Immunology of Endocrine Disease Flashcards
Autoimmune disease
A large group of clinical disorders which are
characterised by tissue or organ damage
mediated through aberrant immunological
mechanisms which are directed against
autoantigens
Autoimmune disease is a multifactorial interaction of:
- Genetic factors (susceptibility)
- Environmental factors (aetiology)
- Autoimmune mechanisms (pathogenesis)
What interacts to influence autoimmune disease?
- Genetic factors -Immune regulatory factors
- Hormonal factors
- Environmental factors
- ‘Other’ factors
What is the pathogenesis behind autoimmune disease?
- Antibody mediated
- Cell mediated
- Complement mediated
- Phagocytes, cytokines, NK cells etc. etc.
- Combinations of the above
What is the proposed sequence of events behind autoimmune disease?
- Initiating event + genetic susceptibility
- Breakdown of self-tolerance
- Autoreactivity
- Humoral+/- cellular
- Tissue damage
Give examples of organ specific diseases.
- Hashimoto’s thyroiditis
- Primary myxoedema
- Thyrotoxicosis
- Pernicious anaemia
- Addison’s disease
- Juvenile diabetes
Give examples on non-organ specific diseases.
- Dermatomyositis
- SLE
- Scleroderma
- Rheumatoid arthritsis
What role does HLA play in autoimmunity?
- Receptors for aetiological agents
- Influence on tolerance induction or positive selection of particular T cell clones
- Molecular cross-reactivity/ molecular mimicry
What can autoimmune reactions on the thyroid result in?
- Grave’s disease
- Myxoedema
- Hashimoto’s
What can autoimmune reactions on the pancreas result in?
T1DM
What can autoimmune reactions on the steroid cell result in?
Gonadal insufficiency
What are primary autoantibodies?
Pathological agents
What are secondary autoantibodies?
Non-pathogenic, disease markers
What are the potential (known) autoantigens in autoimmune thyroid disease?
- TSHr
- Thyroglobulin
- Peroxidase
- Other
What is the autoimmune mechanism of Grave’s disease?
Humoral
Describe the autoimmunity involved in Grave’s disease.
- HLA-B8, DR3
- Class II HLA on thyroid cell surface
- TSHr growth & metabolism antibodies
- Autoimmune ophthalmopathy
What is the autoimmune mechanism of Hashimoto’s disease?
- Humoral (goitre)
- Cellular (tissue destruction leading to hypofunction)
Describe the autoimmunity involved in Hashimoto’s.
- Goitre + thyroid hypofunction
- HLA-DR5
- Growth stimulating antibody
- Lymphocytic infiltrate (CD4, CD8, B cell)
What can mediated autoimmune thyroid diseases?
- Antibody mediated
- Cell mediated
- Both
What are the functional effects of autoimmune thyroid disease?
- Hypofunction
- Hyperfunction
What causes T1DM?
Immune mediated B cell destruction
What causes T2DM?
Insulin resistance/ deficiency/ secretory defect
What causes T3DM?
-Genetic defects of beta cell or insulin function
What causes T4DM?
Gestational diabetes
What evidence is there for hereditary factors in T1DM?
-HLA haplotypes: B8, DR3 B15, DR4 DQβ3.2 -Twin concordance ~35%
What evidence is there for an environmental role in T1DM aetiology?
- Seasonal incidence in onset
- Evidence of viral infection
- Marked geographical variation
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
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
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
Who is usually affected by autoimmune polyendocrine syndromes?
Females
What is type 1 polyendocrine syndrome?
Adrenal, parathyroid, candidiasis
What is type 2 polyendocrine syndrome?
Adrenal, thyroid, T1DM
What is type 3 polyendocrine syndrome?
- Thyroid + one of
a) IDDM
b) Gastric (P.A.)
c) Non-endocrine autoimmune disease (e.g. RA, SLE)
What is the autoimmune role in polyendocrine syndromes?
- HLA B8, DR3
- HLA-DR expression on cells of affected organs
- Circulating Ab to endocrine glands
