bluuebunny/crossref_metadata_2025_split huggingface dataset:
REGULATION OF THE IMMUNE SYSTEM BY SYNTHETIC POLYNUCLEOTIDES
Authors: Cone Robert E. , Johnson Arthur G. 
Published: June 2004

Polyadenylic-polyuridylic acid complexes, a potent adjuvant to the immune response, were tested for action on thymic-influenced and bone marrow-derived lymphocytes in model systems deficient in one or the other of these cells.
Adult mice, thymectomized at birth or mice treated with heterologous antithymocyte serum produced 90–95% fewer splenic rosette-forming cells than normal mice in response to an injection of sheep erythrocytes. Intravenous injection of complexes of homoribopolynucleotides, polyadenylic and polyuridylic acids, poly A:U with SRBC restored immunologic competence to NTx- or ATS-treated mice such that they produced normal or near normal levels of splenic RFC. In addition, injection of poly A:U enabled NTx mice to reject allogeneic skin grafts at the same rate as control mice with an intact thymus. Further reduction in residual thymocytes by combining neonatal thymectomy with ATS treatment reduced the number of anti-SRBC RFC induced by poly A:U.
Lethally irradiated mice which received SRBC, excess bone marrow cells, and as few as 40,000 thymic lymphocytes were stimulated by poly A:U to produce RFC. No adjuvant effect was observed when irradiated mice received excess thymic lymphocytes and low doses of bone marrow cells with poly A:U.
The results suggested that the adjuvant action of poly A:U was exerted on the thymic-influenced, antigen-reactive cell and that restoration of immunocompetence to NTx- or ATS-treated mice was caused by amplification of a small number of residual antigen-reactive cells which were influenced by the thymus in utero before thymectomy, or which survived treatment with ATS.
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: Koster F. T. , McGregor D. D. 
Published: June 2004

A substantial portion of the lymphocyte-like cells in induced peritoneal exudates derive from cells which enter the blood by way of the thoracic duct. The migrant cells have been identified as large and medium lymphocytes, but they may also include short-lived small lymphocytes derived from them. Small lymphocytes which have a potentially long circulating life-span are excluded from exudates, although cells of this type predominate in thoracic duct lymph.
The results imply that many (perhaps all) of the small round cells in inflamed tissue are members of a line of rapidly proliferating lymphocytes. Specifically committed lymphocytes with precisely these properties are added to the blood of rats infected with Listeria monocytogenes. The localization of committed lymphocytes in inflammatory foci could be the crucial event which enables the host to focus his cellular defenses at sites of bacterial implantation.
THE CONTRASTING EFFECTS OF CYCLOPHOSPHAMIDE AND RADIATION ON THE IMMUNE RESPONSES OF THE MOUSE
Authors: Aisenberg Alan C. , Murray Caroline 
Published: June 2004

The immunosuppressant cyclophosphamide easily induces specific immunological tolerance in CBA mice, but is unable to produce an immunological defect in adult thymectomized animals. In contrast, lethal (and sublethal) irradiation does not induce tolerance but readily brings out the deficit of thymectomy. Furthermore, bone marrow cells which protect lethally irradiated animals do not prevent drug deaths.
This sharp dichotomy indicates that the drug and radiation influence the lymphoid system by different mechanisms. It seems likely from the work of others that cyclophosphamide action is markedly dependent on rapid cell proliferation, while radiation is not. From this it follows that the cell which must be depleted to expose the immune defect of the thymectomized animal is a nonproliferating lymphoid element with the slow mitotic rate of the marrow stem cell.
A CELLULAR DEFICIT IN THE RECONSTITUTIVE CAPACITY OF IMMUNE POPULATIONS OF LYMPHOID CELLS DEMONSTRABLE IN STUDIES OF DELAYED HYPERSENSITIVITY IN MICE
Authors: Eidinger David , Ackerman Aleksander 
Published: June 2004

A cell-transfer system was employed in the present work to investigate several characteristics of the capacity of immune and normal lymphoid cells to transfer the delayed response to methylated human serum albumin in lethally irradiated syngeneic recipients. Spleen cells derived from donor mice immunized with goose erythrocytes were far less effective in transferring responsiveness when compared with equal numbers of normal cells. Statistical analyses indicated a frequency of 1 reactive cell or cell unit in 1.3 x 107 normal cells and in 6.2 x 107 immune cells. These findings provided confirmatory evidence that antigen-induced suppression (antigenic competition) employing sequential administration of two non-cross-reacting antigens is due to relative deficits of immunocompetent cells generated by lymphoproliferation in lymphoid tissues secondary to immunization with the initial antigen.
The cellular deficit in the immune population was shown to be resident in a thymus cell population, which restored the number of responders to a level equivalent to the normal population. The thymic cell was akin to the antigen-reactive cell. The cell limiting the degree of response, that is the effector cell for both normal and immune cell populations, was of bone marrow origin. Both populations of cells were shown to act in synergy to reconstitute the delayed response to the antigen.
MECHANISMS OF RECOVERY FROM A GENERALIZED VIRAL INFECTION: MOUSEPOX
Authors: Blanden R. V. 
Published: June 2004

The following passive transfer experiments evaluated the contributions of the various host responses in recovery from mousepox. (a) Immune spleen cells transferred highly efficient antiviral activity, but preinfected recipients of these cells made no detectable splenic interferon or antibody in the 24 hr interval after cell transfer. (b) Passively administered interferon was ineffective. (c) Recipients of hyperimmune serum had much more antibody than recipients of immune spleen cells but significantly less antiviral activity. (d) Immune spleen cell populations with antiviral activity contained mediators of CMI to virus antigens. (e) The antiviral activity of immune spleen cells was specific; it was inhibited by in vitro treatment with ATS, anti-light chain serum, and anti-theta ascitic fluid, but not by removal of mononuclear phagocytes from the immune population.
These results are interpreted to mean that recovery mechanisms conferred by immune spleen cells were triggered by specifically sensitized, thymus-derived lymphocytes, and that antibody and interferon responses were of less importance. A radiosensitive recipient component was necessary for the full expression of the antiviral activity of both immune cells and immune serum. It seemed likely that this component was the blood monocyte.
MECHANISMS OF RECOVERY FROM A GENERALIZED VIRAL INFECTION: MOUSEPOX
Authors: Blanden R. V. 
Published: June 2004

Histological and immunofluorescence techniques showed that mononuclear cells invaded virus-infected foci in the livers of passively immunized mice within 10 hr of the receipt of immune spleen cells or hyperimmune serum; by 24 hr, marked destruction of virus antigens had occurred in these lesions. Immune cell transfer promoted denser packing of mononuclear cells in the foci and more efficient destruction of infectious material than immune serum. Similar liver lesions developed by the 6th day after sublethal, primary, subcutaneous infection in normal mice. In contrast, in mice with GVHR which were immunosuppressed but possessed hyperactive macrophages and unimpaired splenic interferon response, mononuclear cells did not invade liver lesions and the animals died. These results, together with data reported previously, indicated that mononuclear cell invasion of infected liver foci, triggered by CMI, was of key importance in recovery from primary mousepox.
The roles of specifically sensitized lymphocytes and macrophages within lesions were not directly evaluated, but indirect evidence suggested that lymphocytes could cause no more than a halt in virus multiplication, and that macrophages were required for the inactivation of preformed virions. Possible augmentation of the efficiency of macrophages by locally-produced lymphocyte interferon, neutralizing antibody, or stimulation of their phagocytic and intracellular digestive capacity cannot be excluded.
THE NATURE AND THE SPECIFICITY OF MONONUCLEAR CELLS IN EXPERIMENTAL AUTOIMMUNE INFLAMMATIONS AND THE MECHANISMS LEADING TO THEIR ACCUMULATION
Authors: Werdelin Ole , McCluskey Robert T. 
Published: June 2004

The nature and specificity of the mononuclear cells in passively transferred autoimmune encephalomyelitis and adrenalitis were studied. The recipients were prepared by production of a small heat lesion in the target tissue 5 days before transfer. Within 24 hr after transfer of lymph node cells from donors sensitized with the corresponding tissue antigen, a dense mononuclear cell infiltrate developed around the lesion.
When lymph node cells labeled in vitro with 3H-thymidine or 3H-adenosine were transferred, a significant number of labeled lymphocytes was found in the infiltrate at 24 or 48 hr. Lymphocytes labeled with 3H-thymidine showed a greater tendency to accumulate than cells labeled with 3H-adenosine, indicating that newly formed lymphocytes were more prone to enter the reaction than older cells.
Labeled lymphocytes and macrophages of recipient origin and labeled lymphocytes from donors stimulated with B. pertussis were also shown to accumulate around the heat lesion provided the reaction had been initiated by transfer of unlabeled lymphocytes from donors sensitized to the appropriate tissue-specific antigen.
In recipients which were given lymph node cells from two groups of donors, sensitized either to spinal cord or to adrenal antigens, with cells from only one group of donors labeled, equal percentages of labeled cells were found around each lesion. Thus, no evidence of preferential accumulation of specifically sensitized lymphocytes was obtained.
In recipients which received whole body irradiation on the day of production of the heat lesions, 5 days before transfer of lymph node cells from appropriately sensitized donors, neither monocytes nor lymphocytes accumulated around the lesion. However, if the tibial bone marrow was shielded or if bone marrow cells were given to the recipients shortly after irradiation, inflammation developed as in normal recipients.
In recipients which were irradiated 24 hr after the transfer of unlabeled lymph node cells from donors sensitized to the appropriate tissue antigen and then given labeled lymph node cells from B. pertussis-stimulated donors, labeled lymphocytes were found in the reaction 24 hr later. This accumulation occurred although virtually all the lymphocytes present in the lesion at 24 hr after the first transfer were destroyed by the irradiation.
The results are interpreted as follows. The autoimmune reaction is initiated by the arrival at the site of a few specifically sensitized lymphocytes, probably on a random basis. After contact with antigen, factors are produced and released which cause the influx of monocytes and of lymphocytes, in particular newly formed ones, of various specificities. There is no preferential accumulation of specifically sensitized cells. The influx of lymphocytes appears to require the presence of monocytes or macrophages in the reaction.
THE RELATIONSHIP BETWEEN ANTIGENIC STRUCTURE AND THE REQUIREMENT FOR THYMUS-DERIVED CELLS IN THE IMMUNE RESPONSE
Authors: Feldmann Marc , Basten Antony 
Published: June 2004

Certain antigens such as polymerized flagellin are capable of producing relatively normal antibody levels in thymectomized mice, whereas others, including heterologous erythrocytes require the presence of T cells in a helper capacity. The mechanism of thymus-independent antibody production was investigated by comparing the primary IgM responses of spleen cells from ATXBM, XBM, and normal mice to various physical forms of the flagellar antigens of Salmonella adelaide in vitro. No reduction in antibody-forming cell levels to polymerized flagellin over a wide dose range was observed in ATXBM cultures, although the same spleen cells did not respond to an optimal dose of sheep red cells. In contrast, when flagellar determinants were presented in a monomeric form or as flagellin-coated donkey red cells, a highly significant difference was observed between the antibody responses of spleen cells from ATXBM mice and XBM or normal controls. The results suggested that the requirement for T cells in antibody production is not a property of specific antigenic determinants, but depends on the mode of antigenic presentation.
The validity of this conclusion was confirmed by using another antigenic determinant (DNP) coupled either to the thymus-independent carrier, POL, or to the thymus-dependent carrier, DRC. Spleen cells from XBM mice produced comparable AFC levels to both forms of DNP, but the results from ATXBM cultures showed a marked difference. The anti-DNP response to DNP-DRC was greatly reduced compared to controls, whereas that to DNP-POL was normal even after prolonged thoracic duct drainage of the ATXBM donors and pretreatment of their spleen cells with anti-θ-serum and complement. The data presented here imply that the role of T cells in humoral immunity is the presentation of antigen to B cells in such a manner as to initiate optimal antibody synthesis.
INFLUENCE OF GENETIC FACTORS ON THE MAGNITUDE AND THE HETEROGENEITY OF THE IMMUNE RESPONSE IN THE RABBIT
Authors: Eichmann Klaus , Braun Dietmar G. , Krause Richard M. 
Published: June 2004

Selective breeding of rabbits immunized with Group C and Group A streptococcal vaccines was employed to reveal genetic influences on the magnitude and on the restriction in heterogeneity of the immune response to the group-specific carbohydrates. After two generations of selective breeding, complete segregation was achieved between a high-response population (&gt;18 mg precipitins/ml serum, average 33 mg/ml) and a low-response population (&lt;13 mg precipitins/ml serum, average 7.5 mg/ml) to Group C carbohydrate. This suggests that a limited number of genes controls the magnitude of the immune response to this antigen.
Selective breeding of rabbits which were representative of heterogeneous, restricted, and monoclonal responses revealed that the degree of antibody heterogeneity in the parental rabbits is reflected in the offspring. More than 95% of the offspring derived from rabbits which had a heterogeneous immune response developed heterogeneous antibodies. 33% of the offspring derived from rabbits which had restricted and monoclonal immune responses developed monoclonal antibodies. This suggests that the degree of heterogeneity of the antibody response to the streptococcal carbohydrates is under genetic control. The degree of heterogeneity and the magnitude of the immune response appear to be independent variables.
CANINE SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Lewis Robert M. , Schwartz Robert S. 
Published: June 2004

Three breeding lines, originating from dogs with SLE, have been established. Two lines were initiated by mating a female with SLE with a normal male. The third line resulted from a mating of two affected dogs. Brother-to-sister matings have reached the third generation in each line. In addition, backcross and outcross matings were carried out. More than one-third of the autopsied dogs had thymic abnormalities. The commonest lesion was a lymphoid follicle; the thymus of one dog contained multiple granulomas, and in one animal a reticulum cell sarcoma of the thymus was found.
Multiple serological abnormalities, including positive LE cell tests, anti-nuclear antibodies (ANA), and rheumatoid factor, were found in the progeny. The development of ANA appeared unrelated to the incidence of positive LE cell tests. About 10% of the animals had rheumatoid factor in their serum. Control populations of dogs; including house pets; two other, unrelated lines of inbred dogs; and normal dogs housed in the same facility as the SLE colony did not have these abnormalities. The incidence of positive LE cell tests in the inbred, backcross, and outcross matings was not consistent with any conventional genetic mechanism of inheritance. It is conceivable that the results can be explained by vertical transmission of an infectious agent in a genetically susceptible individual.
SPECIFIC IMMUNE RESPONSE GENES OF THE GUINEA PIG
Authors: Bluestein Harry G. , Green Ira , Benacerraf Baruj 
Published: June 2004

The immunogenicity of three random copolymers of amino acids with L-glutamic acid and L-alanine (GA), L-glutamic acid and L-tyrosine (GT), or L-glutamic acid, L-alanine, and L-tyrosine (GAT), administered in complete Freund's adjuvant, was studied in several inbred and random-bred guinea pig strains. The animals were tested for delayed sensitivity and their sera were assayed for the presence of antibody directed against the immunizing polymer. All of the guinea pigs developing delayed hypersensitivity also had significant antibody levels in their sera.
Inbred strain 2 guinea pigs responded to immunization with GA, but failed to form detectable responses to GT. Inbred strain 13 animals, on the other hand, responded to GT, but not to GA. The (2 x 13)F1 hybrids responded to both GA and GT with both delayed hypersensitivity and circulating antibody. Thus, the ability of these inbred guinea pigs to respond immunologically to GA or GT is controlled by distinct autosomal dominant genes.
A variable percentage of random-bred guinea pigs, depending on their source as well as their strain, responded to immunization with GA and with GT.
All guinea pigs, both inbred and random bred, responded to immunization with GAT. The ability to respond immunologically to GAT, therefore, does not seem to be under simple genetic control. However, the levels of anti-GAT antibody found in the sera of animals lacking the ability to respond to GA were much lower than those detected in GA responder animals.
THE ANTIGENIC AND MOLECULAR ALTERATIONS OF C3 IN THE FLUID PHASE DURING AN IMMUNE REACTION IN NORMAL HUMAN SERUM
Authors: Spitzer R. E. , Stitzel A. E. , Pauling V. L. , Davis N. C. , West C. D. 
Published: June 2004

During the reaction of an immune precipitate with fresh human serum, C3 undergoes a number of molecular alterations with the formation of conversion products differing from those obtained when purified components react. Those products which remain in the fluid phase, the subject of the present paper, have been identified by their reaction with monospecific antisera to the three antigenic determinants of C3, A, B, and D, after electrophoresis in agar or polyacrylamide gel.
When purified C3 reacts with EAC1,4,2, C3i is found in the fluid phase. C3i, a loose complex of C3a and C3b, is in a conformational state whereby only the A and D antigens, present on its C3b portion, will consume antibody. The B antigen, present on the C3a portion of C3i, is unavailable for combination with antibody until C3i dissociates.
In the fluid phase of the reaction of an immune precipitate with whole serum, C3i, C3a, and C3b, formed when purified components react, cannot be found. Instead the end products of the reaction appear to be C3c, which contains the A antigen, and C3d, which contains the D antigen. C3c and C3d are similar to the ß1A and α2D produced by the aging of serum but differ in their mobilities in acrylamide gel and in agar. The C3c and C3d generated by an immune precipitate also differ slightly from the C3c and C3d produced by the reaction of trypsin with C3 in whole human serum.
As human serum reacts with an immune complex, native C3 appears to undergo a primary alteration before conversion. This alteration results in a molecular species of C3 which is labile at 56°C for 30 min, fails to expose additional A and D antigenic sites upon aging, and which forms ß1A and C3d rather than ß1A and α2D during aging.
In addition to this altered form of native C3, a new conversion product, C3x, is formed as whole serum reacts with an immune complex. C3x is not found in systems utilizing pure complement components. C3x is like C3 in that it bears all three antigenic determinants but differs in that it has a slightly faster mobility in polyacrylamide gel than does native C3. C3x is not only found in the fluid phase but is also bound to the immune precipitate.
Finally, the fluid-phase kinetics of each of the antigens of C3 have been determined as normal human serum reacts with an immune precipitate. These illustrate that nearly the entire population of native C3 molecules undergoes conversion rapidly as manifested by the disappearance of the B antigen from the fluid phase. Moreover, the kinetics of the fluid-phase A and D antigens reflect that the conversion of C3 in serum is quantitatively not the same as when purified C3 reacts with C4,2.
CONTRIBUTION OF A THYMIC HUMORAL FACTOR TO THE DEVELOPMENT OF AN IMMUNOLOGICALLY COMPETENT POPULATION FROM CELLS OF MOUSE BONE MARROW
Authors: Small Myra , Trainin Nathan 
Published: June 2004

The hypothesis that cells located in mouse bone marrow can acquire immunological competence by a process that involves interaction with a noncellular component of the thymus was tested using an in vitro assay of graft-versus-host reactivity as a criterion of cell competence. When suspensions of C57BL bone marrow cells were incubated in thymus extract and injected into mice incapable of inducing a response in the graft-versus-host assay as a result of neonatal thymectomy, or adult thymectomy plus irradiation, or because of genetic similarity with the (C3H x C57BL)F1 tissue used for challenge in the assay, competent cells were recovered from the spleens of the injected mice. The reactive cells were shown to be of bone marrow origin since immune reactivity was related to the genetic makeup of the bone marrow cells rather than that of the intermediate recipients. A thymic factor was involved in the process leading to immune reactivity by these cells, as bone marrow cells incubated in xenogeneic or syngeneic thymic extracts induced a graft-versus-host response after passage through nonresponsive mice, whereas incubation of bone marrow cells in xenogeneic lymph node or spleen extracts or in culture medium only did not lead to subsequent reactivity. Participation of peripheral lymphoid tissue seemed essential in this process since bone marrow cells tested directly after exposure to thymic extract failed to induce a graft-versus-host response. C57BL bone marrow cells exposed to thymus extract and cultured together with fragments of (C3H x C57BL)F1 spleen tissue in vitro were competent to induce a graft-versus-host response; thus, these components would seem to be sufficient as well as necessary for the immunodifferentiation process leading to graft-versus-host activity.
It is concluded that one step in the process by which bone marrow cells acquire competence vis-a-vis the graft-versus-host response depends upon a thymic agent that is noncellular and extractable, and that another stage in this process is under the influence of components found within the peripheral lymphoid tissue environment. It is suggested that differentiation of precursor cells to competence could occur by progressive development of the cells in separate compartments of the lymphoid system.