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Biomedical subjects

F H Bach

Publications and source records attributed to F H Bach.

At least 433 records · Page 24Linked to original sources
PubMed1976

Genetic and cellular aspects of xenogeneic mixed leukocyte culture reaction.

The nature of the antigens stimulating xenogeneic lymphocytes was studied using "primed LD typing". Human lymphocytes were sensitized in vitro against mouse spleen cells and restimulated with spleen cells of mouse strains sharing non-H-2 antigens or various regions of H-2 with the initial stimulating strain. The largest thymidine uptake was caused by restimulation with cells from the specific primary stimulator or an H-2-identical strain. Species-specific antigens or strain-specific antigens carried in the C57BL/10 background account for less than 15% of the total stimulation; a non-H-2 antigen associated with the Mlsalpha genotype caused moderate restimulation, amounting to 25% of the average H-2 response. Within H-2, the strongest restimulation was caused by antigens controlled by the I-A subregion; the K and D regions caused moderate, the I-C and S regions very weak, and the I-B subregion no restimulation. Thus, the genetic control of antigens stimulating xenogeneic and allogeneic MLC responses requires T cells and adherent cells, but in the human-mouse MLC, both cell types must come from the human responder; the majority of the proliferating cells are T cells. It is suggested that allograft and xenograft reactions are fundamentally identical processes, and that the relative vigor of alloaggression may be explained by secondary potentiating mechanisms depending on species-specific interactions between aggressor and target cells.

Animals↗
PubMed1976

Three HLA-D region antigens defined by primed LD typing.

We have recently described a new method, primed LD typing or PLT, for specific identification of HLA-D antigens. Highly discriminatory PLT cells have been developed which clearly differentiate between cells of individuals that restimulate strongly and those that restimulate weakly. Seven such discriminatory PLT cells have been used to define three antigens called PL1, PL2, and PL3; two more PLT cells may define antigen(s) PL4.

Genes↗
PubMed1976

Cellular basis of neonatal induction of in vitro tolerance.

The LD and SD antigens of the major histocompatibility complex subserve differential roles in the induction of the proliferative phase in mixed lymphocyte culture and in the cytotoxic reaction seen in cell-mediated lympholysis. The present study suggests that they also behave differently in the neonatal induction of tolerance. SD antigens appear to induce tolerance in the cytotoxic T lymphocytes very effectively, whereas LD antigens (or the cytotoxic targets coded by genes in the I and/or S regions) are relatively ineffective in this regard. LD antigens presented neonatally are effective at inducing tolerance in the proliferating helper cells.

Animals↗
PubMed1976

Secondary cell-mediated lympholysis: importance of H-2 LD and SD factors.

Lymphocytes stimulated in mixed leukocyte cultures and left for 13-17 days, i.e. beyond their peak proliferative and cytotoxic reactivities, can be restimulated to give a secondary-type rapid and strong proliferative and cytotoxic response when confronted with cells of the original sensitizing cell donor. We have concerned ourselves primarily with the requirements of restimulation for the presence of LD and/or SD stimuli on the restimulating cells. (a) The low level cell-mediated lympholysis (CML) associated with LD differences in a primary CML can be restimulated to give a secondary-type response by those same LD antigens. (b) If the original sensitizing cells differ from the responding cells by both LD and SD antigens, restimulation with only the LD antigens, or third-party cells presumably carrying cross-reactive LD antigens, can restimulate the secondary CML responses directed against the SD antigens on the original sensitizing cells. (c) The presence of SD antigens on the restimulating cells that are cross-reactive with the primary sensitizing SD antigens (as determined in a primary CML) leads to the preferential activation of cytotoxic T lymphocytes reactive to those antigens although maximum cytotoxicity is still directed at cells carrying the original sensitizing SD antigens. A model to explain these results is presented.

Animals↗
PubMed1976

Differential function of major histocompatibility complex antigens in T-lymphocyte activation.

We have emphasised the functional dichotomy of MHC LD and LD antigens as well as the differences in cellular responses to these antigens. Perhaps in so doing we have failed to stress adequately the similarities that exist. But while the similarities (for example skin graft rejection associated with both K and I region differences) are so very clear, the differences have best allowed our progressive understanding of MHC induced cellular responses from the perspective stressed in this article. Of greatest importance to our understanding of these transplantation antigens are the potentially differential roles for the LD and SD antigens in the complex series of events that are collectively referred to as the "allograft reaction". It has been suggested that these differences may be "merely quantitative". This possibility has been discussed repeatedly in our previous reports on the distinction of LD and SD. In fact, the great bulk of biological phenomena can be reduced to quantitative differences. It would seem to us that sufficient evidence for such differential activity exists to make the LD-SD dichotomy model an heuristically valuable one for purposes of designing future experiments. We have discussed the clinical relevance of this model elsewhere. Many authors have speculated and evidence has been gathered to suggest, that cell surface antigens associated with the MHC are important in developmental and other cell interactions. Some studies have directly addressed the question of the need for MHC compatibility to allow cell interaction to proceed optimally. It thus seems most appropriate that the genetic complex with which we are dealing has been termed the major histocompatibility complex; allowing for the literal interpretation of this term this may be the genetic region that by its influence on "tissue compatibility" may control critical cellular interactions in addition to those observed in allograft reactions. It is the simple good fortune for those whose attention was focused on this complex by transplantation problems to find themselves with a panorama of biological phenomena that require extensive experimental probing and integration, hopefully ultimately leading to an understanding of the MHC in a broader context than has to date been possible.

Animals↗
PubMed1976

Differential cellular immune responsiveness to systems of the major histocompatibility complex.

Antigens determined by genes of the major histocompatibility complex can be divided into two systems" the LD (lymphocyte-defined or L determinant) and SD (serologically defined or S determinant) antigens. This division is based on the differential cellular responsiveness to these two sets of antigens of two subpopulations of T lymphocytes: a proliferating helper cell responds primarily to the LD antigens while a cytotoxic T lymphocyte responds most strongly to the SD antigens.

Animals↗
PubMed1976

A sensitive micromethod for generating and assaying allogeneically induced cytotoxic human lymphocytes.

A sensitive micromethod for generating and assaying allogeneically induced cytotoxic human lymphocytes in vitro is described. Responding lymphocytes are cultured with mitomycin-C treated allogeneic stimulating cells in wells of replicate microtrays for both one-way mixed leukocyte culture (MLC) and cell-mediated lympholysis (CML) assays. On day 5, MLC response is determined by measuring 3H-thymidine (3H-TdR) incorporation directly in wells of the MLC tray. On day 6 or 7 CML response is determined by measuring 51Cr released from labeled target cells added to replicate culture cells in the CML tray. It is thus possible to measure both MLC and CML responses of the 2.5 X 10(4) -U X 10(5) responding lymphocytes originally placed in replicate wells. 51Cr-labeled target cells can be added to wells containing dilutions of the stimulated cells and a log-linear relationship between the per cent specific 51Cr release and number of effector cells is observed. Significant levels of specific cytoxicity are detected at ratios as low as one effector cell per target cell; little cross-killing on third-party cells and no autokilling is observed. Lymphocytes purified from whole blood that is stored overnight at room temperature and purified lymphocytes stored overnight in the cold generate MLC and CML responses comparable to those of lymphocytes purified from fresh blood. Only 2 or 3 ml of whole blood are required to perform both MLC and CML assays, thus enabling the study of both proliferative and cytotoxic lymphocyte responses in young children and other individuals from whom only a few milliliters of blood can be obtained.

Blood Preservation↗
PubMed1976

Pooled stimulating cells as a "standard stimulator" in mixed lymphocyte culture.

Lymphocytes from normal unrelated donors were pooled and used as stimulating cells in mixed lymphocyte culture (MLC). Different pools, each consisting of cells from 20 or 30 different donors, stimulated approximately the same amount of 3H-thymidine incorporation by a given responder, and this "plateau level" of incorporation was different for different responders. Stimulation by pools of 20 cells was highly correlated with the general "responsiveness" of responding cells as measured by their mean response to a large panel of stimulating cells. Such pools may be useful as "standard stimulators" in quantitating MLC stimulation, and perhaps also in evaluating lymphocyte responsiveness of patients.

Bromodeoxyuridine↗
PubMed1976

Recognitive specificity of human cytotoxic T lymphocytes. II. The non-recognition of antigens controlled outside the major histocompatibility complex.

In vitro sensitized cytotoxic T lymphocytes (CTLs) primarily detect antigens controlled within the major histocompatibility complex (MHC) that are associated with the serologically detected (SD) loci LA and FOUR. Frequently CTLs sensitized to cells from one individual kill target cells of a third party that shares no SD cross-reactivities by serological criteria with the initial stimulating cells. We have studied the possibility that this cross-killing is due to the recognition of non-MHC controlled antigens. Allogeneic tissue from MHC identical siblings is rejected in the absence of immunosuppression, demonstrating the importance of non-MHC antigens. Nevertheless, CTLs sensitized simultaneously with mitomycin-C treated cells from an MHC identical sibling and from an unrelated individual were only able to mediate cytotoxicity on the unrelated's target cells. No significant cytotoxicity was observed in any combination on target cells differing only for non-MHC antigens.

Consanguinity↗
PubMed1976

Genetics of transplantation: the major histocompatibility complex.

A genetic region called the major histocompatibility complex of MHC (which plays an important role in the control of graft survival) has been defined in a large number of different species. Several different loci of the MHC have been described, including loci coding for transplantation antigens. These antigens can be divided into two categories: first, the SD antigens that were originally defined serologically and that appear to function as targets for the killer lymphocytes involved in the rejection of a graft and second, the LD antigens that were originally defined by lymphocyte response in the mixed leukocyte culture test and that stimulate helper T lymphocytes. In addition, there are genes for other antigens (referred to as immune response-associated or Ia antigens) and genes that control the ability of an animal to respond immunologically to antigenic stimuli, the immune response or Ir genes. There is evidence for epistatic interaction between these genes in that immune recognition of LD and SD antigens lead to a more pronounced development of cytotoxic (killer) cells than does stimulation by either antigen alone. In addition, the genetic control of immune responsiveness appears, at least in some systems, to reside in two very closely linked genes that may function better in the cis than in the transposition. This latter finding suggests a possible explanation for the strong linkage disequilibrium found between genes of the MHC. A number of new tests have been described to define the antigens of the MHC. Results of these tests have been used for studies of transplantation immunology but in addition to study the very strong associations that exist between some of the MHC antigens in man and various diseases.

Antibody Formation↗