Haemopoiesis Blood cells have limited lifespans, and need

Haemopoiesis Blood cells have limited lifespans, and need

Haemopoiesis Blood cells have limited lifespans, and need to be replaced with precisely matching numbers Hematocytopoiesis Young replacing cells come, by many divisions and steps of differentiation, from stem cells stem cell HEMATOPOIESIS Cell hierarchy (Haemopoiesis schematic representation) HEMATOPOIESIS

Subdivisions Lymphopoiesis stem Lym { Granulopoiesis cell Myelopoiesis Monocytopoiesis Erythropoiesis Megakaryopoiesis Thrombopoiesis

PMN Eos Bas Mon RBC Pla HEMATOPOIESIS Lineages for stem cell Pluripotent stem cell (Hemocytoblast)

Lymphopoiesis Monocytopoiesis Granulopoiesis Erythropoiesis Thrombopoiesis Lymphoblast Monoblast Myeloblast Pro-Myelocyte Lymphocyte Monocyte Pro-erythroblast Basophilic

erythroblast Myelocyte Polychromatic erythroblast Metamylelocyte Orthocromatic erythroblast Band granulocyte Reticulocyte Granulocyte Megakaryoblast

RBC Megakaryocyte Platelets Lym { Granulopoiesis Monocytopoiesis Erythropoiesis Megakaryopoiesis Thrombopoiesis

FURTHER DIFFERENTIATIONS Similar precursor produces Natural killer cells PMN B lymphocytes become Plasma cells Eos Bas Mon RBC Pla Similar precursor

produces Mast cells Monocyte or a related precursor gives rise to many specialized phagocytes & antigen-presenting cells Macrophages Kupffer cells Langerhans cells Dendritic cells Microglia Osteoclasts etc 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 BLOOD IS MADE IN 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 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 Normal bone marrow Cytokines (SCF, IL3) Growth factors (G-CSF) BAS03_20.ppt SCHEMATIC OF

HEMATOPOIESIS B Lymphocyte Pre-B T Lymphocyte Grans / Monos PSC CFUGEMM Erythrocytes BFU-E CFU-E Platelets Mega RES03_3.ppt

Introduction Limited Life span of : Granulocytes Erythrocytes Platelets Lymphocytes Introduction Stem cells Self renewal Plasticity Progenitor cells

Developmentally-restricted cells Mature cells Mature cell production takes place from the more developmentally-restricted progenitors Stem cells 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 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 Regulation of Haemopoiesis Controlled cell death Controlled cell production There should be a balance between cell production and cell death except at the times of requirement

Regulation of Haemopoiesis Local environmental control Stromal cell mediated Haemopoiesis Apoptosis Haemopoietic growth factors (Humoral regulation) Interaction of stromal cells, growth factors and haemopoietic cells Local and Humoral regulation of Haemopoiesis 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 Haemopoietic growth factors Cytokines

IL 1 (Interleukin 1) IL 3 IL 4 IL 5 IL 6 IL 9 IL 11 TGF- 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 Lymphoid Progenitor

LPC Cell T Lymphocyte Megakaryocyte B Lymphocyte CFU-Meg CSC Committed PSC Stem Cell Pluripotent Stem Cell Platelets

BFUE CFUE Colony-forming RBC Unit - Erythroid Myeloid MPC Progenitor Cell CFUM Colony-forming Monocyte Unit -Monocyte CFUGM

Colony-forming Unit Monocyte.Granulocyte HEMATOPOIESIS Early lineages CFUG Neutrophil CFUEo Eosinophil CFUMast Basophil Lymphoid

Progenitor LPC Cell T Lymphocyte Megakaryocyte CFU-Meg CSC Committed PSC Stem Cell Pluripotent SCF Stem Cell IL-1 Myeloid MPC Progenitor

Cell * IL-3, GM-CSF * * CFUGM Colony-forming Unit Monocyte.Granulocyte HEMATOPOIESIS Growth factors TPO BFUE

CFUM * * EPO CFUE CFUG CFUEo CFUMast M-CSF G-CSF IL-6

IL-3 B Lymphocyte Platelets RBC Monocyte Neutrophil Eosinophil Basophil Erythropoiesis and erythrocytes

Lifespan 120 days Non nucleated Biconcave disc Production regulated by Epo Needs Fe, B12, folate & other elements for development 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 basophilic NORMOBLAST polychromatophilic ERYTHROBLAST orthochromatophilic -blast is the common suffix for an immature form of a cell ERYTHROPOIESIS stem cell RBC

basophilic ERYTHROBLAST NORMOBLAST polychromatophilic 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 ERYTHROPOIESIS 2 stem cell

PSC 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 Pluripotent Stem Cell Committed Stem Cell CSC Myeloid Progenitor Cell Used for some specialization, Burst-forming Unit but more for MPC Erythroid massive cell division, as

BFU-E conveyed by burst ERYTHROBLAST

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