L17-T cell differentiation and the concept of tolerance Flashcards
What is tolerance in this sense?
It is the set of mechanisms that prevent the immune system responding to self antigens. More directly it is the process of eliminating or neutralising self-reactive lymphocytes.
What does central tolerance refer to?
Central tolerance refers to tolerance mechanisms that occur in the primary lymphoid organs (thymus and bone marrow)
What is the structure of the thymus?
An encapsulated gland, which is organised into lobules each with a complex meshwork of epithelial and other cells. It can be divided into an outer cortex and an inner medulla.
What is the path t cells take through the thymus?
They pass from the outer cortex through to the medulla
What is the main cell type in the cortex of the medulla?
reticular epithelial cells which express MHC class 2 molecules.
Why are there macrophages present at the boundary between the cortex and the medulla?
To prevent dead or dying cells from entering the medulla.
What happens in the medulla?
The medulla is specialised to allow thymocytes to undergo additional rounds of negative selection.
What is the gene that allows thymic epithelial cells to express antigens from all over the body?
AIRE
Once full diversity of thymocytes have been generated in the cortex what two selection processes must they undergo?
Positive selection - in the cortex, allows T cells that recognise foreign antigen on self MHC molecules to mature.
Negative selection - removes potentially dangerous T cells that recognise self peptides.
How does positive selection help T cells differentiate into different T cell types?
T cells that recognise MHC class I molecules lose expression of CD4 and the same vice versa.
Which cells mediate the process of negative selection?
Dendritic cells
What percentage of T cells generated survive central tolerance?
5%
What are the main mechanisms that contribute to tolerance in the periphery?
Ignorance - suppression of immune response by cytokines
Regulatory T cells- prevent self-reactive t cells from mounting damaging immune responses.
Inappropriate antigen presentation- Prevents T cells from being activated without ‘danger signals’ being released as well as the MHC molecules
Threshold responce- Genes CD28 (acceleration) and CTLA-4 (brake) can be used to switch T cells on and off
How does B cell tolerance take place?
They do not migrate to the thymus however if self antigen is encountered before they reach a secondary lymphoid organ then they are inactivated or deleted. The main source of B cell tolerance is lack of T cell help.
