Immunology of Endocrine Disease Flashcards
what is autoimmunity?
immune response against a self-antigen
what is an autoimmune disease?
tissue damage or disturbed function resulting from an autoimmune repsponse
what are characteristics of non-organ specific autoimmune diseases?
They affect multiple organs
Associated with autoimmune responses against self-molecules which are widely distributed throughout the body
Intracellular molecules involved in transcription and translation
what are characteristics of organ specific autoimmune diseases
Restricted to one organ
Endocrine glands
what disease does TSH receptor cause?
hyperthyroidism or hypothyroidism
what disease does insulin receptor cause?
hyperglycaemia or hypoglycaemia
what disease does acetylcholine receptor cause?
myasthenia gravis
what disease does epidermal cell adhesion molecules cause?
blistering skin diseases
what disease does factor VIII cause?
acquired haemophilia
what disease does beta-2-glycoprotein I and other anticoagulant proteins cause?
antiphospholipid syndrome
what disease does ref blood cells cause?
haemolytic anaemia
what disease does platalets cause?
thrombocytopenic purpura
what disease does thyroid peroxidase cause?
thyroiditis, hypothyroidism
what disease does steroid 21-hydroxylase cause?
adrenocortical failure
what does glutamate decarboxylase cause?
autoimmune diabetes
what disease does lysosomal enzymes cause?
systemic vasculitis
what disease does mitochondrial enzymes cause?
primary biliary cirrhosis
what disease does double stranded DNA cause?
SLE
what disease does histones cause?
SLE
what disease does topoisomerase I cause?
diffuse scleroderma
what disease does amino-acyl t-RNA synthase cause?
polymyositis
what disease does centromere proteins cause?
limited scleroderma
what is immunologic tolerance?
unresponsiveness to an antigen that is induced by previous exposure to that antigen
what are antigens that induce tolerance called?
tolerogens
what are antigens that have tolerance to self antigens are called?
self tolerance
the immune system can generate a diversity of … cells antigens
T
what are characteristics of central tolerances?
Self-tolerance may be induced in immature self-reactive lymphocytes in the generative lymphoid organs
The thymus plays an important role in eliminating T cells with high affinity to self-antigens
Bone marrow is important in B cell tolerance
what are characteristics of peripheral tolerance?
Mature lymphocytes that recognize self antigens in peripheral tissues become incapable of activation by re-exposure to that antigen or die by apoptosis
An important mechanism for the induction of peripheral tolerance is antigen recognition without costimulation or “second signals.”
Peripheral tolerance is also maintained by regulatory T cells (Tregs) that actively suppress the activation of lymphocytes specific for self and other antigens.
what are the mechanisms of peripheral tolerance
Anergy (functional unresponsiveness)
Treg Suppression
Deletion (cell death)
what is the result from overcoming peripheral tolerance
Inappropriate access of self-antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in the ways in which self-molecules are presented to the immune system.
how do you overcome peripheral tolerance?
Oncetolerancehas broken down, the resulting inflammation may allow presentation of further peptides.
The immune response broadens and local tissue damage accelerates (epitope spreading).
This implies that, once the barrier oftoleranceis broken down, autoimmune responses may be easier to sustain.
whats the aetiology of autoimmune disease?
Genetic factors
Clusters within families
Alleles of MHC
whats the aetiology of autoimmune disease?
Environmental factors
Hormones
Males versus Females
Infections
Molecular mimicry
Upregulation of co-stimulation
Antigen breakdown and presentation changes
Increased incidence in animals held in germ free conditions??
Drugs
Molecular mimicry
Genetic variation in drug metabolism
UV radiation
Trigger for skin inflammation
whats the treatment of autoimmune diseases?
Suppression of the damaging immune response
Before irreversible tissue damage
Early detection is a challenge
Problem with specificity of treatments and toxicity
Replacement of the function of the damaged organ
Hypothyroidism
Insulin dependent diabetes mellitus
what is diabetes?
abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action
what is type 1 due to?
destruction of beta cells; insulin dependent
what is type 2 due to?
defective insulin action; treatment by weight reduction and oral hypoglycaemic agents
what are complications of diabetes?
accelerated atherosclerosis, susceptibility to infections and microangiopathy affecting many organs
what is present in endocrine pancreas?
islets of langerhans
what are characteristics of type 1?
Ketoacidosis
Inadequate insulin secretion
Lymphocytic infiltration of the islets of Langerhans with specific destruction of beta cells
Aetiology: Autoimmune destruction, genetic factors, viral infections
what are characteristics of type 2?
More common Middle age Non-ketoic coma (occasional) Normal or increased insulin secretion Reduction of cell surface receptors to insulin Genetic factors Evidence against autoimmunity
whats the aetiology of type 1 diabetes?
Autoimmune destruction
Circulatory antibodies to islet cells
Patients prone to develop other organ specific autoimmune diseases
Genetic factors
Association with certain HLA types
Environmental factors play a role too (40% concordance in twins in comparison to 100% in Type 2)
Viral infection
Antibodies to certain viruses are high in patients.
Viruses may act as triggers for autoimmune destruction
Coxsackie B
Mumps
characteristics of thyroid gland?
Follicles lines by cuboidal cells
Proteinaceous stores secretions
Synthesis of T3 and T4 under negative feedback by TSH (anterior pituitary)
C-cells scattered throughout the gland that secrete calcitonin
what are some thyroid diseases?
Secretory malfunction
Hyperthyroidism
Hypothyroidism
Swelling of the entire gland
Goitre
Solitary masses
Nodular goitre
Adenoma
carcinoma
what are characteristics of hyperthyroidism?
syndrome due to excess T3 and T4
very rarely due to excess TSH
most common cause is graves disease
what does hyperthyroidism result from?
Graves thyroiditis Functioning adenoma Toxic nodular goitre Exogenous thyroid hormone (rare) Ectopic secretion by ectopic thyroid tissue or tumours
wjat is graves thyroiditis?
The most common cause of thyrotoxicosis
Usually associated with a diffuse goitre.
Increased vascularity.
what is the histology of graves thyroiditis?
hyperplasia of the acinar epithelium
reduction of stored colloid
local accumulations of lymphocytes with lymphoid follicle formation
what are the characteristics of hypothyroidism?
syndrome due to insuffucient circulating T3 and T4
if congenital, causes cretinism
most common cause is hashimoto thyroiditis, an autoimmune disorder
what is cretinism?
If hypothyroidism is present in the newborn, physical growth and mental development are impaired, sometimes irreversibly (cretinism).
Cretinism may be endemic in geographical areas where the diet contains insufficient iodine for thyroid hormone synthesis.
Sporadic cases are usually due to a congenital absence of thyroid tissue, or to enzyme defects blocking hormone synthesis.
what is hashimoto thyroiditis?
The most common cause of acquired hypothyroidism in adults is Hashimoto thyroiditis.
Hashimoto thyroiditis may initially cause thyroid enlargement, but later there may be atrophy and fibrosis.
In the early stages of Hashimoto thyroiditis, the damage to the thyroid follicles may lead to release of thyroglobulin causing a transient phase of thyrotoxicosis.
what is the histology of hashimoto thyroiditis
Densely infiltration by lymphocytes and plasma cells, with lymphoid follicle formation.
Colloid content is reduced
Thyroid epithelial cells show a characteristic change in which they enlarge and develop eosinophilic granular cytoplasm due to proliferation of mitochondria; they are then termed Askanazy cells, Hürthle cells or oncocytes.
In advanced cases, there may be fibrosis.
what are autoimmune polyendocrine syndromes?
A diverse group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance.
what are characteristics of autoimmunue polyendocrine syndromes?
Circulating autoantibodies and lymphocytic infiltration of the affected tissues or organs
Eventually leading to organ failure.
The syndromes can occur in patients from early infancy to old age, and new components of a given syndrome can appear throughout life.
Variation in the frequencies and patterns of autoimmunity in affected patients and their families.
Combination of genetic susceptibility and environmental factors.
what is autoimmune polyendocrine syndrome type 1?
APS-1, also named autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy is a rare autosomal recessive disease caused by mutations in the autoimmune regulator gene (AIRE).
what are clinical features of APS-1
At least two of three cardinal components during childhood:
Chronic mucocutaneous candidiasis
Hypoparathyroidism
Primary adrenal insufficiency (Addison’s disease)
whatare other typical components of APS-1
Enamel hypoplasia
Enteropathy with chronic diarrhea or constipation.
Primary ovarian insufficiency (approximately 60% of women with APS-1 before they reach 30 years of age).
what is APS2
APS-2 is far more common than APS-1.
Patients with APS-2 have courses characterized by at least two of the following three endocrinopathies:
Type 1 diabetes
Autoimmune thyroid disease
Addison’s disease.
what is x-linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX)
An extremely rare inherited syndrome characterized by:
Early-onset type 1 diabetes
Autoimmune enteropathy with intractable diarrhea and malabsorption
Dermatitis that may be eczematiform, ichthyosiform, or psoriasiform.
Eosinophilia and elevated IgE levels are frequently present in patients with IPEX.
Kidney disease, most often membranous glomerulonephritis or interstitial nephritis, develops in some patients.
