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Leukopoiesis
dr.jilsha
OBJECTIVES
To get a better understanding of :
 Myeloid series and lymphoid series
 Progenitor cells
 Blast cells
 Promyelocytes and promonocytes
 Myelocytes and Metamyelocytes
 Band form of neutrophils
 Factors regulating leucopoiesis
 Life history of leukocytes
INTRODUCTION
⩥ The process of development and
maturation of Leukocytes is called
Leukopoiesis.
⩥ It is a part of Hemapoeisis (formation of
Blood cells ).
⩥ All Blood cells develop from Pluripotent
Hemapoeitic stem cells.
3
4
INTRODUCTION
⩥ They are formed partially in the bone
marrow (granulocytes, monocytes and a
few lymphocytes) and partially in the
lymph tissue (lymphocytes and plasma
cells).
⩥ After formation, they are transported in
the blood to different parts of the body
where they are needed.
5
INTRODUCTION
 There are two series of leukocytes :
 Myeloid series and
 Lymphoid series.
 Myeloid series matures into granulocytes
and monocytes.
 Lymphoid series matures into
lymphocytes.
6
7
STAGES OF
LEUKOPOEISIS
8
⩥ The pluripotent stem cells in the
bone marrow give rise to committed
stem cells.
⩥ The committed stem cells are
broadly classified into two types :
Myeloid stem cells and Lymphoid
stem cells.
9
MYELOID SERIES
⩥ The stem cells for myeloid series are
trilineage stem cells that form stem cells
for three series of blood cells.
 Erythroid series for red cells
 Megakaryoid series for
platelets
 Stem cells for granulocyte –
monocyte series
10
11
PROGENITOR CELLS
⩥ The stem cells of granulocyte –
monocyte series of myeloid series give
rise to three categories of progenitor cells
– Colony Forming Units (CFUs)
 CFU – GM
 CFU – Eo
 CFU - Bas
12
CONTD..
 CFU – GM : on further differentiation form CFU
– G for Neutrophils and CFU – M for
Monocytes.
 CFU – Eo : Eosinophil lineage
 CFU – Bas : Basophil lineage
13
BLAST CELLS
⩥ The CFUs form blast cells.
⩥ CFU – G forms myeloblasts which on further
development form neutrophils.
⩥ CFU – M forms monoblast that develops into
monocytes.
⩥ CFU – Eo forms eosinophil – myeloblast that
develops into eosinophils.
14
CONTD..
⩥ CFU – Bas forms basophil – myeloblast that
develops into basophils.
⩥ The blast cells are large cells 16 – 20 µm, with
large nucleus containing multiple nucleoli.
⩥ The nucleoli are prominent features of blast
cells and are the sites of assembly of ribosomal
proteins and r-RNA.
15
CONTD..
⩥ The cytoplasm is scanty.
⩥ The cells are actively mitotic.
⩥ Myeloblasts
 The earliest precursor cells for
neutrophils are myeloblasts.
 They have scanty blue cytoplasm with 5
– 10 nucleoli in a large nucleus.
 There are separate myeloblasts for
eosinophils and basophils.
16
17
CONTD..
⩥ Monoblasts
 These are blast cells for monocytes.
 Since they resemble myeloblasts
morphologically, they are also called
myelomonoblasts.
18
19
Promyelocytes and promonocytes
⩥ Myeloblasts give rise to promyelocytes and
promonocytes develop from monoblasts.
⩥ They have the following features :
 Size : 15 – 20 µm
 The cells are large and cytoplasm is
granular.
 Nucleus – round, condensed and
contains less nucleoli (1-2)
 Cells are mitotic. 20
CONTD..
⩥ Promonocytes are larger cells and on further
development form monocytes which are the
largest cells.
⩥ Monocytes form macrophages and Dendritic
cell.
⩥ Promyelocytes are also larger cells and contain
peroxidase-positive granules.
⩥ The granules are large in size with diameter of
500 nm.
21
PROMYELOCYTE PROMONOCYTE
22
MYELOCYTES
⩥ Promyelocytes give rise to myelocyes.
⩥ They have the following features :
 Size : 12 – 20 µm
 Cytoplasm : fine specific granules
which are peroxidase negative.
 Granules are 200 nm and are
spherical or rod shaped
 Nucleus : round, concentric
 Nucleoli are absent.
 Some degree of Mitosis occurs. 23
24
METAMYELOCYTES
⩥ Metamyelocytes develop from
myelocytes
⩥ Size : 12 – 18 µm.
⩥ Cytoplasm : Numerous fine mixed
granules.
⩥ Nucleus : Eccentric, Kidney shaped.
⩥ No mitosis.
⩥ Give rise to band form of neutrophils,
eosinophils and basophils.
25
26
BAND FORM
⩥ Neutrophils that develop from metamyelocytes
are juvenile neutrophils (band forms) that
further grow into matured or segmented
neutrophils.
⩥ Size : 10 – 14 µm
⩥ Cytoplasm : Granular
⩥ Nucleus : U shaped or Horse shoe shaped.
27
28
LYMPHOID SERIES
⩥ Lymphoid stem cells give rise to Lymphoblasts
⩥ Lymphoblasts have the following features :
 Size is 10 – 20 µm
 Fewer nucleoli
 more condensed nuclear chromatin
 Absence of cytoplasmic granules.
29
Contd..
⩥ Lymphoblasts give rise to B cell, T cell and NK
cells (Lymphocytes).
⩥ T cells leave the bone marrow
and mature in the thymus.
⩥ Some of the B cells
differentiate to form
plasma cells.
30
31
Regulation of leukopoiesis
⩥ Leukopoiesis is mainly regulated by cytokines
especially, colony – stimulating factors (CSFs),
Interleukins (ILs) and Tumor Necrosis Factor
(TNF)
⩥ T lymphocytes, monocytes, fibroblasts,
endothelial cells, liver and kidney are the main
sources of Hemopoietic Growth Factors (HGFs)
32
INTERLEUKINS
⩥ IL – 1, IL – 6 and IL – 3 promote
maturation of stem cells.
⩥ IL – 5 helps in the development of eosinophils
hence called eosinophilic growth factor.
⩥ IL – 3 & 4 facilitate development of Basophils
33
COLONY STIMULATING FACTORS
⩥ GM – CSF, G – CSF and M – CSF are the main
CSFs.
⩥ GM – CSF :
 secreted by fibroblasts, vascular
endothelial cells, monocytes and T –
lymphocytes.
 stimulates differentiation and
proliferation of pluripotent stem cells into
committed cells.
34
CONTD..
⩥ G – CSF :
 Produced by monocytes, endothelial
cells and fibroblasts.
 Helps in development and functions of
granulocytes.
35
CONTD..
⩥ M – CSF:
 Also called CSF – 1
 Promotes proliferation of monocytes
and macrophages and also stimulates
functions of monocytes.
 TNF : help in proliferation and differentiation of
stem cells.
36
LIFE HISTORY
⩥ Marrow phase : mitotic pool and maturation
pool.
 The development from myeloblasts to
myelocytes constitute the mitotic pool
 Maturation of metamyelocytes into
mature cells constitute the maturation
pool
 5 days in mitotic pool , 5 days in
maturation pool
37
CONTD..
⩥ Circulation phase : 50 % margination pool, 50 %
circulation pool.
⩥ Tissue phase : undergo apoptosis , monocytes
to macrophages.
38
APPLIED ASPECT
IN EXERCISE LEUKOCYTOSIS
OCCURS DUE TO DISRUPTION OF
THE MARGINATION OF LEUKOCYTES.
39
SUMMARY
40
41

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Leukopoiesis

  • 2. OBJECTIVES To get a better understanding of :  Myeloid series and lymphoid series  Progenitor cells  Blast cells  Promyelocytes and promonocytes  Myelocytes and Metamyelocytes  Band form of neutrophils  Factors regulating leucopoiesis  Life history of leukocytes
  • 3. INTRODUCTION ⩥ The process of development and maturation of Leukocytes is called Leukopoiesis. ⩥ It is a part of Hemapoeisis (formation of Blood cells ). ⩥ All Blood cells develop from Pluripotent Hemapoeitic stem cells. 3
  • 4. 4
  • 5. INTRODUCTION ⩥ They are formed partially in the bone marrow (granulocytes, monocytes and a few lymphocytes) and partially in the lymph tissue (lymphocytes and plasma cells). ⩥ After formation, they are transported in the blood to different parts of the body where they are needed. 5
  • 6. INTRODUCTION  There are two series of leukocytes :  Myeloid series and  Lymphoid series.  Myeloid series matures into granulocytes and monocytes.  Lymphoid series matures into lymphocytes. 6
  • 7. 7
  • 9. ⩥ The pluripotent stem cells in the bone marrow give rise to committed stem cells. ⩥ The committed stem cells are broadly classified into two types : Myeloid stem cells and Lymphoid stem cells. 9
  • 10. MYELOID SERIES ⩥ The stem cells for myeloid series are trilineage stem cells that form stem cells for three series of blood cells.  Erythroid series for red cells  Megakaryoid series for platelets  Stem cells for granulocyte – monocyte series 10
  • 11. 11
  • 12. PROGENITOR CELLS ⩥ The stem cells of granulocyte – monocyte series of myeloid series give rise to three categories of progenitor cells – Colony Forming Units (CFUs)  CFU – GM  CFU – Eo  CFU - Bas 12
  • 13. CONTD..  CFU – GM : on further differentiation form CFU – G for Neutrophils and CFU – M for Monocytes.  CFU – Eo : Eosinophil lineage  CFU – Bas : Basophil lineage 13
  • 14. BLAST CELLS ⩥ The CFUs form blast cells. ⩥ CFU – G forms myeloblasts which on further development form neutrophils. ⩥ CFU – M forms monoblast that develops into monocytes. ⩥ CFU – Eo forms eosinophil – myeloblast that develops into eosinophils. 14
  • 15. CONTD.. ⩥ CFU – Bas forms basophil – myeloblast that develops into basophils. ⩥ The blast cells are large cells 16 – 20 µm, with large nucleus containing multiple nucleoli. ⩥ The nucleoli are prominent features of blast cells and are the sites of assembly of ribosomal proteins and r-RNA. 15
  • 16. CONTD.. ⩥ The cytoplasm is scanty. ⩥ The cells are actively mitotic. ⩥ Myeloblasts  The earliest precursor cells for neutrophils are myeloblasts.  They have scanty blue cytoplasm with 5 – 10 nucleoli in a large nucleus.  There are separate myeloblasts for eosinophils and basophils. 16
  • 17. 17
  • 18. CONTD.. ⩥ Monoblasts  These are blast cells for monocytes.  Since they resemble myeloblasts morphologically, they are also called myelomonoblasts. 18
  • 19. 19
  • 20. Promyelocytes and promonocytes ⩥ Myeloblasts give rise to promyelocytes and promonocytes develop from monoblasts. ⩥ They have the following features :  Size : 15 – 20 µm  The cells are large and cytoplasm is granular.  Nucleus – round, condensed and contains less nucleoli (1-2)  Cells are mitotic. 20
  • 21. CONTD.. ⩥ Promonocytes are larger cells and on further development form monocytes which are the largest cells. ⩥ Monocytes form macrophages and Dendritic cell. ⩥ Promyelocytes are also larger cells and contain peroxidase-positive granules. ⩥ The granules are large in size with diameter of 500 nm. 21
  • 23. MYELOCYTES ⩥ Promyelocytes give rise to myelocyes. ⩥ They have the following features :  Size : 12 – 20 µm  Cytoplasm : fine specific granules which are peroxidase negative.  Granules are 200 nm and are spherical or rod shaped  Nucleus : round, concentric  Nucleoli are absent.  Some degree of Mitosis occurs. 23
  • 24. 24
  • 25. METAMYELOCYTES ⩥ Metamyelocytes develop from myelocytes ⩥ Size : 12 – 18 µm. ⩥ Cytoplasm : Numerous fine mixed granules. ⩥ Nucleus : Eccentric, Kidney shaped. ⩥ No mitosis. ⩥ Give rise to band form of neutrophils, eosinophils and basophils. 25
  • 26. 26
  • 27. BAND FORM ⩥ Neutrophils that develop from metamyelocytes are juvenile neutrophils (band forms) that further grow into matured or segmented neutrophils. ⩥ Size : 10 – 14 µm ⩥ Cytoplasm : Granular ⩥ Nucleus : U shaped or Horse shoe shaped. 27
  • 28. 28
  • 29. LYMPHOID SERIES ⩥ Lymphoid stem cells give rise to Lymphoblasts ⩥ Lymphoblasts have the following features :  Size is 10 – 20 µm  Fewer nucleoli  more condensed nuclear chromatin  Absence of cytoplasmic granules. 29
  • 30. Contd.. ⩥ Lymphoblasts give rise to B cell, T cell and NK cells (Lymphocytes). ⩥ T cells leave the bone marrow and mature in the thymus. ⩥ Some of the B cells differentiate to form plasma cells. 30
  • 31. 31
  • 32. Regulation of leukopoiesis ⩥ Leukopoiesis is mainly regulated by cytokines especially, colony – stimulating factors (CSFs), Interleukins (ILs) and Tumor Necrosis Factor (TNF) ⩥ T lymphocytes, monocytes, fibroblasts, endothelial cells, liver and kidney are the main sources of Hemopoietic Growth Factors (HGFs) 32
  • 33. INTERLEUKINS ⩥ IL – 1, IL – 6 and IL – 3 promote maturation of stem cells. ⩥ IL – 5 helps in the development of eosinophils hence called eosinophilic growth factor. ⩥ IL – 3 & 4 facilitate development of Basophils 33
  • 34. COLONY STIMULATING FACTORS ⩥ GM – CSF, G – CSF and M – CSF are the main CSFs. ⩥ GM – CSF :  secreted by fibroblasts, vascular endothelial cells, monocytes and T – lymphocytes.  stimulates differentiation and proliferation of pluripotent stem cells into committed cells. 34
  • 35. CONTD.. ⩥ G – CSF :  Produced by monocytes, endothelial cells and fibroblasts.  Helps in development and functions of granulocytes. 35
  • 36. CONTD.. ⩥ M – CSF:  Also called CSF – 1  Promotes proliferation of monocytes and macrophages and also stimulates functions of monocytes.  TNF : help in proliferation and differentiation of stem cells. 36
  • 37. LIFE HISTORY ⩥ Marrow phase : mitotic pool and maturation pool.  The development from myeloblasts to myelocytes constitute the mitotic pool  Maturation of metamyelocytes into mature cells constitute the maturation pool  5 days in mitotic pool , 5 days in maturation pool 37
  • 38. CONTD.. ⩥ Circulation phase : 50 % margination pool, 50 % circulation pool. ⩥ Tissue phase : undergo apoptosis , monocytes to macrophages. 38 APPLIED ASPECT IN EXERCISE LEUKOCYTOSIS OCCURS DUE TO DISRUPTION OF THE MARGINATION OF LEUKOCYTES.
  • 39. 39
  • 41. 41