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Created page with '<p>Leukopoiesis is the process of formation of leukocytes (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotenti…'
<p>Leukopoiesis is the process of formation of [[Leukocytes|leukocytes]] (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells ([[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-L]]). </p>
<p>[[Leukocytes|Leukocytes]] developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]] and [[Leukocytes|leukocytes]] developing from [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-L]]'s are lymphocytes (T & B cells, dendritic and NK cells).</p>
[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Granulopoiesis==
All granulocytes develop from the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|<p>[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]</p><sup>©RVC 2008</sup>
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Factors
|<p>GM-CSF</p><p>Il-3</p><p>M-CSF</p>
|<p>GM-CSF</p><p>Il-3</p><p>G-CSF</p>
|valign="top"|<p>GM-CSF</p><p>Il-3</p>
|<p>GM-CSF</p><p>Il-3</p><p>Il-5</p>
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
<Br clear="left">
===[[Neutrophils|Neutrophils]]===
Under the stimulation of GM-CSF, G-CSF and Il-3 the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-G]].
====Stages====
=====Myeloblast=====
Large cell with a large nucleus and stains basophilic. Same stage exists for all granulocytes.
=====Promyelocyte=====
During this stage primary (azurophilic) granules are formed. Same stage exists for all granulocytes.
=====Neutrophilic myelocyte=====
Developing neutrophil can now be differentiated from basophils and eosinophils as specific granules are now being formed.
=====Neutrophilic metamyelocyte=====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer between other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.
=====Band cell=====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
=====Neutrophil=====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
<br>
===[[Basophils|Basophils]]===
Under the stimulation of GM-CSF and Il-3 the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-Ba]].
====Stages====
===== Myeloblast & Promyelocyte=====
These stages are common to all granulocytes and no distinction can be made between different cell lines. See [[#Stages|neutrophil stages]] for further information.
=====Basophilic myelocyte & metamyelocyte=====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
=====Basophil=====
Final nuclear shape is masked by high density of granules.
<br>
===[[Eosinophils|Eosinophils]]===
Under the stimulation of GM-CSF, Il-3 and Il-5 the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-Eo]].
====Stages====
===== Myeloblast & Promyelocyte=====
These stages are common to all granulocytes and no distinction can be made between different cell lines. See [[#Stages|neutrophil stages]] for further information.
=====Eosinophilic myelocyte & metamyelocyte=====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
=====Eosinophil=====
Mature cell has a bilobed nucleus.
<br>
==Monocyte development==
[[Monocytes|Monocytes]] develop from the same precursor as [[Neutrophils|neutrophils]] the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages===
====Monoblast====
First stage after cell has differentiated into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing (acting as a reservoir).
====[[Monocytes|Monocyte]]====
Monocytes are incapable of mitosis and enter circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm.
====[[Macrophages|Macrophage]]====
Once the monocyte has entered tissue it differentiates into a [[Macrophages|macrophage]].
===Dendritic cells===
Develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature dendritic cell under stimulation of TNF-α.
<br>
==Lymphopoiesis==
<p>[[Lymphocytes|Lymphocytes]] develop from the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-L]]'s. Those destined to become [[Lymphocytes#T cells|T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[Lymphocytes#B cells|B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and GALT or proliferate directly from the [[Bone Marrow - Anatomy & Physiology|bone marrow]].</p><p>Follow these links for a more detailed explanation on [[T cell differentiation - WikiBlood|T cell development]] and [[B cell differentiation - WikiBlood |B cell development]].</p>
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|<sup>▼Il-7 & Il-11</sup>
|colspan="3" style="background-color:#e6e6fa"|<sup>▼Il-7 & SCF</sup>
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|<sup>▼Il-3 & Il-7</sup>
|style="background-color:#e6e6fa"|<sup>▼Il-7</sup>
|style="background-color:#e6e6fa"|<sup>▼Il-2, IL-12 & Il-18</sup>
|style="background-color:#e6e6fa"|<sup>▼Il-3, Il-6, GM-CSF & SCF</sup>
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!<p>Maturation</p>site
|style="background-color:#ffffcc"|<p>Bone marrow, spleen or GALT</p>Cloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|<p>'''B cell'''</p><p>▼(Antigen stim.)</p>'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|<p>'''T Cell'''</p><p><sup>Helper</sup></p><p><sup>Cytotoxic</sup></p><p><sup>Regulatory</sup></p>
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
<p>'''Note:'''
*That between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into it's different forms (helper, cytotoxic and T cell with regulator functions) is under stimulation by Il-10 & TNF-γ</p>
==Links==
[[Lymphoreticular System - Anatomy & Physiology|Lymphoreticular System]]
[[Immunology - WikiBlood|Immunology]]
[[Leukocytes|Leukocytes]]
<p>[[Leukocytes|Leukocytes]] developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]] and [[Leukocytes|leukocytes]] developing from [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-L]]'s are lymphocytes (T & B cells, dendritic and NK cells).</p>
[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Granulopoiesis==
All granulocytes develop from the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|<p>[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]</p><sup>©RVC 2008</sup>
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Factors
|<p>GM-CSF</p><p>Il-3</p><p>M-CSF</p>
|<p>GM-CSF</p><p>Il-3</p><p>G-CSF</p>
|valign="top"|<p>GM-CSF</p><p>Il-3</p>
|<p>GM-CSF</p><p>Il-3</p><p>Il-5</p>
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
<Br clear="left">
===[[Neutrophils|Neutrophils]]===
Under the stimulation of GM-CSF, G-CSF and Il-3 the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-G]].
====Stages====
=====Myeloblast=====
Large cell with a large nucleus and stains basophilic. Same stage exists for all granulocytes.
=====Promyelocyte=====
During this stage primary (azurophilic) granules are formed. Same stage exists for all granulocytes.
=====Neutrophilic myelocyte=====
Developing neutrophil can now be differentiated from basophils and eosinophils as specific granules are now being formed.
=====Neutrophilic metamyelocyte=====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer between other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.
=====Band cell=====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
=====Neutrophil=====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
<br>
===[[Basophils|Basophils]]===
Under the stimulation of GM-CSF and Il-3 the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-Ba]].
====Stages====
===== Myeloblast & Promyelocyte=====
These stages are common to all granulocytes and no distinction can be made between different cell lines. See [[#Stages|neutrophil stages]] for further information.
=====Basophilic myelocyte & metamyelocyte=====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
=====Basophil=====
Final nuclear shape is masked by high density of granules.
<br>
===[[Eosinophils|Eosinophils]]===
Under the stimulation of GM-CSF, Il-3 and Il-5 the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GEMM]] differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-Eo]].
====Stages====
===== Myeloblast & Promyelocyte=====
These stages are common to all granulocytes and no distinction can be made between different cell lines. See [[#Stages|neutrophil stages]] for further information.
=====Eosinophilic myelocyte & metamyelocyte=====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
=====Eosinophil=====
Mature cell has a bilobed nucleus.
<br>
==Monocyte development==
[[Monocytes|Monocytes]] develop from the same precursor as [[Neutrophils|neutrophils]] the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages===
====Monoblast====
First stage after cell has differentiated into the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing (acting as a reservoir).
====[[Monocytes|Monocyte]]====
Monocytes are incapable of mitosis and enter circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm.
====[[Macrophages|Macrophage]]====
Once the monocyte has entered tissue it differentiates into a [[Macrophages|macrophage]].
===Dendritic cells===
Develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature dendritic cell under stimulation of TNF-α.
<br>
==Lymphopoiesis==
<p>[[Lymphocytes|Lymphocytes]] develop from the [[Overview of Haematopoiesis - WikiBlood#Colony Forming Units|CFU-L]]'s. Those destined to become [[Lymphocytes#T cells|T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[Lymphocytes#B cells|B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and GALT or proliferate directly from the [[Bone Marrow - Anatomy & Physiology|bone marrow]].</p><p>Follow these links for a more detailed explanation on [[T cell differentiation - WikiBlood|T cell development]] and [[B cell differentiation - WikiBlood |B cell development]].</p>
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|<sup>▼Il-7 & Il-11</sup>
|colspan="3" style="background-color:#e6e6fa"|<sup>▼Il-7 & SCF</sup>
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|<sup>▼Il-3 & Il-7</sup>
|style="background-color:#e6e6fa"|<sup>▼Il-7</sup>
|style="background-color:#e6e6fa"|<sup>▼Il-2, IL-12 & Il-18</sup>
|style="background-color:#e6e6fa"|<sup>▼Il-3, Il-6, GM-CSF & SCF</sup>
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!<p>Maturation</p>site
|style="background-color:#ffffcc"|<p>Bone marrow, spleen or GALT</p>Cloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|<p>'''B cell'''</p><p>▼(Antigen stim.)</p>'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|<p>'''T Cell'''</p><p><sup>Helper</sup></p><p><sup>Cytotoxic</sup></p><p><sup>Regulatory</sup></p>
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
<p>'''Note:'''
*That between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into it's different forms (helper, cytotoxic and T cell with regulator functions) is under stimulation by Il-10 & TNF-γ</p>
==Links==
[[Lymphoreticular System - Anatomy & Physiology|Lymphoreticular System]]
[[Immunology - WikiBlood|Immunology]]
[[Leukocytes|Leukocytes]]