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endocrine system 1 > Immunology of Endocrine Disease > Flashcards

Immunology of Endocrine Disease Flashcards

1
Q

Autoimmune disease

A

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

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2
Q

Autoimmune disease is a multifactorial interaction of:

A
  • Genetic factors (susceptibility)
  • Environmental factors (aetiology)
  • Autoimmune mechanisms (pathogenesis)
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3
Q

What interacts to influence autoimmune disease?

A
  • Genetic factors -Immune regulatory factors
  • Hormonal factors
  • Environmental factors
  • ‘Other’ factors
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4
Q

What is the pathogenesis behind autoimmune disease?

A
  • Antibody mediated
  • Cell mediated
  • Complement mediated
  • Phagocytes, cytokines, NK cells etc. etc.
  • Combinations of the above
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5
Q

What is the proposed sequence of events behind autoimmune disease?

A
  • Initiating event + genetic susceptibility
  • Breakdown of self-tolerance
  • Autoreactivity
  • Humoral+/- cellular
  • Tissue damage
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6
Q

Give examples of organ specific diseases.

A
  • Hashimoto’s thyroiditis
  • Primary myxoedema
  • Thyrotoxicosis
  • Pernicious anaemia
  • Addison’s disease
  • Juvenile diabetes
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7
Q

Give examples on non-organ specific diseases.

A
  • Dermatomyositis
  • SLE
  • Scleroderma
  • Rheumatoid arthritsis
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8
Q

What role does HLA play in autoimmunity?

A
  • Receptors for aetiological agents
  • Influence on tolerance induction or positive selection of particular T cell clones
  • Molecular cross-reactivity/ molecular mimicry
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9
Q

What can autoimmune reactions on the thyroid result in?

A
  • Grave’s disease
  • Myxoedema
  • Hashimoto’s
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10
Q

What can autoimmune reactions on the pancreas result in?

A

T1DM

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11
Q

What can autoimmune reactions on the steroid cell result in?

A

Gonadal insufficiency

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12
Q

What are primary autoantibodies?

A

Pathological agents

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13
Q

What are secondary autoantibodies?

A

Non-pathogenic, disease markers

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14
Q

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

A
  • TSHr
  • Thyroglobulin
  • Peroxidase
  • Other
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15
Q

What is the autoimmune mechanism of Grave’s disease?

A

Humoral

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16
Q

Describe the autoimmunity involved in Grave’s disease.

A
  • HLA-B8, DR3
  • Class II HLA on thyroid cell surface
  • TSHr growth & metabolism antibodies
  • Autoimmune ophthalmopathy
17
Q

What is the autoimmune mechanism of Hashimoto’s disease?

A
  • Humoral (goitre)

- Cellular (tissue destruction leading to hypofunction)

18
Q

Describe the autoimmunity involved in Hashimoto’s.

A
  • Goitre + thyroid hypofunction
  • HLA-DR5
  • Growth stimulating antibody
  • Lymphocytic infiltrate (CD4, CD8, B cell)
19
Q

What can mediated autoimmune thyroid diseases?

A
  • Antibody mediated
  • Cell mediated
  • Both
20
Q

What are the functional effects of autoimmune thyroid disease?

A
  • Hypofunction

- Hyperfunction

21
Q

What causes T1DM?

A

Immune mediated B cell destruction

22
Q

What causes T2DM?

A

Insulin resistance/ deficiency/ secretory defect

23
Q

What causes T3DM?

A

-Genetic defects of beta cell or insulin function

24
Q

What causes T4DM?

A

Gestational diabetes

25
What evidence is there for hereditary factors in T1DM?
``` -HLA haplotypes: B8, DR3 B15, DR4 DQβ3.2 -Twin concordance ~35% ```
26
What evidence is there for an environmental role in T1DM aetiology?
- Seasonal incidence in onset - Evidence of viral infection - Marked geographical variation
27
What evidence is there for autoimmunity in T1DM?
- 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
28
What is the pathogenesis of T1DM?
-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
29
What can be affected by autoimmune endocrine disease?
-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
30
Who is usually affected by autoimmune polyendocrine syndromes?
Females
31
What is type 1 polyendocrine syndrome?
Adrenal, parathyroid, candidiasis
32
What is type 2 polyendocrine syndrome?
Adrenal, thyroid, T1DM
33
What is type 3 polyendocrine syndrome?
- Thyroid + one of a) IDDM b) Gastric (P.A.) c) Non-endocrine autoimmune disease (e.g. RA, SLE)
34
What is the autoimmune role in polyendocrine syndromes?
- HLA B8, DR3 - HLA-DR expression on cells of affected organs - Circulating Ab to endocrine glands

endocrine system 1 (25 decks)

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