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INTRODUCTION

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Normal lymphopoiesis is an essential component in host defense. It involves the proliferation and function of several types of lymphoid cells including B cells, which are the antibody-producing cells; T cells, which carry out cell-mediated immune functions and are largely responsible for regulatory control of the immune system; and the natural killer (NK) cells, which function more in a macrophage-like role in host defense against infection and malignancy. An understanding of normal lymphopoiesis requires knowledge of individual cell characteristics and expected responses of these cells to disease states.

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LYMPHOID STEM CELLS

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The earliest lymphoid stem cell is derived from the totipotent stem cell pool of the marrow. However, both B cells and T cells then mature in other lymphoid tissues. The thymus plays a major role in developing T cells. Precursors leave the marrow and migrate to the thymus, where they develop into immunocompetent cells. It is in the environment of the thymus that the T cell develops its critical ability to distinguish self from non-self and where errors in development form the basis for most, if not all, autoimmune disease. The stages of T-cell development in the thymus are well defined and form the basis for the clinical approach to the classification of T-cell malignancies.

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B-cell development takes place in the marrow and peripheral lymphoid tissues, the lymph nodes, and spleen. The stages of B-cell development are not as clearly defined as those of T cells, forming more of a continuum leading to the end stage plasma cell. In addition to their classical role in the production of antibodies, B cells also serve as antigen-presenting cells. They have the ability to localize and process antigens from the environment and to present these antigens to other cells of the immune system just like macrophages. Regulatory T cells largely control their development and function. Therefore, it is sometimes difficult when presented with a disease secondary to immune dysfunction to assign root cause to the B- or T-cell system simply because the 2 systems are so intimately intertwined.

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The Immune Network

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One important concept for disorders of the immune system is the "immune network." Cells of the immune system make no basic distinction between internal antigen (ie, a component of self) and external antigen (ie, a pathogen or molecule arising from mutation or transplantation). All chemical structures in the body, including proteins, carbohydrates, and to a lesser extent lipids, are recognized by immune cells. This includes the components and products of the immune cells themselves. The "immune network" is balanced in such a way, however, that those cells that recognize self-antigens are suppressed but not eliminated, and those cells recognizing foreign antigens are stimulated but not allowed to become predominant. Thus, the immune system can be looked on as a balanced network of positive and negative interactions that is controlled by intertwined feedback ...

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