T Cell Development and Self Tolerance Flashcards
What is the immune system tolerant to?
- Self
- Harmless antigens (e.g. food and environment)
- Commensal bacteria
What about the repertoire of T cells and B cells means that some may be self-reactive?
The repertoire is very large, so some end up being self-reactive.
What, and where, do T cells originate from and where do they mature?
They are lymphoid progenitors in the bone marrow.
Migrate to the thymus where they then mature.
What do sufferers of DiGeorge’s syndrome suffer a lack of?
Mature T cells
Which chromosome is mutated in DiGeorge’s syndrome?
Chromosome 22
Where does V(D)J recombination occur for T cells and B cells?
B cells in Bone marrow
T cells in Thymus
How does the size of the thymus vary from before brith to adulthood?
Before birth, the thymus is fully developed.
During puberty, it then increases in size.
With age, it then atrophies and fat replaces thymocytes that originally existed.
By what age is degeneration of the thymus usually completed?
30
Are T cells that harm self positively selected or negatively selected?
Negatively selected
Where do T cell receptor genes undergo gene rearrangement?
Thymus
What is thymic stroma made up of and what is the site of?
Consists of epithelial cells and connective tissue.
Site of T cell development and selection.
What are the two parts of the thymus?
Cortex and Medulla
What happens to thymocytes during positive selection and negative selection?
In positive selection, if the thymocyte has a TcR that is able to recognise antigens from self-MHC it is kept.
In negative selection, if the thymocyte recognises self-antigens from self-MHC it is removed.
What happens to thymocytes have TcR that are able to recognise self-MHC expressed on cortical epithelial cells?
They are induced to survive, differentiate and mature
What happens to thymocytes have TcR that are NOT able to recognise self-MHC expressed on cortical epithelial cells?
They die via apoptosis
What cells are found at the cortico-medullary junction of the thymus?
Dendritic cells and macrophages
What happens to T cells that modestly bind to MHC I & II on macrophages and dendritic cells at the corticomedullary junction?
They pass through to the medulla
Where does positive selection and negative selection occur and what cells are involved?
Positive selection occurs in the cortex and is done by cortical epithelial cells
Negative selection occurs in the medulla and is carried out by dendritic cells
What is the only type of cell to not express MHC I and why is this the case?
Red Blood Cells
Because they don’t have a nucleus
What does AIRE stand for and what is it?
Autoimmune Regulator
A transcription factor that is expressed at high levels by thymic medullary epithelial cells. Its role is to eliminate self-reactive T cells
What could a mutation in the AIRE gene lead to?
Autoimmune polyendocrine system (APS-1)
What is anergy?
Absence of a normal immune response to a particular antigen or allergen.
What happens in ignorance during peripheral tolerance?
Self-reactive lymphocytes fail to recognise or respond to some self-antigens of the periphery. Therefore, they don’t die and don’t become anergic.
What are immunologically privileged sites?
Sites where antigens are anatomically sequestered (e.g. eyes, testis and placenta)
What could happen if antigens from anatomically sequestered sites were released?
Autoimmunity
What is sympathetic ophthalmia?
When physical trauma to one of the eyes leads to autoimmunity to both eyes, which can cause blindness.
What is induction of anergy?
When the binding of antigen makes a lymphocyte unresponsive
What is clonal exhaustion?
When the consistent activation of T cells by a specific antigen leads to the activated T cells becoming worn out and eventually dying by apoptosis
What could a deficiency in Tregs lead to?
An autoimmune disorder
What is oral immunotherapy?
Introduction of a small amount of an allergen to induce antigen specific tolerance.
Continuous administration can promote tolerance (hoped to be used for peanut allergies).
