Readings | A Double-Edged Sword: Cellular Immunity in Health and Disease | Biology

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 transcription 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

WEEK #

TOPICS

READINGS

Class introduction

No readings

Development of immune cells

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.

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.

T cells: Th2 and cytotoxic T cells

See the Lecture Summary

Zheng, W., and Flavell, R.A. (1997). The transcription 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Field trip

No readings

Oral presentations

No readings