Lecture 16. T-cell Development and Thymic Education Flashcards
What does every T-cell have ?
A TCR of a different specificity
What is MHC restriction ?
TCR can only recognise peptide presented by MHC
What ensures that T-cells are able to mount an adaptive immune response against any pathogen/antigen ?
The potential to generate 10^9 specificities
Where do T-cells develop and are selected ?
Thymus
What happens to T-cells specific for self-antigens ?
Must be deleted to avoid autoimmunity
What is the only cell not found in bone marrow ?
T-cell
What is the surface marker of the T-cell progenitor ?
CD2+
What are chemotactic cytokines ?
Family of around 4 molecules that regulate trafficking of leukocytes by their interaction with transmembrane, G-couples receptors
What do chemokines do in infection and inflammation ?
- Recruit leukocytes
- Direct movement of progenitors and mature cells
- Promote wound healing, angiogenesis, metastasis and organogenesis of primary and secondary lymphoid organs
What is the chemotactic attractant for neutrophils ?
IL8
What are the cytokines that drive T-cell development ?
IL7, IL2 and IL15
What is apoptosis marked by ?
DNA fragmentation
What is terminal deoxynucleotidyl transderase used for ?
Annealing
Where do thymocyte progenitors enter ?
The thymus in the subcapsular region
How do T-cells develope in the thymus ?
- Become double negative
- Proliferate and differentiate to double positive
- Migrate to cortex
- Positive selection (self-MHC restricted)
- Migrate to cortico-medulary junction
- Negative selection (self tolerant)
- Mature to single positive T-cells
What does AIRE do ?
Generates delf antigens of all tissue types
What is DiGeorge syndrome ?
Have B-cells but no T-cells
What happens during maturation of T and B lymphocytes ?
Go through cycles of proliferation and expression of antigen receptor proteins by gene recombination
What happens at the end of maturation ?
Positive and negative selection
What are all thymocytes programmed to do ?
Die
What is positive seletion mediated by ?
Thymic epithelial cells
What is negative selection mediated by ?
Dendritic cell and macrophages
What is the purpose of seletion events in the thymus ?
To ensure that T-cells entering the peripherery are self MHC restricted and self tolerant
What does positive selection ensure ?
T-cells can recognise peptides in the context of own MHC - only low affinity binding
What does negative selection ensure ?
T-cells whose TCR binds self antigen with high affinity are deleted, those with weak affinity survive
