Myeloid cells are a diverse collection of cells that form the backbone of the body’s immediate, non-specific defense system. They act as the immune system’s first responders, swiftly detecting and containing threats throughout the body. Their primary function is maintaining biological balance, or homeostasis, by constantly surveying tissues for signs of infection, damage, or foreign material. This family includes various types of white blood cells and their tissue-resident counterparts, all working to initiate an immune response.
Origin in the Bone Marrow
The developmental journey of all myeloid cells begins in the bone marrow with the Hematopoietic Stem Cell (HSC). This multipotent stem cell differentiates into all mature blood and immune cells through hematopoiesis. The HSC first divides into two major branches: the common lymphoid progenitor and the common myeloid progenitor (CMP).
The CMP represents the specific lineage that gives rise to the entire myeloid family. This separation distinguishes the myeloid system of innate immunity from the lymphoid system of adaptive immunity. The CMP then undergoes further differentiation, producing the mature cells of the myeloid lineage.
This process is tightly regulated by growth factors and signaling molecules. Most myeloid cells mature within the bone marrow before circulating or residing in peripheral tissues, ensuring a continuous supply for defense.
The Pillars of Innate Immunity
Myeloid cells fulfill their defensive role through specialized, rapid-response mechanisms that constitute the innate immune system. These cells recognize general patterns associated with pathogens and cellular stress, allowing for an immediate, non-specific reaction. Their functions include pathogen clearance, specialized defense, and communication with the adaptive immune system.
Phagocytosis and Pathogen Clearance
Phagocytosis, or “cell eating,” is a primary defensive action carried out by two major myeloid populations: neutrophils and macrophages. Neutrophils are typically the first immune cells to arrive at an infection site, responding rapidly to inflammatory signals. They engulf and destroy invading microbes, such as bacteria, using powerful enzymes and reactive oxygen species contained within their granules. Macrophages develop from circulating monocytes and reside in tissues throughout the body, acting as stationary sentinels. They clear pathogens, dead cells, and cellular debris. The phagocytic activity of both cell types limits the spread of infection and cleans up biological debris.
Allergy and Parasite Defense
Specialized granulocytes, eosinophils and basophils, manage unique immune threats, particularly large parasites and allergic reactions. Eosinophils defend against parasitic infections, which are often too large for phagocytosis. They release toxic proteins and enzymes stored in their granules directly onto the parasite surface to destroy it.
Basophils and their tissue-resident mast cells are involved in triggering inflammatory and allergic responses. Upon encountering an allergen, these cells release potent chemical mediators, such as histamine, causing local inflammation that recruits other immune cells.
Antigen Presentation and Bridging Immunity
Dendritic cells (DCs), which are myeloid-derived, serve a crucial function by connecting the innate and adaptive immune systems. DCs are efficient at capturing and internalizing foreign material in the tissues. After engulfing a pathogen, the dendritic cell processes the material into small protein fragments called antigens.
The cell then migrates to nearby lymph nodes, where it presents these antigens on its surface to specialized T-cells of the adaptive immune system. This presentation “educates” the adaptive immune system, initiating a specific and long-lasting immune response. While macrophages can also perform this function, dendritic cells are considered the most potent antigen-presenting cells.
Roles in Disease and Tissue Repair
Beyond immediate defense, myeloid cells play complex, long-term roles in resolving tissue damage and developing certain diseases. Their involvement shifts from acute defense to regulating chronic conditions and tissue remodeling.
Disease and Malfunction
Malfunction in the myeloid lineage is responsible for a group of blood cancers, including Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS). These conditions arise from genetic alterations in hematopoietic stem cells or early myeloid progenitors in the bone marrow. In AML, myeloid cells fail to mature properly, leading to the rapid proliferation and accumulation of non-functional blast cells that crowd out healthy blood production. MDS is characterized by ineffective hematopoiesis, resulting in low numbers of mature blood cells. An inflammatory microenvironment is common in both AML and MDS, where pro-inflammatory cytokines disrupt normal stem cell function, favoring the expansion of malignant myeloid clones.
Resolution and Repair
Myeloid cells are integral coordinators of tissue healing following injury, a role distinct from pathogen defense. Resident macrophages are active in the post-injury phase, clearing debris left by damaged cells and the remnants of inflammation. This cleaning prepares the site for regeneration. Macrophages also secrete growth factors and signaling molecules that coordinate repair, stimulating the growth of new blood vessels and tissue matrix. By transitioning to a pro-resolving state, myeloid cells manage the entire arc of tissue response.