Immunology of the Endocrine System Flashcards
What is autoimmuinity?
An immune response against an antigen made by the body
Are the majority of autoimmune conditions more common in male or females?
Females
Which autoimmune condition is more common in men?
Ankylosing spondylitis
What is immunological tolerance?
Unresponsiveness to an antigen that the body has had previous exposure to
What name is given to the antigens that induce tolerance?
Tolerogens
What is self-tolerance and why is it important?
Tolerance to the self-antigens
Failure of this tolerance leads to autoimmune disease
To avoid autoimmune disease, what happens to the B and T cells?
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
Which part of the body plays an important role in eliminating the T cells that have a high affinity for self-antigens?
Thymus
Which part of the body plays an important role in B cell tolerance?
Bone marrow
Some cells escape the central tolerance and escape to the periphery. However, there is peripheral tolerance in place. What is meant by peripheral tolerance?
Mature lymphocytes that recognise self antigens in peripheral tissues become incapable of activation by re-exposure
Or, the cell die by apoptosis
Which mechanism induces peripheral tolerance?
Second signals
-> this is antigen recognition without co-stimulation
How is peripheral tolerance maintained by regulatory T cells?
These T cells supress the activation of lymphocytes specific for self and other antigens
Some self antigens are sequestered from the immune system.
What can act as barriers for these self-antigens?
Anatomic barriers, specifically in the CNS, testes and eyes
-> these cannot engage antigen receptors
Name three mechanisms of peripheral tolerance.
Anergy
Treg suppression
Deletion- cell death
->the cell death is of the lymphocytes when they recognise the antigens
(?idk gal soz)
Treg?
Regulatory T cells
When does anergy occur?
In the absence of co-stimulation
What happens in autoimmune disease which allows the cells to attack self-antigens?
Overcoming of peripheral tolerance
Why may autoimmune overcoming of peripheral intolerance occur?
-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
Why is autoimmune disease more likely to occur when there is inflammation of tissue damage present?
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.
How may the structures of self-peptides be altered?
Viruses
Free radicals
Ionising radiation
-> therefore, by changing structure, they bypass previously established tolerance
Is there a genetic disposition to autoimmune disease?
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
What % of the population have some sort of autoimmune disease
3%
The peak years of onset for autoimmune conditions is 15-65yrs.
Which autoimmune condition is the exception to this?
Type 1 diabetes
->often occurs at an earlier age
Non-organ specific organ diseases can affect multiple organs. Why is this?
Associated with autoimmune responses against self-molecules. These self-molecules are widely distributed by the body, hence why affects multiple organs
If autoimmune disease affected the self-antigen of TSH receptor, which condition can this cause?
Hyperthyroidism
Hypothyroidism
If autoimmune disease affected the self-antigen of inulin receptor, which condition can this cause?
Hyperglycaemia
Hypoglycaemia
If autoimmune disease affected the self-antigen of the acetylcholine receptor, which condition can this cause?
Myasthenia gravis
B27 allele has HLA association with which diseases?
Ankylosing spondylitis
DR3 allele has HLA association with which diseases?
Addison’s disease
Hashimoto disease
Myasthenia Gravis
DR4 allele has HLA association with which diseases?
Insulin-dependant diabetes mellitus
How can infections trigger autoimmune disease?
Molecular mimicry
Upregulation of co-stimulation
Antigen breakdown and presentation changes
How can drugs trigger autoimmune disease?
Molecular mimicry
Genetic variation in drug metabolism
How can UV radiation trigger autoimmune disease?
Trigger skin inflammation
Modification of self antigen
Molecular mimicry?
Structural similarities between self-proteins and microbial antigens, triggering autoimmune response
What are the factors involved in the treatment of autoimmune disease?
Suppression of the damaging immune response
Replacement of the function of the damaged organ
How is autoimmune disease related to type 1 diabetes?
Autoimmune destruction of the beta cells of the pancreas which are responsible for secreting insulin
RECAP- which type of diabetes is an autoimmune condition?
Type 1 diabetes
-> literally gave you the answer in the last flashcard
Which viruses may act as a trigger for type 1 diabetes?
Mumps
Coxsackie B
Which type of cells line the follicles of thyroid cells?
Cuboidal cells
RECAP- what does the thyroid gland secrete?
T3 and T4 under negative feedback by TSH
Calcitonin
->reminder that TSH is secreted from the anterior pituitary
RECAP- list some of the causes of hyperthyroidism.
Graves thyroiditis
Functioning adenoma
Toxic nodular goitre
Ectopic secretion from tumours
What can Grave’s disease cause?
Hyperthyroidism
What would be seen histologically in someone with Grave’s thyroiditis?
Hyperplasia of acinar epithelium
Reduction of stored colloid
Local accumulation of lymphocytes
Is Grave’s thyroiditis an example of a non-organ specific or organ-specific autoimmune disease?
Organ specific
Describe the autoimmune pathology behind Grave’s thyroiditis.
LATS (long-acting thyroid stimulator) binds to thyroid epithelial cells and mimics action of TSH
RECAP- what is the most common cause of hypothyroidism?
Hashimoto thyroiditis (autoimmune disorder)
Cretinism?
Hypothyroidism present from birth
akak congenital hypothyroidism
Which deficiency can cause hypothyroidism?
Iodine deficiency
What does Hashimoto thyroiditis do to the thyroid gland?
Initially causes thyroid enlargement
Then atrophy and fibrosis
Histologically, what would be seen in someone with Hashimoto thyroiditis?
Dense infiltration by lymphocytes and plasma cells
Reduced colloid content
Fibrosis in advanced cases
Is Hashimoto’s an organ-specific or non-organ specific autoimmune disease?
Organ specific
Describe the two autoantibodies which can be detected in the serum of most patients with Hashimoto thyroiditis.
One that reacts with thyroid peroxidase
The other reacting with thyroglobulin
What is meant by autoimmune polyendocrine syndromes?
A group of conditions characterised by functional impairment of multiple endocrine glands due to loss of immune tolerance
What do autoimmune polyendocrine syndromes ultimately result in?
Organ failure
What is APS-1 (autoimmune polyendocrine syndrome type 1)?
Autosomal recessive disease cause by mutations in the autoimmune regulator gene
What are some of the clinical features of APS-1?
At least 2/3 in childhood:
-chronic mucocutaneous candiasis
-hypoparathyroidism
-Addison’s (primary adrenal insufficiency)
What is more common APS-1 or APS-2?
APS-2
What are some of the clinical features of APS-2?
2/3 of the following:
-Type 1 diabetes
-Autoimmune thyroid disease
-Addison’s disease
In those with APS-2, which other autoimmune conditions may develop?
Celiac disease
Alopecia
Primary ovarian insufficiency
Pernicious anaemia
Which typically presents earlier APS-1 or APS-2?
APS-1
IPEX is a very rare inherited syndrome. What is it characterised of?
Development of:-Early onset type 1 diabetes
-Autoimmune enteropathy w intractable diarrhoeal and malabsorption
Dermatitis
