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36 Cards in this Set
- Front
- Back
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What do naive T cells do?
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Haven't been exposed to their corresponding Ag yet
Actively circulate through the lympohid tissues by the use of selectin molecules like CD62, L lignad, chemokine receptors |
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What happens when the cells are activated in the lymphoid tissues?
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Change phenotype (expression of proteins)
This dictates how that cell will localize/function Clonal expansion: proliferate once activated |
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What does the genetic programming of the cells allow them to do?
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Differentiate ito a variety of effector functions
-> after activation and proliferation, they differentiate into armed and effective T cells |
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What is required for optimal T cell activation by APCs?
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TCR interactions with MHC
APC needs to be stimnulates B7 molec of APC bind to the CD28 receptor that is constitutively expressed on T cells |
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What do the T cells produce once the signals from the MHC-TCR and the B7-CD28 take place?
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Integration of the 2 signals -> T cells produce Interleukin 2
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What does IL-2 do?
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Growth factor
Autocrine signal (works on itself) critcal for driving proliferation of the cell Initiates transcription of IL-2 receptor genes |
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What percentage of T cells constitutively express the IL-2 receptor? Which T cells do this?
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5-10%
T-reg cells They are anti-inflammatory, immunosuppresors |
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What are the 2 family memebers that make up B7?
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B71 (CD80)
B72 (CD86) Both have the same effect both bind CD28 on T cells Both beling to the Ig superfamily |
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What happens if signal 1 (TCR-MHC) and signl 2 (B7-CD28) are delivered by different APCs?
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No proliferation
Signal 1 and 2 must be delivered by the same APC |
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What happens to T ecells that have not been activated by the additional signal?
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They become anergic or tolerant
->T cells can't proliferate because signal 1 is not sufficient to induce transcription of necessary proteins of the IL-2 path |
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What is anergy?
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Inactivation of T cells after antigen encounter
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Is the double signal requirement the same in memory T cells and naive T cells?
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No
Memory T cells may require co-stimulation, but they don't need is as much as naive cells |
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What is the mechanism of peripheral T cell tolerance (anergy)? (6 steps)
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Normal
1) Naive T cell stimnulated by virus dendritic cell 2) T cell recognizes same antigen on infected epithelial cell 3) Activated T cell kills infected epithelial cells OR Anergy 1) Naive T cell recognizes self Ag on epithelial cell 2) Ag-specific signal alone induces anergy 3) T cell is unresponsive to self Ag on dendritic cell |
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What are signals 1 and 2 for in the T cell?
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Critical for activation
Important for cell cycle progression, proliferation, survival Imprtant for differentiation ->There could be other signals like cytokines that can influence the ultimate effector fct of the T cell |
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Describe Ag-specific T cell responses and co-stimulation
(look at figure, bottom pg 14, NTC) |
1)Naive T cell stimulated by virally infected dendritic cell
2) Stimulated T cell has received and integrated both signals and can now differentiate and expand 3) Activated T cell, after recognizing Ag on its target cell, can mediate its effector fcts ->co-stimulation is not requird for effector fcts, only for the primary activation |
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What happens in the same scenario, but no virally infected cells?
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Have the same T cell, DC, but no viral inflammation
If the T cell rec'z an Ag and it's not a virally infected cell, then it rec'z a self-Ag T-cell rec'z the cell (receives signal 1) but there's no inflammation at the site and therefore no second signal and no co-stimulation |
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What would happen if this cell was introduced into an inflammatory env't?
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It would undergo prolif and diff
(analogous situation in auto-immune disease) |
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Can anergy be rescued?
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No, after an anergic response, even if the T cell can detach and see the DC, even in the context of co-stimnulation, it won't be activated
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What happens if a macrophage uptakes specific non-bacterial ptn antigens?
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Non-bacterial=non-inflammatory ptns
Unstimnulated macrophges do NOT deliver a co-stimulatory signal to T cells recognizing nonbacterial Ag (presentation of Ag alone, while delivering the signal 1 to T cell, is not enough to induce B7 expression on these cells and CD28 won't be engaged) => Anergic T-cells |
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What happens if APCs (DC/macrophages) are exposed to bacteria?
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Bacteria have a llot of potentially inflammatory/activating ligands and ptns. Bacteria is phagocytosed, processed and presented to the T cell.
Bacterial inflammation stimulates APC to deliver secondary co-stimulatory signal to the T cells (also activate macrphages through complement of pattern recognition) B7 will be induced and capable of recognizing CD28 and deliver the 2nd signal Result= proliferation of T cells specific for the bacterial Ag |
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What happens if macrophages are expressed to non/bacterial proteins at the same time?
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APCs may present epitopes that are coming from cells that are not bacterially infected
Since bacteria are present in the environment, it ca provide inflammatory signal to the mac, resulting in the induction of the B7 in T cells, engaging he CD28 ->This lets us break tolerance (similar to auto0immune disease: non-bacterial cell is a self-Ag) |
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Why is this last case not necessarily a bad thing?
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Can be beneficial in the case of tuours
You want to develop immunity towards self tumour-specific Ag |
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What happens when there i Ag recognition an co-stimulation?
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Lead to IL-2 production
Expression of high-affinity IL-2R (alpha) ->Productive IL-2 receptor has 3 subuints |
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How many IL-2R subunits are expressed in normal naive T cells?
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2
β chain and γ chain of IL-2 receptor are usually expressed at high levels on cell surface ->can be induced more -> γ is larger intracellularly: its role is to transduce signals, not bind |
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What happens when IL-2 is activated?
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Alpha subunit (CD25) is expressed
Role: give the receptor high affinity binding to IL-2 -> chaperones it to the β and γ chains and translate IL-2 binding to actual signalling Also makes T cell secrete IL-2 ->absence of CD25, as in the case of naive T cells, the binding to IL-2 is moderate and the ability to translate binding into IL-2 signalling is vey little/none |
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What are Cyclosporin A and Rapamyci involved in?
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Immunosuppression
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What does Cyclosporin A do?
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Blocks IL-2 production
->In transplant patients, suppress anti-graft responses |
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What does Rapamycin do?
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Blocks signalling through IL-2R
->blocks downstream effects |
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What is the consequence of immunosuppressants?
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More sensitive to infection since its systemic treatment
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What are the 2 signals required to regulate T cell activation?
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TCR complex and CD40L & CD28 co-stimulatory molec
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What path must take place before the CD28 path?
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CD40 and CD40 ligand
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How is CD40 expressed?
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Constitutively expressed on APCs
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What happens after the first signal is given to the T cell?
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Integrates the signal and upregulates the CD40-L
CD-40L can now engage CD40 |
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What happens when CD40 is in the APC?
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Activation of APC
Can upregulate B7 in the T cell which can then interact with CD28 |
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What is activation of DC through CD4 important for?
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For activation of CD4+ or CD8+ T cells
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What happens to CD40-L null mice?
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Produce very short clonal expansion when immunized with antigen
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