John R. Kettman

Primary antibody and delayed type hypersensitivity response of mice to ovalbumin

The control of the ability to respond to three doses of ovalbumin has been studied in an attempt to find the minimum dose of antigen necessary for activation of primary antibody response and delayed type hypersensitivity response. In seven of the ten mouse strains studied, concordance of the minimum dose needed to elicit the two responses was observed. Discordance is found in the other strains, suggesting that the ability to respond to ovalbumin is independently controlled in several cells. The antibody and delayed type hypersensitivity responses to ovalbumin are controlled by at least two genes, one localized in the major histocompatibility complex.

Modulation of the acquisition and expression of immunity by Tilorone: I. Delayed-type hypersensitivity responses.

The chronic administration of Tilorone [(2,7-bis(diethylamino)ethoxy]fluoren-9-one) with antigen seems to prevent the generation of DTH effector cells. The administration of Tilorone proximal to DTH challenge blocks the expression of DTH. By local transfer of DTH effector cells, this latter effect can be shown to be due to the lack of nonspecific inflammatory cells. By the use of both systemic and local transfer systems, it is also shown that specific DTH effector cells from animals treated with Tilorone are unable to circulate in the normal manner. Overall, these experiments suggest that Tilorone does not block the generation of DTH effector cells, but it does greatly alter the expression of DTH. The relation between these effects and the known interferon induction capacity on Tilorone remains unclear.

Multigenic regulation of the primary immune response to ovalbumin in mice

At least four genes regulate the primary immune response to ovalbumin in mice. The ability to be sensitized to transfer delayed type hypersensitivity to ovalbumin is controlled by two genes. One gene,OVA-β, is linked to theH-2 complex and maps to the left ofI-E. The linkage of the other gene,OVA-Bg1, has not been determined, but it segregates independently of theLy M locus, of the heavy chain allotype genes and of certain genes controlling coat color. At least two genes regulate the ability to respond with a primary antiovalbumin antibody response. One gene,OVA-α, is linked to theH-2 complex and maps to the right ofI-E. Discordance of the minimum dose of antigen needed to elicit delayed type hypersensitivity response and antibody suggests that non-H-2 gene(s) regulating the primary antibody response are different fromOVA-Bg1.

Modulation of the acquisition and expression of immunity by tilorone: II. Humoral responsiveness

Tilorone (2,7-bis[(diethylamino)ethoxy]fluoren-9-one) can enhance the humoral immune response of mice to SRBC although Tilorone has no effect on functional activity of splenic B cells in the absence of immunogen. Tilorone does not alter the effective level of T cell help but does seem to alter the level of effective suppression. Tilorone seems to be an adjuvant only in the sense of removing a normal homeostatic control mechanism, perhaps suppressor T cells.

Genetic restrictions of transfer of delayed-type hypersensitivity to sheep erythrocytes: Local versus systemic transfer

Abstract Regulation of the transfer of delayed-type hypersensitivity (DTH) reactions to SRBC was studied using two assays. In the systemic transfer, SRBC immune cells were transferred intravenously and the recipient challenged by injecting antigen into the footpad. In the local transfer assay, SRBC immune cells were mixed with antigen before transfer into the footpad of the recipient. These studies utilized B10.D2 and B10.BR mice which are congenic strains differing only at H-2 region. DTH reactions can be transferred across H-2 barriers using a local transfer assay. When the immune cells were transferred intravenously or depleted of adherent cells prior to local transfer, DTH reactions cannot be transferred to an H-2 congenic recipient. Spleen cells from naive mice syngeneic to the intravenously transferred cells supply the necessary accessory cell when mixed with the antigen prior to injection into the footpad. This accessory cell may be a macrophage.

Immune response of guinea pig lymphoid cells in vitro: III. Induction by Concanavalin A of a secondary anti-TNP response in primed guinea pig cells☆

Abstract Spleen and lymph node cells of 2,4,6-trinitrophenyl-ovalbumin (TNP-OVA)-primed guinea pigs, show a secondary anti-TNP plaque-forming cell (PFC) response on culture with Concanavalin A which does not require the addition of TNP-OVA but this response may be modestly stimulated by soluble TNP-OVA. If TNP sheep red blood cells (SRBC) are added instead as antigen, the spontaneous anti-TNP response is suppressed but an anti-SRBC response is induced.

Activation of T cells by glutaraldehyde-fixed erythrocyte antigens: Radiosensitivity of cells mediating delayed-type hypersensitivity reactions in the mouse

Abstract Mice immunized with glutaraldehyde-fixed sheep red blood cells (G-SRBC) show delayed-type hypersensitivity (DTH) reactions to G-SRBC or SRBC. The specificity of the DTH reaction of mice sensitized with glutaraldehyde-fixed antigens is similar to that found after sensitization with unfixed antigens. The dose-response curve for sensitization by glutaraldehyde-fixed SRBC was very different from the curve for normal SRBC. At low doses, both antigens were effective in sensitizing to show DTH but neither induced an antibody response. However, at high antigen doses, only the glutaraldehyde-fixed antigen was efficient in sensitizing to show DTH and it failed to raise an antibody titer. Spleen cells of mice sensitized with fixed RBC can transfer DTH locally but if the donor cells are irradiated (500 R), the transfer is abrogated. In contrast, the transfer of DTH by spleen cells of mice immunized with unfixed antigen is not affected by 500 R. The transfer of DTH by spleen cells of mice immunized with fixed antigen can be blocked by “ in vitro desensitization ” while the transfer of DTH by spleen cells from mice primed with normal antigen is resistant to “ in vitro desensitization .” These results suggest that immunization of mice with different physical states of the same antigen can result in the activation of antigen-specific T cells which exhibit markedly different properties.