Immunology of the Endocrine System

Question 1

What is autoimmuinity?

Answer 1

An immune response against an antigen made by the body

Question 2

Are the majority of autoimmune conditions more common in male or females?

Answer 2

Females

Question 3

Which autoimmune condition is more common in men?

Answer 3

Ankylosing spondylitis

Question 4

What is immunological tolerance?

Answer 4

Unresponsiveness to an antigen that the body has had previous exposure to

Question 5

What name is given to the antigens that induce tolerance?

Answer 5

Tolerogens

Question 6

What is self-tolerance and why is it important?

Answer 6

Tolerance to the self-antigens
Failure of this tolerance leads to autoimmune disease

Question 7

To avoid autoimmune disease, what happens to the B and T cells?

Answer 7

The B and T cells bearing these self-reactive molecules are either eliminated and downregulated so the immune system is made specifically tolerant to self-antigens

Question 8

Which part of the body plays an important role in eliminating the T cells that have a high affinity for self-antigens?

Answer 8

Thymus

Question 9

Which part of the body plays an important role in B cell tolerance?

Answer 9

Bone marrow

Question 10

Some cells escape the central tolerance and escape to the periphery. However, there is peripheral tolerance in place. What is meant by peripheral tolerance?

Answer 10

Mature lymphocytes that recognise self antigens in peripheral tissues become incapable of activation by re-exposure
Or, the cell die by apoptosis

Question 11

Which mechanism induces peripheral tolerance?

Answer 11

Second signals
-> this is antigen recognition without co-stimulation

Question 12

How is peripheral tolerance maintained by regulatory T cells?

Answer 12

These T cells supress the activation of lymphocytes specific for self and other antigens

Question 13

Some self antigens are sequestered from the immune system.
What can act as barriers for these self-antigens?

Answer 13

Anatomic barriers, specifically in the CNS, testes and eyes
-> these cannot engage antigen receptors

Question 14

Name three mechanisms of peripheral tolerance.

Answer 14

Anergy
Treg suppression
Deletion- cell death

->the cell death is of the lymphocytes when they recognise the antigens
(?idk gal soz)

Question 15

Treg?

Answer 15

Regulatory T cells

Question 16

When does anergy occur?

Answer 16

In the absence of co-stimulation

Question 17

What happens in autoimmune disease which allows the cells to attack self-antigens?

Answer 17

Overcoming of peripheral tolerance

Question 18

Why may autoimmune overcoming of peripheral intolerance occur?

Answer 18

-Inappropriate access of self-antigens
-Inappropriate/increased local expression of co-stimulatory molecules
-Alterations in the way these self-antigens are presented to the immune system

Question 19

Why is autoimmune disease more likely to occur when there is inflammation of tissue damage present?

Answer 19

There will be increased activity of proteolytic enzymes, causing intra and extracellular proteins to be broken down.
Therefore, there are higher concentrations of peptides being presented to the responsive T cells.

Question 20

How may the structures of self-peptides be altered?

Answer 20

Viruses
Free radicals
Ionising radiation

-> therefore, by changing structure, they bypass previously established tolerance

Question 21

Is there a genetic disposition to autoimmune disease?

Answer 21

Yes

->if someone in the family has an autoimmune condition, they themselves are more likely to develop another condition but more likely their family will also develop some sort of autoimmune disease

Question 22

What % of the population have some sort of autoimmune disease

Answer 22

3%

Question 23

The peak years of onset for autoimmune conditions is 15-65yrs.
Which autoimmune condition is the exception to this?

Answer 23

Type 1 diabetes

->often occurs at an earlier age

Question 24

Non-organ specific organ diseases can affect multiple organs. Why is this?

Answer 24

Associated with autoimmune responses against self-molecules. These self-molecules are widely distributed by the body, hence why affects multiple organs

Question 25

If autoimmune disease affected the self-antigen of TSH receptor, which condition can this cause?

Answer 25

Hyperthyroidism Hypothyroidism

Question 26

If autoimmune disease affected the self-antigen of inulin receptor, which condition can this cause?

Answer 26

Hyperglycaemia Hypoglycaemia

Question 27

If autoimmune disease affected the self-antigen of the acetylcholine receptor, which condition can this cause?

Answer 27

Myasthenia gravis

Question 28

B27 allele has HLA association with which diseases?

Answer 28

Ankylosing spondylitis

Question 29

DR3 allele has HLA association with which diseases?

Answer 29

Addison's disease Hashimoto disease Myasthenia Gravis

Question 30

DR4 allele has HLA association with which diseases?

Answer 30

Insulin-dependant diabetes mellitus

Question 31

How can infections trigger autoimmune disease?

Answer 31

Molecular mimicry Upregulation of co-stimulation Antigen breakdown and presentation changes

Question 32

How can drugs trigger autoimmune disease?

Answer 32

Molecular mimicry Genetic variation in drug metabolism

Question 33

How can UV radiation trigger autoimmune disease?

Answer 33

Trigger skin inflammation Modification of self antigen

Question 34

Molecular mimicry?

Answer 34

Structural similarities between self-proteins and microbial antigens, triggering autoimmune response

Question 35

What are the factors involved in the treatment of autoimmune disease?

Answer 35

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

Question 36

How is autoimmune disease related to type 1 diabetes?

Answer 36

Autoimmune destruction of the beta cells of the pancreas which are responsible for secreting insulin

Question 37

RECAP- which type of diabetes is an autoimmune condition?

Answer 37

Type 1 diabetes -> literally gave you the answer in the last flashcard

Question 38

Which viruses may act as a trigger for type 1 diabetes?

Answer 38

Mumps Coxsackie B

Question 39

Which type of cells line the follicles of thyroid cells?

Answer 39

Cuboidal cells

Question 40

RECAP- what does the thyroid gland secrete?

Answer 40

T3 and T4 under negative feedback by TSH Calcitonin ->reminder that TSH is secreted from the anterior pituitary

Question 41

RECAP- list some of the causes of hyperthyroidism.

Answer 41

Graves thyroiditis Functioning adenoma Toxic nodular goitre Ectopic secretion from tumours

Question 42

What can Grave's disease cause?

Answer 42

Hyperthyroidism

Question 43

What would be seen histologically in someone with Grave's thyroiditis?

Answer 43

Hyperplasia of acinar epithelium Reduction of stored colloid Local accumulation of lymphocytes

Question 44

Is Grave's thyroiditis an example of a non-organ specific or organ-specific autoimmune disease?

Answer 44

Organ specific

Question 45

Describe the autoimmune pathology behind Grave's thyroiditis.

Answer 45

LATS (long-acting thyroid stimulator) binds to thyroid epithelial cells and mimics action of TSH

Question 46

RECAP- what is the most common cause of hypothyroidism?

Answer 46

Hashimoto thyroiditis (autoimmune disorder)

Question 47

Cretinism?

Answer 47

Hypothyroidism present from birth akak congenital hypothyroidism

Question 48

Which deficiency can cause hypothyroidism?

Answer 48

Iodine deficiency

Question 49

What does Hashimoto thyroiditis do to the thyroid gland?

Answer 49

Initially causes thyroid enlargement Then atrophy and fibrosis

Question 50

Histologically, what would be seen in someone with Hashimoto thyroiditis?

Answer 50

Dense infiltration by lymphocytes and plasma cells Reduced colloid content Fibrosis in advanced cases

Question 51

Is Hashimoto's an organ-specific or non-organ specific autoimmune disease?

Answer 51

Organ specific

Question 52

Describe the two autoantibodies which can be detected in the serum of most patients with Hashimoto thyroiditis.

Answer 52

One that reacts with thyroid peroxidase The other reacting with thyroglobulin

Question 53

What is meant by autoimmune polyendocrine syndromes?

Answer 53

A group of conditions characterised by functional impairment of multiple endocrine glands due to loss of immune tolerance

Question 54

What do autoimmune polyendocrine syndromes ultimately result in?

Answer 54

Organ failure

Question 55

What is APS-1 (autoimmune polyendocrine syndrome type 1)?

Answer 55

Autosomal recessive disease cause by mutations in the autoimmune regulator gene

Question 56

What are some of the clinical features of APS-1?

Answer 56

At least 2/3 in childhood: -chronic mucocutaneous candiasis -hypoparathyroidism -Addison's (primary adrenal insufficiency)

Question 57

What is more common APS-1 or APS-2?

Answer 57

APS-2

Question 58

What are some of the clinical features of APS-2?

Answer 58

2/3 of the following: -Type 1 diabetes -Autoimmune thyroid disease -Addison's disease

Question 59

In those with APS-2, which other autoimmune conditions may develop?

Answer 59

Celiac disease Alopecia Primary ovarian insufficiency Pernicious anaemia

Question 60

Which typically presents earlier APS-1 or APS-2?

Answer 60

APS-1

Question 61

IPEX is a very rare inherited syndrome. What is it characterised of?

Answer 61

Development of:-Early onset type 1 diabetes -Autoimmune enteropathy w intractable diarrhoeal and malabsorption Dermatitis