Leukopoiesis

Stages and regulation of leukopoiesis, life history of leukocytes

1. Leukopoiesis dr.jilsha

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

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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

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8. STAGES OF LEUKOPOEISIS 8

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

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12. PROGENITOR CELLS The stem cells of granulocyte – monocyte series of myeloid series give rise to three categories of progenitor cells – C olony 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

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18. CONTD.. Monoblasts These are blast cells for monocytes . Since they resemble myeloblasts morphologically, they are also called myelomonoblasts . 18

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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

22. PROMYELOCYTE PROMONOCYTE 22

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

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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

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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

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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

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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.

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40. SUMMARY 40

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