T Cell-Mediated Immunity Flashcards
1st phase of T cell response: Ag recognition
Ag recognition of T cells induces IL-2 secretions followed by clonal expansion of T cells, and differentiation into effector and memory cells.
How do effector CD4+ cells respond to binding Ags?
They produce cytokines that regulate the recruitment and activation of leukocytes and activation of B cells.
How do effector CD8+ cells respond to binding Ags?
They kill infected host cells.
How does the number of effector T cells change once the Ag is eliminated?
The number of effector T cells is greatly reduced, but the memory cells remain in high quantity.
3 required signals for proliferation and differentiation of T cells:
Ag recognition
Costimulation
Cytokines
Activation of T cells requires recognition of Ag by:
Only DCs.
Effector T cells can recognize Ags presented by:
Tissue macrophages and B cells.
CD28:CTLA4
Inhibitory signal. Costimulation.
CD28:CD80/86
Activating signal. Costimulation.
LFA1:ICAM1
Adhesion w/ APCs.
ITAMs
The region of signaling proteins that are phosphorylated on Tyr residues and become docking sites for tyrosine kinases.
ITIMs
The region of signaling proteins that are sites for tyrosine phosphatases that counteract the action of ITAMs.
Superantigens
Bind to MHC II molecules and the V region of beta subunit of the TCR. This causes the T cell and APC to stick together and continuously produce TNF, IL-1, and IL-2, which can lead to shock.
Staphylococcus enterotoxins are:
Bacterial SAgs that cause food poisoning and TSS.
DCs’ costimulation mechanism
Usually DCs do not express a high enough quantity of costimulation molecules. However, once the T cell binds the Ag on an APC, it releases cytokines which activate DCs to express the costimulatory molecules.
CD28 binds to:
B7-1 (CD80) and B7-2 (CD86) on activated APCs.
CTLA4 regulation
Naive and memory T cells have high levels of CD28, but little CTLA4. After the TCR is triggered by the Ag, CTLA4 is transported to the cell surface.
The stronger the stimulation through the TCR (and CD28):
The greater the amount of CTLA4 deposited on the T cell surface. Therefore, CTLA4 functions as a signal dampener.
Programmed cell death protein 1 (PD1) function
Regulate inflammatory responses in tissues by effector T cells recognizing Ag in peripheral tissues.
PD1L
Downregulates activity of T cells and limits collateral damage in response to infection.
The best signal for PDL1 induction is INF-gamma.
Excessive induction of PD1 causes:
An anergic state in T cells.
IL-12 causes:
Activation of signaling molecule STAT4 that leads to expression of T-bet, which facilitates the generation of Th1.
IL-4 causes:
Activation of STAT6 that leads to expression of GATA3 which facilitates the generation of Th2.
IL-6 causes:
Activation of STAT3 that leads to expression of RORyt which facilitates the generation of Th17 cells.
IGF-beta causes:
Activation of signaling molecule SMAD2-SMAD4 that promotes expression of FOXP3 and generation of T regulatory cells.
Costimulatory molecules in CTLs
CD28-CD80
T-bet regulates:
Transcription of genes coding for perforin, granzymes, annd IFN-gamma.
Initiation of TCR signaling
ITAMs on zeta chains are phosphorylated.
Phosphorylated ITAMs bind ZAP-70 via the SH2 domains.
ZAP-70 is phosphorylated by Lck and activates ZAP-70 catalytic activity.
Activated ZAP-70 phosphorylates LAT and SLP-76, which functions as a scaffold to recruit other signaling molecules.
Phosphorylated LAT recuits GADS and GRB2, which phosporylates PLC1.
PLC1 mechanism
PLC1 produces IP3 and DAG.
IP3 leads to increase in cytosolic Ca2+ and NFAT activation.
DAG activates both PKC which activates NF-kB.
DAG also actiavtes Ras that activates MAPK pathways and AP-1.
IL-2 induces the:
Anti-apoptotic protein Bcl-2.
IL-2 stimulates the cell cycle by:
Degredation of p27 (cell cycle inhibitor).
IL-2 is required for the survival and function of what cells?
Treg cells.
Changes in CD69 expression after T cell activation:
CD69 binds CD69L and reduces surface expression of S1PR1. This causes activated T cells to remain in the LNs long enough to receive signals that initiate the proliferation/differentiation into effector and memory cells.
After cells division, CD69 expression decreases.
Actvated T cells express how much S1PR1?
High levels, so they can leave the LN.
Expression of CD40L in activated T cells
T cells recognize Ag causing expresion of CD40L.
CD40L binds to CD40 on DCs, which leads to DC expression of B7, which causes secretion of cytokines,
Activated DCs stimulate T cell proliferation and differentiation.
IL-2 starvation triggers:
The mitochondrial intrinsic pathway of apoptosis.
Regulatory mechanisms contributing to normal contraction of immune responses (3):
CTLA4 and PD-1 (inhibitory receptors)
Apoptosis induced by TNFRI and Fas
Inhibition by Treg cell products
T-bet drives differentiation of:
Blimp-1 drives proliferation of:
CD4+ T cells.
Memory cells.
Memory T cells are generated from effector T cells via:
Epigenetic modifications.
Naive T cells respond in __________, while memory T cells respond in __________.
5-7 days
1-3 days
IL-7 and IL-15 induce the expression of:
Anti-apoptotic proteins and stimulate low-level proliferation.
Central memory T cells
Home mainly to spleen and LNs and circulate in the blood.
They are capable of proliferation.
Effector memory T cells
Circulate in blood.
Cannot proliferate, but secrete IFN-gamma and TNF or become cytotoxic.
Resident tissue memory T cells
Reside in the epithelial barrier.
Produce IFN-gamma and TNF and are specific for Ags that have been previously encountered through that barrier epithelium.
