6. Granulocytes and Monocytes

• All leukocytes, except lymphocytes, differentiate, proliferate, and mature in the bone marrow
• There are 5 kinds of mature leukocytes

  neutrophils, basophils, eosinophils, monocytes (macrophages), and lymphocytes
• Leukocytes are released into circulation and circulate until they are needed in which they move into the tissues in response to stimulation
• Granulopoiesis


  development of granulocytes
• Monocytopoiesis 


  development of monocytes
• Various types of leukocytes develop from multipotent HSCs depending on cytokine stimulation and presence of mRNA
• Once mature, granulocytes and monocytes either enter the peripheral blood or remain in the bone marrow storage until they are needed
• The concentration of white blood cells are affected by physiological (pregnancy, activity level) and pathological (infections, disorders) events
• Neutrophils are the most numerous leukocytes in peripheral blood and make up 40 - 80% of total leukocytes
• Segmented neutrophils compose most neutrophils in the peripheral blood and bands make up to 5%
• Monocytes make up 2 - 10% of total leukocytes in the peripheral blood
• Eosinophils make up 0 - 5% of total leukocytes in the peripheral blood
• Basophils make up 0 - 1% of total leukocytes in peripheral blood
• A white blood cell (WBC) differential measures the percentage of each type of WBC in a person's blood. This is done via a blood smear and counting each type out of 100 WBC.
• To accurately interpret whether there has been an increase or decrease in WBC count has occurred, we must calculate the absolute concentration of each
• Calculation of absolute WBC counts

  Absolute cell count = Differential count (in decimal form) * WBC count
• Leukocytosis


  an increase in leukocytes
• Leukopenia 


  a decrease in leukocytes
• A normal leukocyte count does not rule out the presence of disease
• Leukocytes have surface markers that help us identify cell lineage and subsets within the lineage, maturation stage, and activation status
• Immunophenotyping


  A process that use specific antibodies to detect leukocyte surface markers. If the antibodies recognize the same markers, the antibodies are assigned a CD (cluster of differentiation) number.
• CD markers are helpful in differentiating neoplastic hematologic disorders
• Leukocytes protect that host from infectious agents or pathogens
• Innate immune response


  the body's first response to invading pathogens
• PAMPs (pathogen-associated molecular patterns)


  the molecular structures of pathogens
• PRR (pattern recognition receptors)


  receptors that detect PAMPs, which starts a host's innate immune response
• Adaptive immune response


  a slower response that results in long-lasting immunity or memory
• Neutrophil production is primarily regulated by IL-3 (interleukins-3), GM-CSF (granulocyte monocyte colony-stimulating factor), and G-CSF (granulocyte colony-stimulating factor)
• Band neutrophil


  the first maturation stage of neutrophils that is normally found in peripheral blood
• The nucleus of a band neutrophil has a kidney bean shape with condensed chromatin
• The cytoplasm of a band neutrophil stains pink to tan with granules present
• We typically see an increase in the number of band neutrophils in the PB during active infection, in older patients, and in young patients
• Segmented neutrophil


  the more mature form that develops after band neutrophils
• The nucleus of a segmented neutrophil is segmented with two or more (usually three or four) lobes connected by a thin nuclear filament with condensed chromatin
• The cytoplasm of a segmented neutrophil stains pink or tan to clear and contains neutral staining granules
• The bone marrow contains the most number of neutrophils with two pools


  mitotic pool (proliferating) and postmitotic pool (maturation and storage)
• The peripheral blood contains two pools of neutrophils

  circulating pool (circulating freely) and marginating pool (rolling along the endothelial surface
• Most neutrophils move from marginating pool into tissues in response to stimulation
• Neutrophils die either by regulated cell death after phagocytosis of a pathogen or after 1-2 days of no stimulation
• Neutrophils move to the site of infection (chemotaxis) and destroy the pathogen (via phagocytosis or direct bacterial killing via NETosis)