Immunology of Endocrine Disease Flashcards

Question

what are antigens that have tolerance to self antigens are called?

Answer 1

self tolerance

Answer 2

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

Answer 3

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.

Answer 4

Anergy (functional unresponsiveness) Treg Suppression Deletion (cell death)

Answer 5

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.

Answer 6

Once tolerance has 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 of tolerance is broken down, autoimmune responses may be easier to sustain.

Answer 7

Genetic factors Clusters within families Alleles of MHC

Answer 8

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

Answer 9

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

Answer 10

abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action

Answer 11

destruction of beta cells; insulin dependent

Answer 12

defective insulin action; treatment by weight reduction and oral hypoglycaemic agents

Answer 13

accelerated atherosclerosis, susceptibility to infections and microangiopathy affecting many organs

Answer 14

islets of langerhans

Answer 15

Ketoacidosis Inadequate insulin secretion Lymphocytic infiltration of the islets of Langerhans with specific destruction of beta cells Aetiology: Autoimmune destruction, genetic factors, viral infections

Answer 16

``` 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 ```

Answer 17

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

Answer 18

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

Answer 19

Secretory malfunction Hyperthyroidism Hypothyroidism Swelling of the entire gland Goitre Solitary masses Nodular goitre Adenoma carcinoma

Answer 20

syndrome due to excess T3 and T4 very rarely due to excess TSH most common cause is graves disease

Answer 21

``` Graves thyroiditis Functioning adenoma Toxic nodular goitre Exogenous thyroid hormone (rare) Ectopic secretion by ectopic thyroid tissue or tumours ```

Answer 22

The most common cause of thyrotoxicosis Usually associated with a diffuse goitre. Increased vascularity.

Answer 23

hyperplasia of the acinar epithelium reduction of stored colloid local accumulations of lymphocytes with lymphoid follicle formation

Answer 24

syndrome due to insuffucient circulating T3 and T4 if congenital, causes cretinism most common cause is hashimoto thyroiditis, an autoimmune disorder

Answer 25

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.

Answer 26

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.

Answer 27

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.

Answer 28

A diverse group of clinical conditions characterized by functional impairment of multiple endocrine glands due to loss of immune tolerance.

Answer 29

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.

Answer 30

APS-1, also named autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy is a rare autosomal recessive disease caused by mutations in the autoimmune regulator gene (AIRE).

Answer 31

At least two of three cardinal components during childhood: Chronic mucocutaneous candidiasis Hypoparathyroidism Primary adrenal insufficiency (Addison’s disease)

Answer 32

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).

Answer 33

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.

Answer 34

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.