Immunology of Endocrine Disease Flashcards
What is autoimmune disease?
Tissue or organ damage as a result of aberrant immunological mechanisms which are directed against autoantigens
What are the mediators of autoimmune disease?
- Antibody
- Cell mediated
- Complement mediated - enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane.
- Phagocytes, cytokines, NK cells etc
Combinations of the above
What are the HLA associations for type 1 diabetes and addison’s disease?
Type 1 diabetes:
B8
DR3
DR4
DR3/4
HLA haplotypes: B8, DR3, B15, DR4, DQbeta 3.2
Addison’s disease: B8 and DR3
What is the immune disease associated with the following organs?
Thyroid
Stomach
Adrenal
Pancrea
Muscle
Kidney
Skin
Joints
Thyroid - hashimotos thyroiditis
Stomach - pernicious anaemia
Adrenal - addison’s disease
Pancreas - juvenile diabetes
Non - Organ Specific:
Muscle - dermatomyositis
Kidney - SLE
Joints - rheumatoid arthritis
What is the multifactorial aetiology of autoimmune disease?
Genetic factors
Immune regulatory factors
Hormonal factors
Environmental factors
Other factors
What is the sequence of events associated with autoimmune disease?
Initiating event (perhaps an infection) + genetic susceptibility
Leads to Breakdown of self tolerance
Leads to autoreactivity
And therefore tissue damage (humoural and/or cellular)
What causes Graves disease?
The disorder results from an antibody, called thyroid stimulating immunoglobulin (TSI), that has a similar effect to thyroid stimulating hormone (TSH). These TSI antibodies cause the thyroid gland to produce excess thyroid hormone
Hyperthyroidism
What is hashimotos?
an autoimmune disease in which the thyroid gland is gradually destroyed
What endocrine cell type is responsible for myxoedema, gonadal insufficiency and type B gastritis?
Peroxidase - myxoedema
Steroid cell - gonadal insufficiency
Gastrin cells - type B gastritis
Gastrin target cells - pernicious anaemia (type A gastritis)
Which autoimmune diseases develop as a result of a blocking antibody?
Pernicious anaemia (gastrin antibody or intrinsic factor antibody)
Myxoedema - Thyroid stimulating hormone receptor antibody (metabolism inhibiting antibody and growth inhibiting antibody)
Myxoedema is long - term undiagnosed hypothyroidism: swelling of the skin and underlying tissues, typical of patients with an underactive thyroid gland
Independant diabetes mellitus - insulin antibody
Which autoimmune diseases result from cell mediated actions of the body?
Hashimotos - thyroglobulin, peroxidase
Addison’s - adrenal cortex antibody
What are primary and secondary autoantibodies?
Primary - pathological agents
Secondary - non-pathogenic, disease markers
- Diagnosis
- Prognosis
- Response to therapy
What are the known autoantigens for thyroid disease?:
TSHr (thyroid stimulating hormone receptor)
Thyroglobulin
Peroxidase
Other
Look
Graves (diffuse toxic goitre): Stimulation by antibodies
Hashimotos: Destruction of the thyroid gland
Myxoedema: Chronic underactive thyroid
What is the HLA association of Grave’s disease?
HLA B and DR3
Class 2 HLA on thyroid cell surface
TSHr growth and metabolism antibodies (TSI)
Autoimmune opthalmopathy
The autoimune mechanism for grave’s disease is humoural
What epitope of the TSHr does hashimotos affect?
Affects the growth epitope (not the metabolism epitope)
What are the pathogenic agents of hashimotos disease?
Thyroid growth stimulating antibody
T cells sensitised to thyroid cell surface autoantigens
What are the secondary effects as a result of the thyroid growth stimulating autoantibody and T cells that are sensitised to autoantigens?
Growth (goitre)
Tissue damage (lymphocyte infiltration, sensitisation of further lymphocytes, antibody production to peroxidase and thyroglobulin autoantigens)
What is the HLA association for hashimotos disease?
HLA - DR5
What is the mechanism of hashimotos?
Humoural (goitre) - growth stimulating antibody
And cellular (tissue destruction and hypofunction) lymphocytic infiltrate (CD4, CD8, B cell)
What are the types of diabetes mellitus?
Type 1 - immune-mediated β cell destruction
Type 2 - insulin resistance/ deficiency/ secretory defect
Other specific types - genetic defects of beta cell or insulin function, diseases of the exocrine pancreas, endocrinopathies, infection-associated, drug/chemical-induced, diabetes associated with specific genetic syndromes (several)
Gestational diabetes
What is the evidence for hereditary aetiology of type 1 diabetes?
HLA haplotypes
Twin concordance (35%)
What is the environmental aetiology of type 1 diabetes?
Seasonal incidence in onset
Evidence of viral infection
Marked geographical variation
What evidence exists for autoimmune aetiology of type 1 diabetes?
- 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 type 1 diabetes?
Genetic tendancy and environmental factors,
islet inflammation and lymphocyte infiltration, leads to beta cell damage
There is release of beta cell autoantigen which is then structurally modified.
T cells become sensitised to islet antigen
Beta cell destruction
What cells are affected in stomach autoimmune disease?
Parietal cells
Which part of the kidney is affected in addison’s disease?
Adrenal cortex
What is type 1 polyendocrine syndrome?
Adrenal, parathyroid, candidiasis
What is type 2 polyendocrine disorder?
Adrenal, thyroid, IDDM
What is type 3 polyendocrine syndrome?
Thyroid and one of:
IDDM
Gastric (P.A.)
Non-endocrine autoimmune disease
(THE POLYENDOCRINE SYNDROMES ARE IN THE LEARNING OUTCOMES)
