Cellular Hierarchy and Colony-Forming Units
Haematopoiesis is based on a strict hierarchy. The haematopoietic stem cell gives rise to two global lineages via multipotent progenitor cells. In international nomenclature, the terms CFU (Colony-Forming Units) and BFU (Burst-Forming Units) are used to designate them.
Multipotent progenitors:
- CFU-GEMM — common myeloid progenitor. This cell subsequently gives rise to granulocytes, erythrocytes, monocytes, and megakaryocytes.
- CFU-Ly — baseline lymphoid progenitor.
- CFU-GM — a more specialized progenitor giving rise to granulocytes and monocytes.
- CFU-G — progenitor for neutrophils and basophils.
Next are unipotent progenitors, committed to generating only a single cell type:
- BFU-E and CFU-E — develop exclusively into erythrocytes.
- CFU-Meg — responsible for megakaryocyte formation.
- CFU-Eo — differentiate into eosinophils.
- CFU-M — become mature monocytes.
Main Differentiation Lineages
Three main myeloid blood cell lineages branch off from the multipotent CFU-GEMM cell:
- Erythroid lineage: development proceeds along the chain CFU-GEMM $\rightarrow$ BFU-E $\rightarrow$ CFU-E, ultimately culminating in the formation of a mature erythrocyte.
- Megakaryocytic lineage: the pathway from CFU-GEMM to CFU-Meg leads to the appearance of a giant cell—the megakaryocyte. Subsequently, blood platelets pinch off from it, forming platelets (thrombocytes).
- Granulocyte-monocyte lineage: proceeds via the intermediate CFU-GM stage. The line then diverges: neutrophils and basophils form via CFU-G, eosinophils mature via CFU-Eo, and monocytes form via CFU-M.
The lymphoid lineage develops from a separate progenitor—CFU-Ly. Final maturation of B cells occurs directly in the bone marrow. Conversely, cells destined to become T cells migrate to and undergo differentiation in the thymus.
Functional Self-Regulation System
The body must maintain an optimal level of cellular elements in the blood, adequate to the current metabolic rate. A unique feature of this functional system is that it possesses exclusively an internal self-regulation link (maintaining homeostasis without engaging external behavioral responses).
Local mechanisms within the bone marrow play a special role in this process. A crucial factor is the process of cell destruction. The death of old formed elements occurs not in the circulating blood, but in specialized organs: the spleen, lymph nodes, and bone marrow. Furthermore, the degradation products of destroyed cells act as stimulators of haemopoiesis, activating the corresponding lineages (erythropoiesis, leukopoiesis, or thrombopoiesis).
Neurohumoral Regulation of Haemopoiesis
Haemopoiesis is controlled by an extensive network of mechanisms:
- Neural factors: activity of the sympathetic and parasympathetic nervous systems.
- Hormones: the endocrine system actively modulates cell maturation. Pituitary hormones (ACTH, growth hormone), thyroid hormones, and thymic hormones (signaling molecules specifically regulating leukocyte counts) exert regulatory influences.
- Thrombopoietin: synthesized in the liver, it specifically stimulates megakaryocyte production.
- Interleukin-3 (IL-3): a potent cytokine secreted by T cells and bone marrow stromal cells. Its targets are stem cells and myeloid progenitors. IL-3 supports the proliferation of these early cells and stimulates the formation of most myeloid cells.