Page 33 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Organization of the Immune System

Dorothy E. Lewis, Sarah E. Blutt

The human immune system consists of organs and movable banked, and methods to increase levels of HSC self-renewal,
cells. This design provides central locations for the initial produc- including three-dimensional scaffolding, are under intensive
tion and differentiation of committed cells from naïve precursors, study. 6
such as the fetal liver, the bone marrow, and the thymus; and
more dispersed sites for the selection and further differentiation Tools Essential to an Understanding of Immune
of cells into mature effector cells, such as the spleen, lymph Cell Biology
nodes, and intestinal Peyer patches. This arrangement also allows Understanding of the categorization and development of hema-
regulation of immune responses at locations peripheral to primary topoietic cells greatly depends on the use of monoclonal antibodies
lymphoid organs to provide local control of infectious processes. and flow cytometry to identify stage-specific leukocyte cell surface
This chapter covers the basic features and the ontogeny of cells antigens. Leukocyte differentiation antigen workshops have
involved in the immune response, as well as the essential structure grouped monoclonal antibodies that recognize the same single
of lymphoid organs and sites of organized immune cells, including molecules on leukocytes by the cluster pattern of cells with which
skin, the large intestine, and adipose tissue. they are identified, hence the term cluster of differentiation (CD)
antigen (Table 2.1, Appendix 1).
IMMUNE CELL DEVELOPMENT
Ontogeny of the Cells of the Immune System HEMATOPOIESIS AND LYMPHOPOIESIS
In the first month of embryogenesis, stem cells capable of produc- All mature cells of the hematopoietic and lymphoid lineages are
ing white blood cell progenitors are found in erythropoietic derived from pluripotent stem cells that produce progenitors
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islands that are in the yolk sac. The aorta–gonad–mesonephros for lineage specific cells. Hematopoietic progenitors mature into
(AGM), which is adjacent to the liver, produces progenitor cells cells of the granulocytic, erythroid, monocytic–dendritic, and
that develop into hematopoietic stem cells (HSCs). In the sixth megakaryocytic lineages. Likewise, lymphoid progenitors mature
week of gestation, or just after the embryonic liver can be identi- into B, T, and innate lymphoid cells (ILCs), including natural
fied, progenitor stem cells in the liver begin blood cell production. killer (NK) cells (Fig. 2.1).
By the eleventh week, the liver is the major source of hematopoiesis The site of development differs by cell type. After birth,
and remains so until the sixth month of gestation. 2 granulocytes, monocytes, dendritic cells (DCs), erythrocytes,
HSC-derived progenitor cells can differentiate into granulo- platelets, and B cells develop in bone marrow through the mature
cytes, erythrocytes, monocytes, megakaryocytes, and lympho- B-cell stage (Chapter 7) (Table 2.2). T-cell progenitors leave bone
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cytes. Subsequent to skeleton formation, which occurs between marrow and differentiate into αβ and γδ T cells in the thymus
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the second and fourth months of gestation, white blood cell (Chapter 8). Some NK cells develop in the thymus. Tissue-specific
development starts shifting to bone marrow. This transition NK-cell development occurs outside the thymus, including bone
is completed by 6 months’ gestation. Cells that differentiate marrow, lymph nodes, and the uterus. 8
from early stem cells begin to populate the primary lymphoid
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organs, such as the thymus, by 7 to 8 weeks’ gestation. B-cell Characteristics of Hematopoietic Stem Cells
precursors initiate immunoglobulin (Ig) rearrangements by 7 to HSCs are rare in human bone marrow: 1 in 10 000 cells. They
8 weeks’ gestation (Chapter 7), and T-cell precursors that have occupy distinct niches. One is close to bone and contains
initiated T-cell receptor (TCR) rearrangement (Chapter 8) can be osteoblasts (endosteal niche), and the other is associated with
detected in thymus by 8 weeks’ gestation. In bone marrow, B-cell the sinusoidal endothelium (vascular niche). Quiescent HSCs
progenitors congregate in areas adjacent to the endosteum and can be found near the arterioles in the endosteum. Actively
differentiate in the direction of the central sinus. HSC differentia- dividing HSCs are located near the sinusoid regions close to the
tion is a continuous process and is thus associated with many central veins. Different lineages of progenitors have preferred
phenotypic stages. In the bone marrow of aged humans, there is niches for development, and many HSCs are closely associated
evidence for a myeloid predominance, with a restricted diversity with perivascular mesenchymal stem cells. 3
of HSCs. 5 Long-term human HSCs divide once or twice per year. HSCs
Stem cells with different characteristics and limited self-renewal have characteristic flow cytometric light-scattering properties
can be induced into peripheral blood via injection of granulocyte– (low side scatter, medium forward scatter), no lineage-specific
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colony-stimulating factor (G-CSF). Cord blood cells are being markers (Lin ; e.g., lacking CD2, CD3, CD5, CD7, CD14, CD15,
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