The effect of a polyanion, polyacrylic acid, on the primary immune response in mice inoculated with sheep red blood cells was investigated. Polyacrylic acid caused early appearence and enhancement of 19 S and 7 S plaque‐forming cell response in mice from 48 h to 10 days after antigen inoculation. Hemolytic antibody titers confirm these results. The degree of the stimulation of the immune response by PAAC was dependent on the antigen and PAAC doses and their routes of administration. The polyanion also increased the background of 19 S plaque‐forming cells in nonimmunized mice and the serum γ‐globulin levels. The effects of polyacrylic acid and the effects caused by natural or synthetic polynucleotides and pyrancopolymer on immune response suggest that the polyanionic structure common to these substances may be responsible for their stimulating activity.
Dextran sulfate enhanced immune response in mice immunized with sheep red blood cells. This stimulation took place only when dextran sulfate was given close t o the time of antigen injection. Dextran sulfate injected one day prior or one hour after antigen inoculation was ineffective. The degree of stimulation of immune response by dextran sulfate depends on the polyanion doses and on antigen doses used. Maximum stimulation of immune response could be noticed when 500 pg dextran sulfate was injected one hour prior t o inoculation of a suboptimal antigen dose, both dextran sulfate and 2 x lo6 sheep red blood cells given via the same route intraperitoneally. However, significant stimulation of immune response also took place when dextran sulfate and antigen were given by different routes. Dextran has no effect on immune response, whereas DEAE-dextran inhibits immune response in mice immunized with suboptimal antigen doses. Results obtained by these experiments clearly demonstrate that the polyanionic structure of polymers is a requirement for their adjuvant activity.
3) The third possibility is that polyanions may induce differentiation and/or proliferation of a distinct type of cells present in bone marrow population whose action is capable of replacing the helper cell function of T cells.Moreover the experiments of Cone and Johnson [ 121 mentioned above and our results might Suggest that genetic defects of the immune system located at the level of "helper-cells" can be corrected by polyanions.
sulfate enhances secondary immune response as well as primary immune response in mice primed and challenged with suboptimal doses of sheep red blood cells. Enhancement of primary response by dextran sulfate did not diminish secondary responses towards suboptimal antigen dose. However, in mice primed and challenged with an optimal antigen dose and injected at the time of priming with dextran sulfate, immunological memory seems t o be increased. In primary as well as in secondary response the number of both 19 S and 7 S PFC were increased.
The mechanism of the Stimulation of humoral antibody formation by polyanionsThe effect of the polyanion polyacrylic acid on humoral antibody synthesis was studied in mice -immunised with sheep erythrocytes. The synthesis of antibodies against sheep erythrocytes was determined by counting antibody-forming cells in the spleen, and by titration of the antibody circulating in the serum. With low doses of antigen, which alone induce no significant response, the presence of polyacrylic acid resulted in a nearly optimal response, giving values 100 to 260 times higher than the control. With suboptimal doses of antigen, which elicit an easily measurable primary response, the immuno-response is also significantly increased (3-to 4-fold) by the polyanion. At optimal doses of antigen, the polyanion has no stimulatory effect. The same order of stimulation of the immuno-response by the polyanion at low doses of antigen is demonstrable in thymectomised mice. Possible mechanisms for the induction or stimulation of the immuno-response by polyanions are discussed. The possible significance of these mechanisms in elucidating the role and function of the different cooperative cells necessary for the formation of antibodies is discussed.
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