Difference between revisions of "Leukopoiesis"
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==Granulopoiesis== | ==Granulopoiesis== | ||
All granulocytes develop from the [[Haematopoiesis - Overview#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=== | ||
| − | |||
{| cellpadding="10" cellspacing="0" border="1" align="left" | {| cellpadding="10" cellspacing="0" border="1" align="left" | ||
| | | | ||
| Line 15: | Line 15: | ||
!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 | ||
| Line 26: | Line 26: | ||
|CFU-Eo | |CFU-Eo | ||
|- | |- | ||
| − | ! | + | !Cytokines |
| − | |<p>GM-CSF</p><p> | + | |<p>GM-CSF</p><p>IL-3</p><p>M-CSF</p> |
| − | |<p>GM-CSF</p><p> | + | |<p>GM-CSF</p><p>IL-3</p><p>G-CSF</p> |
| − | |valign="top"|<p>GM-CSF</p><p> | + | | valign="top" |<p>GM-CSF</p><p>IL-3</p> |
| − | |<p>GM-CSF</p><p> | + | |<p>GM-CSF</p><p>IL-3</p><p>IL-5</p> |
|- | |- | ||
| − | ! | + | ! 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 | ||
| Line 45: | Line 45: | ||
|- | |- | ||
|Neutrophilic Metamyelocyte | |Neutrophilic Metamyelocyte | ||
| − | |rowspan="2"|Basophilic Metamyelocyte | + | | rowspan="2" |Basophilic Metamyelocyte |
| − | |rowspan="2"|Eosinophilic Metamyelocyte | + | | rowspan="2" |Eosinophilic Metamyelocyte |
|- | |- | ||
|Band Cell | |Band Cell | ||
| Line 54: | Line 54: | ||
|Eosinophil | |Eosinophil | ||
|} | |} | ||
| − | |||
<Br clear="left"> | <Br clear="left"> | ||
==Neutrophils== | ==Neutrophils== | ||
| − | Under the stimulation of GM-CSF, G-CSF and | + | 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==== | ||
| Line 79: | Line 78: | ||
==Basophils== | ==Basophils== | ||
| − | Under the stimulation of GM-CSF and | + | 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]]. |
===Stages:=== | ===Stages:=== | ||
====Myeloblast & Promyelocyte==== | ====Myeloblast & Promyelocyte==== | ||
| Line 92: | Line 91: | ||
==Eosinophils== | ==Eosinophils== | ||
| − | Under the stimulation of GM-CSF, | + | 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==== | ||
| Line 100: | Line 99: | ||
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> | ||
==Monocytes== | ==Monocytes== | ||
| − | + | 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==== | ||
| − | + | 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 | + | 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==== | ====Monocyte==== | ||
| − | Monocytes are incapable of mitosis and enter circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm. | + | 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==== | ====Macrophage==== | ||
| − | Once the monocyte has entered tissue it differentiates into a | + | Once the monocyte has entered tissue it differentiates into a macrophage. |
| + | |||
===Dendritic cells=== | ===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 [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α. | |
<br> | <br> | ||
==Lymphopoiesis== | ==Lymphopoiesis== | ||
| − | + | [[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" | ||
| | | | ||
| Line 128: | Line 129: | ||
|colspan="4"|CFU-L | |colspan="4"|CFU-L | ||
|-align="center" | |-align="center" | ||
| − | |style="background-color:#ffffcc"|<sup> | + | |style="background-color:#ffffcc"|<sup>▼IL-7 & IL-11</sup> |
| − | |colspan="3" style="background-color:#e6e6fa"|<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> | + | |style="background-color:#ffffcc"|<sup>▼IL-3 & IL-7</sup> |
| − | |style="background-color:#e6e6fa"|<sup> | + | |style="background-color:#e6e6fa"|<sup>▼IL-7</sup> |
| − | |style="background-color:#e6e6fa"|<sup> | + | |style="background-color:#e6e6fa"|<sup>▼IL-2, IL-12 & IL-18</sup> |
| − | |style="background-color:#e6e6fa"|<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 | ||
| Line 155: | Line 156: | ||
|} | |} | ||
<p>'''Note:''' | <p>'''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 | + | * T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by IL-10 & TNF-γ |
[[Category:Haematopoiesis]] | [[Category:Haematopoiesis]] | ||
Latest revision as of 16:04, 11 April 2022
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 |
| |
|---|---|---|---|---|---|
| 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