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Haemopoiesis

Haemopoiesis. Maj Gen Dr Muhammad Ayyub MBBS, PhD (London), MRCPath (London), FRCPath (UK) Prof & HOD AM College. Blood cells have limited lifespans, and need to be replaced. with precisely matching numbers -. Hematocytopoiesis.

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Haemopoiesis

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  1. Haemopoiesis Maj Gen Dr Muhammad Ayyub MBBS, PhD (London), MRCPath (London), FRCPath (UK) Prof & HOD AM College

  2. Blood cells have limited lifespans, and need to be replaced with precisely matching numbers - Hematocytopoiesis Young replacing cells come, by manydivisionsand steps ofdifferentiation, fromstem cells stem cell HEMATOPOIESIS

  3. Cell hierarchy (Haemopoiesis schematic representation)

  4. HEMATOPOIESIS Subdivisions Lym PMN stem cell Eos Bas Mon RBC Pla Lymphopoiesis { Granulopoiesis Monocytopoiesis Myelopoiesis Erythropoiesis Megakaryopoiesis Thrombopoiesis

  5. HEMATOPOIESIS Lineages for Lymphopoiesis stem cell Monocytopoiesis Pluripotent stem cell (Hemocytoblast) Granulopoiesis Erythropoiesis Thrombopoiesis Pro-erythroblast Lymphoblast Monoblast Myeloblast Megakaryoblast Basophilic erythroblast Pro-Myelocyte Polychromatic erythroblast Myelocyte Orthocromatic erythroblast Metamylelocyte Reticulocyte Megakaryocyte Band granulocyte Lymphocyte RBC Platelets Granulocyte Monocyte

  6. FURTHER DIFFERENTIATIONS Similar precursor produces Natural killer cells Lym { B lymphocytes become Plasma cells PMN Granulopoiesis Eos Similar precursor produces Mast cells Bas Monocyte or a related precursor gives rise to many specialized phagocytes & antigen-presenting cells Monocytopoiesis Mon Erythropoiesis Macrophages Kupffer cells Langerhans cells Dendritic cells Microglia Osteoclasts etc RBC Megakaryopoiesis Pla Thrombopoiesis

  7. Sites of Haemopoiesis • Yolk sac • Liver and spleen • Bone marrow • Gradual replacement of active (red) marrow by tissue inactive (fatty) • Expansion can occur during increased need for cell production

  8. BLOOD IS MADEIN THE BONE MARROW • Axial skeleton • Inner spongy bone • Bone marrow is in the holes • Bone marrow is a highly organized / regulated organ DMM00_B3.ppt

  9. BONE MARROW: THE SOURCE OF BLOOD AND OUR IMMUNE SYSTEM • All blood cells arise from “mother” (stem) cells • Self renewing • Safe from harm • Pluripotent • Blood production is highly regulated • Messages from the body (e.g. erythropoietin from kidney) • Microenvironments produce specific cells • Cytokines (SCF, IL3) • Growth factors (G-CSF) Normal bone marrow BAS03_20.ppt

  10. B Lymphocyte Pre-B T Lymphocyte Grans / Monos CFU- GEMM PSC Erythrocytes BFU-E CFU-E Platelets Mega SCHEMATIC OF HEMATOPOIESIS RES03_3.ppt

  11. Introduction • Limited Life span of : • Granulocytes • Erythrocytes • Platelets • Lymphocytes

  12. Introduction • Stem cells • Self renewal • Plasticity • Progenitor cells • Developmentally-restricted cells • Mature cells • Mature cell production takes place from the more developmentally-restricted progenitors

  13. Stemcells • Self-renewal • Normally in G0 phase of cell cycle • The capacity for self-reproduction is vastly in excess of that required to maintain cell production for normal lifetime • As cells increase in number they differentiate as well • Multipotentiality • Capacity to generate cells of all the lymphohaemopoietic lineages

  14. Progenitor cells • Encompasses from immediate progeny of stem cells to differentiation cells committed to one lineage • Progenitor cells become progressively more restricted in their differentiation and proliferation capacity • Late progenitor cells eventually restricted to one lineage

  15. Regulation of Haemopoiesis Controlled cell production Controlled cell death • There should be a balance between cell production and cell death except at the times of requirement

  16. Regulation of Haemopoiesis

  17. Interaction of stromal cells, growth factors and haemopoietic cells

  18. Local and Humoral regulation of Haemopoiesis

  19. Haemopoietic growth factors • GM-CSF • Granulocyte-Macrophage colony stimulating factor • M-CSF • Macrophage colony stimulating factor • Erythropoietin • Erythropoiesis stimulating hormone (These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation) • Thrombopoietin • Stimulates megakaryopoiesis

  20. Haemopoietic growth factors • Cytokines • IL 1 (Interleukin 1) • IL 3 • IL 4 • IL 5 • IL 6 • IL 9 • IL 11 • TGF-β • SCF (Stem cell factor, also known as kit-ligand) Cytokines have no (e.g IL-1) or little (SCF) capacity to stimulate cell proliferation on their own, but are able to synergise with other cytokines to recruit nine cells into proliferation

  21. Lymphoid Progenitor Cell T Lymphocyte LPC B Lymphocyte Megakaryocyte CFU-Meg CommittedStem Cell CSC Platelets PSC Pluripotent Stem Cell BFU-E CFU-E RBC Colony-forming Unit - Erythroid Myeloid Progenitor Cell MPC Monocyte CFU-M Colony-forming Unit -Monocyte CFU-G Neutrophil CFU-GM Colony-forming Unit - Monocyte.Granulocyte CFU-Eo Eosinophil HEMATOPOIESIS Early lineages CFU-Mast Basophil

  22. Lymphoid Progenitor Cell T Lymphocyte LPC B Lymphocyte Megakaryocyte CFU-Meg CommittedStem Cell TPO CSC Platelets PSC Pluripotent Stem Cell SCF IL-1 BFU-E EPO * CFU-E RBC Myeloid Progenitor Cell MPC Monocyte CFU-M M-CSF * * * IL-3, GM-CSF CFU-G G-CSF Neutrophil CFU-GM * Colony-forming Unit - Monocyte.Granulocyte CFU-Eo Eosinophil IL-6 HEMATOPOIESISGrowth factors CFU-Mast Basophil IL-3

  23. Erythropoiesis and erythrocytes • Lifespan – 120 days • Non nucleated • Biconcave disc • Production regulated by Epo • Needs Fe, B12, folate & other elements for development

  24. ERYTHROPOIESIS In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages and into less easily detected early stages * * stem cell RBC NORMOBLAST basophilic polychromatophilic ERYTHROBLAST orthochromatophilic -blast is the common suffix for an immature form of a cell

  25. ERYTHROPOIESIS stem cell RBC NORMOBLAST basophilic polychromatophilic ERYTHROBLAST orthochromatophilic polychromatophilic because, in the cell, orange-staining hemoglobin is accumulating, while the blue ribosomes necessary for its synthesis are present, but declining This idea continues in the form of the reticulocyte which is an RBC released to the blood, but still with a network of blue ribosomal material persisting amongst the hemoglobin

  26. ERYTHROPOIESIS 2 In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages and into less easily detected early stages stem cell Pluripotent Stem Cell PSC Committed Stem Cell CSC Myeloid Progenitor Cell Used for some specialization, but more for massive cell division, as conveyed by “burst” Burst-forming Unit - Erythroid MPC BFU-E ERYTHROBLAST

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