Central lymphoid tissues

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. 

The studies reviewed in this chapter demonstrate that a strong and reciprocal relationship exists between the central nervous system and the immune system. Indeed, the term neuroim-mune system is clearly justified and appropriate to emphasize the fact that nervous and lymphoid tissues constitute a unified system that functions in the maintenance of homeostasis. The conventional division between the two systems has blurred, as well as the distinction between neuropeptides on the one hand, and immune cytokines on the other. Two lines of research have altered our perspective on neuroimmune interactions (a) the identification of conventional neuropeptides and then-receptors, especially those related to the HPA axis, in most lymphoid tissues, and (b) the large body of evidence that cytokines, historically associated with immune system communication, play vital roles in nervous function. 

In the steady state, the surface marker profile of the vast majority of the population is superficially consistent with that of mature tissue macrophages. However, closer examination reveals additional expression of markers which are generally seen only in tissue sections from central lymphoid organs, such as the murine marker NLDC145 which stains interdigitating cells (IDCs Bilyk... 

The lymphoid tissues include primary (or central) lymphoid organs (bone marrow, thymus and bursa of Fabricius in birds), and secondary (or peripheral) lymphoid organs (lymph nodes, spleen, tonsils, appendix, Peyer s patches). 

Autoimmune regulator (AIRE). An important DNA binding protein involved in immunoregulation (probably in the establishment and maintenance of tolerance). AIRE is expressed mostly in cells of lymphoid tissues. In the thymus, AIRE is expressed in two types of antigen-presenting cells that are central in the negative selection of self-reactive T cells. The absence of a functional AIRE protein (caused by mutations in both copies of the AIRE-1 gene) results in... 

Clonal deletion. Elimination (e.g. by apoptosis, receptor editing) of self-reacting B or T cells during their maturation in central or peripheral lymphoid tissues. Primary mechanism involved in the induction and maintenance of - self-tolerance. 

Enhanced histopathology involves the semiquantitative description of lymphoid tissue changes and is considered central to the Best Practice Guideline for lymphoid tissue microscopic examination. This approach is rooted in the concept that (i) each lymphoid organ has separate compartments that support specific immune functions (ii) these compartments can and should be evaluated individually for changes and (iii) descriptive, rather than interpretative terminology, should be used to characterize changes within these compartments. 

Memory CD4 and CD8 T cells can be divided in effector and central memory Tcells. Effector memory cells are thought to home to nonlymphoid tissues, whereas the central memory T cells localize more to secondary lymphoid tissue [29]. Although originally distinguished by the expression of CCR7 by the central memory T cells, it is clear that both subsets express CCR7 [29, 34]. However, it is thought that these memory cells can express every appropriate chemokine receptor [29]. 

The cells involved in the immune responses are organized into tissues and organs in order to perform their functions most effectively. These structures are collectively referred to as the lymphoid system, and are arranged into either discretely encapsulated organs or accumulations of diffuse lymphoid tissue. The major lymphoid organs and tissues are classified as either primary (central) or secondary (peripheral). Lymphocytes are produced in the primary lymphoid organs and function within the secondary lymphoid organs and tissues. 

A lymph node consists of a cortex and an inner medulla. The cortex is composed of an outer cortex, which contains B-lymphocytes, within lymphoid follicles, and paracortical areas, which contain mainly T-lymphocytes and dendritic cells. The proliferation of B-cells occurs in central areas, called germinal centres. The medulla consists of strings of macrophages and the B-cells that secrete the antibodies (i.e. the effector cells) these are the medullary cords (Figure 17.42). Lymph carries immune cells (e.g. lymphocytes, antigen-presenting cells) and pathogens from the tissues to the lymph nodes, via the afferent lymphatics. 

Cancer is uncommon during the first two decades of life, but is nonetheless a substantial concern. In the United States, cancer is diagnosed in approximately 12 400 children and adolescents annually and is the most common cause of death from any kind of disease between 1 and 19 years of age. In the United States and other developed countries, lymphoid neoplasms (leukaemia, lymphoma) and cancers of the central nervous system are the most common paediatric malignancies. Other kinds of childhood tumours include embryonal tumours of the retina, sympathetic nervous system, kidney, and liver tumours of bone and soft connective tissues and certain gonadal neoplasms. Different kinds of cancer (e.g. carcinomas of liver or thyroid) may predominate in children in parts of the world where specific environmental risk factors are more prevalent. 

In cases where Fc receptors in the tissue are a problem (cells of the lymphoid system, central nervous system and some epithelia) the use of Fab may offer a solution. Pretreatment of the samples with 2% normal serum may also obviate this problem. 

Lymphoid Elements. The thymus plays a central role in the differentiation of T lymphocytes (Cantor and Weissman, 1976), and although much recent emphasis has focused on the thymic epithelial cells, it must be emphasized that the thymus is a lymphoid structure composed predominantly of thymic lymphocytes or thyntocytes. The thymus can be viewed as a solid epithelial organ, penetrated by blood vessels and infiltrated with thymocytes in four discrete areas the subcapsular cortex, the inner cortex, the medulla, and the perivascular connective tissue. 

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