Thymus-Marrow Cell Combinations. Synergism in Antibody Production.

105

A marked enhancement of anti-hapten antibody synthesis in response to immunization with a hapten-protein conjugate occurs as a result of pre-immunization of animals with unmodified carrier. This is true both for primary and secondary antihapten responses and is most strikingly demonstrated when an animal which has received a primary immunization with a hapten conjugate of a given carrier is boosted with the same hapten conjugated to a different carrier, to which the animal has been preimmunized (1-6).This phenomenon indicates the existence of independent recognition units for hapten and for carrier. Cooperative interaction between these units may be essential to the production of an anti-hapten antibody response, or may amplify a modest immune response which occurs in the absence of carrier-specific recognition.An understanding of the nature of the carrier recognition unit and of the range of substances which it recognizes and acts upon is required in order to construct a coherent picture of cooperative interactions in the immune response. Studies presented both by Mitchison and Rajewsky, et al. (4,5) and those reported in the first paper of this series (6) show that humoral antibody is not the carrier recognition unit.In the adoptive secondary antibody response in mice, hapten-carrier cooperative interactions appear to be mediated by hapten-specific and carrier-specific lymphoid cells (4, 7). In the present communication we show that live lymphoid cells from strain 2 guinea pigs immunized to bovine gamma globulin (BGG) enable syngeneic animals immunized with 2,4-dinitrophenyl ovalbumin (DNP-OVA) to form a secondary anti-DNP response to DNP-BGG. Thus, in both species the carrier recognition unit appears to be associated with a lympboid cell.Several relevant questions may then be asked concerning the significance of this phenomenon and the mechanism by which carrier-specific cells enhance anti-hapten antibody response. One suggested function of the carrier-specific cell is the concentration and presentation of antigen (4, 7). Such cells would bind multideterminant antigens by one of their determinants and simply present other determinants to appropriate hapten-specific cells ill certain anatomical locations. However, the possibility must also be considered that 283 on

Section: Discussionmentioning

confidence: 63%

Carrier Function in Anti-Hapten Immune Responses

Paul

Katz

Goidl

et al. 1970

105

“…There is ample evidence that this interaction occurs (32)(33)(34)(35)(36) but the exact nature of the cooperation is uncertain. There may be transfer of nonspecific factor(s) or translocation of specific genetic information (Fig.…”

Section: Discussionmentioning

confidence: 99%

Immune Response to Chemically Modified Flagellin

Parish

1971

171

In the preceding paper (1) some chemical, antigenic, and biological properties of a series of acetoacetylated derivatives of Salmonella adelaide flagellin were described. Several chemical and antigenic tests revealed that as flagellin was acetoacetylated to increasing extents there was a steady decline in the affinity of the molecule for anti-flagellin antibodies. This loss in antigenic activity appeared to be accompanied on the one hand by a reduced capacity to initiate antibody formation but on the other hand b y an enhanced ability to induce antibody tolerance. In this paper the antibody tolerance induced by these acetoacetylated flagellins is studied in more detail. Furthermore, the ability of these acetoacetyl derivatives to induce delayed-type hypersensitivity is reported. F r o m these studies it was found that suppression of antibody formation in adult rats was accompanied by enhanced cell-mediated immunity. In fact, it appears that in adult animals antibody formation and cell-mediated immunity m a y well be opposing immunological processes. By contrast, tolerance induced in neonatal rats by acetoacetyl flagellin existed at the level of both humoral and cell-mediated immunity. Some preliminary aspects of this work have been reported elsewhere. 1 Materials and MethodsAnimals.--Randomly bred Wistar rats of either sex were used. Animals were either obtained directly from the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia, or bred in Canberra from Wistar breeders supplied by the Walter and Eliza Hall Institute. Both adult (6-10 wk of age) and neonatal rats were used.Antigens.--Flagellin and polymerized flagellin from S. adelaide (strain SW 1338; H antigen--fg) and flagellin from S. typhimurium (strain SL 871; H antigen--l, 2) were prepared as described previously (2). A cyanogen bromide (CNBr) digest of S. adelaide flagellin was prepared and fractionated into fragment A and a mixture of fragments B, C, and D as de-1 Parish, C. R. 1971. Suppression of antibody formation and concomitant enhancement of cell-mediated immunity by acetoacetylated derivatives of Salmonella flage]lin.

“…The accompanying report (11) describes several examples of synergy in the GVH reaction between different populations of lymphoid cells obtained from Balb/c mice. The relationship of synergy in GVH reactions to other instances of cell-to-cell interaction in immune responses (12)(13)(14)(15)(16) will be discussed in that paper.…”

Section: Discussionmentioning

confidence: 99%

Synergy Among Lymphoid Cells Mediating the Graft-Versus-Host Response

Cantor

Asofsky

Talal

1970

100

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.