Immunology of Endocrine Disorders Flashcards
What are Non-organ specific autoimmune diseases?
Affect multiple organ diseases
Assocaited with autoimmune responses to widely distributed self-molecules
Intracellular molecules for Transcription/translation
What are organ specific autoimmune diseases?
Resticted to one organ or endocrine glands
Antigens against what receptor are associated with thyroid disease?
TSH receptor
Antigens against what are associated with glycaemic disease?
Insulin receptors
Antigens against what are associated with myasthenia gravis?
Acetylcholine receptor
Self antigens against what enzymes are associated with diabetes?
Glutamate decarboxylase
Self antigens against what enzymes are associated with thyroiditis/hypothyroidism?
Thyroid peroxidase
Self antigens against what enzymes are associated with Addison’s disease?
21-hydroxylase
When is peak onset for autoimmune diseases?
15-65
Except T1D
What is immunological tolerance?
Unresponsiveness to an antigen that is introduced by previous exposure to said antigen
What are tolerogens?
Antigens which induce tolerance
What is central tolerance?
Immature self-reactive lymphocytes
Thymus eliminates T-cells with high affinity to self antigens
Bone marrow - B cell tolerance
What is peripheral tolerance?
Mature lymphocytes that recognise self antigens in peripheral tissues become incapable of activation by re-exposure, or die
What are the mechanisms of peripheral tolerance?
Anergy (functional unresponsiveness)
T regulatory suppression
Deletion (cell death)
What are the mechanisms of central tolerance?
Apoptosis
Change in receptors
Development of T-regulatory lymphocytes
What factors can cause cells to overcome peripheral tolerance?
Inappropriate access of self-antigens
Inappropriate/increased local expression of co-stimulatory molecules
Alterations in the ways which self-molecules are presented
When is overcoming peripheral tolerance more likely?
Inflammation or tissue damage
Increased proteolytic enzymes increasing the concentrations of peptides
Which microbial antigen is associated with T1D?
Coxsackie B4 nuclear protein
Mumps
What is molecular mimicry?
Structural similarities between self proteins and microbial antigens causing an autoimmune response
What is epitope spreading?
Immune response broadens and local tissue damage accelerates
The B27 HLA association is associated with which diseases?
Ankylosing spondylitis
Reiter disease
Which HLA association is associated with T1D?
DR4
Which environmental factors are associated with causing autoimmune diseases?
Hormones
Infections
Drugs
UV radiation
How are autoimmune diseases treated?
Suppression of the damaging immune response
Replacement of the function of the organ
How is Type 1 diabetes classified?
Ketoacidosis
Inadequate insulin secretion
Lymphocytic infiltration of islets
Autoimmune, genetic, viral
How is Type 2 diabetes classified?
More common Middle age Non-ketotic coma Normal/increased insulin Reduced cell surface receptors
What are the causes of T1D?
Autoimmune destruction
Genetic factors
Viral infection
What is the mechanism of Graves’ thyroiditis?
IgG which binds to thyroid epithelial cells and mimics TSH
What is the cause of Exophthalmos in graves’?
Infiltration of the orbital tissues by fat, mucopolysaccharides and lymphocytes
Autoantibody reacting with these tissues
Why does Hashimoto thyroiditis present early with transient hyperthyroidism?
Damage to thyroid follicles causing a release of thyroglobulin
Which autoantibodies are seen in Hashimoto’s thyroiditis?
Antibodies reacting with:
Thyroid peroxidase
Thyroglobulin
What is APS-1?
Autoimmune Polyendocrine Syndrome Type 1 AIRE gene mutation Polyendocrinopathy Candidiasis Ectodermal dystrophy
How does APS-1 present?
Atleast 2 of: Chronic candidiasis Hypoparathyroidism Addison's disease \+ Enamel hypoplasia Diarrhoea or constipation Primary ovarian insufficiency
What is APS-2?
Type 1 diabetes Autoimmune thyroid disease Addison's disease More common in women Young adult onset Celiac disease
What is IPEX?
X-linked Immunodysregulation, polyendocrinopathy, enteropathy
Early onset T1D
Autoimmune enteropathy - diarrhoea and malabsorption
Dermatitis
Eosinophilia
Elevated IgE
