3. T cells Flashcards
What are the 3 checkpoints that need to be passed in T cell maturation?
TCR
Positive selection/ recognise MHC
Negative selection/ weakly recognise self antigen
Describe the structure of the T cell receptor
Membrane bound protein with an a and B chain
Each has a variable and constant region
Each TCR is unique due to gene rearrangement
What segments make up the V part of the TCR?
V
D
J
What chromosome is the a chain of the TCR expressed?
14
What chromosome is the B chain of the TCR expressed?
7
Describe the process of positive selection
Epithelial and dendritic cells in the thymus express high MHC
Immature T cells bind and get positive signal to survive
How is the type of T cell determined?
Whether it bound to MHC-I or -II in the thymus
Describe the process of negative selection/central tolerance
MHC in the thymus only expresses self peptide
If the TCR binds too tightly to self-peptide then the T-cell commits apoptosis
Where do immature T cells circulate?
secondary lymph organs
How does a naive T cell become an effector T cell?
Activated once it recognises an antigen bound to MHC on DC
That T cell undergoes clonal expansion
Now an effector T cell
What are the 3 signals needed to activate a T cell?
Antigen specific signal
Costimulation
Instructive cytokines
How does the antigen specific signal work?
TCR recognises peptide of MHC-II
CD4 co-receptor reacts with residues on the side of MHC-II
What does the activation of the TCR complex due to the antigen specific signal cause?
T cell starts to produce cytokines
Adhesion molecules on T cells bind to ligands on APC to stabilise the connection
T cell is primed but needs signal 2 to be activated
What is costiumulation needed for?
Proliferation and differentiation of naive T cells
Describe costimulation
Microbes stimulate APCs to express B7 which binds to CD28 (T cell surface receptor)
What receptors inhibit activation of CD28?
CTLA-4
PD-1
Which cytokine does the APC produce to ‘instruct’ T cells to become effect T cells?
IL-12
How is clonal expansion initiated?
Activated T cells produce IL-2
The same cell increases IL-2 receptors
Autocrine signalling allows proliferation
What defines the subset of T helper cells?
What cytokine it produces
What are the functions of T helper cells?
Instruct macrophages to enhance killing
Instruct B cells to enhance antibody production
Which cell does Th1 work with?
Macrophages
Which cell does Th2 work with?
Eosinophils
Which cell does Th17 work with?
Neutrophils
How is homeostasis achieved after T cell activation?
Most will undergo apoptosis after the antigen is cleared
Deprived of activation signals (Cd28 and IL-2)
Activation of inhibitory pathways
T reg cells can dampen response
Why is there poor T cell production in Di George syndrome?
Absent or hypoplastic thymus due to deletion on chromosome 22
What are SCIDs?
Severe Combined Immunodeficiency
Mutations in genes that affect T and B cells
What is the most common SCID in the world?
X-linked severe SCID
Mutation in IL-2R
Reduction in T cells, NK cells,
Non-functioning B cells
What is the most common SCID in Ireland
Adenosine Deaminase Deficiency
dATP accumulates which inhibits cell division so that T and B cells can’t clone
