hemopoiesis[med]
TRANSCRIPT
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Prasit Chanarat Clinical microscopy AMS. CMU.
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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
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Whole Blood
• Fluid - Plasma • Cell - WBC (Leukocytes) - Platelets (Thrombocytes) - RBC (Erythrocytes)• Clotted blood ----- Serum• Anticoagulated blood ----- Plasma• Fibrinogen ----(thrombin)-> Fibrin• Antocoagulants : EDTA, Heparin• EDTA : removes Ca+2
• Heparin : neutralizes thrombin
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Plasma
• Protein : Albumin, Globulin (alpha-1, alpha-2, Beta, gamma), fibrinogen, clotting factors (Coagulation factors)• Amino acids, peptides, glucose, lipids, lactic acid, enzymes, vitamins, hormones, BUN, uric acid, creatinine, electrolytes (Na+, K+, Ca+2, Mg+2, Ci-, HCO
3-, SO4
-2, etc.)
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Hemopoiesis
Hemapoiesis (Hematopoiesis) Hemo = Hemato = Blood Poiesis = Production
Hemopoiesis system Bone marrow, spleen, liver, thymus, lymphnode
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Hematopoiesis Production and
Development of Blood Cells Pluripotent Stem Cell - Continuous Self-
Replication- Gives Rise to All Blood Cell Lines
Growth Factors (Cytokines) - Promote Differentiation Into Mature Blood Elements
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Hemopoiesis Phases
1. Embryonic or prenatal phase - mesoblastic peroid - hepatic period - myeloid period
2. Post-natal phase - medullary hemopoiesis - extramedullary hemopoiesis
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Hemopoiesis
PHSC CSC Diff. Compartment Circulation
<------ Proliferation ---------------------> Differentiation --------------------> Maturation -----------------------> Release ------------------------->
PHSC = Pluripotent hemopoietic stem cellsCSC = Committed stem cells
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Theories of Hemopoiesis
I. Monophyletic theory Totipotential stem cells II Polyphyletic theory Dualists Trialists Polyphyletists
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Stem Cells and theirTherapeutic Potential
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What are “stem cells”?
Stem cells
Embryonic Adult
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The defining properties of a stem cell
- It is not terminally differentiated.
- It can divide without limit.
- When it divides, the daughter cell has 2 “choices”:
• Remain a stem cell.
• Terminally differentiate.
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Varying Potentials of Stem Cells:
– Totipotent cells. Fertilized oocyte (zygote) & progeny of the first two cell divisions. Cells able to form the whole organism.
– Pluripotent cells. Obtained from the inner cell mass of the blastocyst, able to differentiate into almost all cells of the three germ layers – but not into an embryo.
– Multipotential cells. Found in most tissues, these cells can produce a limited range of differentiated cell lineages appropriate to their location (e.g., Hematopoietic stem cells from the bone marrow).
– Unipotential cells. Cells capable of generating only one cell type (epidermal stem cells, adult liver stem cells).
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Leukopoiesis
Objective:
1. Classification of WBC
2 . Leukopoiesis
2 1. Granulopoiesis
2 2. Monopoiesis
2 3. Lymphopoiesis
2 4. P lasmopoiesis
3. Factors affecting leukopoiesis
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Classification of WBC
1. Shape of the nucleus
11. mononuclear : Lymphocyte, Monocyte
1 2. Polymorphonuclear : PMN, Eos, Baso
2. Granules
2 1. Granulocytes : PMN, Eos, Baso
22. Agranulocyte : Lymphocyte, Monocyte
3. Site of origin
Myeloid cells / Lymphoid cells
4. Function / Phagocyte :
- Macrophage Monocyte
- Microphage PMN
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Leukopoiesis Study
1. Morphology
2 . Biochemical markers
3 . Immunological markers
4 . Gene markers
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Stage of Granulopoiesis
Stem cell
Myeloblast
Promyelocyte
Basophilic Neutrophilic Eosinophilic
Myelocyte Myelocyte Myelocyte
Metamyelocyte Metamyelocyte Metamyelocyte
Band Band Band
Basophil Neutrophil (PMN) Eosinophil
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Regulation of Neutrophil Production
Bone Marrow Blood stream Tissue
Proliferatrion Circulating Move freely
compartment compartment
Storage Marginating Move
compartment compartment restricted
(( ((( (( ((((((((((
( (((((( (((((((
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Neutropenia : PMN decrease
Neutrophilia : PMN increase
- -Cytokine : Multi CSF (IL 3)
-GM CSF
-G CSF
-(6
Granulopoietin (Granulocytic
growth factor)
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Eosinophilia : Eos. increase
-Cytokine : IL 3
-5IL
( ( -( ((
- ECF A (Eosinophilic chemotactic factor of anaphylaxis)
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((((( ((((((((: .
-Cytokine : GM CSF
-4IL
-9IL
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Monopoiesis
Stem cell
Monoblast
Promonocyte
Monocyte
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Monocytosis : Monocyte increase
-Cytokine : IL 3
-GM CSF
-M CSF
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Tissue macrophage
Osteoclast : Bone
Macrophage : Lymphoid tissue
( (((((( (((( ( ((((( Microglia cell : Brain
Serosal macrophage : Pleural cavity
Alveolar macrophage : Lung
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Lymphopoiesis
Within thymus : is not antigen dependent
• Within lymphnode / spleen : mediated by
antigen stimulation
- molecular nature of antigen
- antigen dose
- circulating antibody levels
- handling ofantigen by RE cells
- - proliferation of thymus derived cells
- thymic humoral factors
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Central Lymphoid Peripheral Lymphoid
(((( (( (-((( (( ( ( (
Stem Th Ts
cel l s
- Bursal B lymph Plasma cell
equivalent
( ( (
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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)
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Biochemical marker
Thymocyte
-Stage I II III T cell
-TdT ++ ++ +
(( ( ( ( ( ( ( ( ( ( PNP + + ++ ++
dCK +++ + + +
- 5 ’ + + / + + + +
Tdt = Terminal deoxytransferase; ADA = Adenosine deaminase; PNP = Purine nucleoside phosphorylase
; -dCK = Deoxycytidine kinase; 5’NT = 5’ Nucleotidase
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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 ------------------- 3 mRNA --------------------------Cytoplasmic --------------------3
Surface -----------3CD /TCR
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Stage of Human B-cell
Stem cell
Pre-B
Resting
Activated
Proliferating
Differentiating
Secretory
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Plasmopoiesis
B-cell
Plasmoblast (Plasmablast)
Proplasmocyte (Proplasmacyte)
Plasma cell
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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
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Factors Affecting Lymphopoiesis
• Age
• Diet
• - Steroid Testosterone
• Thyroxine
• Thymosine
• - Infection Viral
- - Bacterial Pertussis
- - Chronic disease TB
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Factors Affecting Lymphopoiesis
• Age
• Diet
• - Steroid Testosterone
• Thyroxine
• Thymosine
• - Infection Viral
- - Bacterial Pertussis
- - Chronic disease TB
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Erythroid Maturation Sequence
Proerythroblast(Pronormoblast)
BasophilicNormoblast
PolychromatophilicNormoblast
OrthochromatophilicNormoblast
Reticulocyte
Erythrocyte
Early Intermediate Late
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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
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Hemopoietic growth factors
• A family of hormones• As cytokines• Regulatation - proliferation - differentiation - maturation of progenitor cells - survival and function of mature cells• Hemopoietin
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Cytokines
• Produced by - monocyte - fibroblast - lymphocyte - endothelial cells• Act several target cells - fibroblast - hemopoietic cell - lymphoid cell - hepatocyte - endocrine cell
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Cytokines Family
• Interferons - - - -IFN alpha, IFN beta, IFN gamma• Interleukins - - - - - -IL 1, IL 2, IL 3, IL 4, ……. IL 15• CSF (Colony stimulating factors) - - - - G CSF, GM CSF, M CSF, EPO• Growth factors - - - - - - -TGF beta 1 , TGF beta 2 , …. TFG beta5
- EGF, FGF ( T = transforming, E = epidermal, F = fibroblast)
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Cellular Cytokines Production (1)
• Endothelial cells - GM-CSF, G-CSF, M-CSF, IL-6• Macrophage - GM-CSF, G-CSF, M-CSF, IL-3, IL-6, EPO, SCF • T cells - GM-CSF, IL-2, IL-3, IL-4, IL-5• Fibroblast - GM-CSF, G-CSF, M-CSF, IL-6, SCF
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Cellular Cytokines Production (2)
• NK cells - GM-CSF• PMN - G-CSF, GM-CSF • B cells - GM-CSF, M-CSF, IL-2, IL-5, IL-6 • Marrow stroma - GM-CSF, G-CSF, M-CSF, IL-6, IL-3, SCF, IL-11• Renal parenchyma, Liver, Bone marrow - EPO
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Control Mechanism of Hemopoiesis
Depend on1. Nature cells2.Humoral factors : EPO, Granulopoietin, thrombopoietin, CSF, GM-CSF, IL-1, Cytokines, etc.3. Cell-cell interaction4. Pharmacologic substances : Chalone (inhibit stem cells)
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