摘要:

AbstractAn IgG1‐secreting myeloma possesses Ig‐related surface antigen, Ig‐mem, detected both by a cytotoxic and a125I‐labeled anti‐Ig binding assay. The properties of Ig‐mem were studied by examining the fate of125I‐labeled rabbit anti‐Ig and the complement sensitivity of cells sensitized by the binding of labeled antibody at 0 °C. Shifting the temperature to 24 °C or 37 °C leads to a rapid loss of sensitivity to lysis by complement, as well as a loss in the capacity to detect the rabbit antibody on the cell surface. These reactions occur without any appreciable loss of radioactivity from cells at 24 °C. The125I‐labeled antibody is subsequently degraded to amino acids (detected as iodotyrosine) more rapidly at 37 °C than at 24 °C.We interpret these results as an antibody‐induced interiorization of the IG‐mem, together with its bound antibody. The interiorization reaction does not occur if125I‐labeled, univalent Fab fragment of the rabbit antibody is used. Instead, most of this reagent remains bound to cells for at least an hour at 24 °C or 37 °C. These latter findings suggest that the bulk of Ig‐mem may not be an immediate precursor of the secreted IgG1, in tr

ISSN:0014-2980    

DOI:10.1002/eji.1830030502

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

Abstract(AS2 x AS)F1hybrid rats were made completely or partially tolerant to an adjuvant challenge of human serum albumin (HSA) by prior treatment with fluid HSA (tolerogen). Single doses (10 μg to 200 mg) of fluid HSA failed to elicit a detectable immune response. However, rats made partially tolerant by repeated small doses (10 – 100 μg) synthesized significant quantities of antibody in response to the treatment.Completely unresponsive rats (100 mg fluid HSA 3 x/week for 8 weeks) contained no detectable antigen‐binding antibody in their serum and no plaque‐forming cells (PFC) in their spleens. Thoracic duct lymphocytes from these animals failed to respond when adoptively transferred to irradiated, bone marrow restored recipients and did not inhibit the response of equal numbers of normal thoracic duct cells. Normal lymphocytes responded normally in completely tolerant rats, whether the recipients were irradiated or not. Cells from the bone marrow of tolerant rats were able to restore HSA responsiveness to irradiated rats within weeks of repopulation.Partial tolerance was characterized by a reduction in PFC per spleen, a diminished antigen‐binding capacity (ABC) in the serum, a rapid decline in ABC with time and inhibition or abolition of a memory response. Analysis of the dosage requirements for HSA‐tolerance failed to support the concept that tolerance was induced at two separate dosage thresholds of antigen,i.e.“high” and “low” zone tolerance. To the contrary, the degree of unresponsiveness increased continuously in proportion to the dose of antigen and the number of injections, implying that tolerance induction can be explained by a single mec

ISSN:0014-2980    

DOI:10.1002/eji.1830030503

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractComplete and partial states of tolerance were induced in (AS2 x AS)F1hybrid rats after single or repeated injections of high, medium and low doses of fluid HSA (100 mg to 10 μg). Changes in antibody avidity, following challenge with HSA plus adjuvant, were used to detect those affinity subclasses of HSA‐specific cells which were not eliminated by tolerogenic antigen.Rats undergoing prolonged low dose treatments of fluid HSA induced an appreciable quantity of high avidity antibody before challenge. The avidity decreased significantly following challenge, indicating a progressive loss of high affinity cells, but only after the synthesis of antibody. Rats made partially tolerant against large and medium doses of fluid HSA when challenged, synthesized antibody which failed to mature to a high level, indicating again that high affinity cells were among the first to be deleted. The higher affinity cells in primed rats (including partially unresponsive rats) were the first to disappear during the memory response which was also triggered by fluid HSA. It is proposed that protein antigens induce a state of tolerance by eliminating B cells, but only after driving them through a stage of antibody synthesis.Avidity of antibody was measured following restoration of HSA responsiveness. Antibody failed to mature to a high level in previously tolerant rats that were allowed to recover naturally (stem cell replacement) or were given normal thoracic duct lymphocytes after the tolerance inducing treatme

ISSN:0014-2980    

DOI:10.1002/eji.1830030504

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractThe basic copolymer of alanine, glutamic acid, lysine and tyrosine, denoted Cop 1, is an efficient suppressor of experimental allergic encephalomyelitis (EAE) induced with the bovine basic encephalitogen in guinea pigs and rabbits. The suppression was very effective also when the experimental disease was induced with the basic protein from human source. Two related polymers, one in which glutamic acid was replaced with aspartic acid, and one devoid of tyrosine, were less effective in the suppression of the experimentally induced disease.The route of administration of Cop 1 plays an important role in its suppressive effectiveness, with intravenous injections being the most efficient. The injection schedule and dose of injection are also of great importance; thus, repeated doses of Cop 1 starting five days after the administration of the basic protein are suppressive, whereas a single dose of 5 mg given 72 h after challenging with the basic protein does not suppress EAE. Cop 1 is not a nonspecific immunosuppressant, as it does not affect the immune response towards a variety of antigens, including the rejection of a skin graft.When EAE was induced with the human encephalitogen, the histological changes observed included demyelination and fibrosis in the guinea pig brain.

ISSN:0014-2980    

DOI:10.1002/eji.1830030505

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractA significant extent of immunological cross‐reactivity has been demonstrated between the basic encephalitogenic protein of bovine origin and several synthetic amino acid copolymers which have suppressive effect on experimental allergic encephalomyelitis (EAE). This cross‐reactivity has been conclusively established on the cellular level, bothin vivoby means of delayed hypersensitivity skin tests andin vitrousing transformation of sensitized lymphocytes, as measured by incorporation of radioactive thymidine. Thein vitroexperiments have been conducted with lymph node cells from guinea pigs of both random bred and inbred strains, and on spleen and lymph node cells from rabbits. Definite cross‐reactivity was observed between the basic encephalitogen and all the synthetic copolymers which were previously shown effective in suppression of EAE, whereas ineffective copolymers or unrelated proteins did not show any cross‐reactivity. In the case of strain 2 guinea pigs and rabbit lymph node cells the cross‐reactivityin vitrowas manifested by direct cross‐stimulation of the lymphocytes, whereas in random‐bred or strain 13 guinea pigs and rabbit spleen cells, the cross‐reaction was detected only by means of specific inhibition of the homologous stimulation by the heterologous antigen.A limited extent of cross‐reactivity was observed on the humoral level as well; antibodies provoked in guinea pigs against the synthetic copolymer Cop 1 cross‐reacted in the passive cutaneous anaphylaxis assay with the bovine b

ISSN:0014-2980    

DOI:10.1002/eji.1830030506

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractWith the aid of a lymph node cell transformation test and several fragments of the bovine encephalitogenic protein, attempts have been made to examine more closely various parts of the protein that stimulate DNA‐synthesis of lymph node cells from immunized rabbits. Evidence was obtained for the presence of at least two strongly stimulating regions within residues 44–170: one resides in peptide 44–89 and the other in peptide 93–170. When parts of these regions and other oligopeptide derivatives of region 44–170 were tested, only a slight or no stimulating effect was observed, and a closer localization of all reactive sites – corresponding to that made in guinea pigs with the macrophage migration inhibition technique – could not be made unequivocally. However, peptides 44–68 and 154–170 were shown to have transformation‐inducing effects.Further evidence for the nonreactivity of the tryptophan region was obtained in accordance with previous findings. For at least one region of the encephalitogenic protein – the tryptophan region – there is thus no correlation between disease‐inducing activity and ability to stimulate lymph node cells from immunized rab

ISSN:0014-2980    

DOI:10.1002/eji.1830030507

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractIt has previously been shown that bovine immunoglobulins of the more positively charged IgG2class are confined exclusively to the serum and are incapable of being transferred to the colostrum by the dry mammary gland. Since recent studies have demonstrated that antigens with a negative net charge preferentially provoke the synthesis of more positively charged antibodies, it could be expected that antibodies against such antigens would not be transferred to the colostrum. In the present study, however, acidic antigens (p‐azobenzenearsonate edestin and its maleylated derivative) failed to stimulate predominantly the synthesis of precipitating, binding and phage neutralizing antibodies of the positively charged IgG2class. As expected, immunization of cattle with lysozyme, (a basic antigen), resulted in the production of antibodies almost exclusively confined to the more negatively charged IgGsfraction. In analyzing the precipitin reaction of IgGsclass antibodies, it could be shown that maximum precipitation was achieved at pH 5.0 and decreased significantly at higher pH value

ISSN:0014-2980    

DOI:10.1002/eji.1830030508

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractMouse spleen cells were successfully activated by mitogens in serum‐free medium. The T cell mitogen, concanavalin A (ConA), was found to activate DNA synthesis in the presence or absence of serum to the same extent, although the dose response curve was shifted. Thus, concentrations ten times lower were optimally stimulating in serum‐free medium. The strain differences existing with regard to Con A activation were the same whether serum was present or not. B cell mitogens, such as lipopolysaccharide (LPS) and purified protein derivative (PPD) of tuberculin, were equally active in the presence or absence of serum with regard to dose response curves and kinetics for the induction of DNA synthesis.When added to normal spleen cells in culture in the absence of serum, Con A also activated antibody synthesis against a variety of antigens and haptens. It had no such effect on spleen cells from nude animals, indicating that it exerted its B cell‐activating effect via T cells. It was also effective when DNA synthesis in the lymphocytes had been suppressed with mitomycin.LPS and PPD activated antibody synthesis to haptens in normal and nude spleen cells, the response in nude animals being markedly stronger.Since there is virtually no background antibody synthesis in unstimulated cultures in the absence of serum, but a substantial background in serum, it follows that the factor of activation caused by T and B cell mitogens is more pronounced in the absence of

ISSN:0014-2980    

DOI:10.1002/eji.1830030509

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractConcanavalin A (Con A) has been shown to act differently on bone marrow‐derived (B) cell responses to antigenin vitrodepending on the presence or absence of thymus‐derived (T) cells. When T cells were present, Con A suppressed the immune response to polymeric flagellin (POL) ofSalmonella adelaide(a T‐independent antigen) and sheep erythrocytes (SRBC) (a T‐dependent antigen). In contrast, when T cells were absent, Con A enhanced the anti‐POL response and allowed an otherwise very low anti‐SRBC response to return to normal levels. Con A inhibited POL‐induced capping in a manner that was apparently independent of the presence of T cells. In a number of cases, the effects noted with Con A were also found with another mitogen, phytohemagglutinin. Some possible implications of these findings on the mechanism of T‐B cell collaboration and the relationship between capping and immune inductio

ISSN:0014-2980    

DOI:10.1002/eji.1830030510

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY

摘要:

AbstractImmunization of mice with two non‐cross‐reacting erythrocytes results in the appearance of double rosettes. Injection of sera from doubly immunized animals into normal mice also results in double rosette appearance when spleen cells are examined after rosette formation and incubation at 0 °C for 1 h. However, passive rosettes entirely disappear after overnight incubation at 4 °C or after incubation for 1 h at 37 °C, whereas active ones persist in significant numbers. These treatments therefore provide an accurate discrimination between cells passively sensitized by cytophilic antibody and cells actively forming antibody.Removal of cells adhering to plastic surfaces from spleen cells of doubly immunized animals provokes a decrease of simple rosettes and a disappearance of doubles among non‐adherent cells.When adherent cells are tested for existence of hemolytic plaque‐forming cells (PFC), it was found that PFC also adhere. Conversely, the non‐adherent cell population is severely depleted of such cells. Moreover, double PFC, again found in initial cell populations, were recovered with adherent cells but were absent in the final non‐adher

ISSN:0014-2980    

DOI:10.1002/eji.1830030511

出版商:WILEY‐VCH Verlag GmbH    

年代:1973

数据来源: WILEY