CHAPTER 12Leukopoiesis

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

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)

GRANULOCYTES Can be found in four locations also

called granulocyte pools:a) In the bone marrowb) Circulating in peripheral bloodc) Marginating against the endothelium

of blood vesselsd) In the tissues

BONE MARROW POOL Has 3 functions: a) Proliferationb) Maturationc) Storage Proliferating component – contain cell

capable of mitotic divisions (myeloblasts, promyelocytes, and myelocytes)

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

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

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

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

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 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 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

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

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)

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

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

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

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

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

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

BASOPHILS

•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

QUESTIONS 1. last stage of granulopoesis that is

capable of mitosisa) 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

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 progenitora) 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