Lecture 18 Immunology of Endocrine Diseases Flashcards
Define immunological tolerance
unresponsiveness to an antigen that is induced by previous exposure to that antigen.
Tolerance to self antigens is called
Self-tolerance
What happens to antigen-specific receptors that bind to self molecules to avoid autoimmune disease
self-reactive molecules must be either eliminated or downregulated so that the immune system is made specifically tolerant to self-antigens.
Define Central Tolerance
Self-tolerance induced in immature self-reactive lymphocytes.
The thymus plays an important role in eliminating T cells with high affinity to self antigens. Bone marrow is important in B cell tolerance
Define Peripheral Tolerance
Mature lymphocytes that recognise self-antigens in peripheral tissues become incapable of activation by re-exposure or die by apoptosis
Name an important mechanism for induction of peripheral tolerance and how is it maintained
Co-stimulation or second signals Tregs maintain peripheral tolerance by suppressing the activation of lymphocytes specific for self or other antigens 1. Anergy (functional unresponsiveness) 2. Treg suppression 3. Deletion (cell death)
How can peripheral intolerance be bypassed
inflammation or tissue damage is present due to the increased activity of proteolytic enzymes which can cause intra- and extracellular proteins to be broken down, leading to high concentrations of peptides (cryptic epitopes) being presented to responsive T cells.
• The structures of self-peptides may be altered by viruses, free radicals or ionising radiation, thus bypassing previously established tolerance
What is the HLA association of Addison disease and Hashimoto thyroiditis
DR3
What is the HLA association of insulin dependent DM
DR4
What are the causes of autoimmune disease
Environmental factors
Infections - co stimulation, molecular mimicry
Drugs
UV radiation
What is Molecular Mimicry
• Structural similarity between self-proteins and microbial antigens may trigger an autoimmune response
List aetiologies of type 1 diabetes
Autoimmune destruction
Association with certain HlA types
Viral infections- Coxsackie B, Mums
Complications in large blood vessels in diabetes
MI
Stroke
Ischaemic limbs
Complications in small blood vessels in diabetes
Retinopathy
Nephropathy
Neuropathy
Complications in pregnancy in diabetes
Preeclamptic toxaemia
Large babies
Neonatal hypoglycaemia
What is the most common cause of Grave’s Disease
Lon-acting thyroid stimulating immunoglobulin that mimics the action of TSH
What are the features of Grave;s
Exopthalmos
Pretibial Myxodema
Finger clubbing
Why does Grave’s Disease cause exopthalmos
Infiltration of the orbital tissues by fat, mucopolysaccharides and lymphocytes and may be due to an additional autoantibody reacting with these tissues
What is called when hypothyroidism is present in neonates and what are the consequences
Cretinism
Physical growth and mental development are impaired, sometimes irreversibly
Can an individual with Hashimoto’s develop thyrotoxicosis? If so why
Yes, damage to the thyroid follicles may lead to release of thyroglobulin causing a transient phase of thyrotoxicosis
Describe histological features of Hashimoto’s disease
Eosinophilic granular cytoplasm due to proliferation of mitochondria (Askanazy cells, Hürthle cells or oncocytes)
Fibrosis
What autoantibodies can be detected in Hashimoto’s
Thyroid peroxidase
Thyroglobulin
What is Autoimmune Polyendocrine Syndromes
Functional impairment of multiple endocrine glands due to loss of immune tolerance
Name the manifestation of APS-1
Addison’s
Hypoparathyroidism
Name manifestation of APS-2
Addison’s
Auto-immune thyroid disease
Type 1 diabetes
Clinical features of APS-1
- Chronic mucocutaneous candidiasis
- Hypoparathyroidism
- Primary adrenal insufficiency (Addison’s disease)
- Enamel hypoplasia
- Enteropathy with chronic diarrhoea or constipation.
- Primary ovarian insufficiency
Which APS is more common APS-1 or APS-2
APS-2
What are other manifestations for APS-2
- Celiac disease
- Alopecia, vitiligo
- Primary ovarian insufficiency
- Pernicious anemia
What is IPEX
X-Linked Immunodysregulation, Polyendocrinopathy, and Enteropathy
– Early-onset type 1 diabetes
– Autoimmune enteropathy with intractable diarrhea and malabsorption
– Dermatitis that may be eczematiform, ichthyosiform, or psoriasiform
What are clinical manifestation of IPEX
Eosinophilia and elevated IgE Kidney disease – Autoimmune thyroid disease – Alopecia – Various autoimmune cytopenias – Hepatitis – Exocrine pancreatitis.
