1. Chapter 12
Leukopoiesis

2. Leukopoiesis
the development of white blood cells (WBCs) except lymphocytes occurse in the same location as erythropoiesis
Leukocytes – it exist to defend the organism against nonself agents through intricate cooperation among cells.
- divided into granulocytes and lymphocytes

3. Granulocytes
Contain visible granules and develop solely in the bone marrow
Subdivided as granulocytes containg large granules (neutrophil, basophil, eosinophil) and granulocytes containing minute granules (monocytes)

4. Granulocytes
Can be found in four locations also called granulocyte pools:
In the bone marrow
Circulating in peripheral blood
Marginating against the endothelium of blood vessels
In the tissues

5. Bone Marrow Pool Has 3 functions: Proliferation Maturation Storage
Proliferating component – contain cell capable of mitotic divisions (myeloblasts, promyelocytes, and myelocytes)

6. Maturation component – contain cells that are incapable of mitosis but not yet fully functional (metamyelocytes and bands)
Storage component – contains bands and polymorphonuclear leukocytes
Circulating pools contain approximately 50% of total peripheral blood granulocytes levels and the other 50% in the marginating pools

7. Stem cell to Myeloblast
Hematopoietic stem cell – mature into a stem cell specific for bone marrow-derived or myeloid cells (CFU-GEMM)
CFU-GEMM – matures into another progenitor cell called the colony-forming unit granulocyte-monocyte/macrophage (CFU- GM)
- this is controlled by by a complexof interaction humoral factors, such as interluekins and CSFs

8. Myeloblast Usually 15-20 micrometers
Nucleus is delicate with prominent nucleoli
Cytoplasm is meager that contains RER, developing Golgi apparatus, and the initial presence of primary or azurophilic granules
The granules colors positive for enzyme MYELOPEROXIDASE
Incapable of motility, adhesion, and phagocytosis
< 1% in the normal bone marrow compartment
Myeloblast

9. Promyelocyte (Proganulocyte)
Size may exceed 20 micrometers
Nuclear chromatin pattern may show slight clumping
Nucleoli begin to fade
Dominant characteristic of PRIMARY GRANULES
Motility may be present
1 to 5% in the bone marrow
reduced nicotinamide adenine dinucleotide phosphate oxidase and flavocytochrome B – activates neutral proteinases cathepsin G, elastase, proteinases for killing to take place
Promyelocyte (Proganulocyte)

10. Neutrophilic Myelocyte
<10% of the total marrow cell population
Nucleus may be round to oval with flattened side near Golgi apparatus
Nuclear chromatin shows clumping and nucleoli no longer visible
characteristic is the production of SECONDARY OR NEUTROPHILIC granules
Last stage capable of mitosis
Second of the 3 major type of granules is synthesized causing “dawn of neutrophilia or faint blush of pink near the Golgi apparatus
Neutrophilic Myelocyte

11. Neutrophilic Metamyelocyte
Result after the cessation of all active DNA synthesis
Nucleus is indented
Cytoplasm has collection of primary and secondary granules ( major feature of cytoplasm)
The granules constitute the major component necessary to kill and degrade non self agents
Incapable of reacting to chemotactic factors
13 – 22% of normal bone marrow differential
At the end of this stage GELATINASE GRANULE is made
Neutrophilic Metamyelocyte

12. Neutrophilic Band (Nonsegmented Form)
Band shape, a transitional form because it is considered to be part of maturation and storage pools in the bone marrow and peripheral blood
constitutes 40% of white blood cells but < 6% in the peripheral blood
Non segmented
Nucleus have uniform or parallel width
Nuclear indention is less than half the width of the nucleus (horse shoe shaped)
Possess full motility, adhesion properties and phagocytic ability
Membrane is characterized by changes in the cytoskeleton, surface charge and presence of receptors
Neutrophilic Band (Nonsegmented Form)

13. Polymorphonuclear Neutrophil (Segmented Neutrophil)
Nucleus continues its indention until thin it become a lobed nucleus
Nucleus is easily deformable because of active motility of the cell
Polymorphonuclear means “many shaped nucleus”
Part of storage pool in bone marrow and circulating and marginating pools
50 – 70% of total WBC differential
Nuclei have visible segments
10 – 12 microns
Polymorphonuclear Neutrophil (Segmented Neutrophil)

14. Studies have indicated that there is a heterogeneous population of mature neutrohils
Neutrophils with increased mobility, numbers of CD 15 receptors in lymphocye homing, CD21 that binds to C3
Positive for CD62 – an adhesion molecule active on neutrophils and epithelial cells
Performs phagocytosis (involves larger material) and pinocytosis (involves small material)

15. Phagocytosis
chemotactic factors cause the polymorphonuclear cell to migrate to source
Neutrophils periodically determine whether the vessel endothelium is expressing surface molecules, which enhance a more firm contact (adhesion)
Egress of neutrophil outside the blood circulation (diapedesis) in response to chemical gradient

16. It adhere to particles that initiated the attraction then pseudopods extend the around the particle, engulfing it and forming a phagosome
Cytplasmic granules combine with the phagosome forming phagolysosome and dump their contents in it
Primary granules – contribute to proteolysis
Secondary granules – increase complement fixation and chemotactic response
- causes degradation and detoxification of material

17. Eosinophil Maturation
Prominent secondary granules are stained heavily with the eosin dye with Romanowsky based stains
Requires IL-3, IL-5 and GM-CSF and inhibited by interferon
Developed from CFU-GEMM to CFU-Eo
Similar to neutrophil in the myeloblast and promyelocyte stage

18. In the myelocyte stage, it is distinguish from neutrophil by presence of numerous large round granules containing crystalloid compound compromising major basic protein
Its granules contain proteolytic enzymes but no secretory vesicles
Spends less than 1 week in the peripheral blood

19. Eosinophil Nucleus with 2 or 3 lobes connected by thin strand
Large, uniform sized granules stain orange red with acidic dyes that do not obscure the nucleus
10 – 12 microns
1 -3 % of circulating WBCs
Charcot-Leyden crystals – water soluble, needle shaped crystals as the result of eosinophil disintegration
Eosinophil

20. Basophil Maturation
Process of maturation from the stem cell in not well known
May parallel the development of eosinophils
Can be differentiated into myelocytes, metamyelocytes, bands and polymorphonuclear cells on the basis of nuclear development, although nuclei with more than two lobes are extremely rare

21. Large dark purple variable sized granules stain with basic dyes that obscure the nucleus
Irregular shaped bilobed nucleus
8 – 10 microns
0 – 1% of circulating WBCs
Have specific high affinity for the Fc region of IgE
Involved in allergic inflammation and initiate localized and system anaphylaxis
- granules contain heparin, chondroitin sulfate, histamin, serotonine, and other vasoactive and immunomodulatory mediators
Basophils

22. Questions 1. last stage of granulopoesis that is capable of mitosis
a) Myeloblast b) promyelocyte c) myelocyte d) metamyelocyte
2. neutrophil maturation stage where it is part of both storage and maturation pool in the bone marrow
a) Metamyelocyte b) band c) myelocyte d) segmented neutrophil

23. 3. responsible for the staining of the granules of eosinophils
a) Major basic protein b) peroxidase c) proteolytic enzymes d) myeloperoxidase
4. the common myeloid progenitor
a) CFU-GM b) GM-CSF c) CFU-GEMM d) G-CSF
5. involved in allergic inflammation and initiate localized and system anaphylaxis
a) BAND neutrophil b) basophil c) PMN d) eosinophil