Lecture 18 - Linking Innate & Adaptive Immunity (Costimulation and Proliferation) Flashcards
True or False?:
Costimulatory molecules are required for optimal T-cell activation and proliferation.
True
How do positive costimulatory receptors like CD28 contribute to T-cell activation?
They facilitate activation.
How do negative costimulatory receptors like CTLA-4 and PD-1 contribute to T-cell activation?
They help turn activation off.
What costimulatory ligands are found on APCs?
CD80 and CD86 (B7.1 and B7.2)
What is CD28?
CD28 is a transmembrane glycoprotein expressed as a homodimer on all naive T-cells under resting contions. It binds CD80 and CD86.
What happens when CD28 binds CD80/CD86?
It triggers phosphorylation of CD28 by a kinase, which recruits another kinases and leads to additional signaling.
What happens to T-cells in the absence of costimulation?
They become anergic.
What does it mean for a T-cell to be anergic?
Anergic T-cells can no longer respond to stimulation.
How is IL-2 an example of an autocrine cytokine response system?
It is autocrine because T-cells produce both the cytokine and the receptor for it.
What happens when a T-cell binds IL-2?
Il-2 binding induces a very strong proliferation signal during activation stages. This causes the production of memory and effector clonal cell populations.
What must signal 1 and 2 converge to produce the transcription of?
IL-2 Gene and IL-2Rα (CD25)
How does IL-2Rα expression contribute to T-cell signaling?
The cell surface already has IL-2R βγ chains, but they are low affinity for IL-2. When IL-2Rα is expressed, the affinity of the receptor for IL-2 is much higher.
What is the outcome of stimulating one activated T-cell with IL-2?
- Production of many T-cells, each cell with a different specificity.
- Production of many T-cells, all the cells with identical specificity.
- Production of many T-cells, each cell able to recognize different peptide-MHC combinations.
- Productions of many Th1 cells, each capable of secreting cytokines.
Production of many T-cells, all the cells with identical specificity.
What parts of the IL-2R are found in resting T-cells?
IL-2Rβ and IL-2Rγ
You are studying T-cell activation and you have come across a T-cell mutant that does not respond to activation signals. You conduct a series of experiments with the following results: low levels of IL-2 mRNA, high levels of ITAM phosphorylation, and low levels of transcription factors in the nucleus. What is the most logical next step in order to identify the cause of this defect in T-cell activation?
- Measure surface expression of CD3.
- Measure transcription factor binding to response elements.
- Measure the activity of the Zap-70 kinase.
- Measure the expression of co-receptors.
- Measure the expression of the TCR.
Measure the activity of the Zap-70 kinase.
