1 Leukopoiesis

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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

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