Wbc

• White Blood Cells (WBCs) are also known as leukocytes and are the cellular components of the immune system
• WBCs mediate the immune response of the body against pathogens such as bacteria, viruses, fungi, and other foreign antigens
• There are five main types of WBCs: neutrophils, eosinophils, basophils, monocytes, and lymphocytes
• The normal white blood cell count is usually between 4.5 to 11.5 × 10^9 /L
• Changes in the number of leukocytes may indicate a variety of conditions and are an important subset of complete blood count
• Classification of White Blood Cells:

  • Granulocytes include neutrophils, eosinophils, and basophils
  • Nongranulocytes include monocytes and lymphocytes
• According to function, WBCs are categorized as phagocytes (neutrophils, eosinophils, basophils, and monocytes) and immunocytes (lymphocytes)
• Granulopoiesis is the process where myeloid progenitor cells give rise to granulocytes
• Stages of Granulocyte Maturation:

  • Myeloblast: round/oval nucleus, dark blue cytoplasm
  • Promyelocyte: larger than myeloblast, dark blue cytoplasm with granules
  • Myelocyte: round nucleus, light blue to light pink cytoplasm with specific granules
  • Metamyelocyte: indented nucleus, pink cytoplasm with granules
  • Stab/Band Cell: elongated nucleus, pink cytoplasm with granules
  • Mature Granulocyte: Neutrophil, Eosinophil, Basophil
• Three Pools of Granulocytes in the Bone Marrow:

  • Stem Cell Pool (HSCs)
  • Proliferation (Mitotic) Pool: myeloblasts, promyelocytes, and myelocytes
  • Maturation (Post-mitotic/Storage) Pool: metamyelocytes, bands, and segmenters
• Total Blood Granulocyte Pool:

  • Circulating Pool: 50% of WBC in peripheral blood
  • Marginal Pool: 50% of WBC in peripheral blood, adhere to blood vessels or sequestered in capillaries
• Neutrophils are also known as segmented neutrophils or PMN leukocytes

  • Neutrophils have a coarse, clumped chromatin nucleus with lobes connected by thin filaments
  • Neutrophils have light pink cytoplasm with specific granules
  • Neutrophils are part of the innate immune system and function in phagocytosis
• Neutrophils have a lifespan of 9-10 days from myeloblast to death

  • Mature neutrophils stay for 10 hours in peripheral blood before entering tissues
  • Lifespan of mature neutrophils is about 5 days
  • Neutrophils contain primary and secondary granules
• Neutrophils are capable of diapedesis and chemotaxis

  • Process of Phagocytosis involves motility with chemotaxis and diapedesis
• Process of phagocytosis involves several steps:
• Motility:

  • Chemotaxis (directed locomotion)
  • Chemotaxins include C5a, Starch/bacteria, dead tissue
  • Diapedesis (locomotion through walls of blood vessels)
• Recognition and Ingestion:

  • Opsonins involved are antibodies and C3b
  • Pseudopodia are extended around foreign particle and enclose it within a “phagosome”
• Killing and Digestion:

  • O2 dependent process involves respiratory burst through activation of NADPH oxidase
  • O2 independent process occurs once the lysosomes fuse with the phagosome membrane (phagolysosome), emptying their contents into the phagosome
• Testing of Neutrophil Function includes:
• Boyden micropore filter technique: Test for chemotactic activity of phagocytes

  • Rebuck skin window: Evaluates the speed, type, and number of phagocytes that respond to a skin abrasion
  • Nitroblue tetrazolium (NBT) test: Screening test for Chronic Granulomatous disease (CGD) where normal enzyme activity in PMN results in colorless NBT being reduced to blue-black formazan
• Eosinophils have the following characteristics:
• Morphology:

  • Size: 12-16 μm
  • Nucleus: dark purple, usually band-shaped or segmented into 2 segments (bilobed)
  • Cytoplasm: contains large, bright red-orange granules which rarely overlie the nucleus
  • Eosinophil (Eo) is also called acidophil due to the acidophilic staining of its granules
• Functions of Eosinophils:

  • Destroy worms expressing Fc receptors for IgE; granules contain major basic protein
  • Act as antigen-presenting cells
  • Involved in phagocytosis with slower movement and less intracellular killing ability than PMNs
  • Have anti-inflammatory properties by inactivating substances released by basophil/mast cells; eosinophils modulate the allergic response
  • Contains histaminase that inactivates histamine
• Basophils have the following characteristics:
• Morphology:

  • Size: 10-15 μm
  • Nucleus: round, indented, band-shaped, or lobulated; light purple with smudged/indistinct chromatin pattern
  • Cytoplasm: contains irregular purplish-black water-soluble granules; granules may obscure the nucleus or wash out in staining and leave empty areas in the cytoplasm
• Characteristics of Basophils:

  • Least in number with a lifespan of 60 hours
  • Responsible for allergic manifestations by reacting with specific antigens causing rapid degranulation and anaphylactic shock
  • Granules contain serotonin, peroxidase, histamine, heparin, platelet-activating factor, E CFA
• Monocytes undergo monopoiesis and have the following stages of maturation:
• Monoblast:

  • Size: 12-18 μm; N:C ratio 4:1
  • Nucleus: round/oval with fine chromatin; 1-2 nucleoli
  • Cytoplasm: dark blue with no cytoplasmic granules
• Promonocyte:

  • Size: 12-20 μm; N:C ratio 3:1
  • Nucleus: slightly indented or folded with fine chromatin; 0-1 nucleoli
  • Cytoplasm: blue to gray with fine azurophilic granules
• Monocyte:

  • Size: 12-20 μm
  • Nucleus: “horseshoe”, “tulip” or “kidney-bean” shaped with lacy pattern chromatin
  • Cytoplasm: abundant, dull, pale, faded, gray-blue containing many fine azurophilic granules
  • Macrophages are derived from monocytes and can remain in tissues for several months
• Functions of Monocytes and Macrophages include defense against microorganisms and tumor cells, removal of damaged/old cells, participation in iron metabolism, processing antigen information for lymphocytes, and production and secretion of various substances
• Dendritic cells are the most efficient antigen-presenting cells (APC)
• Dendritic cells are active in cell-mediated immunity
• Dendritic cells produce and secrete various substances, including lysosomal enzymes that decompose tissue components, high levels of pyrogen (causes fever), prostaglandins, and transcobalamin II
• Lymphocytes are not obligate end cells and can undergo blastic transformation
• Lymphocytes are a heterogeneous group of cells with 3 subsets: T cells (60-80%), B cells (20-25%), and NK cells (10-15%)
• Lymphocytes migrate from bone marrow to thymus to peripheral tissue and recirculate from blood into lymphoid tissue and back to blood
• Pluripotential stem cells give rise to lymphoid progenitor cells, which are acted upon by CSF/IL/cytokines to produce B and T lymphocytes
• 1. cells and T-cells enter the blood and populate secondary lymphoid tissues (lymph nodes, spleen, and Peyer's patches) where antigen contact occurs
• Lymphocyte maturation stages include lymphoblast, prolymphocyte, and mature lymphocyte