Exam 2: Dr. Pinchuk T-cell Mediated Immunity 1 Flashcards
What are the 3 signals to activate naive T cells?
1) Antigen-specific signal
2) Co-stimulatory signal
3) Cytokine signal
When do naive T cells encounter antigen?
During their recirculation through secondary lymphoid organs
Describe how naive T cells encounter their antigen
T cell enter a lymph node across high endothelial venues in the cortex
T cells monitor antigen presented by macrophages and DCs
T cells which do not encounter specific antigen leave the node in the efferent lymph
T cells that encounter specific antigen proliferate and differentiate to effector cells
What are the broad roles of cell adhesion molecules in the generation of immune response?
Migration of the 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
What are adhesion molecules doing?
Initiating and controlling T cell contacts with APC
What is the affinity like with adhesion?
First adhesion is low affinity and then it becomes his affinity to increase contact time
What is the first signal?
Specific, T cell receptors and MHC-antigen interactions
What does the first part of TCR complex do?
Recognize antigen
What does CD3 complex do?
Signals
What does TCR complex plus CD3 do?
Provides antigen recognition plus signaling
What deliver a signal 1?
Binding of the TCR and its co-receptor(s) CD4/CD8 to the peptide:MHC class II/MHC class I complex(es) on the DC
What delivers signal 2?
Binding of the T cell CD28 to B7 expressed on DC
What does T tolerance to antigens expressed on non-professional APC result from?
Antigen recognition in the absence of the co-stimulatory signal
What is CD80? CD86?
B7-1
B7-2
What is the co-stimulatory signal very important for?
Proliferation
What is signal 2 known as? Why?
Survival signal
Without it, T cells will die
What does the second signal need to work?
Specific signal
What causes the initiation of signal transduction?
Clustering of the TCR and accessory molecules together on the cell surface
Phosphorylation of cytoplasmic portion of the CD3 and z chains
Activation of adaptor proteins and biochemical intermediates
Concentration of intracellular signaling molecules around the receptors
What causes the transmission and amplification of the signal?
Activation of certain intracellular enzymes
What causes the transmission of the signal to the nucleus?
Transcriptional activation of genes that are silent in resting T lymphocytes
Look at signaling through TCR chart
Look at signaling through TCR chart
What do activated T cells do?
Secrete and respond to interleukin-2
What does rapamycin target?
IL-2 receptor and secretion
What do resting T cells express?
A moderate affinity IL-2 receptor
What do activated T cells express?
A high affinity IL-2 receptor and secrete IL-2
What does the binding of IL-2 to its receptor do?
Signals the T cell to enter the cell cycle
Do effector T cells depend on co-stimulatory signals?
No