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Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology Summer Project 2004

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Page 1: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Hematopoiesisfrom pluripotent stem cells to

mature, differentiated, cellular effectors of immunity

and moreRichard A. Poirier for HHMI/Harvard Immunology Summer Project 2004

Page 2: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click on one of the following effector cells to see the sequence of different cells that lead to its production

• Th- Helper Cell• B Cell• Macrophage• Neutrophil (alternative path)

• Mast Cell• Platelets

• Tc Cytotoxic Cell• Dendritic Cell• Neutrophil• Eosinophil• Basophil• Erythrocyte

Page 3: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

T - helper cell pathway

Page 4: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 5: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Lymphoid Stem CellDaughter cell of the Pluripotent Stem Cell, this cell will divide to produce progenitors to either B cell or

T cell lines.

Page 6: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

T cell progenitor leaves the bone marrow and settles in the thymus; will produce Thymocyte cells in the thymus which can, in turn differentiate

into T helper cells, T killer cells, or T memory cells

Page 7: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

The Thymocyte is located in the thymus and divides to produce mature T effector cells…..

Th (helper)Tc (cytotoxic-killer) or Tm (memory)

Page 8: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Th (helper) cell…when activated by an Antigen Presenting Cell like a macrophage with

antigen, the Th cell will induce rapid growth of white blood cells which help fight infection

Page 9: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

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Page 10: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Tc (cytotoxic/”killer”) cell pathway

Page 11: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 12: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Lymphoid Stem CellDaughter cell of the Pluripotent Stem Cell, this cell will divide to produce progenitors to either B cell or

T cell lines.

Page 13: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

T cell progenitor leaves the bone marrow and settles in the thymus; will produce Thymocyte cells in the thymus which can, in turn differentiate

into T helper cells, T killer cells, or T memory cells

Page 14: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

The Thymocyte is located in the thymus and divides to produce mature T effector cells…..

Th (helper)Tc (cytotoxic-killer) or Tm (memory)

Page 15: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Tc (cytotoxic or “killer”) Cells…Sometimes called CTLs (cytotoxic T lymphocytes,

these may recognize infected “self” cells and destroy them.

Page 16: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 17: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

B cell pathway

Page 18: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 19: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Lymphoid Stem CellDaughter cell of the Pluripotent Stem Cell, this cell will divide to produce progenitors to either B cell or

T cell lines.

Page 20: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

B Cell progenitor…found in the bone marrow of higher vertebrates and the Bursa of

Fabricius in birds, these cells will produce antibody producing B cells.

Page 21: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

B Cells… these are found in the blood and , when activated will produce antibodies against particular antigens. Each cell produces antigen

specific antibodies of only one type.

Page 22: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

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Page 23: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Dendritic cell pathway

Page 24: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 25: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 26: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Granulocyte -Monocyte Progenitor cells can differentiate into monocytes or neutrophils

Page 27: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Monocytes… act as antigen presenting cells (APCs), as Antibody-Dependent Cytotoxic Cells

(ADCC) , and promote inflammation.

Page 28: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Dendritic Cell… like the macrophage, this cell is phagocytic it inhabits the tissues looking for

foreign intruders to devour.

Page 29: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 30: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Macrophage pathway

Page 31: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 32: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 33: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Granulocyte -Monocyte Progenitor cells can differentiate into monocytes or neutrophils

Page 34: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Monocytes… act as antigen presenting cells (APCs), as Antibody-Dependent Cytotoxic Cells

(ADCC) , and promote inflammation.

Page 35: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Macrophage…functions as antigen presenting cell (APC), in inflammation, and in

ADCC (antibody-dependent cell-mediated cytotoxicity

Page 36: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 37: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Neutrophil Pathway

Page 38: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 39: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 40: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Granulocyte -Monocyte Progenitor cells can differentiate into monocytes or neutrophils

Page 41: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Monocytes… act as antigen presenting cells (APCs), as Antibody-Dependent Cytotoxic Cells

(ADCC) , and promote inflammation.

Page 42: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Neutrophils…function in antimicrobial activity, inflammation response, and antibody-dependent, cell-mediated cytotoxicity (ADCC)

Page 43: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 44: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Alternative Neutrophil pathway

Page 45: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 46: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 47: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Granulocyte -Monocyte Progenitor cells can differentiate into monocytes or neutrophils

Page 48: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Neutrophils…function in antimicrobial activity, inflammation response, and antibody-dependent, cell-mediated cytotoxicity (ADCC)

Page 49: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 50: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Eosinophil Pathway

Page 51: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 52: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 53: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Eosinophil Progenitor…will produce eosinophils

Page 54: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Eosinophil…these cells are active in the immune response to asthma, allergies, and parasites.

Page 55: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 56: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Mast Cell Pathway

Page 57: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 58: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 59: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Basophil Progenitor… a product of the specialization of Myeloid stem cells, this cell will

produce either Mast Cells or Basophils

Page 60: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Mast Cell…like the related basophils these cells function in inflammation and allergic response. When mature, they become granulated and are found

in tissues, not in peripheral blood.

Page 61: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 62: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Basophil pathway

Page 63: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 64: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 65: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Basophil Progenitor… a product of the specialization of Myeloid stem cells, this cell will

produce either Mast Cells or Basophils

Page 66: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Basophil…this IgE responsive cell is characterized by cytoplasmic granules which, when

released, function in destruction of parasites and also in allergic reactions. The cell releases histamine and

platelet activator and other chemical signals.

Page 67: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 68: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Platelet pathway

Page 69: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 70: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 71: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Megakaryocyte…fragments into subcellular pieces called platelets

Page 72: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Platelets…are blood elements without nuclei that circulate and are involved in blood clotting and

inflammation.

Page 73: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Click HERE to return to menu

Page 74: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Erythrocyte Pathway

Page 75: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Pluripotent Stem CellThis is the undifferentiated precursor to all of the

blood cells, red and white, and other immune effector cells, and platelets.

Page 76: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Myeloid Stem Cells… daughters of the Pluripotent Stem Cells, these are the progenitors of a host of

specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Page 77: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Erythroid Progenitor…derived from a myeloid stem cell, this is destined to produce the

most common blood cell, the erythrocyte.

Page 78: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

Erythrocytes…or red blood cells (RBCs)are enucleated cells that travel throughout the Circulatory System and carry Oxygen to all parts of the body via

the abundant hemoglobin found within them.

Page 79: Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more Richard A. Poirier for HHMI/Harvard Immunology

To learn more about Hematopoiesis click HERE

To see slides of real blood cells, click HERE