bluuebunny/crossref_metadata_2025 huggingface dataset:
SERUM CONCENTRATIONS AND ALLOTYPES OF IMMUNO-GLOBULINS IN TWO LINES OF MICE GENETICALLY SELECTED FOR "HIGH" OR "LOW" ANTIBODY SYNTHESIS
Authors: Biozzi Guido , Asofsky Richard , Lieberman Rose , Stiffel Claude , Mouton Denise , Benacerraf Baruj
Published: June 2004

Random-bred Swiss mice were selectively bred for 16 generations; selection was based on their agglutinin response to sheep and pigeon erythrocytes to produce a high and a low responder line.

The serum levels of individual immunoglobulins differed significantly in these two lines before immunization. The differences in the levels of immunoglobulins were much more marked after immunization with pigeon or sheep erythrocytes. Greater differences between the two lines were noted in IgM and IgG levels than in IgA.

Another remarkable finding was the presence of different immunoglobulin phenotypes in the two lines. The high responders were homozygous or heterozygous for heavy-chain linkage groups found separately in the prototype BALB/c and C57BL inbred strains. The low responders were homozygous for a heavy-chain linkage group not present in bred mice in the United States, but observed as a recombinant type among wild mice probably representing a crossover between the heavy-chain linkage groups of the prototype DBA/2 and NH inbred mice.
INTRARENAL COMPLEMENT FIXATION BY CYTOTOXIC ANTIBODIES
Authors: Sellin D. , Kövary M. , Rother U. , Rother K.
Published: June 2004

The reactivity of histocompatibility antigens with serum antibodies and complement was studied in a short term model of allotransplantation. Lewis and DA rat kidneys were perfused with cytotoxic antisera and tissue sections analyzed for adsorption of fluorescent antibodies against γ-globulin and complement (ß1C protein). Both, the presumed cytotoxic antibody and C were localized at similar sites in the endothelial lining and in the walls of the arterial vessels and of the larger veins.

The pattern of immune globulin deposition was distinct from that observed in glomerulonephritis. It may thus become helpful in the differential diagnosis between graft rejection and glomerulonephritis.

At the sites of the deposits, the endothelial cells appeared enlarged and their nuclei protruded into the lumen.

The findings are in line with the hypothesis that an antibody-mediated local activation of serum complement may be involved in the destruction of allografted tissue.
MECHANISMS OF RECOVERY FROM A GENERALIZED VIRAL INFECTION: MOUSEPOX
Authors: Blanden R. V.
Published: June 2004

Agglutination and immunofluorescence tests in vitro showed that the ATS used in these experiments cross-reacted with macrophages and RBC. However, ATS was not toxic in vivo, and small doses given subcutaneously depleted thymus-dependent areas of lymphoid tissues and selectively depressed blood lymphocyte counts without affecting other cell types in the blood. Furthermore, the function of littoral macrophages as indicated by the clearance of blood-borne virus and its subsequent behavior over a 48 hr period in the liver and spleen was not changed by ATS. Thus, the innate resistance of these vital target organs was not depressed. A similar regimen of subcutaneous ATS caused a highly significant increase in mortality from mousepox with an associated failure to control virus growth in the liver and spleen which was manifest by 6 days after infection. The interferon and neutralizing antibody responses were not impaired in ATS-treated mice, but the cell-mediated immune response was significantly suppressed. This evidence, and consideration of the timing of these host responses during the course of infection in relation to the control of virus growth in the liver and spleen, led to the conclusion that cell-mediated immunity probably contributed an essential acquired recovery mechanism. However, no evidence was obtained concerning the nature of this antiviral mechanism.
STUDIES OF DNA-INDUCED HERITABLE ALTERATION OF MAMMALIAN CELLS
Authors: Borenfreund Ellen , Honda Yuji , Steinglass Mildred , Bendich Aaron
Published: June 2004

An intercellular interaction between mouse Ehrlich ascites tumor and non-malignant Chinese hamster cells occurred when these were co-cultured. That the intercellular processes which formed had emanated from the EA cells was revealed by immunofluoroscopy using anti-EA antiserum, and by direct microscopic examination. A passage of DNA from the EA to the CH cells was also observed. On long-term co-culture, new cell forms arose which were isolated, cloned, and propagated. They showed a CH karyotype and had acquired oncogenic potential and the ability to synthesize murine-specific antigens. These same heritable properties were also acquired by CH cells following their exposure to DNA isolated from EA cells.
CELLULAR DIFFERENTIATION IN THE THYMUS
Authors: Colley D. G. , Wu A. Y. Shih , Waksman B. H.
Published: June 2004

Young adult rat thymus and lymph node cell subpopulations were obtained by differential flotation on discontinuous BSA density gradients and assayed for properties characteristic of mature thymus-derived lymphocytes. One such subpopulation (C) of thymocytes was enriched in its ability to respond mitotically to a hemiallogeneic MLR stimulus, to localize in the parenchyma of lymph nodes and spleen, and to initiate a GVH reaction in a suitable host. These cells did not respond well to mitotic stimulation by PHA, they were lighter in density than the majority of mature lymph node thymus-derived lymphocytes, and they possessed a thymus-specific antigen (RTA) not present on peripheral lymphoid cells. We conclude that the acquisition of peripheral properties occurs sequentially, during an intrathymic differentiation cycle or shortly after the cells leave the thymus.
ANTIGEN-SPECIFIC CELLS IN MOUSE BONE MARROW
Authors: Miller Harold C. , Cudkowicz Gustavo
Published: June 2004

Graded numbers of marrow cells and 5 x 107 thymocytes were mixed in vitro and transplanted into X-irradiated (C3H x C57BL/10)F1 mice. Upon injection of sheep or chicken erythrocytes, splenic plaque-forming cells secreting IgM (direct PFC) or IgG (indirect PFC) hemolytic antibody were enumerated at the time of peak responses.

Anti-sheep and anti-chicken primary PFC responses elicited by nonimmune marrow cells differed sharply from each other under the conditions of limiting dilution assays. The frequencies of anti-chicken responses in recipients of different numbers of marrow cells conformed to the predictions of the Poisson model, while the frequencies of anti-sheep responses did not. Hence, the function of certain marrow-derived cells was expressed differentially during the two immune responses, to exclude that the same precursor units generated anti-sheep or anti-chicken PFC. The former precursor cells or units were functionally more heterogeneous than the latter.

Immunization of marrow donors against sheep erythrocytes did not alter the population of cells engaged in anti-chicken responses, since limiting dilution assays with immune and nonimmune marrow cells gave identical results. However, anti-sheep immunization altered specifically the cell population engaged in anti-sheep responses, in two ways: (a) potentially immunocompetent marrow cells underwent antigen-dependent differentiation or maturation, to become functionally homogeneous. Consequently, the frequencies of PFC responses in limiting dilution assays conformed to the Poisson model; the changes occurred independently in class-restricted precursors of direct and indirect PFC. (b) marrow cells capable of inhibiting precursors of direct anti-sheep PFC arose in primed mice. The inhibition, which was specific, could have been effected directly by marrow cells or by a diffusable product such as IgG antibody. Results indicated that potentially immunocompetent cells of mouse marrow with distinct functions were antigen specific and antigen sensitive.
HISTOCOMPATIBILITY TYPE AND IMMUNE RESPONSIVENESS IN RANDOM BRED HARTLEY STRAIN GUINEA PIGS
Authors: Martin William John , Ellman Leonard , Green Ira , Benacerraf Baruj
Published: June 2004

Outbred Hartley strain guinea pigs capable of responding immunologically to 2,4-dinitrophenylated poly-L-lysine were shown to display a histocompatibility specificity in common with inbred strain 2 guinea pigs. This histocompatibility specificity was not detected in guinea pigs unable to respond immunologically to DNP-PLL. The result suggests that the poly-L-lysine specific immune response gene is very closely linked or even identical with a gene determining a major histocompatibility antigen in guinea pigs.
INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO
Authors: Hartmann Klaus-Ulrich
Published: June 2004

The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.
REGULATION OF ANTIBODY FORMATION BY SERUM ANTIBODY
Authors: Bystryn Jean-Claude , Graf Martin W. , Uhr Jonathan W.
Published: June 2004

Rabbits were immunized to two antigens and 18–55 days later exchange transfusion was performed using blood of rabbits immunized to one antigen only. By this means, serum antibody levels to one antigen were reduced 50–84% while maintaining serum antibody levels to the second antigen. After exchange, serum antibody levels of the removed antibody rose rapidly for 24–48 hr and then more slowly, reaching peak titers an average of 8 days later. The peak titer was 48–222% higher than the preexchange titer. The specificity of this rebound excluded as a cause nonspecific changes in Ig levels. Passive administration of antibody to a third antigen 4–7 days before the exchange indicated that re-equilibration of preformed antibody was not a major factor in the rebound. A change in the ratio of IgM to IgG antibodies as a cause of an increased neutralization titer in the postexchange sera was also excluded. It was therefore suggested that a change in the rate of antibody formation had occurred, although other changes in the quality of serum antibody were not excluded.
DIFFERENTIAL MEMBRANOLYTIC EFFECTS OF MICROCRYSTALLINE SODIUM URATE AND CALCIUM PYROPHOSPHATE DIHYDRATE
Authors: Wallingford Walter R. , McCarty Daniel J.
Published: June 2004

Microcrystals of sodium urate produced direct lysis of erythrocyte membranes, as had been described previously for silica. Calcium pyrophosphate crystals induced modest erythrocyte hemolysis, also, and time-course experiments showed a markedly different reaction curve from those produced by silica and urate. Polyvinylpyridine-N-oxide, a strong hydrogen acceptor, was bound from solution to urate and silica, but not to calcium pyrophosphate crystals; this compound effectively blocked urate and silica, but not calcium pyrophosphate or control hemolysis. Dextran and heparin inhibited urate-but not silica-induced hemolysis.

If erythrocyte and lysosome membranes react similarly to these particles, then the absence of phagosomes in gouty synovial fluid leukocytes, and the presence of these structures in pseudogout, may be explained.
IN VITRO AND IN VIVO ACTIVITY OF A LYMPHOCYTE AND IMMUNE COMPLEX-DEPENDENT CHEMOTACTIC FACTOR FOR EOSINOPHILS
Authors: Cohen Stanley , Ward Peter A.
Published: June 2004

When cultured in the presence of specific antigen, lymphocytes from delayed-hypersensitive guinea pigs release a number of biologically active substances into the culture medium. Such active supernatants can react with immune complexes in vitro to generate a factor which is chemotactic for eosinophils. The factor involved is unique, since previously described chemotactic factors for other cell types require for their generation either immune complexes or substances released into lymphocyte culture, but not both. In the case of the eosinophil chemotactic factor, the interaction between the substance elaborated by the lymphocytes and the immune complexes appears to be specific in that the immune complexes must contain the same antigen as that used to activate the lymphocyte cultures. Although this factor was generated in an in vitro system, it has been shown to possess in vivo as well as in vitro activity. It is therefore possible that this factor may be of biological significance in situations where eosinophils are participants in inflammatory or immunologic reactions.
IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS
Authors: Feizi Ten , Kabat Elvin A. , Vicari Giuseppe , Anderson Byron , Marsh W. Laurence
Published: June 2004

A partially purified blood group-like substance obtained from milk showed I activity with 2 of 21 anti-I sera. With these antisera, certain human ovarian cyst substances considered to be precursors of the A, B, H, Lea, and Leb substances also showed I activity comparable to the milk material. Strong I activity could be produced by one-stage periodate oxidation and Smith degradation of human ovarian cyst A and B substances, or of hog mucin A + H substance, or by mild acid hydrolysis of human saliva or ovarian cyst blood group B substance. The two sera indicate that I specificity appears at intermediate stages in the biosynthesis of the A, B, H, Lea, and Lea substances. Anti-I sera differ strikingly in their specificities, indicating substantial heterogeneity of the I determinants.
PRODUCTION OF ULTRASTRUCTURAL MEMBRANE LESIONS BY THE FIFTH COMPONENT OF COMPLEMENT
Authors: Polley Margaret J. , Müller-Eberhard Hans J. , Feldman Joseph D.
Published: June 2004

A direct quantitative relationship has been demonstrated between the number of cell bound C4,2 complexes or C5 molecules and the number of ultrastructural lesions visualized on the cell membrane subsequent to immune hemolysis. When bound C4,2 complexes exceeded bound C5 molecules, the number of ultrastructural lesions seen corresponded to the number of C5 molecules. However, in the reverse situation, with bound C5 molecules in excess of bound C4,2 complexes, the latter determined the number of lesions. During the complement-reaction sequence, the lesions first became visible in the nonlytic intermediate complex EAC1,4,2,3,5 and their number was unaffected when lysis was induced by C6–C9. Since the lesions were also demonstrable on the intermediate complex EC5,6,7, it is concluded that the protein C5 is responsible for their production. Once formed, the physical presence of the C5 molecule is no longer required for the manifestation of the lesions as indicated by persistence of lesions after removal of C5 protein by trypsin. The C5-dependent ultra-structural phenomenon has therefore been interpreted to represent a true structural change of the membrane which, however, is not accompanied by a permeability defect.
MEASUREMENT OF RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN ALBINO MICE
Authors: Costello Richard , Izumi Takateru
Published: June 2004

Enhanced resistance against experimental tuberculosis was acquired by albino mice after peritoneal vaccination with living BCG.

Prolongation of life was used as a measure of resistance against massive intravenous challenge infection. The average degree of prolongation of life was found to be directly related to the size of the vaccinating dose. The ultimate numbers of BCG bacilli recovered from the animal's organs were also directly related to the quantity of vaccine initially administered. It appears therefore that the relative degree of antitubercular resistance achieved by immunized mice is closely related to the vaccinal population present in the animal's organs.
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: McGregor D. D. , Koster F. T. , Mackaness G. B.
Published: June 2004

Thoracic duct cells from rats which have survived an infection with Listeria monocytogenes can confer a high level of antimicrobial resistance upon normal recipients. The cells which confer protection appear in the thoracic duct during the 1st wk of the immunizing infection, at a time when newly formed lymphocytes are being added to the lymph in substantially increased numbers. The protective cells differ in at least two respects from the majority of small lymphocytes in central lymph: they have a rapid turnover rate and a short life-span in the circulation.

Evidence was also obtained that lymphopoiesis affecting the long-lived small lymphocyte, which belongs to the recirculating pool, is not increased during an acute Listeria infection.
THE PRESENCE OF A GROUP A VARIANT-LIKE ANTIGEN IN STREPTOCOCCI OF OTHER GROUPS WITH SPECIAL REFERENCE TO GROUP N
Authors: Elliott S. D. , Hayward John , Liu T. Y.
Published: June 2004

A Group A variant-like antigen has been detected in streptococci belonging to Groups D, E, G, M, and N. In Groups D and N the variant-like antigen was located in the streptococcal cell walls.

In two strains of Group N streptococci (C559 and B209) the cell walls were chemically different and serologically distinct. In strain C559 N-acetylgalactosamine, and in strain B209, N-acetylglucosamine were the major determinants of serological specificity.

The cell walls of strain C559 contained at least three serologically reactive components: a rhamnose-containing fraction that precipitated with an antiserum to Group A-variant carbohydrate; a strain-specific polysaccharide composed of galactosamine and glucosamine, both in the N-acetylated form and probably polymerized with an unidentified phosphorylated substance; and a component of unknown composition serologically related to a Group D streptococcus strain C3 (S. durans). An analogy is drawn between the cell wall structure in streptococcus and Salmonella.
REGULATION OF THE IMMUNE SYSTEM BY SYNTHETIC POLYNUCLEOTIDES
Authors: Johnson Herbert G. , Johnson Arthur G.
Published: June 2004

Incubation of antigen with normal mouse peritoneal exudate cells in vitro and subsequent reinjection of the washed cells into syngeneic mice resulted in increased antibody titers as compared to mice injected with antigen alone. Several of the variables influencing this system were studied with and without the stimulus of complex homoribopolynucleotides (poly A:U or poly I:C) as adjuvants to determine the cellular site of action of the latter. It was found that addition of poly A:U or poly I:C caused a further rise in circulating antibody levels which correlated with increased RNA synthesis, suggesting that the macrophage was one cell affected by this adjuvant. Actinomycin D was found to inhibit the rise in titer induced by PEC and this inhibition could be overcome by poly A:U. Injection of the polynucleotides 18 hr before antigen resulted in depression of circulating antibody levels, and poly A:U or poly I:C injected 18 hr before harvesting PEC and incubation with antigen also inhibited the capacity of the PEC to increase antibody levels.

A 4S RNA-rich fraction was purified after treatment with phenol of PEC exposed to antigen in vitro, and under the stimulus of poly A:U this RNA was capable of inducing specific antibody titers and rosette-forming cells on injection into mice. Antigen contamination of Pronase-treated RNA, active biologically, was below 10–11 g as determined isotopically.
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.
SYNTHESIS AND ASSEMBLY OF IMMUNOGLOBULINS BY MALIGNANT HUMAN PLASMACYTES AND LYMPHOCYTES
Authors: Buxbaum J. , Zolla Susan , Scharff M. D. , Franklin E. C.
Published: June 2004

Bone marrow or lymph node cells from 10 patients whose sera contained large amounts of monoclonal IgM proteins were incubated with radioactive amino acids in short-term tissue culture. Samples of soluble cytoplasmic extracts and secreted material were examined by immunologic precipitation with specific antisera, acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and sucrose gradient centrifugation. In all samples studied, 8S IgM was the major intracellular precursor of the fully assembled 19S protein. Cells obtained from some patients contained little or no fully assembled 19S protein intracellularly; however, cells from most patients seemed to accumulate fully assembled 19S molecules intracellularly before secretion. Secreted material from both groups contained large amounts of 19S IgM. The differentiation between accumulating and nonaccumulating cells did not correlate with heavy or light chain antigenic type. Synthesis and assembly appeared to be identical in cells obtained from different anatomic sites in the same patient Studies carried out in one patient before and after therapy revealed no qualitative differences in the pathway of assembly and reflected only a decrease in the total number of immunoglobulin-producing cells.
ANTIGENIC SPECIFICITIES ON MURINE SARCOMA CELLS
Authors: Haywood Gerald R. , McKhann Charles F.
Published: June 2004

Five methylcholanthrene-induced sarcomas were compared for their capacity to (a) absorb monospecific H-2 antisera, (b) induce tumor-specific immunity in syngeneic mice, and (c) metastasize early to the lungs. Comparison of the uptakes of monospecific H-2 antisera by the five different tumors showed that each of the tumors had a high, intermediate, or low surface representation of all of the seven specificities tested. No antigenic specificity was completely absent from any tumor, and no tumor had an unusually large or small amount of any individual specificity. The tumors could be placed in the sequence from one to five with respect to their H-2 antigenicity. The same five tumors were also ranked with respect to their capacity to induce a tumor-specific immune response in syngeneic mice. The tumor-specific immunogenicity had an inverse relationship to the H-2 antigenicity in that highly immunogenic tumors were those that had quantitatively less H-2 antigen on their surface and vice versa. Early metastases to the lung was associated with low levels of tumor-specific immunogenicity and high levels of H-2 antigenicity.
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.
DIFFERENTIAL IMMUNOFLUORESCENCE OF FERTILIZED MOUSE EGGS WITH H-2 AND NON H-2 ANTIBODY
Authors: Palm Joy , Heyner Susan , Brinster R. L.
Published: June 2004

Mouse embryos at the two-cell and blastocyst stages, as well as unfertilized eggs, have been studied by indirect immunofluorescence for the expression of H-2 and non-H-2 histocompatibility antigens on surface membranes. Serologically-specific reactivity to non-H-2 antibody (H-3 and H-6) was observed as diffuse, patchy staining over the entire surface of the blastomeres at the two-cell stage. In contrast, no reactivity of two-cell or unfertilized egg embryos of four inbred strains was observed when antisera containing only multispecific H-2 cytolytic antibody were used. Antisera containing H-2 along with non-H-2 antibody of unknown specificity showed varying degrees of reactivity, which could be shown by absorption studies to be due to the non-H-2 content of the serum. The results suggest that the initial expression of histocompatibility genes varies and support the hypothesis that the appearance of these cell components may relate to specific stages of differentiation.
INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO
Authors: Hartmann Klaus-Ulrich
Published: June 2004

Spleen cells of bone marrow chimeras (B cells) and of irradiated mice injected with thymus cells and heterologous erythrocytes (educated T cells) were mixed and cultured together (17). The number of PFC developing in these cultures was dependent both on the concentration of the B cells and of the educated T cells. In excess of T cells the number of developing PFC is linearly dependent on the number of B cells. At high concentrations of T cells more PFC developed; the increase in the number of PFC was greatest between the 3rd and 4th day of culture. Increased numbers of educated T cells also assisted the development of PFC directed against the erythrocytes. It is concluded that the T cells not only play a role during the triggering of the precursor cells but also during the time of proliferation of the B cells; close contact between B and T cells seems to be needed to allow the positive activity of the T cells.
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 (>18 mg precipitins/ml serum, average 33 mg/ml) and a low-response population (<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.
INFECTION AND TRANSFORMATION OF MOUSE PERITONEAL MACROPHAGES BY SIMIAN VIRUS 40
Authors: Mauel J. , Defendi V.
Published: June 2004

The stimulation of DNA synthesis in mouse (C57BL) macrophages explanted in vitro was demonstrated after treatment with conditioned medium or infection with SV40. In the latter case, induction of SV40 T antigen was detected before TdR-3H incorporation. Even though all macrophages were infected (T antigen-positive), they exhibited considerable pleomorphism, accompanied by functional differences. Permanent lines of SV40-transformed macrophages were eventually established, and one clone was isolated which replicates indefinitely and has many properties of primary macrophages: high acid phosphatase and phagocytic activity, lysozyme production, and specific antigenic determinants. These cells differ from normal macrophages in that they contain the SV40 genome, can be trypsinized, and do not require conditioned medium for continued replication.
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.
CAPSULATION OF PNEUMOCOCCUS WITH SOLUBLE CELL WALL-LIKE POLYSACCHARIDE
Authors: Schiffman Gerald , Bornstein Donald L. , Austrian Robert
Published: June 2004

Methods are described for the separation of the C or cell wall polysaccharide from the Cs or soluble C-like capsular polysaccharide of Cs pneumococcal strains. Immunologic analysis has shown that both the C and Cs polysaccharides of a variety of pneumococcal strains are heterogeneous and that the dissimilarities appear to reside in the mucopeptide portion of the molecule or in the region of its attachment to the teichoic acid moiety of the molecule rather than in the teichoic acid fraction. Differences of the type described have been observed in the C polysaccharides of wild-type capsulated strains of several types, in those of independently isolated noncapsulated variants derived from a single strain of a given capsular type, and in the C and Cs polysaccharides of spontaneous mutant or transformed strains of pneumococci producing capsules of Cs polysaccharide.
PREVENTION OF THE LOCALIZED AND GENERALIZED SHWARTZMAN REACTIONS BY AN ANTICOMPLEMENTARY AGENT, COBRA VENOM FACTOR
Authors: Fong Jack S. C. , Good Robert A.
Published: June 2004

Both localized and generalized Shwartzman reactions were induced in the same rabbits by simultaneous administration of preparatory intravenous and intradermal doses of endotoxin followed in 24 hr by the provocative dose. Control rabbits with more than 80% positive responses showed corresponding changes of platelet, white blood cell, fibrinogen, and hemolytic complement levels. Circulating fibrinogen and fibrin degradation products were detected shortly after the preparatory dose and persisted for at least 3 days. Rabbits given cobra venom anticomplementary factor showed hypocomplementemia (less than 10% of normal), leukocytosis, and elevated fibrinogen levels. After the administration of endotoxin, only one of 15 CVF-treated animals developed a Shwartzman reaction and that was mild. These rabbits showed only minor changes of platelet and fibrinogen levels throughout the experiment although their white blood cell responses were similar to those of the control group. No detectable fibrinogen and fibrin degradation products appeared in circulation, and the hemolytic complement activity increased gradually beginning with the preparatory dose of endotoxin. Thus depletion of terminal complement components (mainly C3) in rabbits is protective against the development of both localized and generalized Shwartzman reactions; its mechanism of action is probably through the sparing of platelets by inhibiting platelet-endotoxin interaction. The essential role of the complement system in Shwartzman reaction indicates that this coagulopathy probably represents a manifestation of immunologic injury.