimmune ophthalmopathy

Question 17

What is the autoimmune mechanism of Hashimoto’s disease?

Answer 17

• Humoral (goitre)

- Cellular (tissue destruction leading to hypofunction)

Question 18

Describe the autoimmunity involved in Hashimoto’s.

Answer 18

• Goitre + thyroid hypofunction
• HLA-DR5
• Growth stimulating antibody
• Lymphocytic infiltrate (CD4, CD8, B cell)

Question 19

What can mediated autoimmune thyroid diseases?

Answer 19

• Antibody mediated
• Cell mediated
• Both

Question 20

What are the functional effects of autoimmune thyroid disease?

Answer 20

• Hypofunction

- Hyperfunction

Question 21

What causes T1DM?

Answer 21

Immune mediated B cell destruction

Question 22

What causes T2DM?

Answer 22

Insulin resistance/ deficiency/ secretory defect

Question 23

What causes T3DM?

Answer 23

-Genetic defects of beta cell or insulin function

Question 24

What causes T4DM?

Answer 24

Gestational diabetes

Question 25

What evidence is there for hereditary factors in T1DM?

Answer 25

-HLA haplotypes: 
   B8, DR3
   B15, DR4
   DQβ3.2
-Twin concordance ~35%

Question 26

What evidence is there for an environmental role in T1DM aetiology?

Answer 26

• Seasonal incidence in onset
• Evidence of viral infection
• Marked geographical variation

Question 27

What evidence is there for autoimmunity in T1DM?

Answer 27

• Association with Hashimoto’s, Grave’s,
• P.A., atrophic gastritis, Addison’s
• Lymphocytic infiltration in islets
• Islet cell ab (2°)
• Insulin ab / insulinr ab
• Ab to glutamate decarboxylase
• Evidence of response (clinical & experimental) to immunosuppressive therapy

Question 28

What is the pathogenesis of T1DM?

Answer 28

-Genetic tendency + environment
-Islet inflammation / lymphocyte infiltration / ß cell damage
-Release of (non-tolerised) ß cell autoantigen or
Structural modification of ß cell autoantigen
-Sensitisation of autoreactive T cells to islet cell antigen + Inappropriate HLA expression on islet cells
-T cell recognition of autoantigen
-B cell destrution

Question 29

What can be affected by autoimmune endocrine disease?

Answer 29

-Hypothalamus (rare)
-Pituitary (probably rare, prolactin)
-Thyroid (common)
-Parathyroid (rare)
-Stomach (parietal cells)
-Pancreas (islet β cells only)
-Adrenal cortex (Addison’s, rarely Cushing’s)
Ovary / testis

Question 30

Who is usually affected by autoimmune polyendocrine syndromes?

Answer 30

Females

Question 31

What is type 1 polyendocrine syndrome?

Answer 31

Adrenal, parathyroid, candidiasis

Question 32

What is type 2 polyendocrine syndrome?

Answer 32

Adrenal, thyroid, T1DM

Question 33

What is type 3 polyendocrine syndrome?

Answer 33

• Thyroid + one of
  a) IDDM
  b) Gastric (P.A.)
  c) Non-endocrine autoimmune disease (e.g. RA, SLE)

Question 34

What is the autoimmune role in polyendocrine syndromes?

Answer 34

• HLA B8, DR3
• HLA-DR expression on cells of affected organs
• Circulating Ab to endocrine glands