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White Myeloid Cells: Histology

The myeloid lineage produces a diverse group of blood cells (leukocytes) involved in the defense of the body against foreign substances or infectious agents. Monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation, neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation, eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation, basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation, and mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation all arise from the common myeloid progenitor (CMP), which develops from bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis stem cells. However, leukocytes have different functions. Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation kill invading bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology and fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology, eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation increase in parasitic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation and mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation are key to allergic response as sources of histamine, and monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation are released from bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis to become macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation in the tissues. The development in the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis is regulated by different cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.

Last updated: Dec 12, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

White myeloid cells are leukocytes developed from the common myeloid progenitor (CMP), which is derived from hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis (HSCs) of the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis.

  • Not all leukocytes (WBCs) are derived from the myeloid progenitor.
  • 2 major groups of leukocytes:
    • Granulocytes (derived from the myeloid progenitor):
      • Basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation
      • Eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation
      • Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation
      • Mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation
    • Agranulocytes (derived from myeloid and lymphoid progenitors):
      • Monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation (myeloid)
      • Lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology (lymphoid)

Cell description

Table: Cell description of agranulocytes
Type Nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles Granules Characteristics and functions
Monocyte (3%–7% of differential count) Kidney shaped (indented or C shaped) None Characteristics:
  • Lifespan: hours to days
  • Largest leukocyte

Functions:
  • Differentiate into populations of tissue macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation (including dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions and osteoclasts Osteoclasts A large multinuclear cell associated with the bone resorption. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. Bones: Development and Ossification)
  • All cells derived from monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation are antigen-presenting cells Antigen-presenting cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include macrophages; dendritic cells; langerhans cells; and B-lymphocytes. Follicular dendritic cells are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of immune complexes for b-cell recognition they are considered so by some authors. Adaptive Immune Response.
  • Search for microbial cells and mount an immune response
Table: Cell description of granulocytes
Type Nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles Granules Characteristics and functions
Neutrophil (50%–70% of differential count) Multilobed (3–5 lobes)
  • Fine
  • Faintly pink
Lifespan:
  • Approximately 6 hours (circulating)
  • Days (in tissues)

Target and function:
  • Kill and phagocytose bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology
  • Destruct fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology, restrict the growth of larger fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology
Eosinophil (1%–3% of differential count) Bilobed
  • Large
  • Dark pink
Lifespan:
  • Approximately 6 hours (circulating)
  • Days (in tissues)

Target and function:
  • Kill parasites and helminths Helminths Commonly known as parasitic worms, this group includes the acanthocephala; nematoda; and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. Anthelmintic Drugs
  • Immune response to allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions
Basophil (0.5%–1% of differential count) Bilobed or trilobed
  • Large
  • Dark blue
Lifespan:
  • Hours to days

Target and function:
  • Modulation of the inflammatory response by histamine secretion Secretion Coagulation Studies
  • Surface receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors for IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
  • Supplements actions of mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation
Mast cell Mast cell Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Angioedema Round (margins obscured by packed granules) Purple to red
  • Granules rich in histamine and heparin
  • Found in tissues, but not in blood
  • Modulation of the type 1 Type 1 Spinal Muscular Atrophy hypersensitivity reaction through IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors

Myelopoiesis

Myeloid cell production

  • Hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis:
    • 1st to 2nd month in utero: mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation of the yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development
    • By the 2nd month: moves to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy (and spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy)
    • By the 5th month: occurs in the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis, which becomes the predominant source of blood cells
  • Myelopoiesis starts with multipotent HSCs in the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis.
  •  HSCs → multipotent progenitor ( MPP MPP Specialized stem cells that are committed to give rise to cells that have a particular function; examples are myoblasts; myeloid progenitor cells; and skin stem cells. Bone Marrow: Composition and Hematopoiesis) cells → CMP (which eventually differentiates into granulocytes, monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, and erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
Bone marrow hematopoiesis

Bone marrow hematopoiesis: proliferation and differentiation of the formed elements of blood.
IL-3: interleukin-3
CFU-GEMM: colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte
IL-2: interleukin-2
IL-6: interleukin-6
CFU-GM: colony-forming unit–granulocyte-macrophage
GM-CSF: granulocyte-macrophage colony-stimulating factor
M-CSF: macrophage colony-stimulating factor
G-CSF: granulocyte colony-stimulating factor
IL-5: interleukin-5
NK: natural killer
TPO: thrombopoietin
EPO: erythropoietin

Image by Lecturio. License: CC BY-NC-SA 4.0

Regulation

Table: Comparison of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response/growth factors
Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response/growth factors Activities Source
Stem cell factor Stem cell factor A hematopoietic growth factor and the ligand of the cell surface c-kit protein (proto-oncogene proteins c-kit). It is expressed during embryogenesis and is a growth factor for a number of cell types including the mast cells and the melanocytes in addition to the hematopoietic stem cells. Bone Marrow: Composition and Hematopoiesis (SCF) Stimulates all hematopoietic progenitor cells Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis stromal cells
Granulocyte-macrophage colony-stimulating factor (GM-CSF) Stimulates myeloid progenitor cells Myeloid progenitor cells Stem cells derived from hematopoietic stem cells. Derived from these myeloid progenitor cells are the megakaryocytes; erythroid cells; myeloid cells; and some dendritic cells. Acute Myeloid Leukemia Endothelial cells, T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions
Granulocyte colony-stimulating factor (G-CSF) Stimulates neutrophil precursor cells Endothelial cells, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation
Monocyte colony-stimulating factor (M-CSF) Stimulates monocyte precursor cells Endothelial cells, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation
Interleukin-1 Interleukin-1 A soluble factor produced by monocytes; macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, interleukin-1alpha and interleukin-1beta. The biological effects of il-1 include the ability to replace macrophage requirements for t-cell activation. Interleukins (IL-1) Regulation of cytokine secretion Secretion Coagulation Studies of many leukocytes Macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, T helper cells
Interleukin-3 Interleukin-3 A multilineage cell growth factor secreted by lymphocytes; epithelial cells; and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Platelets: Histology (IL-3) Mitogen for all granulocyte and megakaryocyte Megakaryocyte Very large bone marrow cells which release mature blood platelets. Platelets: Histology/erythrocyte progenitor cells T helper cells
Interleukin-4 Interleukin-4 A soluble factor produced by activated T-lymphocytes that induces the expression of mhc class II genes and fc receptors on B-lymphocytes and causes their proliferation and differentiation. It also acts on T-lymphocytes, mast cells, and several other hematopoietic lineage cells. Interleukins (IL-4) Development of basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation and mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation, and activation of B-lymphocyte T helper cells
Interleukin-5 Interleukin-5 A cytokine that promotes differentiation and activation of eosinophils. It also triggers activated B-lymphocytes to differentiate into immunoglobulin-secreting cells. Interleukins (IL-5) Development and activation of eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation T helper cells

Development

Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation, eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation, basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation

  • Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation are derived from the colony-forming unit granulocyte-macrophage (CFU-GM).
  • Eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation (Eo) and basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation (Ba) come from progenitor-cell CFU-Eo and CFU-Ba, respectively.
  • Subsequent stages:
    1. Myeloblast: 
      • 1st granulocytic precursor
      • Cytoplasm with no granules
      • Large nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and faint nucleoli
    2. Promyelocyte:
    3. Myelocyte: 
      • 1st sign of differentiation: Specific granules develop for the particular cell type.
      • Different sets of genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure are activated; lineages for the 3 types of granulocytes form.
      • Cell division Cell Division A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle ceases.
    4. Metamyelocyte:
      • Granules are dispersed.
      • Nuclear indentation and lobulation occur.
      • Neutrophilic, basophilic, and eosinophilic metamyelocytes undergo further condensation of their nuclei.
  • Differentiation:
    • Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation:
      • From the neutrophilic-metamyelocyte stage, neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation become band neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation or stab cells (intermediate stage with an elongated, not polymorphic, nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles)
      • Segmented neutrophil: nearly mature
      • Mature neutrophil: exits to the peripheral blood
    • Eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation: from eosinophilic metamyelocyte → mature eosinophil
    • Basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation: from basophilic metamyelocyte → mature basophil
Granulopoiesis

Granulopoiesis: Images depict the stages of granulocyte development.
In the most immature stage, the myeloblast is characterized by a large nucleus with faint nucleoli and a nongranular, basophilic cytoplasm.
During the promyelocyte stage, the cell enlarges and azurophilic granules appear in the cytoplasm.
In the myelocyte stage, cell division ceases and specific granules appear in the cytoplasm.
During the metamyelocyte stage, the size of the cell decreases and nuclear morphology changes; the nucleus begins to indent. For neutrophils, the nucleus forms a horseshoe shape as a band cell and is multilobulated in the mature neutrophil.
For eosinophils, the nucleus becomes bilobed and the cytoplasm has eosinophilic granules.
For basophils, the nucleus is bilobed and the cell has basic granules.

Image by Lecturio. License: CC BY-NC-SA 4.0

Monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation

  • Derived from the CFU-GM (similar to neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation)
  • Stages:
    • Monoblast:
      • 1st monocyte precursor
      • Round nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles
    • Promonocyte:
      • Convoluted, indented nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles
      • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables basophilic granules
    • Monocyte:
      • Lobulated, indented nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles
      • Occasional or no granules
      • Once recruited into tissues, the cell differentiates into macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation.
Development of monocyte

Monocyte development starts from hematopoietic stem cells (HSCs) and progresses through stages to the colony-forming unit granulocyte-macrophage (CFU-GM):
The 1st monocyte precursor is the monoblast, which has a round or oval nucleus.
The promonocyte follows and has a convoluted nucleus.
The monocyte arises with an indented nucleus and is released from the bone marrow to become a macrophage in the tissues.

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Mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation

  • Mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation arise from the bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis: HSCs → CMP → CFU-GM → mast cell Mast cell Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Angioedema progenitor
  • Unlike other HSC-derived cells, mast cell Mast cell Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Angioedema progenitors (immature form) are released into the blood.
  • Mast cell Mast cell Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Angioedema progenitors are recruited to mucosal and epithelial tissues, undergo terminal differentiation, and become mature mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation.

Clinical Relevance

  • Acute myeloid leukemia Acute Myeloid Leukemia Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia ( AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia): characterized by uncontrolled proliferation of myeloid precursor cells. Acute myeloid leukemia Acute Myeloid Leukemia Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia includes an accumulation of myeloblasts. Normal marrow is replaced by malignant cells, which leads to impaired hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis. A clinical presentation consisting of fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, bleeding, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and infection is related to anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and lack of functional WBCs. Diagnosis is via peripheral blood smear Peripheral Blood Smear Anemia: Overview and Types and bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma showing myeloblasts. The precursor cells contain Auer rods Auer Rods Acute Myeloid Leukemia
  • Chronic myeloid leukemia Chronic myeloid leukemia Chronic myeloid leukemia is a malignant proliferation of the granulocytic cell line characterized by a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome, an abbreviated chromosome 22, resulting from reciprocal (9;22)(q34;q11) translocation. Chronic Myeloid Leukemia ( CML CML Chronic myeloid leukemia is a malignant proliferation of the granulocytic cell line characterized by a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome, an abbreviated chromosome 22, resulting from reciprocal (9;22)(q34;q11) translocation. Chronic Myeloid Leukemia): malignant proliferation of the granulocytic cell line, with a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome Philadelphia chromosome An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia. Acute Lymphoblastic Leukemia, an abbreviated chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 22 resulting from reciprocal (9;22)(q34;q11) translocation. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can be asymptomatic, or have sternal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly. Laboratory studies show elevated WBC with increased immature cells. Philadelphia chromosome Philadelphia chromosome An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia. Acute Lymphoblastic Leukemia demonstration by cytogenetic techniques is considered the gold standard of diagnostic testing. 
  • Chronic eosinophilic leukemia Chronic eosinophilic leukemia Chronic eosinophilic leukemia (CEL) is a chronic myeloproliferative neoplasm caused by autonomous clonal proliferation of normal-appearing eosinophils, resulting in increased eosinophils in the peripheral blood and bone marrow. The disorder is a myeloid variant of hypereosinophilic syndrome (HES) and is associated with tissue infiltration leading to end-organ damage. Chronic Eosinophilic Leukemia ( CEL CEL Chronic eosinophilic leukemia (CEL) is a chronic myeloproliferative neoplasm caused by autonomous clonal proliferation of normal-appearing eosinophils, resulting in increased eosinophils in the peripheral blood and bone marrow. The disorder is a myeloid variant of hypereosinophilic syndrome (HES) and is associated with tissue infiltration leading to end-organ damage. Chronic Eosinophilic Leukemia): a chronic myeloproliferative neoplasm caused by autonomous clonal proliferation of normal-appearing eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation, resulting in elevated eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation in the peripheral blood and bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis. The disorder is a myeloid variant of hypereosinophilic syndrome Hypereosinophilic syndrome A heterogeneous group of disorders with the common feature of prolonged eosinophilia of unknown cause and associated organ system dysfunction, including the heart, central nervous system, kidneys, lungs, gastrointestinal tract, and skin. There is a massive increase in the number of eosinophils in the blood, mimicking leukemia, and extensive eosinophilic infiltration of the various organs. Chronic Eosinophilic Leukemia ( HES HES A heterogeneous group of disorders with the common feature of prolonged eosinophilia of unknown cause and associated organ system dysfunction, including the heart, central nervous system, kidneys, lungs, gastrointestinal tract, and skin. There is a massive increase in the number of eosinophils in the blood, mimicking leukemia, and extensive eosinophilic infiltration of the various organs. Chronic Eosinophilic Leukemia) and associated with tissue infiltration, which leads to end-organ damage. Studies show an absolute eosinophilic count of ≥ 1.5 x 10⁹/L and bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma of 5%–19%. Evidence of clonal abnormality or elevated blasts Blasts Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system. Blunt Chest Trauma is needed for diagnosis. Without either, idiopathic Idiopathic Dermatomyositis HES HES A heterogeneous group of disorders with the common feature of prolonged eosinophilia of unknown cause and associated organ system dysfunction, including the heart, central nervous system, kidneys, lungs, gastrointestinal tract, and skin. There is a massive increase in the number of eosinophils in the blood, mimicking leukemia, and extensive eosinophilic infiltration of the various organs. Chronic Eosinophilic Leukemia is the appropriate term. 
  • Mastocytosis: a group of disorders with excessive accumulation of mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation in the tissue. Cutaneous mastocytosis is limited to the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions. Systemic mastocytosis infiltrates multiple organs outside the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions. KIT mutations are a major contributing factor. Symptoms include flushing, pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), and chronic allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions.

References

  1. Dahlin, J., Hallgren, J. (2015). Mast cell progenitors: Origin, development and migration to tissues. Molecular Immunology, Volume 63, Issue 1, Pages 9–17. https://doi.org/10.1016/j.molimm.2014.01.018.
  2. Espinoza, V.E., Emmady, P.D. (2021). Histology, Monocytes. StatPearls. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557618/
  3. Kuijpers T. (2021). Structure and composition of neutrophils, eosinophils, and basophils. Kaushansky K, & Prchal J.T., & Burns L.J., & Lichtman M.A., & Levi M, & Linch D.C. (Eds.), Williams Hematology, 10e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2962&sectionid=252530906
  4. Mescher A.L. (Ed.). (2021). Blood. Junqueira’s Basic Histology Text and Atlas, 16e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=3047&sectionid=255121436

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