Activation of naive T cells Flashcards
Where do naive T cells encounter antigen?
During recirculation through secondary lymphoid organs
T cell antigen encounter process
T cells enter a lymph node across high endothelial venules in the cortex –> T cells monitor antigen presented by macrophages and DCs –> T cells which do not encounter specific antigen leave the node via efferent vessel –> T cells that encounter specific antigen proliferate and differentiate to effector cells
If an DC is mature, then it is expressing _____ and ______
High levels of MHC; co stimulatory molecules
Role of cell adhesion molecules in the generation of immune responses
- migration of naive T cells through the lymph nodes
- initial interactions with APC
- migration of the effector T cells into the peripheral tissues
- interactions with target cells
Adhesion molecules are ______ and _____ T cell contacts with APC
Initiating and controlling
- T cells initially bind DC through low affinity LFA-1: ICAM-1 interactions –> subsequent binding of T cell receptors signals LFA-1 –> conformational change in LFA-1 increases affinity and prolongs cell-cell contact
First signal
Specific, T cell receptors and MHC-antigen interactions
Difference between TCR and TCR complex
CD3 complex does not recognize antigen, only signaling function
TCR is capable of recognizing antigen, but not signaling
TCR+CD3 can provide signaling and antigen presentation
MHC-CD4/8 interactions
Binding of TCR and its co receptors CD4/8 to the peptide:MHC class 2/MHC class 1 complex on the DC delivers a signal
Second signal
Co-stimulatory
- binding of the T cell CD28 to B7 expressed on DC delivers a signal
- T cell tolerance to antigens expressed on nonprofessional APC results from antigen recognition in the absence of the co stimulatory signal
Co stimulatory signal alone
Without antigen recognition, co stimulatory will not do anything to the T cell
Specific signal alone
If antigen reception is not supported by signal 2, then it will not respond and just float in the circulation
- anergy
B7-1
CD80
B7-2
CD86
Co stimulatory signal is important for ___ and _____ of naive T cells
proliferation; survival
Specific signal recognition, initiation of signal transduction
- clustering of TCR and accessory molecules together on the cell surface
- phosphorylation of cytoplasmic portions of CD3 and z chains
- activation of adapter proteins and biochemical intermediates
- concentration of intracellular signaling molecules around the receptors
What does signal transduction lead to?
Clonal expansion and differentiation
What is the one important step in signal recognition and transduction (is the first signal)?
Antigen recognition
Transmission and amplification of the signal
Activation of certain intracellular enzymes
- diacylglyceral (DAG) and inositol trisphospate (IP3)
IP3
Increases intracellular calcium concentration, activating a phosphatase, calcineurin
Transmission of the signal to the nucleus
Transcriptional activation of genes that are silent in resting T lymphocytes
- NFkB, NFAT, and AP-1 change the pattern of gene expression
Last step in signal transduction
Cell division, proliferation and differentiation to effector T cells
Cyclosporin tacrolimus
Only targets calcineurin
- will deactivate entire chain
Activated T cells secrete and respond to ______
Inerleukin 2 (IL-2)
T cells and IL-2
- resting T cells express moderate affinity IL-2 receptor (IL-2Rbeta and gamma)
- activated T cells express high affinity IL-2 receptor (IL-2R alpha, beta, and gamma) and secrete IL-2
- binding of IL-2 to its receptor signal T cell to enter mitosis
= induces T cell proliferation
