摘要:

AbstractAntibody specificity is determined by structural v‐genes that code for the amino acid sequences of the variable regions of antibody polypeptide chains. The present hypothesis proposes that the germ‐cells of an animal carry a set of v‐genes determining the combining sites of antibodies directed against a complete set of a certain class of histocompatibility antigens of the species to which this animal belongs. The evolutionary development of this set of v‐genes in phylogeny is traced back to the requirements for cell to cell recognition in all metazoa. The hypothesis leads to a distinction between two populations of antigen‐sensitive cells. One population consists of cells forming antibodies against foreign antigens; these lymphocytes have arisen as mutants in clones descending from lymphocytic stem cells which expressed v‐genes belonging to the subset (subset S) coding for antibody against histocompatibility antigens that the individual happens to possess. The other population consists of allograft rejecting lymphocytes that express v‐genes of the remaining subset (subset A) coding for antibody against histocompatibility antigens of the species that the individual does not possess. The primary lymphoid organs are viewed as mutant‐breeding organs. In these organs (e. g.in the thymus), the proliferation of lymphocytes expressing the v‐genes of subset S and the subsequent suppression of the cells of these “forbidden” clones, leads to the selection of mutant cells expressing v‐genes that have been modified by spontaneous random somatic mutation. This process generates self‐tolerance as well as a diverse population of antigen‐sensitive cells that reflects antibody diversity. The proliferation in the primary lymphoid organs of lymphocytes expressing v‐genes of subset A generates the antigen‐sensitive cell population that is responsible for allo‐aggression.The theory explains how a functional immune system can develop through a selection pressure exerted by self‐antigens, starting during a period in early ontogeny that precedes clonal selection by foreign antigens. The hypothesis provides explanations for the variability of the N‐terminal regions of antibody polypeptide chains, for the dominant genetic control of specific immune responsiveness by histocompatibility alleles, for the relative preponderance of antigen‐sensitive cells directed against allogeneic histocompatibility antigens, for antibody‐idiotypes, for allelic exclusion, for the precommitment of any given antigen‐sensitive lymphocyte to form antibodies of only one molecular species and for the cellul

ISSN:0014-2980    

DOI:10.1002/eji.1830010102

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractA carrier effect is obtained typically when a hapten‐protein conjugate is injected into an animal which has previously been primed with the same hapten conjugated to another carrier protein. Under these circumstances the anti‐hapten secondary response is usually less than that which would have been obtained had the animal been injected with a conjugate prepared with the same carrier as that originally used for priming. Attempts have been made to account for the phenomenon in terms of the local environment hypothesis, which assumes that the receptor on immunologically competent cells recognises the hapten jointly with the area on the complete antigen which surrounds it. Alternatively the phenomenon can be accounted for by the hypothesis of cooperation, which assumes that the antigen is recognised by two receptors, one directed to the hapten and the other to a determinant on the carrier protein.Methods are described which enable carrier effects to be studied quantitatively in mice. They involve a cell transfer system in which cell suspensions prepared from large numbers of donors are distributed among irradiated syngeneic recipients. In these recipients the transferred cells can be made to perform a secondary response by appropriate antigenic stimulation. The response is monitored by binding tests in which the capacity of serum to bind highly radioactive haptens or proteins is measured. The haptens employed in this system are NIP (4‐hydroxy‐5‐iodo‐3‐nitro‐phenacetyl‐) and DNP (2,4‐dinitrophenyl‐) and the proteins comprise chicken γ‐globulin, bovine serum albumin, human serum albumin, ovalbumin, bovine γ‐globulin, keyhole limpet hemocyanin and mouse γ‐globulin.A carrier effect was regularly obtained when the proteins were tested against one another as carriers, for priming and for the secondary response. The effect could best be measured by comparing the relative potencies in the secondary response of the homologous conjugate (i. e.one with the carrier which had originally been used for priming) with heterologous conjugates (i. e.ones with new carriers). In this way the intrinsic potency of the individual protein could also be measured and allowance made for it in calculating the magnitude of the carrier effect. An average carrier effect of one thousand‐fold relative potency was obtained. Priming by NIP‐ovalbumin or NIP‐chicken γ‐globulin with secondary stimulation by NIP‐bovine serum albumin (or the corresponding DNP conjugates) could be identified as the combination best suited to further study.Support for the cooperation hypothesis, particularly for that version of the hypothesis which postulates that recognition of carrier determinants allows an antigen‐concentrating mechanism to operate, could be found in the parallel slopes of the dose‐response curves obtained with homologous and heterologous conjugates. On the other hand the local environment hypothesis failed to pass either of the tests to which it was subjected. One, the weaker, was to compare haptens with and without spacer groups inserted between themselves and the carrier protein, in the expectation that spacers might reduce the local environment contribution: no difference could in fact be detected. The other, the stronger, was to attempt to inhibit the response with an excess of carrier protein even though the anti‐hapten antibody had no detectable affinity for the carri

ISSN:0014-2980    

DOI:10.1002/eji.1830010103

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractThe adoptive secondary response of mice to conjugates of NIP (4‐hydroxy‐5‐iodo‐3‐nitro‐phenacetyl‐) and DNP (2,4‐dinitrophenyl‐) is here used to elucidate the mechanism of cellular cooperation. The framework into which the experiments fit can be formulated as follows. Priming immunization raises a crop not only of specific antibody‐forming‐cell‐precursors (AFCP) but also of specific helper cells. Upon secondary stimulation the helper cells serve a role as handlers or concentrators of antigen, thus enabling AFCP which would otherwise be incapable of reacting to initiate antibody synthesis. In this act of cooperation both cells recognise antigen; in the system examined here the helpers recognise carrier determinants and the AFCP recognise either the hapten or other carrier determinants.The first aim of the experiments was to raise populations of helpers and AFCP of distinguishable specificity. Mice were primed with NIP‐Ovalbumin (OA) mixed with chicken γ‐globulin (CGG) and bovine serum albumin (BSA); in comparison with controls primed with unmixed NIP‐OA, their cells after transfer were relatively more sensitive to secondary stimulation with NIP‐CGG or NIP‐BSA and similar findings were obtained in cross‐checks of these carriers. For reasons which are not entirely clear, non‐transferred cells did not show the same effect. In further experiments cells primed with one conjugate (e. g.NIP‐OA) were mixed with cells primed with another protein (e. g.BSA), transferred and challenged with the hapten conjugated to the second protein (i. e.NIP‐BSA). In comparison with controls lacking the protein‐primed cells, the mixture regularly showed greater sensitivity to stimulation. NIP and DNP were tested in many of the possible combinations with BSA, OA and CGG with the same result. The mixture system was used in the further analysis.Tests with allotype‐marked protein‐primed cells showed that these cells did not participate in the production of the anti‐hapten antibody and could therefore properly be regarded as helpers. Tests of specificity showed that physical union of the hapten and carrier were required: cells primed with BSA, for example, would not help NIP‐OA‐primed cells to make a response to NIP‐HSA even when stimulated at the same time with BSA. Transfer of less than one‐tenth of the spleen gives a maximum helper effect, whereas AFCP activity continues to rise as larger numbers of cells are transferred. Helper cells are therefore normally present in excess.Helper activity is more resistant than AFCP activity to irradiation, drugs and semi‐allogeneic cell transfer across an H‐2 barrier. This suggests that helper cells play a relatively passive role in the immune response.Several observations indicate that helper cells are thymus‐derived mediators of cellular immunity. Passively transferred antibody did not substitute for helper cells. After immunization helper activity developed faster than AFCP activity. Spleen cells obtained from lethally‐irradiated, thymocyte‐repopulated, immunized donors provided help. Cells from the thymus‐derived fraction of thymus/marrow chimeras also appear to provide help.Thus, the hapten‐carrier cooperative response maps onto the well‐establ

ISSN:0014-2980    

DOI:10.1002/eji.1830010104

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractUsing the theta (Θ) alloantigen of mice as a marker of thymus‐derived cells, we have studied the distribution of these lymphocytes in adult and developing lymphoid tissues of CBA and Balb/c mice. In adult mice, lymphoid tissues can be arranged in the following order according to the approximate proportions of Θ‐bearing (thymus‐derived) lymphocytes they contain: thymus (100%), thoracic duct lymphocytes (80–85%), blood lymphocytes (70%), lymph nodes (65–70%), spleen (30–35%), peritoneal lymphocytes (30–35%) and Peyer's patches (20–25%).Results obtained in newborn mice show that the development of peripheral lymphoid tissues is largely dependent on the inflow (and possibly the proliferation) of thymus‐derived lymphocytes.The presence of Θ‐bearing lymphocytes in developing Peyer's patches indicates that lymphoid differentiation in these organs is, in part at l

ISSN:0014-2980    

DOI:10.1002/eji.1830010105

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractAntilymphocyte antibody prepared by elution from glutaraldehyde fixed thymocytes is cytotoxic and prolongs the life of allogeneic skin grafts in mice. Radioactively labeled antibody is slightly more effective in prolonging skin grafts than the unlabeled material.

ISSN:0014-2980    

DOI:10.1002/eji.1830010106

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractThe immunogenicity of the synthetic multichain polypeptide (T,G)‐A–L in rabbits was investigated under a variety of conditions. The polymer led to antibody production with as little as four micrograms in complete Freund's adjuvant per immunization. The pattern of antibody formation as a function of time varied from dose to dose, the highest initial response corresponding to the lowest dose administered. The synthetic polypeptide was immunogenic also when incorporated in an alum precipitate, but not when injected intravenously in buffered saline. Tolerance to (T,G)‐A–L was produced in adult rabbits upon intravenous in

ISSN:0014-2980    

DOI:10.1002/eji.1830010107

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractTwo allotypic specificities (W‐1 and SD‐1) of rat immunoglobulin are described. These allotypic specificities are detected by a passive hemagglutination assay. Both specificities are located on the L‐chains of rat immunoglobulin and were found to be present in both IgG2and IgM. The gene loci controlling the allotypic determinants are inherited in a simple Mendelian fashion. Rats of 27 different strains tested possessed either the W‐1 or the SD‐1 sp

ISSN:0014-2980    

DOI:10.1002/eji.1830010108

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractThe group‐specific (Gc) proteins have been purified by an immunochemical method from human sera of Gc 1–1 and Gc 2–2 phenotypes. The two electrophoretic components of the Gc 1 protein, Gc 1F and Gc 1S were isolated by electro‐focusing. Tryptic peptide maps on cellulose thin layers of Gc 1, Gc 1F, Gc 1S and Gc 2 revealed one peptide specific for Gc 2, another peptide specific for Gc 1 and a third characteristic for Gc 1F. The amino acid composition of these peptides was determined. From these and previous results a hypothesis based on one gene locus is put forward to explain the Gc polym

ISSN:0014-2980    

DOI:10.1002/eji.1830010109

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractThe observation that newborn calves develop a proteinuria reaching a maximum between 25 and 30 hours of life after feeding colostrum was confirmed.Among the proteins precipitable at 3.6 M ammonium sulfate, two components with IgG specificity but differing in electrophoretic mobility have been found.Antisera were produced in rabbits against Fab or Fc fragments derived from colostral IgGs by papain digestion. Using these antisera, a urinary Fab was demonstrated to be antigenically identical to the papain Fab. In contrast, the urinary Fc was found to be at least in part antigenically deficient with respect to the papain Fc.With the aid of an immunoadsorbent, the antigen binding activity of the urinary Fab could be demonstrated in calves after the ingestion of colostrum which contained antibody.The site where the degradation of IgGs occurs could not be elucidated.

ISSN:0014-2980    

DOI:10.1002/eji.1830010110

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY

摘要:

AbstractMouse lymphoid cells producing lytic antibody against alloantigens have been detectedin vitrowith the help of a plaque assay using allogeneic tumor cells as indicator cells. In C3H mice injected with 30 × 106DBA/2 tumor cells, alloantibody plaque forming cells appeared in the spleen by day 3 and increased in number until day 9

ISSN:0014-2980    

DOI:10.1002/eji.1830010111

出版商:WILEY‐VCH Verlag GmbH    

年代:1971

数据来源: WILEY