2. HEMOPOIESIS Objectives   1. Describe the ontogeny of hemopoiesis 2. Discuss the theories of hemopoiesis 3. Discuss the totipotential stem cells, committed stem cells, progenitor sells, precursor cells 4. Discuss a regulation of hemopoiesis and hemopoietic proliferation 5. Describe composition and function of blood

5. Hemopoiesis Hemapoiesis (Hematopoiesis) Hemo = Hemato = Blood Poiesis = Production Hemopoiesis system Bone marrow, spleen, liver, thymus, lymphnode

7. Hemopoiesis Phases 1. Embryonic or prenatal phase - mesoblastic peroid - hepatic period - myeloid period 2. Post-natal phase - medullary hemopoiesis - extramedullary hemopoiesis

12. Hemopoiesis PHSC CSC Diff. Compartment Circulation <------ Proliferation ---------------------> Differentiation --------------------> Maturation -----------------------> Release -------------------------> PHSC = Pluripotent hemopoietic stem cells CSC = Committed stem cells

13. Theories of Hemopoiesis I. Monophyletic theory Totipotential stem cells II Polyphyletic theory Dualists Trialists Polyphyletists

14. Stem Cells and their Therapeutic Potential

15. What are “stem cells”? Stem cells Embryonic Adult

19. Leukopoiesis Objective: 1. Classification of WBC 2. Leukopoiesis 2.1 Granulopoiesis 2.2 Monopoiesis 2.3 Lymphopoiesis 2.4 Plasmopoiesis 3. Factors affecting leukopoiesis

20. Classification of WBC 1. Shape of the nucleus 1.1 mononuclear : Lymphocyte, Monocyte 1.2 Polymorphonuclear : PMN, Eos, Baso 2. Granules 2.1 Granulocytes : PMN, Eos, Baso 2.2 Agranulocyte : Lymphocyte, Monocyte 3. Site of origin Myeloid cells / Lymphoid cells 4. Function / Phagocyte : Macrophage - Monocyte Microphage - PMN

21. Leukopoiesis Study 1. Morphology 2. Biochemical markers 3. Immunological markers 4. Gene markers

22. Stage of Granulopoiesis Stem cell Myeloblast Promyelocyte Basophilic Neutrophilic Eosinophilic Myelocyte Myelocyte Myelocyte Metamyelocyte Metamyelocyte Metamyelocyte Band Band Band Basophil Neutrophil (PMN) Eosinophil

23. Regulation of Neutrophil Production Bone Marrow Blood stream Tissue Proliferatrion Circulating Move freely compartment compartment Storage Marginating Move compartment compartment restricted (Area of infection) Release control

24. Neutropenia : PMN decrease Neutrophilia : PMN increase Cytokine : Multi-CSF (IL-3) GM-CSF G-CSF IL-6 Granulopoietin (Granulocytic growth factor)

25. Eosinophilia : Eos. increase Cytokine : IL-3 IL-5 GM-CSF ECF-A (Eosinophilic chemotactic factor of anaphylaxis)

26. Basophilia : Baso. increase Cytokine : GM-CSF IL-4 IL-9

27. Monopoiesis Stem cell Monoblast Promonocyte Monocyte

28. Monocytosis : Monocyte increase Cytokine : IL-3 GM-CSF M-CSF

29. Tissue macrophage Osteoclast : Bone Macrophage : Lymphoid tissue Kupffer cell : Liver Microglia cell : Brain Serosal macrophage : Pleural cavity Alveolar macrophage : Lung

31. Central Lymphoid Peripheral Lymphoid Thymus T-lymph CMI Stem Th Ts cells Bursal B-lymph Plasma cell equivalent HMI

32. Stage of T-cell differentiation Thymic cortex - Stage I (Early thymocyte) - Stage II (Common thymocyte) Thymic medulla - Stage III (Late thymocyte) Peripheral blood - Mature cell - Activated T-cell (See picture of Immunophenotype of Ontogeny T-cell)

33. Biochemical marker Thymocyte Stage I II III T-cell TdT ++ ++ + - ADA ++ ++ ++ ++ PNP + + ++ ++ dCK +++ + + + 5’NT + +/- ++ ++ Tdt = Terminal deoxytransferase; ADA = Adenosine deaminase; PNP = Purine nucleoside phosphorylase; dCK = Deoxycytidine kinase; 5’NT = 5’-Nucleotidase

34. Molecular Marker Thymocyte Stage I II III T-cell TCR- beta rearr. -------------------------- TCR- beta mRNA ------------------- TCR -gamma gene rearr. -------------------------- TCR -gamma mRNA --------- TCR -alpha mRNA ------------------- CD3 mRNA -------------------------- Cytoplasmic CD3 -------------------- Surface CD3/TCR -----------

35. Stage of Human B-cell Stem cell Pre-B Resting Activated Proliferating Differentiating Secretory

36. Plasmopoiesis B-cell Plasmoblast (Plasmablast) Proplasmocyte (Proplasmacyte) Plasma cell

37. Lymphocyte Growth Factor Cytokine Cell Function IL-1 Monocyte T-cell activation IL-2 T-cell Proliferation of activated T-cell IL-3 T-cell For T-cell subset and myeloid cell BGCF T-cell For B-cell BCDF T-cell For B-cell Ig synthesis

43. Erythroid Maturation Sequence Proerythroblast (Pronormoblast) Basophilic Normoblast Polychromatophilic Normoblast Orthochromatophilic Normoblast Reticulocyte Erythrocyte Early Intermediate Late

44. Hemopoietic progenitor cells CFU-GEMM (Granulocyte, erythrocyte, monocyte, megakaryocyte) CFU-GM (Granulocyte, monocyte) CFU-Eo (Eosinophil) CFU-Baso (Basophil) CFU-Meg (Megakaryocyte) BFU-E (Erythrocyte) CFU-E (Erythrocyte) CFU = Colony forming unit; BFU = Burst forming unit

50. Control Mechanism of Hemopoiesis Depend on 1. Nature cells 2.Humoral factors : EPO, Granulopoietin, thrombopoietin, CSF, GM-CSF, IL-1, Cytokines, etc. 3. Cell-cell interaction 4. Pharmacologic substances : Chalone (inhibit stem cells)

51. THE END