Lymphoid circulation

The extensive lymphoid circulation found in mammals complicates studies of thymus cell function. Clearly, cells can get in and out of the thymus after birth (cf. Yoffey et al., 1959 Harris and Ford, 1964 Linna and Stillstrom, 1966 Galton and Reed, 1966 Toro and Ol, 1967). This fact makes studies involving thymus cell function in immunological reactions difficult to interpret (e.g., Cohen et al., 1963 Yunis et al, 1964 Csaba et al, 1965 Davies et al, 1967). 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

Yoneyama H, Matsuno K, Zhang Y, et al. Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. J Exp Med 2(X)I I93(I) 35M9. 

The lymphatic system, lined with epithelial cells, contains a highly proteinaceous (albumin) fluid with prominent electrolytes, which are characterized by the associated cations of Na , K, and Ca. In health as well as most disease states lymphatic fluid contains no red cells or cells directly derived from the circulating blood system in addition to the lymphoid cells, it does contain macrophages, another major cell type. 

As mentioned previously, glucocorticoids promote apoptosis and reduce survival, differentiation, and proliferation of a number of inflammatory cells. While there is an increase in the number of polymorphonuclear leukocytes in the circulation, corticosteroids cause the involution and atrophy of all lymphoid tissue and decrease the number of circulating lymphocytes. The striking lymphocytopenia is caused in large part by an inhibition of lymphocyte proliferation, although diminished growth with preferential accumulation of cells in the Gi-phase of the cell cycle is followed by cell death. These effects are mainly mediated by alterations in cytokine production and action. 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

Antilymphocyte antibody acts primarily on the small, long-lived peripheral lymphocytes that circulate between the blood and lymph. With continued administration, "thymus-dependent" lymphocytes from lymphoid follicles are also depleted, as they normally participate in the recirculating pool. As a result of the destruction or inactivation of T cells, an impairment of delayed hypersensitivity and cellular immunity occurs while humoral antibody formation remains relatively intact. ALG and ATG are useful for suppressing certain major compartments (ie, T cells) of the immune system and play a definite role in the management of solid organ and bone marrow transplantation. 

Causes emigration of circulating T cells from intravascular tissue compartment to lymphoid tissue... 

Thus, human exposure to PCBs in Japan (Yusho accident) and China has been associated with increased respiratory infections and decreased levels of immunoglobulins in serum. In animals exposed to these compounds, there is atrophy of both primary and secondary lymphoid organs, lower circulating immunoglobulins, and decreased antibody responses after exposure to antigens. Similarly, the exposure of both humans and farm animals to polybrominated biphenyls, which occurred in Michigan in 1973, resulted in depressed immune responses. 

Figure 31-1 (A) Locations of the primary and secondary tissues of the immune system. The primary lymphoid organs are the thymus, which makes T cells, and the hone marrow, which forms B cells. After moving from these organs into the blood circulation the cells reach one of the secondary lymphoid organs, which include lymph nodes, spleen, tonsils, and Peyer s patches on the small intestine. Immature dendritic cells are found in body tissues including skin and mucous membranes and respond to foreign proteins by inducing attack by T lyphocytes and antibody formation by B cells. (B) Schematic drawing of a lymph node. From Nossal.1 Courtesy of Gustav J. V. Nossal.

Both the B cells and T cells arise in the fetal liver or bone marrow (Fig. 31-1) from pluripotent stem cells. In birds the B cells develop in a special organ, the bursa of Fabricius. Mammalian B cells complete their differentiation into mature lymphocytes within the bone marrow. However, the T cells must travel to the thymus, where they complete their maturation. The T lymphocytes include the previously mentioned NK cells as well as the somewhat similar cytolytic T cells and immunoregulatory T cells. The latter are further characterized as helper T cells41 or suppressor T cells. The adaptive response requires cooperation of helper T cells in many instances. Tire mature B and T cells leave the bone marrow and thymus, which are known as the primary lymphoid tissues, and enter the blood circulation. Following "homing" signals42 they take up residence in a variety of locations... 

An additional line of defense is provided by natural killer cells (NK cells), a type of circulating lymphoid cell able to kill cancer cells, to participate in antiviral defenses, and to help control immune responses.273 -276 NK cells, which utilize their own signaling pathways, are also able to use MHC class I molecules to recognize and to spare the lives of normal, healthy cells.277/277a b Partial deprivation of a night s sleep can reduce NK cell activity, damaging the cellular immune response.278... 

Circulating dendritic cells Langerhans cells Interdigitating dendritic cells Interstitial dendritic cells Blood, lymph Skin, mucous membrane Secondary lymphoid tissue (with T cells), thymus Gastrointestinal tract, heart, liver, lungs, kidney... 

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