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Chapter 12
Leukopoiesis
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Leukopoiesis
the development of white blood cells (WBCs)except lymphocytes occurse in the samelocation as erythropoiesis
Leukocytes it exist to defend the organismagainst nonself agents through intricatecooperation among cells.
- divided into granulocytes and
lymphocytes
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Granulocytes
Contain visible granules and develop solely inthe bone marrow
Subdivided as granulocytes containg large
granules (neutrophil, basophil, eosinophil)and granulocytes containing minute granules(monocytes)
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Granulocytes
Can be found in four locations also calledgranulocyte pools:
a) In the bone marrow
b) Circulating in peripheral blood
c) Marginating against the endothelium ofblood vessels
d) In the tissues
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Bone Marrow Pool
Has 3 functions:
a) Proliferation
b) Maturation
c) Storage
) Proliferating component contain cellcapable of mitotic divisions (myeloblasts,
promyelocytes, and myelocytes)
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Maturation component contain cells that areincapable of mitosis but not yet fully functional(metamyelocytes and bands)
Storage component contains bands andpolymorphonuclear leukocytes
Circulating pools contain approximately 50% of total
peripheral blood granulocytes levels and the other50% in the marginating pools
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Stem cell to Myeloblast
Hematopoietic stem cell mature into astem cell specific for bone marrow-derivedor myeloid cells (CFU-GEMM)
CFU-GEMM matures into another progenitorcell called the colony-forming unitgranulocyte-monocyte/macrophage (CFU-GM)
- this is controlled by by a complexofinteraction humoral factors, such asinterluekins and CSFs
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Myeloblast Usually 15-20 micrometers
Nucleus is delicate withprominent nucleoli
Cytoplasm is meager thatcontains RER, developingGolgi apparatus, and theinitial presence of primaryor azurophilic granules
The granules colors positivefor enzymeMYELOPEROXIDASE
Incapable of motility,adhesion, and phagocytosis
< 1% in the normal bone
marrow compartment
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Promyelocyte(Proganulocyte)
Size may exceed 20 micrometers
Nuclear chromatin pattern mayshow slight clumping
Nucleoli begin to fade
Dominant characteristic ofPRIMARY GRANULES
Motility may be present
1 to 5% in the bone marrow
reduced nicotinamide adeninedinucleotide phosphate oxidaseand flavocytochrome B activates neutral proteinasescathepsin G, elastase,proteinases for killing to take
place
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NeutrophilicMyelocyte
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NeutrophilicMetamyelocyte
Result after the cessation of allactive DNA synthesis
Nucleus is indented
Cytoplasm has collection of primaryand secondary granules ( majorfeature of cytoplasm)
The granules constitute the majorcomponent necessary to kill anddegrade 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
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Band(Nonsegmen
ted Form)
Band shape, a transitional formbecause it is considered to be part ofmaturation and storage pools in thebone marrow and peripheral blood
constitutes 40% of white blood cellsbut < 6% in the peripheral blood
Non segmented
Nucleus have uniform or parallelwidth
Nuclear indention is less than halfthe width of the nucleus (horse shoeshaped)
Possess full motility, adhesionproperties and phagocytic ability
Membrane is characterized by
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PolymorphonuclearNeutrophil(SegmentedNeutrophil)
Nucleus continues its indention untilthin it become a lobed nucleus
Nucleus is easily deformable because
of active motility of the cell
Polymorphonuclear means manyshaped nucleus
Part of storage pool in bone marrowand circulating and marginating pools
50 70% of total WBC differential
Nuclei have visible segments
10 12 microns
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Studies have indicated that there is a heterogeneouspopulation of mature neutrohils
Neutrophils with increased mobility, numbers of CD 15receptors in lymphocye homing, CD21 that binds to C3
Positive for CD62 an adhesion molecule active onneutrophils and epithelial cells
Performs phagocytosis (involves larger material) andpinocytosis (involves small material)
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Phagocytosis
chemotactic factors cause thepolymorphonuclear cell to migrate to source
Neutrophils periodically determine whether
the vessel endothelium is expressing surfacemolecules, which enhance a more firmcontact (adhesion)
Egress of neutrophil outside the blood
circulation (diapedesis) in response tochemical gradient
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It adhere to particles that initiated the attractionthen pseudopods extend the around the particle,engulfing it and forming a phagosome
Cytplasmic granules combine with the phagosomeforming phagolysosome and dump their contents in it
Primary granules contribute to proteolysis
Secondary granules increase complement fixationand chemotactic response
- causes degradation anddetoxification of material
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Eosinophil Maturation
Prominent secondary granules are stainedheavily with the eosin dye with Romanowskybased stains
Requires IL-3, IL-5 and GM-CSF and inhibitedby interferon
Developed from CFU-GEMM to CFU-Eo
Similar to neutrophil in the myeloblast andpromyelocyte stage
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In the myelocyte stage, it is distinguish fromneutrophil by presence of numerous large roundgranules 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
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Eosinophil Nucleus with 2 or 3 lobes connected
by thin strand
Large, uniform sized granules stain
orange red with acidic dyes that donot obscure the nucleus
10 12 microns
1 -3 % of circulating WBCs
Charcot-Leyden crystals watersoluble, needle shaped crystals as
the result of eosinophil disintegration
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Basophil Maturation
Process of maturation from the stem cell innot well known
May parallel the development of eosinophils
Can be differentiated into myelocytes,metamyelocytes, bands andpolymorphonuclear cells on the basis ofnuclear development, although nuclei with
more than two lobes are extremely rare
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Basophils Large dark purple variable sized
granules stain with basic dyes thatobscure the nucleus
Irregular shaped bilobed nucleus
8 10 microns
0 1% of circulating WBCs
Have specific high affinity for the Fcregion of IgE
Involved in allergic inflammationand initiate localized and system
anaphylaxis
- granules contain heparin,
chondroitin sulfate, histamin,serotonine, and other vasoactive
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Questions
1. last stage of granulopoesis that is capableof mitosis
a) Myeloblast b) promyelocyte c) myelocyte d)
metamyelocyte2. neutrophil maturation stage where it is
part of both storage and maturation pool inthe bone marrow
a) Metamyelocyte b) band c) myelocyte d)segmented neutrophil
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3. responsible for the staining of the granulesof eosinophils
a) Major basic protein b) peroxidasec) 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 andinitiate localized and system anaphylaxis
a) BAND neutrophil b) basophil c) PMN d)
eosinophil