Difference between revisions of "Leukopoiesis"

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<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 ([[Haematopoiesis#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis#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 [[Haematopoiesis#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''']]
 
[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
 +
==Introduction==
 +
<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 ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]). </p>
 +
<p>Leukocytes developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]].
 +
Leukocytes developing from CFU-Ls are [[:Category:Lymphocytes|lymphocytes]] (T & B cells, dendritic and NK cells).</p>
  
 
==Granulopoiesis==
 
==Granulopoiesis==
−
All granulocytes develop from the [[Haematopoiesis#Colony Forming Units|CFU-GEMM]] cells.
+
All granulocytes develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] cells.
 +
 
 
===Summary of pathways===
 
===Summary of pathways===
−
<div style="text-align: center;">
 
 
{| cellpadding="10" cellspacing="0" border="1" align="left"
 
{| cellpadding="10" cellspacing="0" border="1" align="left"
 
|
 
|
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!Basophil
 
!Basophil
 
!Eosinophil
 
!Eosinophil
−
|rowspan="10"|<p>[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]</p><sup>©RVC 2008</sup>
+
| rowspan="10" |<p>[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]</p><sup>©RVC 2008</sup>
 
|-
 
|-
 
!Stem cell
 
!Stem cell
−
|colspan="4"|CFU-GEMM
+
| colspan="4" |CFU-GEMM
 
|-
 
|-
 
!CFU
 
!CFU
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|CFU-Eo
 
|CFU-Eo
 
|-
 
|-
−
!Factors
+
!Cytokines
−
|<p>GM-CSF</p><p>Il-3</p><p>M-CSF</p>
+
|<p>GM-CSF</p><p>IL-3</p><p>M-CSF</p>
−
|<p>GM-CSF</p><p>Il-3</p><p>G-CSF</p>
+
|<p>GM-CSF</p><p>IL-3</p><p>G-CSF</p>
−
|valign="top"|<p>GM-CSF</p><p>Il-3</p>
+
| valign="top" |<p>GM-CSF</p><p>IL-3</p>
−
|<p>GM-CSF</p><p>Il-3</p><p>Il-5</p>
+
|<p>GM-CSF</p><p>IL-3</p><p>IL-5</p>
 
|-
 
|-
−
!Rowspan="6"|Stages
+
! rowspan="6" |Stages
 
|Monoblast
 
|Monoblast
−
|colspan="3"|Myelocyte
+
| colspan="3" |Myelocyte
 
|-
 
|-
 
|Promonocyte
 
|Promonocyte
−
|colspan="3"|Promyelocyte
+
| colspan="3" |Promyelocyte
 
|-
 
|-
−
|rowspan="4"|Monocyte
+
| rowspan="4" |Monocyte
 
|Neutrophilic Myelocyte
 
|Neutrophilic Myelocyte
 
|Basophilic Myelocyte
 
|Basophilic Myelocyte
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|-
 
|-
 
|Neutrophilic Metamyelocyte
 
|Neutrophilic Metamyelocyte
−
|rowspan="2"|Basophilic Metamyelocyte
+
| rowspan="2" |Basophilic Metamyelocyte
−
|rowspan="2"|Eosinophilic Metamyelocyte
+
| rowspan="2" |Eosinophilic Metamyelocyte
 
|-
 
|-
 
|Band Cell
 
|Band Cell
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|Eosinophil
 
|Eosinophil
 
|}
 
|}
−
</div>
 
 
<Br clear="left">
 
<Br clear="left">
  
−
===[[Neutrophils|Neutrophils]]===
+
==Neutrophils==
−
Under the stimulation of GM-CSF, G-CSF and Il-3 the [[Haematopoiesis#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into the [[Haematopoiesis#Colony Forming Units|CFU-G]].
+
Under the stimulation of [[Cytokines|cytokines]] GM-CSF, G-CSF and IL-3 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-G]].
−
====Stages====
+
===Stages:===
−
=====Myeloblast=====
+
====Myeloblast====
−
Large cell with a large nucleus and stains basophilic. Same stage exists for all granulocytes.
+
Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.
−
=====Promyelocyte=====
+
 
−
During this stage primary (azurophilic) granules are formed. Same stage exists for all granulocytes.
+
====Promyelocyte====
−
=====Neutrophilic myelocyte=====
+
During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.
−
Developing neutrophil can now be differentiated from basophils and eosinophils as specific granules are now being formed.
+
 
−
=====Neutrophilic metamyelocyte=====
+
====Neutrophilic myelocyte====
−
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.
+
The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil 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 from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.
  
−
=====Band cell=====
+
====Band cell====
 
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
 
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
−
=====Neutrophil=====
+
====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.
 
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>
 
<br>
−
===[[Basophils|Basophils]]===
+
 
−
Under the stimulation of GM-CSF and Il-3 the [[Haematopoiesis#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis#Colony Forming Units|CFU-Ba]].
+
==Basophils==
−
====Stages====
+
Under the stimulation of GM-CSF and IL-3, the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-Ba]].
−
===== Myeloblast & Promyelocyte=====
+
===Stages:===
−
These stages are common to all granulocytes and no distinction can be made between different cell lines. See [[#Stages|neutrophil stages]] for further information.
+
====Myeloblast & Promyelocyte====
−
=====Basophilic myelocyte & metamyelocyte=====
+
These stages are common to all granulocytes and no distinction can be made between different cell lines.
−
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
+
 
−
=====Basophil=====
+
====Basophilic myelocyte & metamyelocyte====
−
Final nuclear shape is masked by high density of granules.
+
Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.
 +
 
 +
====Basophil====
 +
Final nuclear shape is masked by the high density of cytoplasmic granules.
 
<br>
 
<br>
  
−
===[[Eosinophils|Eosinophils]]===
+
==Eosinophils==
−
Under the stimulation of GM-CSF, Il-3 and Il-5 the [[Haematopoiesis#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis#Colony Forming Units|CFU-Eo]].
+
Under the stimulation of GM-CSF, IL-3 and IL-5 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-Eo]].
−
====Stages====
+
===Stages:===
−
===== Myeloblast & Promyelocyte=====
+
====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.
+
These stages are common to all granulocytes and no distinction can be made between different cell lines.
−
=====Eosinophilic myelocyte & metamyelocyte=====
+
 
 +
====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.
 
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
−
=====Eosinophil=====
+
====Eosinophil====
−
Mature cell has a bilobed nucleus.
+
Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
 
<br>
 
<br>
  
−
==Monocyte development==
+
==Monocytes==
−
[[Monocytes|Monocytes]] develop from the same precursor as [[Neutrophils|neutrophils]] the [[Haematopoiesis#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
+
Monocytes develop from the same precursor as neutrophils - the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
−
===Stages===
+
===Stages:===
 
====Monoblast====
 
====Monoblast====
−
First stage after cell has differentiated into the [[Haematopoiesis#Colony Forming Units|CFU-M]].
+
This is the first stage after cell has differentiated into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]].
 
====Promonocyte====
 
====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).
+
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.
 +
====Monocyte====
 +
Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.
  
−
====[[Monocytes|Monocyte]]====
+
====Macrophage====
−
Monocytes are incapable of mitosis and enter circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm.
+
Once the monocyte has entered tissue it differentiates into a macrophage.
−
====[[Macrophages|Macrophage]]====
 
−
Once the monocyte has entered tissue it differentiates into a [[Macrophages|macrophage]].
 
  
 
===Dendritic cells===
 
===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.
+
These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α.
 
<br>
 
<br>
  
 
==Lymphopoiesis==
 
==Lymphopoiesis==
−
<p>[[Lymphocytes|Lymphocytes]] develop from the [[Haematopoiesis#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>
+
[[Lymphocytes - Introduction|Lymphocytes]] develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]'s. Those destined to become [[T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
 
{|cellpadding="5" cellspacing="1" border="1"  
 
{|cellpadding="5" cellspacing="1" border="1"  
 
|
 
|
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|colspan="4"|CFU-L
 
|colspan="4"|CFU-L
 
|-align="center"
 
|-align="center"
−
|style="background-color:#ffffcc"|<sup>▼Il-7 & Il-11</sup>
+
|style="background-color:#ffffcc"|<sup>▼IL-7 & IL-11</sup>
−
|colspan="3" style="background-color:#e6e6fa"|<sup>▼Il-7 & SCF</sup>
+
|colspan="3" style="background-color:#e6e6fa"|<sup>▼IL-7 & SCF</sup>
 
|-align="center"
 
|-align="center"
 
|style="background-color:#ffffcc"|B lymphoid cell progenitor
 
|style="background-color:#ffffcc"|B lymphoid cell progenitor
 
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
 
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
 
|-align="center"
 
|-align="center"
−
|style="background-color:#ffffcc"|<sup>▼Il-3 & Il-7</sup>
+
|style="background-color:#ffffcc"|<sup>▼IL-3 & IL-7</sup>
−
|style="background-color:#e6e6fa"|<sup>▼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-2, IL-12 & IL-18</sup>
−
|style="background-color:#e6e6fa"|<sup>▼Il-3, Il-6, GM-CSF & SCF</sup>
+
|style="background-color:#e6e6fa"|<sup>▼IL-3, IL-6, GM-CSF & SCF</sup>
 
|-align="center"
 
|-align="center"
 
|style="background-color:#ffffcc"|Pre-B cell
 
|style="background-color:#ffffcc"|Pre-B cell
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|}
 
|}
 
<p>'''Note:'''
 
<p>'''Note:'''
−
*That between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.  
+
*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>
+
* T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by IL-10 & TNF-γ
−
 
+
[[Category:Haematopoiesis]]
−
==Links==
 
−
[[Lymphoreticular System - Anatomy & Physiology|Lymphoreticular System]]
 
−
 
 
−
[[Immunology - WikiBlood|Immunology]]
 
−
 
 
−
[[Leukocytes|Leukocytes]]
 

Latest revision as of 16:04, 11 April 2022

Leukopoiesis pathway

Introduction

Leukopoiesis is the process of formation of leukocytes (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells (CFU-GEMM) or multipotential lymphoid stem cells (CFU-L).

Leukocytes developing from CFU-GEMM’s are granulocytes (neutrophils, basophils and eosinophils) or monocytes. Leukocytes developing from CFU-Ls are lymphocytes (T & B cells, dendritic and NK cells).

Granulopoiesis

All granulocytes develop from the CFU-GEMM cells.

Summary of pathways

Monocyte Neutrophil Basophil Eosinophil

Developing granulocytes

©RVC 2008
Stem cell CFU-GEMM
CFU CFU-M CFU-G CFU-Ba CFU-Eo
Cytokines

GM-CSF

IL-3

M-CSF

GM-CSF

IL-3

G-CSF

GM-CSF

IL-3

GM-CSF

IL-3

IL-5

Stages Monoblast Myelocyte
Promonocyte Promyelocyte
Monocyte Neutrophilic Myelocyte Basophilic Myelocyte Eosinophilic Myelocyte
Neutrophilic Metamyelocyte Basophilic Metamyelocyte Eosinophilic Metamyelocyte
Band Cell
Neutrophil Basophil Eosinophil


Neutrophils

Under the stimulation of cytokines GM-CSF, G-CSF and IL-3 the CFU-GEMM differentiates into the CFU-GM, the common precursor for both neutrophils and monocytes. This then further differentiates into CFU-G.

Stages:

Myeloblast

Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.

Promyelocyte

During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.

Neutrophilic myelocyte

The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil 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 from 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.

Basophils

Under the stimulation of GM-CSF and IL-3, the CFU-GEMM differentiates into CFU-Ba.

Stages:

Myeloblast & Promyelocyte

These stages are common to all granulocytes and no distinction can be made between different cell lines.

Basophilic myelocyte & metamyelocyte

Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.

Basophil

Final nuclear shape is masked by the high density of cytoplasmic granules.

Eosinophils

Under the stimulation of GM-CSF, IL-3 and IL-5 the CFU-GEMM differentiates into the CFU-Eo.

Stages:

Myeloblast & Promyelocyte

These stages are common to all granulocytes and no distinction can be made between different cell lines.

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. There are species specific variations in granule size once stained.

Monocytes

Monocytes develop from the same precursor as neutrophils - the CFU-GM. This then differentiates into the CFU-M under the influence of GM-CSF, IL-3 and M-CSF.

Stages:

Monoblast

This is the first stage after cell has differentiated into the CFU-M.

Promonocyte

Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.

Monocyte

Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.

Macrophage

Once the monocyte has entered tissue it differentiates into a macrophage.

Dendritic cells

These 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.

Lymphopoiesis

Lymphocytes develop from the CFU-L's. Those destined to become T cells leave the bone marrow and migrate to the thymus, and those destined to be B cells migrate to the spleen and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.

B cell T cell
Differentiation CFU-L
▼IL-7 & IL-11 ▼IL-7 & SCF
B lymphoid cell progenitor T lymphoid cell progenitor
▼IL-3 & IL-7 ▼IL-7 ▼IL-2, IL-12 & IL-18 ▼IL-3, IL-6, GM-CSF & SCF
Pre-B cell Pre-T cell Pre-NK cell Pre-Dendritic cell

Maturation

site

Bone marrow, spleen or GALT

Cloacal bursa (birds) 		Thymus
Mature

B cell

▼(Antigen stim.)

Plasma & Memory cell

T Cell

Helper

Cytotoxic

Regulatory

 NK cell Dendritic cell

Note:

  • Between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
  • T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by IL-10 & TNF-γ
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