Tolerance Induction Flashcards
What is central thymic tolerance induction?
Education of T cells to recognize non-self and ignore self
Occurs during development of host
What is peripheral tolerance induction?
Occurs outside thymus, throughout life of host
What is autoimmunity?
Defined as an abnormal immune response against self tissue and organs mediated by T cells and antibody produced by B cells
What is DiGeorge Syndrome?
Thymus fails to develop, resulting in absence of T cells
No adaptive immune response, so patients suffer from opportunistic infections
What is the thymic cortex?
Outermost region of a thymic lobule
This is where positive selection occurs
What is the thymic medulla?
Innermost region of a thymic lobule
Mainly negative selection
What is the cortico-medullary junction?
Region where immature thymocytes enter the organ
Mature cells leave via vasculature
What is Hassall’s Corpuscle?
Located in the medulla
Concentric arrangement of reticular epithelial cells, secrete cytokine TSLP
Direct mutation of dendritic cells and aid in DC generation of Tregs
What occurs as the thymus involutes?
It develops adipose tissue, but retains islands of thymic tissue which can continue to make T cell precursors if needed
What event is responsible for the initiation of gene transcription leading to T cell differentiation?
Notch protein cleavage
Describe T cell differentiation.
Uncommitted progenitor cell enters the thymus and differentiates into a double-negative thymocyte, this then transforms into a committed y:d cell and an uncommitted double positive (CD4+CD8+)
This further differentiates into a committed a:B T cell
What is positive selection?
Double + T cells (CD4+/CD8+)
Epithelial cells present self Class I or II + peptide
If the T cell does not bind - Apoptosis
If the T cell binds to self MHC signal - T cell survives
What is negative selection?
If Class I bound: CD8 retained, CD4 lost
If Class I bound: CD4 retained, CD8 lost
T cell has High affinity binding: Apoptosis
T cell has Low affinity binding: T cell survives and seeds peripheral lymphoid organs
Where do the antigens that are expressed on thymic epithelial cells come from?
APCs and debris from the thymic microenvironment
What is AIRE?
Transcription factor that allows for the expression of several hundred tissue specific genes by subpopulation of thymic epithelial cells, allowing T cells to beocme tolerant of antigens that are expressed in the periphery
Expression of AIRE is in the thymic medulla
