Immunology of endocrine disease Flashcards
What is immunological tolerance?
Unresponsiveness to an antigen that is induced by previous exposure to that antigen
In healthy bodies, this is what prevents autoimmunity - as there is tolerance to self-antigens
When lymphocytes encounter antigens, they may be activated, leading to _________, or they may be _______ or ________, leading to tolerance
When lymphocytes encounter antigens, they may be activated, leading to immune responses, or inactivated or eliminated, leading to tolerance.
In terms of tolerance, what causes autoimmunity?
Failure of tolerance to self-antigens
Failure results in attack against these autologous antigens
How is it that our bodies ensure that there are no self-reactive immune cells?
Some of our T and B cells have self antigen receptors
These are usually identified and promptly dominated
What is meant by central tolerance?
This is the process of eliminating immature lymphocytes
Self-tolerance may be induced in immature self-reactive lymphocytes in the generative lymphoid organs
Where does central tolerance with T cells occur?
The thymus
plays an important role in eliminating T cells with high affinity to self-antigens
Where does central tolerance for B cells happen?
Bone marrow
What is meant by peripheral tolerance?
Process in which mature lymphocytes that have escaped central tolerance are inactivated or killed off
How are self-reactive lymphocytes dealt with, in peripheral tolerance?
Mature lymphocytes that recognize self antigens in peripheral tissues become incapable of activation by re-exposure to that antigen or die by apoptosis
also maintained by regulatory T cells (Tregs) that actively suppress the activation of lymphocytes specific for self and other antigens.
What are the 3 mechanisms of peripheral tolerance?
Anergy
Suppression
Deletion
What is anergy?
Functional unresponsiveness
Even when correctly bound to (activated) - there is no immune response made by the lymphocyte
What is meant by suppression?
Treg suppression
Regulatory T cells suppress lymphocyte activation
What is meant by deletion?
Binding to self-antigen causes the self-reactive lymphocyte to undergo apoptosis
What can happen to self-reactive lymphocytes in central tolerance?
If immature self-reactive lymphocytes encounter their antigen when in their generative tissue - 3 things can happen:
1) Apoptosis (deletion)
2) Changes to their specificity (B cells only)
3) Conversion to Treg cells (CD4+ T cells only)
What can cause peripheral tolerance to fail?
It can result from:
- Inappropriate access of self-antigens
- Inappropriate or increased expression of co-stimulatory molecules
- Alterations of the ways in which self-antigens are presented to the immune system
What damage to tissue can cause peripheral tolerance to fail?
Why?
More likely to happen when inflammation or tissue damage is present due to the increased activity of proteolytic enzymes
What features cause autoimmune disease to occur
Combination of:
Genes
Infections
Environmental factors
What is the significance of Genetics as a cause of autoimmunity?
(incl gender)
Autoimmune diseases show clustering within families
Almost all types of autoimmune diseases are more common in women (Exception, ankylosing spondylitis).
What are the peak years of onset for autoimmune disease?
15-65 years old
except for T1DM
So autoimmune questions will have patients that are likely to be middle-aged
What is the pathological difference between non-organ specific autoimmune disease and organ specific autoimmune disease?
Non-specific (multi-organ):
- Associated with autoimmune responses against self-molecules which are widely distributed throughout the body
Organ-specific:
- affect a single (endocrine gland) organ
- Autoimmune responses against cells found in that organ
What autoimmune conditions arise from problems with hormone receptors?
TSH receptor - Hyper/hypothyroidism
Insulin receptor - Hyper/hypoglycaemia
What autoimmune conditions arise from problems with neurotransmitter receptors?
Acetylcholine receptor - Myasthenia gravis
What autoimmune conditions arise due to defects in cell adhesion molecules?
Epidermal cells adhesion molecules
Cause of blistering skin diseases
What autoimmune condition arises due to defects in plasma proteins?
Factor VIII - Acquired haemophilia
Beta-2 glycoprotein (& others) - Antiphospholipid syndrome
