Organization of the human immune system.

During the past decade, our knowledge concerning immunologic development and function has expanded rapidly as a result of the interplay between fundamental studies of antigen receptors and lymphokine molecules and the genes encoding them and studies of patients with leukemias, autoimmune disorders, and immunodeficiency diseases. The latter have been particularly valuable in defining the critical stages in the differentiation of stem cells into mature lymphoid effector cells and the roles played by different subpopulations of cells in regulating immune responses. Several categories of defects in these cellular maturation and cellular interaction events lead to immunodeficiency diseases, including intrinsic defects in the lymphoid cells; abnormalities in the microenvironments necessary for the generation of the differentiation signals essential for the maturation of lymphoid cells; disorders of regulatory cells that normally control humoral and cellular immune responses; and, finally, disorders in which the production of lymphoid cells and immunoglobulins is normal but in which host environment abnormalities lead to excessive endogenous catabolism or excessive loss of immune elements. A second area of major advance has been in defining the arrangement of immunoglobulin and T-cell receptor genes. These genes in their germline form are organized as discontinuous DNA elements that are joined by recombinations during lymphocyte development. The analysis of immunoglobulin gene structure and arrangement has contributed to the study of human lymphoid neoplasms. In addition, the analysis of rearranged immunoglobulin and T-cell receptor genes has been valuable in defining the lineage (T or B cell) of neoplasms whose origins were previously unknown; in determining the clonality of abnormal lymphocyte proliferation; in diagnosing and monitoring the therapy of lymphoid malignancies; in determining the state of maturation and the causes for failure of maturation of cells of the B-cell series; and in providing insights into the causes of malignant transformation of B and T lymphoid cells. It is apparent that the application of this molecular genetic approach has great potential for complementing conventional marker analysis, cytogenetics, and histopathology, thus broadening the scientific basis for the classification, diagnosis, and monitoring of the therapy of lymphoid neoplasia. A final area of dramatic advance has been in defining an array of lymphokine molecules that regulate T-cell and B-cell growth and differentiation. One of the best studied of these lymphokine systems is that of IL-2 and its receptor. Antigen-induced activation of resting T cells induces the synthesis of IL-2 as well as the expression of specific cell surface high-affinity receptors for this lymphokine.(ABSTRACT TRUNCATED AT 400 WORDS)