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The principal function of the human immune system is to provide protection from the myriad potential pathogens that inhabit the natural world.1 An initial line of defense consists of mechanical barriers such as the skin and ciliated, mucus-covered membranes. Once a microorganism succeeds in breaching one of these barriers, it is typically engaged by an intricate and tightly regulated network of cells and soluble proteins that function collectively to eliminate it or render it harmless, without causing undue injury to the body. The preformed elements of this network provide a rapid response. Over several days to weeks, a more potent and specific immune response develops against unique microbial molecules.

To effectively carry out its role in host defense, the immune system must perform two additional tasks. First, in order to avoid forming “autoimmune” responses against the body itself, there must be mechanisms to maintain self-tolerance. Second, since an overly exuberant or prolonged reaction could be detrimental, there must be ways to “turn off” an immune response once a potential threat has been contained.

The first progenitor cells of the immune system are found in the yolk sac at a gestational age of approximately 3 weeks. These pluripotent hematopoietic stem cells (Fig. 186-1) seed the liver at 5 weeks, and hematopoiesis begins at 6 weeks of gestation. By the 12th week, hematopoiesis has shifted to the bone marrow.2 Delivery of growth, differentiation, and migration signaling to and from immune cells is mediated in large part by soluble proteins termed cytokines and chemokines and their respective receptors.3 Lymphoid precursor cells either mature locally into bone marrow-derived B cells or are exported to the thymus where they further mature into T cells. Other cells of hematopoietic origin with important immune roles include natural killer (NK) cells and antigen-presenting cells. Each cell type expresses a unique collection of cell surface molecules, the composition of which changes during development and during an immune response. These surface molecules have been classified by the World Health Organization as “cluster of differentiation” (CD), and include coreceptors, adhesion molecules, homing molecules, and cytokine receptors (eTable 186.1). Identifying and characterizing immune cells based on their cluster of differentiation surface phenotype has become an indispensable tool of the modern immunologist.

Figure 186-1.

CD34+ stem cells give rise to all cells in the hematopoietic lineage. This section focuses on the development of T, B, NK (natural killer), and dendritic cells.

eTable 186.1. Cluster of Differentiation (CD) Classification and Function of Selected Molecules

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