bluuebunny/crossref_metadata_2025_split huggingface dataset:
A PURIFIED GROUP A STREPTOCOCCAL PYROGENIC EXOTOXIN
Authors: Kim Yoon Berm , Watson Dennis W. 
Published: June 2004

Purified pyrogenic exotoxin from Group A streptococcal filtrates (Streptococcus pyogenes, type 10, strain NY-5) has been characterized primarily as a protein complexed with hyaluronic acid. Amino acid composition and analysis revealed a typical acidic protein with an average molecular weight of 29,000. The purified exotoxin was free of streptolysins O and S, nicotinamide adenine dinucleotidases (NADases), deoxyribonucleases (DNases), mucopeptide, and endotoxins. The biological activity was destroyed when the exotoxin was heated at 65°C for 30 min or boiled for 2 min.
The biological activities investigated were pyrogenicity in rabbits (minimal pyrogenic dose-3 hr, 0.07 µg/kg), lethality in rabbits (LD50, 3500 µg/kg), skin test dose in human skin (&gt; 109 skin test doses, per mg toxin), cytotoxicity of rabbit spleen macrophage (Cytotoxic Index 0.5–10 µg/ml), enhancement of susceptibility to endotoxin shock (in rabbits &gt; 100,000-fold), and antigenic analysis (A-type toxin).
The exotoxin was immunogenic and it was possible, therefore, to immunize animals against the various toxic activities. The immunity was specific for the A-type toxin.
The clinical implications of the highly significant enhancement effect of these exotoxins are discussed. It is suggested that clinical or subclinical infection with Group A streptococci could prepare the host for fatal shock from Gram-negative infections or the inadvertent injection of small amounts of Gram-negative bacterial endotoxins.
REACTIVE LYSIS: THE COMPLEMENT-MEDIATED LYSIS OF UNSENSITIZED CELLS
Authors: Thompson R. A. , Lachmann P. J. 
Published: June 2004

This paper describes the characteristics of the indicator factor (I) which takes part in reactive hemolysis and its identification as the seventh component of complement.
I was shown to be a beta globulin with a sediment coefficient of 5.7S and a molecular weight of about 140,000.
Experiments on the depletion of I activity with anti-I antiserum or with activated R euglobulin showed that I was a late acting complement component necessary for the lysis of cells after the EAC142 stage. Complement component analysis of purified I fractions excluded all known components except C7. The physicochemical characteristics of I are compatible with published data on C7. The method of quantitation described represents a convenient method of testing for C7.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Bowman Catharine G. , Bonventre Peter F. 
Published: June 2004

The effect of diphtheria toxin on subcellular components of protein synthesis was determined. Polyribosomes prepared from intoxicated guinea pigs functioned normally in an in vitro assay system, while the activity of soluble enzymes (transferases) from toxin-treated animals was significantly reduced. At high toxin dosages, this reduction was widespread, but when levels of toxin comparable to those which might be generated in a natural infection were given, inhibition of soluble enzyme activity was found only in extracts from heart and skeletal muscle. Possible nonspecific inhibition in the assay system due to interference by free toxin or by a serum component was eliminated.
Since it was possible to demonstrate reactivation of soluble enzyme activity with nicotinamide and toxin, it was suggested that diphtheria toxin acts in the intact sensitive animal in a manner analogous to its action in tissue culture or in cell-free systems. It was hypothesized that the lethal biochemical lesion of the toxin in sensitive animals was the inactivation of transferase enzymes, principally in the heart. It was also suggested that the lethal lesion induced in diphtheria-sensitive and resistant species may not be identical.
THE PROLIFERATIVE AND ANAMNESTIC ANTIBODY RESPONSE OF RABBIT LYMPHOID CELLS IN VITRO
Authors: Theis G. A. , Thorbecke G. J. 
Published: June 2004

Both primary and secondary responses to sheep erythrocytes and to Brucella abortus antigen have been obtained in cultures of dispersed rabbit spleen cells. Removal of adherent cells by repeated incubation of spleen cells on absorbent cotton diminished the ability of the spleen cell suspensions to give secondary as well as primary responses in vitro.
When comparing cultures made in dishes and in tubes, the loss of responsiveness after incubation on cotton was much more evident in the dish cultures. It was concluded that the cell-to-cell interaction needed for immune responses to particulate antigens in vitro was more readily interfered with when the cells were spread over a larger surface area.
The proliferative response to antigen, as measured by uptake of 3H-thymidine in tube cultures of the sensitive spleen cells, appeared particularly resistant to the depletion effect of adherent cell removal.
Dispersed spleen cells from sensitized mice gave a secondary response to sheep erythrocytes. This response was readily abolished by one incubation on absorbent cotton when the cells were cultured in dishes.
IMMUNOLOGICAL MEMORY IN MICE
Authors: L'age-Stehr Johanna , Herzenberg Leonard A. 
Published: June 2004

Plaque forming cells (PFC) of different immunoglobulin classes producing antibodies against sheep erythrocytes were separated according to their buoyant densities by means of equilibrium centrifugation in a stepwise BSA gradient. In the period of 7–10 days after immunization γM PFC are markedly enriched in fractions of low density and relatively depleted in fractions of high density. The distribution of total γG PFC shows less enrichment in the lower density fractions and less depletion in the higher density fractions. The density profile for γG2a PFC is even flatter, with a significant difference (depletion) relative to the unseparated spleen cells only in the highest density fraction.
The density gradient distributions of cells able to transfer an adoptive immune response of the various immunoglobulin classes are markedly different from the PFC distribution.
Cells obtained 7–10 days after immunization able to transfer an IgM response are present in the same proportions across the density gradient, whereas memory cells for γG2a obtained at this time are markedly enriched in fractions of low density and virtually depleted from high density fractions. With increasing time after primary immunization, the γG2a memory cells increase progressively in density and by 6 weeks the higher and lower density fractions have the same proportions of γG2a memory cells. The total γG (mainly γG1) memory cells by 7–10 days show slight enrichment in low density fractions and no depletion in high density fractions. The conclusions were reached that (a) memory for γG1 develops earlier than memory for γG2a and (b) that memory for anti-SRBC antibodies of different classes is carried in separate cells.
When gradient fractions enriched for PFC and memory cells for all classes were completely depleted of PFC using glass bead columns, the ability of this fraction to transfer memory for all classes was not diminished. This shows that memory cells are not identical with cells secreting antibodies.
IMMUNOLOGICAL MEMORY IN MICE
Authors: Jacobson E. B. , L'age-Stehr Johanna , Herzenberg Leonard A. 
Published: June 2004

Congenic mice, differing genetically only at the loci coding for immunoglobulin H chain (or Fc) structures, have been used to study cell interactions in the 7S (γG2a) antibody response to sheep erythrocytes (SRBC), as detected by the Jerne plaque-forming cell (PFC) method.
The interaction between thymus and bone marrow cells was studied in adult thymectomized irradiated recipients, protected with syngeneic bone marrow and injected with thymus cells from the partner congenic strain. All of the γG2a PFC detected in the spleens of these mice were of bone marrow allotype.
Adoptive secondary immune responses were then studied to determine whether a similar interaction between memory cells and bone marrow derived cells could be detected. Primed spleen cells from the partner congenic strain, or a subpopulation of these cells obtained by BSA density gradient fractionation, were injected into irradiated recipients alone, or together with syngeneic nonimmune spleen or bone marrow cells. All γG2a PFC detected in these experiments were of primed cell allotype. There was no evidence that antibody forming cell precursors in normal spleen or bone marrow participate in the adoptive secondary immune response detected 7 days after transfer of primed spleen cells. This was true regardless of whether the bone marrow cells were injected at the time of transfer, or were injected 1–2 wk earlier and allowed to become established in the spleens of recipient mice. Although no specific cell interaction was seen, bone marrow (and, to a lesser degree, normal spleen) cells were found to have a nonspecific enhancing effect on the adoptive secondary response when they were injected together with the primed spleen cells. This enhancement was not evident if the bone marrow cells were injected 1 or 2 wk prior to primed cell transfer.
THE EMERGENCE OF ANTIBODIES WITH EITHER IDENTICAL OR UNRELATED INDIVIDUAL ANTIGENIC SPECIFICITY DURING REPEATED IMMUNIZATIONS WITH STREPTOCOCCAL VACCINES
Authors: Eichmann Klaus , Braun Dietmar G. , Feizi Ten , Krause Richard M. 
Published: June 2004

Electrophoretically monodisperse antibody components in rabbit antisera to the carbohydrates of the Groups A and C streptococci have been examined for their individual antigenic specificity. In these antibody components which were isolated by preparative electrophoresis, individual antigenic specificity was confined to the specific antibody and was absent in the nonantibody γ-globulin. Radioprecipitation experiments and the use of immune absorbent columns constructed from goat anti-antisera, which had been absorbed with fraction II, revealed that all the specific antibody in an electrophoretically monodisperse component was reactive with the homologous anti-antibody.
Antibodies with either identical or distinct individual antigenic specificities may occur in the same rabbit with repeated immunizations. Antibodies with identical antigenic specificity had identical electrophoretic mobility, whereas antibodies with unrelated antigenic specificities had distinct electrophoretic mobilities. In the interval between immunizations, if antibody to the carbohydrate antigen was absent, there was no detectable antibody with individual antigenic specificity.
CHARACTERISTICS OF A NON-COMPLEMENT-DEPENDENT C3-REACTIVE COMPLEX FORMED FROM FACTORS IN NEPHRITIC AND NORMAL SERUM
Authors: Vallota Enrique H. , Forristal Judith , Spitzer Roger E. , Davis Neil C. , West Clark D. 
Published: June 2004

When serum from a patient with membrano-proliferative glomerulonephritis and normal serum are mixed at 37°C, C3 is rapidly broken down to two more rapidly migrating components. In the mixture, a heat-labile pseudoglobulin, designated as the C3 nephritic factor or C3NeF, reacts with a pseudogolbulin in the normal serum, designated as cofactor, to form a C3 inactivator. By analogy with the cobra venom factor, the C3 inactivator is most likely a complex of the nephritic factor and cofactor. The complex has been designated as the C3 lytic nephritic factor or C3LyNeF. The reaction which results in the Formation of C3LyNeF requires the presence of Mg++, is highly temperature sensitive but occurs very rapidly at 37°C. In 20 min at 37°C, C3LyNeF can break down over 80% of the C3 in a mixture of normal and nephritic serum.
The two-step reaction which leads to C3 breakdown has an optimum pH ranging from 6.0 to 9.0. Experiments employing serum depleted of C4 and C2, as well as certain characteristics of the C3NeF system provide evidence that C3 breakdown with nephritic serum is not dependent on complement-inactivating immune complexes or on the action of convertase (C4, 2). Data relating rate of C3 breakdown to the concentrations of C3NeF, C3, and C3LyNeF in the reaction mixture are similar to those for the reaction of enzyme with substrate. The biological significance of C3LyNeF in the production of glomerular inflammation has not been established.
CONTACT SENSITIVITY IN THE MOUSE
Authors: Asherson G. L. , Zembala M. 
Published: June 2004

Contact sensitivity skin reactions were produced in mice by immunization with 2-phenyl-4-ethoxymethylene oxazolone (oxazolone) and detected by the increase in ear thickness after challenging the ears with 2% oxazolone. These skin reactions can be transferred from immunized donors to irradiated recipients by peritoneal exudate cells induced by thioglycollate.
The peritoneal exudate cells were separated into purified macrophage and purified lymphocyte populations. Both cell populations transferred skin reactions. However, their time course was different. The reactions produced by lymphocytes were greater at 24 hr than at 12 hr while the reactions produced by macrophages declined slightly between 12 and 24 hr.
The working hypothesis was formed that the peritoneal lymphocytes conveyed a factor (presumptive cytophilic antibody) to peritoneal macrophages which enabled them to transfer ear reactions. Experiment showed that peritoneal and lymph node lymphocytes from sensitized donors within a Millipore chamber conveyed a factor to macrophages outside the chamber which enabled them to transfer ear reactions. In contrast, peritoneal macrophages (from sensitized donors) within the chamber and peritoneal lymphocytes outside the chamber were inactive.
These findings suggested that there are three modes of immunological tissue damage: hypersensitivity mediated by lymphocytes (classical delayed hypersensitivity), hypersensitivity mediated by circulating antibody (classical immediate type hypersensitivity), and hypersensitivity mediated by macrophages which have passively acquired a factor (macrophage-mediated hypersensitivity).
ANTIBODY-MEDIATED SUPPRESSION OF THE IMMUNE RESPONSE IN VITRO
Authors: Diener Erwin , Feldmann Marc 
Published: June 2004

Immunological tolerance to H antigens of Salmonella adelaide may be induced in vitro by the exposure of mouse spleen cells for 6 hr to an immunogenic dose of polymerized flagellin in the presence of low concentrations of specific antibody. Such antibody-mediated tolerance requires an optimal antigen: antibody ratio for its induction. A shift in this ratio in favor of the antibody concentration results in failure of tolerance induction and leads to immune suppression commonly known as antibody-mediated feedback inhibition which is not analogous to immunological tolerance.
Fragment A of flagellin fails to induce immunological tolerance in vitro. Tolerance to polymerized flagellin may however be induced in vitro, provided the spleen cells are exposed to fragment A in the presence of specific antibody for 6 hr. The results are discussed in the light of current theories of the mechanism of tolerance induction.
ELECTROPHORETICALLY HOMOGENEOUS ANTIBODY SYNTHESIZED BY SPLEEN FOCI OF IRRADIATED REPOPULATED MICE
Authors: Luzzati A. L. , Tosi R. M. , Carbonara A. O. 
Published: June 2004

106 splenocytes from primed donors were injected, together with sheep erythrocytes (SRBC), into X-irradiated syngeneic mice. 8 days later the spleens were excised and cut into small fragments, keeping track of their location in the organ. Each fragment was cultured individually for 24 hr in the presence of 14C amino acids and the culture fluids were assayed for antibody activity. The antibody-producing fragments were found to be clustered in few restricted areas (foci) surrounded by negative tissue.
The anti-SRBC antibody from single foci was purified by absorption on stroma followed by acid elution. Thereafter, it was subjected to electrophoresis and immunoelectrophoresis. The radioautography of the runs showed a considerable degree of homogeneity. Distinct and sharp spikes were localized in the beta and gamma region. The pattern of each focus is unique from the point of view of the number of spikes and their mobility. Eluates obtained from many pooled fragments gave a broad radioactive smear in beta-gamma region.
Many foci synthesized antibody migrating as a single band. This homogeneous protein is probably the product of a clone of cells homogeneously differentiated. However, some foci producing two and probably more antibody bands were also encountered. Two interpretations of the finding can be given. Either more than one precursor may participate in the formation of a focus or a differentiation switch may occur during the clonal expansion.
CELLULAR BASIS OF THE GENETIC CONTROL OF IMMUNE RESPONSES TO SYNTHETIC POLYPEPTIDES
Authors: Mozes Edna , Shearer G. M. , Sela Michael 
Published: June 2004

SJL mice are high responders to the synthetic multichain polypeptide antigen (T,G)-Pro--L, whereas DBA/1 mice are low responders (10, 11). In order to determine whether the genetic control of immune response can be correlated with the number of antigen-sensitive precursor cells, spleen cell suspensions from normal and immunized SJL and DBA/1 donor mice were transplanted into lethally X-irradiated syngeneic recipients (incapable of immune response) along with (T, G)-Pro--L. Anti-(T, G)-Pro--L responses (donor-derived) were assayed in the sera of the hosts 12–16 days later. By transplanting graded and limiting numbers of spleen cells, inocula were found which contained one or a few antigen-sensitive precursors reactive with the immunogen. Using this method to estimate the relative numbers of such cells for the high responder SJL strain, one precursor was detected in ∼1.3 x 106 and ∼7.2 x 106 spleen cells from immunized and normal donors, respectively. In contrast, one precursor was detected in about 30 x 106 spleen cells from low responder DBA/1 mice, irrespective of whether the donors had been immunized.
These results indicate that the genetic control of immunity to the synthetic polypeptide antigen investigated is directly correlated to the relative number of precursor cells reactive with the immunogen in high and low responder strains.
A POPULATION OF LYMPHOCYTES BEARING A MEMBRANE RECEPTOR FOR ANTIGEN-ANTIBODY-COMPLEMENT COMPLEXES
Authors: Bianco Celso , Patrick Richard , Nussenzweig Victor 
Published: June 2004

A population of lymphoid cells from several animal species, including man, was identified through a membrane receptor which binds sheep red blood cells treated with antibody and complement. When cells from different lymphoid organs were incubated with EAC at 37°C, only part of the lymphocytes (named CRL) bound EAC and formed rosettes, and this interaction was shown to be C3-dependent.
Mouse lymphoid cells could be specifically depleted of CRL by allowing them first to interact with EAC and then submitting the mixture to ultracentrifugation in a gradient of BSA. After ultracentrifugation, a population of cells containing 95% or more of non-CRL were recovered from the upper layers of the gradient.
In addition to their different abilities to bind EAC, CRL and non-CRL from mouse lymphoid organs could be distinguished by the following properties: (a) CRL adhered preferentially to nylon wool at 37°C in the presence of mouse serum. (b) After differential flotation in a gradient of BSA, a significantly higher proportion of CRL were recovered from the upper layers of the gradient. (c) The population of CRL contained most of the lymphocytes bearing immunoglobulin determinants on their membranes. (d) The distribution of CRL was quite different among lymphocytes obtained from various lymphoid organs, and they were never found in the thymus. (e) The membrane receptor for EAC was not detected in plaque-forming cells of mice which had been previously immunized with burro red cells.
CRL and non-CRL could not be distinguished by their life span, as they were found in similar proportions among long-lived and short-lived lymphocytes from mouse peripheral lymph nodes.
The function of this receptor on the membrane of certain lymphoid cells may be related to (a) the trapping and localization of antigen in lymphoid organs or (b) the localization of lymphoid cells in inflammatory sites.
DETERMINATION OF ANTIBODY CLASS IN A SYSTEM OF COOPERATING ANTIGENIC DETERMINANTS
Authors: Schirrmacher Volker , Rajewsky Klaus 
Published: June 2004

19S and 7S memory is analyzed in a system of cooperating antigenic determinants. Cooperation occurs in the induction of both 19S and 7S secondary antibodies, and for both responses carrier specificity can be entirely accounted for by presensitization of the animal to carrier determinants.
The class distribution of secondary anti-hapten antibody depends on the dose of the hapten primary-carrier conjugate used for priming, and on the time interval between priming with the hapten primary-carrier conjugate and secondary injection. The conditions of priming with the secondary carrier influence the extent of the secondary response but not the class distribution of secondary antibody. The data confirm the cooperation hypothesis of antibody induction. Specifically, we interpret them to mean that in hapten-carrier cooperation, the hapten-specific memory cells are predetermined for the class of the emerging antibodies. Together with the hapten-specific memory cells, the carrier-specific helpers are responsible for the extent of the secondary response.
CELLULAR AND VASCULAR COMPONENTS OF THE ALLOGRAFT REACTION
Authors: Lambert Peter B. , Frank Howard A. 
Published: June 2004

In order to gain added insight into the mechanisms of allograft destruction, skin grafts were returned to their original donors after remaining as allografts long enough to induce immunity in the intermediate host but not long enough to cause destruction of the graft.
Upon their return to unmodified donors, such grafts became revascularized and remained viable. An intense cellular infiltration was incited within the graft and its draining lymph node by the interaction between immunologically competent cells, some antigenically activated, that were transferred from the intermediate host with the graft, and those of the final host, the original donor. This immune interaction excited a nonspecific granulocytic and histiocytic response, which led to the destruction of the adjacent epithelium already re-accepted within its native habitat. This mechanism of epithelial destruction required vascular connection to permit the cellular infiltration, and was unlikely to have primarily involved circulating antibody.
When similar grafts were returned to donors that had been sensitized to the intermediate host, vascularization and reacceptance of the graft did not occur. No cellular infiltration took place in the graft and no lymph node response was evoked. The returned grafts were cast off as full-thickness sloughs. Here the mechanism of graft rejection was apparently an interaction between the preformed antibody of the specifically sensitized host and the allogeneic cells transferred from the intermediate host; this interaction prevented the vascularization of the graft, even though the endothelia involved were autologous.
In unmodified allografts, both the character and the variability of the histologic patterns can be accounted for by the superimposition, in differing rates and degrees, of humoral vascular effects upon cellular events already in progress.