Immunology of Endocrine Disorders

Question 1

Describe autoimmunity

Answer 1

Immune response against a self antigen
Tissue damage or disrupted function resulting from autoimmune response
Commoner in females

Question 2

What is immunologic tolerance?

Answer 2

Unresponsiveness to an antigen that is induced by previous exposure to that antigen When lymphocytes encounter antigens they may be activated or eliminated/ inactivated leading to tolerance

Question 3

What are antigens which induce tolerance called?

Answer 3

Tolerogens

Question 4

How is autoimmune disease avoided - immunological tolerance?

Answer 4

T and B cells bearing these self reactive molecules must be eliminated or downregulated so immune system is made specifically tolerant to self antigens

Question 5

Describe central tolerance

Answer 5

Bone marrow is important in B cell tolerance
Thymus plays important role in eliminating T cells with high affinity to self antigens

Question 6

Describe peripheral tolerance

Answer 6

Mature lymphocytes that recognise self antigens in peripheral tissues become incapable of activation by re-exposure to that antigen or die by apoptosis

Question 7

What is an important mechanism for the induction of peripheral tolerance?

Answer 7

Antigen recognition without co-stimulation or second signals

Question 8

How does regulatory T cells help peripheral tolerance?

Answer 8

Actively suppress the activation of lymphocytes specific for self and other antigens

Question 9

How are antigens sequestered from immune system?

Answer 9

Anatomic barriers like in the CNS, testes and eyes
So cannot engage antigen receptors

Question 10

What are the mechanisms of peripheral tolerance?

Answer 10

Anergy - functional unresponsiveness
Treg suppression
Deletion - cell death

Question 11

How can peripheral tolerance be overcome?

Answer 11

Inappropriate access of self antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in ways in which self molecules are presented to immune system

Question 12

What causes a breakdown of tolerance?

Answer 12

Genes
Infections
Environmental factors

Question 13

Describe the epidemiology of autoimmune diseases

Answer 13

Show clustering in families
Peak onset 15-65 yrs
More common in females except ankylosing spondylitis

Question 14

What is the difference between organ and non organ specific diseases?

Answer 14

Non - affect multiple, autoimmune response against self molecules widespread through body and intracellular molecules involved in transcription and translation
Organ - one organ and usually endocrine

Question 15

What are the genetic factors of autoimmune disease?

Answer 15

Cluster in families
Alleles of MHC
HLA association

Question 16

What is the aetiology of autoimmune diseases?

Answer 16

Susceptible genes and failure of self tolerance leads to tissue injury and inflammation
Activation of tissues APCs
Then activation of self reactive lymphocytes

Question 17

What are some environmental factors leading to autoimmune disease?

Answer 17

Infections - molecular mimicry, upregulation of co-stimulation and antigen breakdown
Drugs - molecular mimicry and genetic variation
UV radiation - trigger of skin inflammation and modification of self antigen

Question 18

Explain molecular mimicry

Answer 18

Structural similarity between self proteins and microbial antigens may trigger autoimmune response
Cross reactivity will cause expansion of responsive T cell population recognising self peptise

Question 19

Describe treatment of autoimmune disease

Answer 19

Suppression of damaging immune response
Replacement of the function of damaged organ

Question 20

What is the aetiology of type I diabetes?

Answer 20

Autoimmune destruction, genetic factors (HLA types) and viral infections

Question 21

What viruses can trigger autoimmune destruction?

Answer 21

Coxsackie B
Mumps

Question 22

Describe the thyroid gland

Answer 22

Follicles lined by cuboidal cells and c cells scattered throughout gland - secrete calcitonin
Synthesis of T3 and T4
Negative feedback by TSH

Question 23

Describe graves thyroiditis

Answer 23

Organ specific
Autoantibody, long acting thyroid stimulator which binds to epithelial cells and mimics actions of TSH
Stimulates function and growth of follicular epithelium
Exophthalmos, pretibial myxoedema and finger clubbing

Question 24

Describe cretinism

Answer 24

If hypothyroidism is present in new born - physical and mental development are impaired
In areas where diet is insufficient in iodine
Sporadic - congenital absence of thyroid tissue or enzyme defect

Question 25

Describe Hashimoto thyroiditis

Answer 25

Most common cause of acquired hypothyroidism in adults May initially cause thyroid enlargement - later can be atrophy and fibrosis Damage of follicles leads to release of thyroglobulin causing thyrotoxicosis

Question 26

What is Hashimoto thyroiditis histologically?

Answer 26

Densely infiltration by lymphocytes and plasma cells - lymphoid follicle formation Colloid content is reduced Thyroid epithelium enlarges - eosinophilic cytoplasm May be fibrosis

Question 27

What autoantibodies are detected in serum of patient with Hashimoto thyroiditis?

Answer 27

One reacting thyroid peroxidase Other reacting with thyroglobulin These are formed by plasma cells infiltrating thyroid as loss of specific suppressor T lymphocytes

Question 28

What are autoimmune polyendocrine syndromes?

Answer 28

Diverse group of conditions characterised by functional impairment of multiple endocrine glands due to loss of immune tolerance Ex. alopecia, coeliac disease, autoimmune gastritis

Question 29

What does autoimmune polyendocrine syndrome lead to?

Answer 29

Circulating autoantibodies and lymphocytic infiltration of affected tissues or organs Eventually leading to organ failure

Question 30

Describe autoimmune polyendocrine syndrome type I

Answer 30

Ectodermal dystrophy - rare autosomal recessive disease caused by mutations in autoimmune regulator gene - AIRE

Question 31

What are 3 cardinal components during childhood of APS-1?

Answer 31

Chronic mucocutaneous candidiasis Hypoparathyroidism Primary adrenal insufficiency

Question 32

What are some other findings of APS-1?

Answer 32

Enamel hypoplasia Enteropathy with chronic diarrhoea or constipation Primary ovarian insufficiency

Question 33

Describe APS-2

Answer 33

More common Have 2/3 of - type I diabetes, autoimmune thyroid disease and Addison's disease Women mainly Typically younger onset than APS-1

Question 34

What other autoimmune conditions develop in affected APS-2 patients?

Answer 34

Coeliac disease, alopecia, vitiligo, primary ovarian insufficiency and pernicious anaemia

Question 35

Describe IPEX (immunodysregulation, polyendocrinopathy ad enteropathy)

Answer 35

An extremely rare inherited syndrome characterised by type I diabetes, autoimmune enteropathy with diarrhoea and malabsorption and dermatitis Early development Fatal in first few years of life - immunosuppressive agents or bone marrow transplant

Question 36

What are some manifestation of IPEX?

Answer 36

Autoimmune thyroid disease Alopecia Various autoimmune cytopenia Hepatitis Exocrine pancreatitis