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It is generally accepted that a class of bone marrow lymphocytes migrates to the thymus where the small lymphocytes adapt to certain specific immune functions by virtue of some crucial influence of the thymus. These thymus-derived lymphocytes, referred to as T cells, are responsible for the various phenomena of cell-mediated immunity, such as delayed hypersensitivity, transplantation reactivity, including cell-mediated cytotoxicity and mixed lymphocyte reactions, and cell-mediated resistance to infection; T cells are also the predominant cell type concerned with regulation of other lymphoid cells in the immune system. The second lymphocyte cell type, referred to as B cells, arises also in the bone marrow and settles ultimately in distinct anatomical sites in peripheral lymphoid tissues where they give rise to the precursors of antibody-secreting cells. Among the more helpful tools available to the cellular immunologist are experimental systems in which analyses can be made of the respective functions of T cells and B cells, either independently of one another or in an interdependent manner.

THE TWO MAJOR CLASSES OF IMMUNOCOMPETENT LYMPHOCYTES

One of the major advances in immunobiology in the past two decades has been the recognition of two pathways for the differentiation of antigen-reactive cells. It is generally accepted that a class of bone marrow lymphocytes migrates to the thymus where these small lymphocytes adapt to certain specific immune functions by virtue of some crucial influence of the thymus. These thymus-derived lymphocytes, referred to as T cells, are responsible for the various phenomena of cell-mediated immunity, such as delayed hypersensitivity, transplantation reactivity, including cell-mediated cytotoxicity and mixed lymphocyte reactions, and cell-mediated resistance to infection; T cells are also perhaps the predominant cell type concerned with regulation of other lymphoid cells in the immune system. The second lymphocyte cell type, referred to as B cells, arises also in the bone marrow and settles ultimately in distinct anatomical sites in peripheral lymphoid tissues where they give rise to the precursors of antibody-secreting cells (339, 448, 1051, 1381).

Among the more helpful tools available to the cellular immunologist are experimental systems in which analyses can be made of the respective functions of T cells and B cells, either independently of one another or in an interdependent manner. The introduction of defined haptenic determinants onto immunogenic carriers by Landsteiner (1201) has provided a most convenient method for the analysis of specific interactions between antigens and specific cells of the immune system. For many years it has been known that immunization with a hapten elicits anti-hapten antibody responses only when the hapten is coupled to a carrier substance which is itself immunogenic; nonimmunogenic substances serve only poorly, or not at all, as functional carriers for haptens. Moreover, as mentioned above, optimal hapten-specific secondary responses require challenge with the hapten–carrier conjugate used for primary immunization (i.e., the “carrier effect”). Since the anti-hapten antibodies produced by such immunizations were highly specific for the haptenic determinant employed (e.g., little, if any, contribution to binding energy was attributable to determinants on the carrier) and since the assumption was made that the specificity of antibody accurately expresses the specificity of the antigen-binding receptor molecules on the precursors of antibody-forming cells, then these observations suggested the operation of an additional recognition mechanism for the carrier molecule. Indeed, the demonstration that cooperative interactions between distinct lymphocytes respectively specific for carrier and haptenic determinants are essential for the development of anti-hapten immune responses validated this interpretation (reviewed in 1051; see Chapter X). Two basic in vivo experimental models have been employed to establish the latter point:

The adoptive transfer experimental system is based on the use of a lethally or sublethally irradiated animal as a relatively immunologically inert recipient of primed or unprimed lymphoid cells whose functions is under analysis. Under usual circumstances inbred animals are employed in this technique, and the cell donors and recipients are syngeneic at the major histocompatibility locus. Modifications from this usual approach will be discussed in Chapters X and XII.

A schematic illustration of the basic approach for studying cooperative lymphocyte interactions in responses to hapten-protein (carrier) conjugates in mice is shown in Fig. I.1. In such systems, two types of donor syngeneic spleen cell populations are employed: One of these is obtained from donors previously immunized with a hapten–carrier conjugate, in this case, 2,4-dinitrophenyl (DNP)-keyhole limpet hemocyanin (KLH); the second donor population is obtained from donors previously immunized with an unrelated carrier alone, in this case bovine γ-globulin (BGG), or from normal unprimed donors as a control. Appropriate numbers of the...