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The bone marrow is the anatomical site where all hematopoietic cells originate from the self‐renewing hematopoietic stem cell (HSC) (Figure 1.1). During fetal development, the process of hematopoiesis occurs in the yolk sac and paraaortic mesenchyme. Hematopoiesis then shifts to the liver between the third and fourth months of gestation, and finally shifts to the bone marrow. During times of exceptional demand for blood cells (e.g., hemorrhage) or when the bone marrow is injured, the liver and spleen become sites of extramedullary hematopoiesis.

As shown in Figure 1.1, the HSC gives rise to common lymphoid progenitor cells and myeloid progenitors. The former then differentiates into lymphocyte populations (B and T cells) in a process known as lymphopoiesis. Lymphoid progenitor cells also give rise to a subpopulation of dendritic cells as well as natural killer (NK) cells and innate immune cells (ILC). Myeloid progenitor cells ultimately differentiate into neutrophils, eosinophils, basophils, erythrocytes (red blood cells), and monocytes which further differentiate into macrophages and dendritic cells. Myeloid progenitors also give rise to megakaryocytes which undergo an intricate series of remodeling that results in the release of thousands of platelets from a single megakaryocyte. In later chapters, we will discuss in more detail the major characteristics of each of the hematopoietic cells as well as the major steps of lymphocyte development.

Figure 1.1. Self‐renewing hematopoietic stem cells differentiate into lymphoid and myeloid progenitors. These cells differentiate along lineage‐specific lines in the bone marrow. Most of these cells mature there and then travel to peripheral organs via the blood. Mast cells and macrophages undergo further maturation outside the bone marrow. T cells develop into mature T‐cell subsets in the thymus before entering the periphery.

The immune system has evolved to exploit each of the hematopoietic cell populations. As we have already pointed out, it is convenient to discuss the major arms of the immune system beginning with elements of the innate immune system followed by the adaptive immune system. But it is important to underscore the interrelationship of these two arms of our immune system. Clearly, they are interrelated developmentally due to their common hematopoietic precursor, the hematopoietic stem cell. A classic example of their functional interrelationship is illustrated by the roles played by innate immune cells involved in antigen presentation. These so‐called antigen‐presenting cells (APCs) do just what their name implies: they present antigens (e.g., pieces of phagocytized bacteria) to T cells within the adaptive immune system. As will be discussed in great detail in subsequent chapters, T cells must interact with APCs that display antigens for which they are specific in order for the T cells to be activated to generate antigen‐specific responses.