(i) Explain the role of Ras.GTP and Rac.GTP in the formation of active AP-1 during T- cell activation. (ii) Cadmium ions have been shown to be selective blockers of membrane calcium channels. Suppose T lymphocytes are cultured in the presence of cadmium chloride, explain what happens to TCR-triggered signal transduction.

Antigen recognition by T cells in the absence of co-stimulation results in a. upregulation of B7 b. expression of the high-affinity IL-2 receptor c. T-cell anergy d. T-cell apoptosis e. phosphorylation of immunoreceptor tyrosine-based activation motifs.

The first JAK kinase inhibitor to be developed, tofacitinib, inhibits JAK1 and JAK3. These two JAK kinases are required for the signaling pathways induced by multiple cytokines, including all of the receptors that share the cytokine receptor common gamma chain (gc; includes the receptors for IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21), all of the receptors that share gp130 (includes the receptor for IL-6), the receptors for GM-CSF, IL-12, and IL-23, and both type I and type II (i.e., IFN-g) interferon receptors. Tofacitinib has recently been shown to be effective in the treatment of severe rheumatoid arthritis, an autoimmune disease characterized by inflammation of the joints with prominent inflammatory cell infiltrates, autoantibodies, and eventual cartilage and bone destruction. A likely explanation for the therapeutic benefits of tofacitinib in this disease is: Its ability to inhibit the T cell functions that eventually lead to other disease symptoms Its ability to prevent T cell…

During the early developmental stages of α:β T cells in the thymus, there are two key checkpoints that must be satisfied to permit the progression of T-cell development. Explain what occurs at each checkpoint.