T cell activation Flashcards
How are T cells activated?
- Dendritic cells in the sites of infection take up pathogen derived antigens
- When triggered by PAMPs and inflammation at the sites of infection, DC migrate to draining lymph nodes
- They undergo maturation, enhancing their ability to present antigen and activate T cells
- when they get to the lymph nodes, they interact with T cells in a dynamic process
Naive T cells
Prior to recognition and antigen
Need several signals (MHC and costimulation) to become activated. Will die within weeks without antigen stimulation
Effector T cell
Activated cell, antigen experienced, needs only 1 signal to respon to MHC-Peptide.
Short lived
Memory T cell
Antigen experienced, remain in an easily activated state indefinitely, require only 1 signal to become re-activated
long lived
Naive T cells require:
2 signals for activation.
- specific MHC peptide complex
- Costimulation through B7-1 or B7-2
B7 interacts with
CD28
B7-1 and B7-2
Costimulatory molecules that are uniquely expressde by DC, macrophages or B cells when they have been activated (or matured) by infection or inflammation.
B7 other name
CD80 or CD86
CD28 expressed by
T cells
B7-1 and B7-2 are expressed by
antigen presenting cells
Naive T cells reside in
secondary lymphoid organs
Complex that stabilizes the interaction between T cell and antigen presenting cell
adhesion molecules
Which of the following is considered signal 2 for T cell activation?
Costimulatory molecules
What happens when T cells recognize their cognate antigen?
- TCR initiate signaling cascade through CD3 and CD4 or CD8
- Immune synapse forms at site of T cell-APC interaction
- T cell and APC remain in sustained interaction for many hours, up to and beyond 24hr.
- T cell disengages, divides and emigrates from lymph node to seek out infected cells in periphery
ITAM
Immunoreceptor tyrosine based activation motifs
In a resting T cell …
- ITAMs are not phosphorylated
Binding of MHC ligand to T cell leads to
phosphorylation of the ITAMs by receptor associated kinases
CD3
main signaling complex
CD4
provides another important aspect of the singaling process
Signaling at the cell membrane through signaling molecules ..
through calcium flux, leads to general activation of transcription factors.
Ultimately leads to cell division, proliferation, differentiation and different effector T cell functions
synapse location
between T cell and APC
or
between T and B cell
in peripheral SMAC
peripheral supra-molecular cluster (P-SMAC)
adhesion molecules
central SMAC
Central supra molecular acticvation cluster(C-SMAC)
T cell receptor, signaling molecules
most important cytokine for T cell proliferation
IL-2
binds to IL-2 receptor, expressed by activated T cell receptors with high affiity
IL2 T cell Proliferation factor
Positive feedback
Costimulatory signal and MCH signal leads to
activated T cell
MHC (specific) signal alone on T cell leads to
anergic cell
enter a period of nonresponsiveness, and then ultimately die
Co-stimulatory signal alone leads to
no effect on T cell
CD4 / T helper cell types
- TH1 cell
- TH2 cell
- TH17 cell
- Tregs
- Follicular helper T cell
depends on the cytokines produced by the DC or APC during activation of T cell.
Th1 cell
neutrophil, activated macrophage
Th2 cell
mast cell, eosinophil, basophil, alternatively activated macrophage
Th17 cell
neutrophil
Follicular T helper cell associated with
Naive B cell
CD8-T cell Type
Proliferation and Cytotoxic T cell (kills virus infected cells)
if naive T cells is induced to undergo anergy, it must have recieved
Signal 1 without signal 2
Cytotoxic T cells are activated by
Antigen presenting cells
Cytotoxins (upregulated for killing)
CD8
Perforin
Granzymes
Granulysin
Cytokines (upregulated for killing)
CD8
IFNy
LT
CTL (cytolytic T Cell) can use Fas ligand
to interact with Fas and send an apoptotic signal into the target cell
Need Signal 1 and 2
CTL are activated by one APC
but as they undergo proliferation and differentiation they are dependent on IL2
When CD8-T cells move out into the periphery, they
recognize virally infetced target cells and can kill many different target cells without stopping.
they are very efficienct.
SIGNAL 1 is sufficient to stop and kill the cell presenting an antigen
granules of CD8 T cell
localizes to the area interacting with infected target cell
and released the toxic granules onto the surface of the target cell
