GIVE NOW about ocw help & faqs contact us
7.342 | Fall 2018 | Undergraduate

# A Double-Edged Sword: Cellular Immunity in Health and Disease

WEEK # | TOPICS | READINGS
--- | --- | ---

1 | Class introduction See the Lecture Summary | No readings

2 | Development of immune cells See the Lecture Summary | Kondo, M., Weissman, I.L., and Akashi, K. (1997). Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661-672. Schulz, C., Gomez Perdiguero, E., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S.E., Pollard, J.W., Frampton, J., Liu, K.J., and Geissmann, F. (2012). A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336, 86-90.

3 | DNA rearrangements in adaptive immune cells See the Lecture Summary | Schatz, D.G., Oettinger, M.A., and Baltimore, D. (1989). The V(D)J recombination activating gene, RAG-1. Cell 59, 1035-1048. Jain, S., Ba, Z., Zhang, Y., Dai, H.Q., and Alt, F.W. (2018). CTCF-binding elements mediate accessibility of RAG substrates during chromatin scanning. Cell 174, 102-116 e114.

4 | T cells: Th2 and cytotoxic T cells See the Lecture Summary | Zheng, W., and Flavell, R.A. (1997). The transc ription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89, 587-596. Trautmann, L., Janbazian, L., Chomont, N., Said, E.A., Gimmig, S., Bessette, B., Boulassel, M.R., Delwart, E., Sepulveda, H., Balderas, R.S., Routy, J.P., Haddad, E.K., and Sekaly, R.P. (2006). Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nature Medicine 12, 1198-1202.

5 | Cell death and immune processes See the Lecture Summary | Yuan, J., Shaham, S., Ledoux, S., Ellis, H.M., and Horvitz, H.R. (1993). The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75, 641-652. Kayagaki, N., Stowe, I.B., Lee, B.L., O’Rourke, K., Anderson, K., Warming, S., Cuellar, T., Haley, B., Roose-Girma, M., Phung, Q.T., Liu, P.S., Lill, J.R., Li, H., Wu, J., Kummerfeld, S., Zhang, J., Lee, W.P., Snipas, S.J., Salvesen, G.S., Morris, L.X., Fitzgerald, L., Zhang, Y., Bertram, E.M., Goodnow, C.C., and Dixit, V.M. (2015). Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666-671.

6 | Lymphocytes in disease See the Lecture Summary | Erikson, J., ar-Rushdi, A., Drwinga, H.L., Nowell, P.C., and Croce, C.M. (1983). Transcriptional activation of the translocated c-myc oncogene in burkitt lymphoma. Proceedings of the National Academy of Sciences of the United States of America 80, 820-824. Doitsh, G., Galloway, N.L., Geng, X., Yang, Z., Monroe, K.M., Zepeda, O., Hunt, P.W., Hatano, H., Sowinski, S., Munoz-Arias, I., and Greene, W.C. (2014). Cell death by pyroptosis drives CD4 T cell depletion in HIV-1 infection. Nature 505, 509-514.

7 | Th17 cells See the Lecture Summary | Ivanov, II, McKenzie, B.S., Zhou, L., Tadokoro, C.E., Lepelley, A., Lafaille, J.J., Cua, D.J., and Littman, D.R. (2006). The orphan nuclear receptor RORgt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121-1133. McAllister, F., Bailey, J.M., Alsina, J., Nirschl, C.J., Sharma, R., Fan, H., Rattigan, Y., Roeser, J.C., Lankapalli, R.H., Zhang, H., Jaffee, E.M., Drake, C.G., Housseau, F., Maitra, A., Kolls, J.K., Sears, C.L., Pardoll, D.M., and Leach, S.D. (2014). Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia. Cancer Cell 25, 621-637.

8 | T cells (adoptive immune transfer) See the Lecture Summary | Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., and Minato, N. (2002). Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proceedings of the National Academy of Sciences of the United States of America 99, 12293-12297. Eyquem, J., Mansilla-Soto, J., Giavridis, T., van der Stegen, S.J., Hamieh, M., Cunanan, K.M., Odak, A., Gonen, M., and Sadelain, M. (2017). Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543, 113-117.

9 | Autoimmunity See the Lecture Summary | Fontenot, J.D., Gavin, M.A., and Rudensky, A.Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunology 4, 330-336. Wen, L., Ley, R.E., Volchkov, P.Y., Stranges, P.B., Avanesyan, L., Stonebraker, A.C., Hu, C., Wong, F.S., Szot, G.L., Bluestone, J.A., Gordon, J.I., and Chervonsky, A.V. (2008). Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455, 1109- 1113.

10 | Innate lymphoid cells (ILC) See the Lecture Summary | von Moltke, J., Ji, M., Liang, H.E., and Locksley, R.M. (2016). Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529, 221-225. Sui, P., Wiesner, D.L., Xu, J., Zhang, Y., Lee, J., Van Dyken, S., Lashua, A., Yu, C., Klein, B.S., Locksley, R.M., Deutsch, G., and Sun, X. (2018). Pulmonary neuroendocrine cells amplify allergic asthma responses. Science 360.

11 | Macrophages See the Lecture Summary | Brouard, S., Otterbein, L.E., Anrather, J., Tobiasch, E., Bach, F.H., Choi, A.M., and Soares, M.P. (2000). Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. The Journal of Experimental Medicine 192, 1015-1026. Jaiswal, S., Jamieson, C.H., Pang, W.W., Park, C.Y., Chao, M.P., Majeti, R., Traver, D., van Rooijen, N., and Weissman, I.L. (2009). CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 138, 271-285.

12 | Trained immunity See the Lecture Summary | Saeed, S., Quintin, J., Kerstens, H.H., Rao, N.A., Aghajanirefah, A., Matarese, F., Cheng, S.C., Ratter, J., Berentsen, K., van der Ent, M.A., Sharifi, N., Janssen-Megens, E.M., Ter Huurne, M., Mandoli, A., van Schaik, T., Ng, A., Burden, F., Downes, K., Frontini, M., Kumar, V., Giamarellos-Bourboulis, E.J., Ouwehand, W.H., van der Meer, J.W., Joosten, L.A., Wijmenga, C., Martens, J.H., Xavier, R.J., Logie, C., Netea, M.G., and Stunnenberg, H.G. (2014). Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345, 1251086. Kaufmann, E., Sanz, J., Dunn, J.L., Khan, N., Mendonca, L.E., Pacis, A., Tzelepis, F., Pernet, E., Dumaine, A., Grenier, J.C., Mailhot-Leonard, F., Ahmed, E., Belle, J., Besla, R., Mazer, B., King, I.L., Nijnik, A., Robbins, C.S., Barreiro, L.B., and Divangahi, M. (2018). BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176-190 e119.

13 | Emerging technologies in immunology See the Lecture Summary | Bendall, S.C., Simonds, E.F., Qiu, P., Amir el, A.D., Krutzik, P.O., Finck, R., Bruggner, R.V., Melamed, R., Trejo, A., Ornatsky, O.I., Balderas, R.S., Plevritis, S.K., Sachs, K., Pe’er, D., Tanner, S.D., and Nolan, G.P. (2011). Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332, 687-696. Villani, A.C., Satija, R., Reynolds, G., Sarkizova, S., Shekhar, K., Fletcher, J., Griesbeck, M., Butler, A., Zheng, S., Lazo, S., Jardine, L., Dixon, D., Stephenson, E., Nilsson, E., Grundberg, I., McDonald, D., Filby, A., Li, W., De Jager, P.L., Rozenblatt-Rosen, O., Lane, A.A., Haniffa, M., Regev, A., and Hacohen, N. (2017). Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356.

14 | Field trip | No readings

15 | Oral presentations | No readings

## Course Info

##### Instructor

- Dr. Haiting Ma

##### Departments

- Biology

##### As Taught In

Fall 2018

##### Level

Undergraduate

##### Topics

- Health and Medicine
  - Cancer
  - Immunology
- Science
  - Biology
    - Cell Biology

##### Learning Resource Types

assignment Presentation Assignments
assignment Written Assignments

# You are leaving MIT OpenCourseWare

Please be advised that external sites may have terms and conditions, including license rights, that differ from ours. MIT OCW is not responsible for any content on third party sites, nor does a link suggest an endorsement of those sites and/or their content.