1/30/24, 12:41 AM Case Study: T Cell Signaling Defects Case Study: T Cell Signaling Defects Start Assignment Due Monday by 11:59pm Points 20 Submitting a text entry box or a file upload Instructions Case studies provide you with an opportunity to test and refine your diagnostic skills. After reviewing the following case study, answer the ten questions below (not the three questions in the scanned document). You are encouraged to also consult the textbook to help with the answers. R. Geha & L. Notarangelo. "Case Studies in Immunology: A Clinical Companion 7th Edition." Case Studies in Immunology: A Clinical Companion. Garland Science. Case Study 54_T Cell Signaling_.pdf (https://doane.instructure.com/courses/14644/files/2109119?wrap=1) (https://doane.instructure.com/courses/14644/files/2109119/download?download_frd=1) Case Study questions: 1) What are the components of the the T cell receptor (TCR) complex and what is its function? 2) What are the components CD3, and what's its function? 3) Briefly describe the events following the engagement of the T cell receptor (TCR). 4) Which molecules are involved in proximal TCR signaling ? 5) Which molecules involved in downstream signaling events 6) Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes in signal transduction. Referring to Figure 54.1 and its caption, which signaling molecule causes the release of Ca2+ ? 7) Phytohemagglutinin (PHA) is a particularly potent T-cell mitogen (a small molecule usually a peptide that induces mitosis). PHA binds to the T cell receptor (TCR). Phorbol 12-myristate 13-acetate (PMA) and ionomycin is used in vitro to activate T cells to proliferate and synthesize cytokines. PMA activates protein kinase C, while ionomycin is a calcium ionophore (a substance which can transport particular ions across a lipid membrane in a cell). Stimulation with PMA + ionomycin bypasses the T cell membrane receptor complex and will lead to activation of several intracellular signaling pathways, resulting in T cell activation and proliferation. Carmen showed a poor T-cell proliferation in response to stimulation with phytohemagglutinin (PHA) but her T cells proliferated normally in response to phorbol myristic acetate (PMA) combined with ionomycin. Based on the signaling events you have described above-provide an explanation for this. 8) What is ZAP-70?Why was a deficiency of ZAP-70 suspected in Carmen's case? 9) Patients who have mutations in ZAP-70 lack circulating CD8+ T lymphocytes, while CD4+ cells are https://doane.instructure.com/courses/14644/assignments/205677?module_item_id=457985 1/2 1/30/24, 12:41 AM present, but are non-functional. What is the reason for this? 10) What is the prognosis of patients with ZAP-70 deficiency, and what possible therapies are recommended? Case Study: T Cell Signaling Defects https://doane.instructure.com/courses/14644/assignments/205677?module_item_id=457985 2/2

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1/30/24, 12:41 AM Case Study: T Cell Signaling Defects Case Study: T Cell Signaling Defects Start Assignment Due Monday by 11:59pm Points 20 Submitting a text entry box or a file upload Instructions Case studies provide you with an opportunity to test and refine your diagnostic skills. After reviewing the following ca