CST BLOG: Lab Expectations

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Immunology: Which cells have a myeloid lineage and how are they identified?

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During hematopoiesis in humans, cells of the myeloid lineage are derived from a common myeloid progenitor (CMP) in the bone marrow. This lineagewhich includes monocytes, granulocytes, erythrocytes, and plateletsis a primary component of the innate immune system and serves as a first line of defense against infection.

Immune Cell Marker Pathway

Types of Myeloid Lineage Cells

To date, as many as 25 distinct myeloid lineage cells have been characterized, each of which perform a unique role in mounting an immune response. The ability to identify and quantify each of the myeloid subtypes is essential for understanding why different populations are activated in response to certain pathogens and how they contribute to the resolution of an immune challenge.

Myeloid Cell Lineage

CMPs give rise to a stunning array of terminally differentiated myeloid cell types. Major lineage branches derived from CMPs include the genesis of:

  • Megakaryocytes, which produce the platelets necessary for normal blood clotting
  • Erythrocytes (red blood cells), which are responsible for carrying oxygen to tissues
  • Mast cells, which are best known for their participation in allergic response through the release of histamine
  • Myeloblasts, which give rise to a series of granulocytes, including basophils, neutrophils, and eosinophils
  • Monoblasts, which serve as progenitors for monocytes, macrophages, and dendritic cells

Each terminal effector cell typethe end product of each branch of the myeloid lineage—participates in the immune response in a unique way. For example, basophils act in many inflammatory reactions and secrete the anticoagulant heparin to slow the formation of blood clots. Eosinophils are well known for their role in combating parasitic and viral infections through their release of major basic proteins and ribonucleases. Neutrophils, the most abundant granulocyte, are front-line responders to sites of inflammation and infection and are able to attack and remove invading microorganisms through phagocytosis. Macrophages are present in most tissues and recognize foreign antigens and damaged cells for immediate destruction via phagocytosis, a process that can also lead to antigen presentation and the activation of other immune cells. Upon tissue injury or pathogen infection, monocytes in the blood are recruited to the affected tissue and differentiate into macrophages. Dendritic cells have the capacity to engulf cellular and foreign material by phagocytosis, which is then processed for presentation as antigens to T cells. As such, dendritic cells serve to relay information about pathogens between the innate and adaptive immune systems.

Identifying Types of Myeloid Lineage Cells

Distinguishing between each of the cell types within the myeloid lineage can be accomplished using a variety of methods. First, subsets of myeloid cells can be characterized based on their morphology and distribution with tissues or blood. However, fine-grained classification of different cell classes requires immunophenotyping, which exploits the expression of distinct cell surface molecules that can be recognized by antibodies and visualized by immunohistochemistry or flow cytometry. Groups of antibodies with reactivity to these cell surface molecules at various stages of differentiation are used to identify “cluster of differentiation” (CD) antigens. Patterns of CD antigen immunoreactivity, in addition to immunophenotyping, can be used to detect and quantify the presence of a specific immune cell in a heterogeneous population.

Examples of myeloid lineage markers include pan-myeloid marker CD11b, CD206 for M2-type macrophages, CD68, and CD15 for neutrophils. While some markers are unique to each cell class, often a combinatorial analysis of multiple markers is required to assess the true phenotype of the myeloid cell lineages.

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