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
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.
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 ||Download (.pdf)
eTable 186.1. Cluster
of Differentiation (CD) Classification and Function of Selected Molecules
|CD1||B, Mφ, DC, T||“Nonclassical” MCH model; present glycolipids|
|CD2||T, NK||Binds CD58 (LFA-3); costimulation|
|CD3||T||Associated with TCR; signal transduction|
|CD4||T||Binds HLA class II; coreceptor|