WBC development

• Leukocytes


  White blood cells
• Granulocytes


  • Leukocytes whose cytoplasm is filled with granules with differing staining characteristics and whose nuclei are segmented or lobulated
  • Include eosinophils, basophils, and neutrophils
• Mononuclear cells


  • Categorized into monocytes and lymphocytes
  • Have nuclei that are not segmented but are round, oval, indented, or folded
• Leukocyte development


  1. Occur in the bone marrow

  2. Most undergo differentiation and maturation

  3. Then are released into the circulation
• Kinetics


  The movement of cells through developmental stages, into the circulation, and from the circulation to the tissues, including the time spent in each phase of the cell's life
• The overall function of leukocytes is in mediating immunity, either innate (nonspecific), as in phagocytosis by neutrophils, or specific (adaptive), as in the production of antibodies by lymphocytes and plasma cells
• Neutrophils


  Present in the peripheral blood in two forms: segmented and band
• Neutrophil development


  1. Occurs in the bone marrow

  2. Shares a common progenitor with monocytes, distinct from eosinophils and basophils (granulocyte-monocyte progenitor)

  3. Stimulated by granulocyte colony-stimulating factor (G-CSF)
• Bone marrow pools of developing neutrophils

  • Stem cell pool
  • Proliferation (mitotic) pool
  • Maturation (storage) pool
• Myeloblasts


  • Make up 0% to 3% of nucleated cells in the bone marrow
  • Subdivided into type I, type II, and type III
• Promyelocytes


  • Comprise 1% to 5% of nucleated cells in the bone marrow
  • Relatively larger than myeloblasts
  • Cytoplasm is evenly basophilic and full of primary (azurophilic) granules
• Myelocytes


  • Make up 6% to 17% of nucleated cells in the bone marrow
  • Final stage in which cell division (mitosis) occurs
  • Begin to manufacture secondary (specific) neutrophil granules
• Metamyelocytes


  • Constitute 3% to 20% of nucleated marrow cells
  • No longer capable of division
  • Nucleus is indented (kidney bean shaped or peanut shaped)
• Bands


  • Make up 9% to 32% of nucleated marrow cells and 0% to 5% of nucleated peripheral blood cells
  • All evidence of RNA (cytoplasmic basophilia) is absent
  • Tertiary granules continue to be formed
• Promyelocytes


  • Nucleoli present
  • Large number of azure granules
• Myelocytes


  • Light areas in cytoplasm where specific granules are beginning to appear
  • Few if any primary granules, lavender secondary granules easily seen
• Metamyelocytes


  • No remaining basophilia in cytoplasm
  • Nucleus indented
• Band neutrophils


  Nucleus indented more than 50% of the width of the nucleus, but actual segmentation has not yet occurred
• There has been considerable controversy over the definition of a band and the differentiation between bands and segmented forms</b>
• The Clinical and Laboratory Standards Institute (CLSI) recommends that bands should be included within the neutrophil count and not reported as a separate category because of the difficulty in reliably distinguishing bands from segmented neutrophils
• Segmented neutrophils


  • 2 to 5 nuclear lobes connected by thread-like filaments
• Segmented neutrophils make up 7% to 30% of nucleated cells in the bone marrow
• Segmented neutrophils are present in the highest numbers in the peripheral blood of adults (50% to 70% of leukocytes in relative numbers and 2.3 to 8.1 × 10%/L in absolute terms)
• Pediatric values for segmented neutrophils can be as low as 18% of leukocytes in the first few months of life and do not begin to climb to adult values until after 4 to 7 years of age
• Neutrophil kinetics


  Movement of neutrophils and neutrophil precursors between the different pools in the bone marrow, the peripheral blood, and tissues
• Neutrophil production has been calculated to be on the order of between 0.9 and 1.0 × 10⁹ cells/kg per day
• The proliferative pool contains approximately 2.1 × 10⁹ cells/kg, whereas the maturation pool contains roughly 5.6 × 10 cells/kg, or a 5-day supply
• The transit time from myeloblast through myelocyte has been estimated to be roughly 6 days, and the transit time through the maturation pool is approximately 4 to 6 days
• Granulocyte release from the bone marrow is stimulated by G-CSF
• Circulating neutrophil pool (CNP) and marginated neutrophil pool (MNP)


  Neutrophils in the peripheral blood are divided randomly into these two pools
• The ratio of the CNP and MNP is roughly equal overall, however, marginated neutrophils in the capillaries of the lungs make up a considerably larger portion of peripheral neutrophils
• The half-life of neutrophils in the blood is relatively short at approximately 7 hours
• Integrins and selectins


  Allow neutrophils to marginate as well as exit the blood and enter the tissues by a process known as diapedesis
• Neutrophils that do not migrate into the tissues eventually undergo programmed cell death or apoptosis and are removed by macrophages in the spleen, bone marrow, and liver
• Neutrophil functions


  Phagocytosis and destruction of foreign material and microorganisms
• Neutrophil extravasation


  1. Rolling

  2. Adhesion

  3. Crawling

  4. Transmigration
• Neutrophil phagocytosis


  • Recognition and attachment
  • Ingestion
  • Killing and digestion
  • Formation of neutrophil extracellular traps
• Neutrophils are a source of transcobalamin I or R binder protein, which is necessary for the proper absorption of vitamin B12
• Neutrophils are a source of a variety of cytokines
• Eosinophils


  • Make up 1% to 3% of nucleated cells in the bone marrow
  • Slightly more than a third are mature, a quarter are eosinophilic metamyelocytes, and the remainder are eosinophilic promyelocytes or eosinophilic myelocytes
  • Account for 1% to 3% of peripheral blood leukocytes, with an absolute number of up to 0.4 × 10%/L in the peripheral blood