Humoral and Cellular Aspects of the Immune Response to the Somatic Antigen of Salmonella Enteritidis

Abstract

In 1927 White (1) established that the somatic polysaccharides on the surface of Gram-negative bacteria confer on these organisms their characteristic serologic specificities. This was followed in the early 1930's by the pioneer work of Boivin (2) who extracted and isolated these enterobacterial "glucidolipids" and revealed that the same complex carried both the antigenic and toxic attributes of Enterobacteriaceae. The tempo of investigations on these endotoxins increased considerably thereafter, but most studies were concerned with the diverse physiologic derangements and pharmacologic effects evoked in mammals by these materials. The biologic effects of these agents were so dramatic as to largely overshadow their antigenic properties. Nonetheless, a few studies were made which still account for much of the present information on the immunogenic properties of these endotoxic polysaccharide complexes (3, 4).A number of contemporary investigations established additional capabilities for these bacterial polysaccharides, notably their capacity non-specifically to increase resistance to infection (5), to function as powerful adjuvants (6), and to exert proliferative effects on the reticuloendothelial system and lymphoid elements (7). In retrospect these findings were portents that the somatic polysaccharide complexes might possess unique immunological attributes. Recently several methods have been developed which seemed especially useful for further assessment of the immune response to these antigens, ~/z., the highly sensitive bactericidal assay for antibacterial "O" antibodies (8), the detection of both 7S and 19S forms of these antibodies (9, 10), and the adaptation of these antigens to the procedure for in vitro enumeration of antibody-forming cells (11). This communication records the results of an investigation in which these methods were employed to ascertain the characteristics of the immune response to the somatic antigens of Gram-negative bacteria.

Cell Populations and Cell Proliferation in the in Vitro Response of Normal Mouse Spleen to Heterologous Erythrocytes

“…Similar conclusions as to the extent of proliferation have been reached from the rise in the number of plaqueforming cells following antigenic stimulation (2,27). Doubling times in the number of antibody cells less than 6 hr have been found, however (28), and this has led some to conclude that this data cannot be interpreted solely in terms of cell proliferation. It should be pointed out that these data do not demand a generation time of 6 hr or less if the antibody-forming cells are derived from the proliferation of a somewhat larger number of non-antibody-forming precursor cells.…”

Quantitative Studies of Febrile Tolerance and Levels of Specific Antibody Evoked by Bacterial Endotoxin*

“…In seeking to explain the latter findings, it should be noted that the series of daily intravenous injections generally employed to evoke tolerance represents a departure from the usual methods of antigenic stimulation. This may be important in that the same amount of antigen given as a single injection has been found to give rise to essentially 19 S antibody (28). Although it has been possible to produce significant amounts of 7 S antibodies to this kind of antigen in the rabbit (11), massive doses (1,500 ug) were used in comparison to that employed to induce tolerance (2.25 Mug).…”

Nonlinear Response of the Reticuloendothelial System upon Stimulation

“…Data from other laboratories [5,6,[10][11][12]15] indicate that other in vestigators studying the experimental modification of the RES have also observed different segments of the W-or M-shaped dose-response rela tionship, apparently without considering it in its entirety. This may explain why different results have been obtained by different investigators, even when they have used the same stimulant in the same model system.…”