The Immune Response to Sheep Erythrocytes in the Mouse

Abstract

The biological mechanisms associated with the development of the primary immune response have occupied the attention of numerous investigators. Such fundamental immunological features as the induction phase (1-3), the duration of the latent period (4-6), the cellular dynamics associated with antibody formation (5-9), the homeostatic mechanisms controlling the course of the immune response (10-12), and the development of immunological memory (13-15) have all been extensively considered.The various parameters of the primary immune response have been characterized in the past largely in terms of the appearance of various kinds of circulating antibodies. Such studies may fail to delineate some aspects of the immune response which can only be derived by analyses of the immune reaction on a cellular level. The plaque technique of Jerne and coworkers (16), which demonstrates the production of 19S immunoglobulin to sheep erythrocytes, permits such an analysis. Moreover, the recent modification by Dresser and Wortis (17) for the detection of 7S immunoglobulin production to sheep erythrocytes now allows the assessment of the immune response with respect to both types of immunoglobulins.In the present work, some of the biological features of the primary immune response were studied on a cellular level in a group of Swiss white mice. Such factors as the sequential pattern in 19S and 7S immunoglobulin production with respect to time of onset and duration of immune response were assessed after intradermal (footpad) and intravenous administration of sheep erythrocytes. Several additional features, such as the characteristics of the 19S and 7S peaks, were also considered and compared with similar manifestations in the seconddary response. Comparison was also made of the relative contributions of the proximal and distal lymphoid tissues to the total immune response of the host.

The Effect of Antigenic Competition on Various Manifestations of Humoral Antibody Formation and Cellular Immunity

“…Previous work had established that the parameters of induction of 19S and 7S antibody formation might possess basic differences which were accountable by the origin of these immunoglobulins from differing precursors (9)(10)(11)(12). This view led to an investigation of the differential effect of antigenic competition upon the induction of these two phases of the primary immune response leading to humoral antibody formation.…”

“…Use of particulate antigens injected via various routes initiates an immune response in proximal lymphoid tissues (9), which would tend to rule out competition for space or phagocytic cells. In the present work, the possibility that competition was mediated at the level of a phagocytic cell was investigated by injecting the two antigens in sequence by different routes.…”

“…In addition, all antisera were assayed after treatment with 0.1 ~r 2-mereaptoethanol (2-ME) as previously described (9,13). Serial twofold dilutions of 0.5 ml in phosphate-buffered saline, pH 7.2 were made in Wassermann tubes, and 0.2 ml of 0.3% washed RBC were added per tube.…”

“…demonstrated that the predominantly active tissue in response to an intravenous injection of sheep erythrocytes was contained in the spleen, whereas, the active proximal lymphoid tissue following footpad administration of antigen was the draining popliteal lymph node (9).…”

“…Previous work by this investigator as well as by a number of other investigators, provided evidence for the sequential production of 19S and 7S immunoglobulins by cells arising from differing progenitors (9)(10)(11)(12). These findings implied that the induction phase of these two events in the immune response might possess important biological differences which could be delineated by a model of antigenic competition.…”