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2nd year- endocrine OC > Immunology of Endocrine Disease > Flashcards

Immunology of Endocrine Disease Flashcards

1
Q

what is autoimmunity?

A

immune response against a self-antigen

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2
Q

what is an autoimmune disease?

A

tissue damage or disturbed function resulting from an autoimmune repsponse

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3
Q

what are characteristics of non-organ specific autoimmune diseases?

A

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

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4
Q

what are characteristics of organ specific autoimmune diseases

A

Restricted to one organ

Endocrine glands

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5
Q

what disease does TSH receptor cause?

A

hyperthyroidism or hypothyroidism

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6
Q

what disease does insulin receptor cause?

A

hyperglycaemia or hypoglycaemia

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7
Q

what disease does acetylcholine receptor cause?

A

myasthenia gravis

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8
Q

what disease does epidermal cell adhesion molecules cause?

A

blistering skin diseases

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9
Q

what disease does factor VIII cause?

A

acquired haemophilia

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10
Q

what disease does beta-2-glycoprotein I and other anticoagulant proteins cause?

A

antiphospholipid syndrome

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11
Q

what disease does ref blood cells cause?

A

haemolytic anaemia

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12
Q

what disease does platalets cause?

A

thrombocytopenic purpura

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13
Q

what disease does thyroid peroxidase cause?

A

thyroiditis, hypothyroidism

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14
Q

what disease does steroid 21-hydroxylase cause?

A

adrenocortical failure

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15
Q

what does glutamate decarboxylase cause?

A

autoimmune diabetes

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16
Q

what disease does lysosomal enzymes cause?

A

systemic vasculitis

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17
Q

what disease does mitochondrial enzymes cause?

A

primary biliary cirrhosis

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18
Q

what disease does double stranded DNA cause?

A

SLE

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19
Q

what disease does histones cause?

A

SLE

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20
Q

what disease does topoisomerase I cause?

A

diffuse scleroderma

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21
Q

what disease does amino-acyl t-RNA synthase cause?

A

polymyositis

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22
Q

what disease does centromere proteins cause?

A

limited scleroderma

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23
Q

what is immunologic tolerance?

A

unresponsiveness to an antigen that is induced by previous exposure to that antigen

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24
Q

what are antigens that induce tolerance called?

A

tolerogens

25
Q

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

A

self tolerance

26
Q

the immune system can generate a diversity of … cells antigens

A

T

27
Q

what are characteristics of central tolerances?

A

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

28
Q

what are characteristics of peripheral tolerance?

A

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.

29
Q

what are the mechanisms of peripheral tolerance

A

Anergy (functional unresponsiveness)

Treg Suppression

Deletion (cell death)

30
Q

what is the result from overcoming peripheral tolerance

A

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.

31
Q

how do you overcome peripheral tolerance?

A

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.

32
Q

whats the aetiology of autoimmune disease?

A

Genetic factors
Clusters within families
Alleles of MHC

33
Q

whats the aetiology of autoimmune disease?

A

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

34
Q

whats the treatment of autoimmune diseases?

A

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

35
Q

what is diabetes?

A

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

36
Q

what is type 1 due to?

A

destruction of beta cells; insulin dependent

37
Q

what is type 2 due to?

A

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

38
Q

what are complications of diabetes?

A

accelerated atherosclerosis, susceptibility to infections and microangiopathy affecting many organs

39
Q

what is present in endocrine pancreas?

A

islets of langerhans

40
Q

what are characteristics of type 1?

A

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

41
Q

what are characteristics of type 2?

A 
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
42
Q

whats the aetiology of type 1 diabetes?

A

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

43
Q

characteristics of thyroid gland?

A

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

44
Q

what are some thyroid diseases?

A

Secretory malfunction

Hyperthyroidism
Hypothyroidism

Swelling of the entire gland

Goitre

Solitary masses

Nodular goitre
Adenoma
carcinoma

45
Q

what are characteristics of hyperthyroidism?

A

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

46
Q

what does hyperthyroidism result from?

A 
Graves thyroiditis
Functioning adenoma
Toxic nodular goitre
Exogenous thyroid hormone (rare)
Ectopic secretion by ectopic thyroid tissue or tumours
47
Q

wjat is graves thyroiditis?

A

The most common cause of thyrotoxicosis

Usually associated with a diffuse goitre.

Increased vascularity.

48
Q

what is the histology of graves thyroiditis?

A

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

49
Q

what are the characteristics of hypothyroidism?

A

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

50
Q

what is cretinism?

A

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.

51
Q

what is hashimoto thyroiditis?

A

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.

52
Q

what is the histology of hashimoto thyroiditis

A

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.

53
Q

what are autoimmune polyendocrine syndromes?

A

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

54
Q

what are characteristics of autoimmunue polyendocrine syndromes?

A

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.

55
Q

what is autoimmune polyendocrine syndrome type 1?

A

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

56
Q

what are clinical features of APS-1

A

At least two of three cardinal components during childhood:

Chronic mucocutaneous candidiasis

Hypoparathyroidism

Primary adrenal insufficiency (Addison’s disease)

57
Q

whatare other typical components of APS-1

A

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).

58
Q

what is APS2

A

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.

59
Q

what is x-linked Immunodysregulation, Polyendocrinopathy, and Enteropathy (IPEX)

A

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.

2nd year- endocrine OC (27 decks)

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