bluuebunny/crossref_metadata_2025 huggingface dataset:
TERMINATION OF ACQUIRED IMMUNOLOGICAL TOLERANCE TO PROTEIN ANTIGENS FOLLOWING IMMUNIZATION WITH ALTERED PROTEIN ANTIGENS
Authors: Weigle William O.
Published: June 2004

Acquired tolerance to BSA in rabbits was terminated following the injection of certain preparations of altered BSA. Injections of Freund's adjuvant containing BSA complexed to anti-BSA, heat-denatured BSA, acetyl-BSA, picryl-BSA, or arsanil-BSA failed to terminate the tolerant state. Except in an occasional tolerant rabbit, injections of these preparations failed to cause the production of precipitating antibody to the altered preparation. Similar results were obtained following injections of alum-precipitated preparations of pepsin-degraded BSA, acetyl-BSA, and picryl-BSA. Injections of Freund's adjuvant containing sulfanil-BSA terminated the tolerant state, but only small amounts of non-precipitating anti-BSA were produced. Injections of Freund's adjuvant containing picryl-acetyl-BSA terminated the tolerant state in two of six rabbits, but again, only small amounts of non-precipitating anti-BSA were produced. Injections of an alum-precipitated preparation of picryl-acetyl-BSA failed to terminate the tolerant state. On the other hand, injections of Freund's adjuvant containing arsanil-sulfanil-BSA terminated the tolerant state in eleven of eleven rabbits and caused the production of precipitating anti-BSA in all nine of the rabbits tested. The tolerant state was terminated also in six of six rabbits injected with an alum-precipitated preparation of arsanil-sulfanil-BSA. Only one of these rabbits produced precipitating anti-BSA. In addition, the injection of BGG-tolerant rabbits with arsanil-BGG, sulfanil-BGG, or arsanil-sulfanil-BGG terminated the tolerant state. These results were discussed in relation to both the clonal selection theory of antibody production and autoimmunity.
DISSOCIATION OF THE BIOLOGICAL PROPERTIES OF BACTERIAL ENDOTOXIN BY CHEMICAL MODIFICATION OF THE MOLECULE
Authors: Freedman Henry H. , Sultzer Barnet M.
Published: June 2004

The preparation and properties of three fractions isolated from the acetylation of endotoxin by acetic anhydride in the presence of anhydrous sodium acetate are described. One fraction is of primary interest for it allows the experimental dissociation of some of the myriad biological activities of the parent endotoxin. Pyrogenicity and acute toxicity are markedly reduced, and ability to confer tolerance to the lethality and pyrogenicity of homologous or heterologous endotoxins is equivalently diminished. In contrast, this acetylated derivative retains the ability to stimulate phagocytosis and, as shown in the following paper, to enhance non-specific host resistance to infection. Detoxification is reversible, the original toxicity and pyrogenicity being recovered following mild saponification.

The implications of the findings are discussed, and it is suggested that the observed dissociation of biological properties is explained neither by deacetylation of the derivative in vivo nor by the observable alteration of physical state in the gross.
INTERFERON PRODUCTION BY MOUSE LEUKOCYTES IN VITRO AND IN VIVO
Authors: Glasgow Lowell A. , Habel Karl
Published: June 2004

Vaccinia virus penetrates, or is phagocytosed by, mouse leukocytes in vitro. A cytotoxic effect is observed, but no new infectious virus is produced. Vaccinia virus, as infectious particles, is eliminated from a culture of leukocytes at a more rapid rate than can be accounted for by thermal inactivation. Leukocytes infected with vaccinia virus produce a substance with the properties of interferon. The evidence presented suggests that leukocytes also produce interferon in vivo and that this interferon is related to the observed protective effect on the outcome of intracerebral vesicular stomatitis virus challenge in mice. It is postulated that leukocytes, in this manner, may make a positive contribution to the host's defense mechanism and to the process of recovery from viral infections.
THE SPECIFICITY OF ALLERGIC REACTIONS
Authors: Coe John E. , Salvin S. B.
Published: June 2004

"Gastric feeding" of adult guinea pigs with dinitrochlorobenzene (DCB) resulted in a specific unresponsiveness to sensitization with the specific contact hapten. The more DCB gastric-fed to a guinea pig, the more complete the unresponsiveness to the hapten. When mycobacteria were incorporated into the sensitizing emulsion, the state of unresponsiveness to the dinitrophenyl (DNP) group was less apparent. When animals gastric-fed with DCB were later sensitized with an in vitro conjugate of the hapten combined with a heterologous protein such as dinitrophenyl-hen egg albumin (DNP·HEA), an immune response similar to that in the controls occurred both to the hapten and to the protein carrier. However, when the tolerant animals were sensitized with a conjugate containing a homologous protein carrier such as dinitrophenyl guinea pig serum (DNP·GPS), they showed diminished immune responses in comparison with those in the non-tolerant controls. The presence of circulating anti-DNP antibodies from sensitization with DNP-HEA did not affect the unresponsiveness to the specific contact hapten, regardless of whether these antibodies are present before or after induction of tolerance. Sensitization with picryl chloride (PiCl) (a cross-reacting hapten), either before or after gastric feeding of DCB, did not affect the state of unresponsiveness to DNP. Similarly when the DNP-tolerant animal was sensitized with PiCl, the subsequent immune response was similar to that in the controls; cross-reactions with the DNP group both in the contact and circulating antibody phase occurred at a rate similar to that in the controls.

The foregoing relationships can be explained by presuming that, upon the gastric feeding of DCB, an in vivo conjugate is formed with a somatic protein, which determines the basic specificity of the tolerance. Acquired tolerance seems to manifest an immunologic specificity similar to that of delayed hypersensitivity, a relationship not unexpected if delayed hypersensitivity is an early phase of the immune response.
PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY
Authors: Najarian John S. , Feldman Joseph D.
Published: June 2004

Passive transfer of transplantation immunity was accomplished in inbred guinea pigs with tritiated thymidine-labeled lymphoid cells sensitized to homologous tissues. Autoradiographs of the homologous skin graft sites disclosed the presence of relatively few or no labeled cells at the site of rejection.

Passive transfer of transplantation immunity was also accomplished with sensitized lymphoid cells enclosed in cell-impenetrable Millipore chambers. Previous studies with passive transfer of tuberculin sensitivity in guinea pigs revealed that the specifically sensitized cells could be easily found at the site of challenge in the presence of specific antigen and were ineffective when enclosed in Millipore chambers. It appeared, then, that the homograft reaction and delayed sensitivity of tuberculin type were achieved by different immunologic mechanisms within the same species.
ANTIBODY FORMATION
Authors: Uhr Jonathan W. , Finkelstein Martin S.
Published: June 2004

Injection of a sufficient dose of bacteriophage ϕX 174 into guinea pigs results in the formation of rapidly sedimenting antibody molecules (19S), and later, slowly sedimenting molecules (7S). Above a threshold dose of antigen, the relative rate of 19S formation is maximal and dose-independent; below this dose, slower relative rates are obtained. The time for doubling the serum 19S level is as short as 6 to 8 hours, suggesting that the absolute rate of antibody formation per cell is increasing in addition to proliferation of antibody-producing cells. Synthesis of 19S after injection of 1010 ϕX virtually ceases at 10 days after which 19S antibody activity disappears from the circulation with a half-life of approximately 24 hours. A second injection of ϕX on day 5 or 9 prolongs 19S synthesis, indicating that antigen not only can regulate the relative rate, but also is essential for continued synthesis of 19S. 19S synthesis is also prolonged in guinea pigs by injection of ϕX with endotoxin or by 400 r whole body x-irradiation 24 hours after injection of phage into rabbits.

The primary 7S response is not detected until approximately 1 week after immunization and relative rates are antigen-dependent. Primary 7S synthesis can continue for many months and leads to preparation for a secondary antibody response (immunological memory) during which only 7S is detected. In contrast, in animals that form precipitating 19S without detectable 7S, a second injection of phage 1 month later results in a second 19S response which closely resembles the first. These findings have led to the suggestion that formation of 19S does not lead to persisting immunological memory.
FURTHER STUDIES ON IMMUNITY IN EXPERIMENTAL CRYPTOCOCCOSIS
Authors: Louria Donald B. , Kaminski Theresa , Finkel Gerald
Published: June 2004

Following infection with 103 cells of Cryptococcus neoformans, progressive multiplication occurred in all tissues for 7 to 28 days. Thereafter, most mice gained control of the infection so that 3 to 6 months after inoculation, tissues were usually sterile or contained only small numbers of cryptococci. Survivors challenged 1 to 4 months after infection with 103 cells lived longer than controls and had an increased survival rate. Pretreatment with bacterial endotoxin also resulted in protection against cryptococcal challenge. Endotoxin-protected animals showed no ability to limit the infection until circulating antibody could be demonstrated.

Histologic studies revealed an increased cellular infiltration in the brains of specifically protected and endotoxin-protected mice 1 to 2 weeks after challenge. However, control of cryptococcal multiplication could be correlated with the presence of antibody but could not be correlated with the enhanced cellular response.

Although protection against cryptococcal challenge appears to be antibody-dependent, it is unclear whether protective antibody is to be found in plasma or is tissue-bound.
INDUCTION OF TOLERANCE TO HETEROLOGOUS PROTEINS AND THEIR CATABOLISM IN C57BL/6 MICE
Authors: Dietrich Felix M. , Weigle William O.
Published: June 2004

C57BL/6 mice were rendered tolerant to one or another of 13 soluble protein antigens. Tolerance was induced by a single injection of 20 mg protein within 24 hours after birth. The duration of the unresponsive state was measured and compared with the rates of catabolism of the antigens as determined in adult and new born mice. The data presented fail to show a correlation between the persistence of labeled protein antigen and the duration of tolerance. In several occasions, even an inverse relationship between duration of the unresponsive state and persistence was demonstrated. The results, therefore, strongly indicate that the duration of tolerance is not dependent on the rates of catabolism of the antigens.

Several of the commercial protein preparations used in this study contained minor impurities to which the animals were generally not rendered tolerant. By means of diffusion in agar techniques, it was demonstrated that mice injected at birth with a tolerance-inducing dose of antigen would generally not reveal precipitating antibodies to this antigen after the tolerant state had been abolished. A speculative explanation was given in terms of quantitative or qualitative differences of antibodies found in such animals as compared to the immunized control mice.

After the 3rd or 4th day of life, newborn mice catabolized I131-labeled heterologous proteins at the same rates as adult mice. The apparent slow elimination during the first days of life was, at least in part, the result of retention of nonprotein-bound I131.
A HEMOLYTIC SYSTEM ASSOCIATED WITH ENTERITIS IN RABBITS
Authors: Evans Robert S. , Bingham Margaret , Weiser Russell S.
Published: June 2004

A disease characterized by frequent association of enteritis and polyagglutinable cells often develops in weanling rabbits. The red cell lesion renders the cells susceptible to agglutination and hemolysis in normal rabbit sera. The degree of red cell abnormality varies among different animals and disappears when the animals recover.

The abnormality of the red cells responsible for their polyagglutinability and susceptibility to hemolysis was resistant to the action of trypsin or papain and persisted in heated stroma preparations derived from polyagglutinable cells.

The factors necessary for agglutination and hemolysis of the polyagglutinable cells are present in normal rabbit sera but are lacking in the sera of affected rabbits. These factors returned to normal levels as the polyagglutinable cell lesion disappeared. The sera of rabbits with polyagglutinable cells contained normal levels of complement and properdin.

Whereas the agglutinating factor in normal sera is heat-stable at 56°C for 30 minutes, the hemolytic factor is heat labile. The hemolytic factor is apparently distinct from complement and properdin since it was adsorbed from normal rabbit serum by zymosan or by polyagglutinable cells at 0°C. However, complement was fixed when normal rabbit serum was reacted with stroma from polyagglutinable cells.

Hemolysis of polyagglutinable cells by normal rabbit serum at 25°C was inhibited by preliminary incubation of the mixture at 0°C prior to incubation at 25°C. Evidence was obtained which indicated that this inhibition was due to progression of a reaction involving Ca++ independent of a reaction involving Mg++.
IN VITRO STUDIES OF ULCERATIVE COLITIS
Authors: Broberger Ove , Perlmann Peter
Published: June 2004

By means of immunofluorescent methods it has been shown that sera from children with ulcerative colitis contain antibodies which react with fetal colon cells in tissue culture. 5 out of 13 sera from patients reacted positively when tested for staining antibodies while 12 sera from healthy individuals yielded negative results. The specificity of the staining reactions was confirmed by inhibition experiments. The staining capacity of various sera was correlated to their hemagglutinating titer when tested against phenol-water extracts of human colon.

The presence of blood group substances of the ABO system on fetal colon cells in tissue culture could be demonstrated by application of fluorescent H agglutinins from eel. Cross-inhibition experiments indicated that the H agglutinins stained colon antigens which were different from those reacting with the antibodies of ulcerative colitis sera.

The reactivity of cultured fetal colon cells with the antibodies in ulcerative colitis sera was retained for up to 12 days, with optimal staining at 4 to 5 days. Reactivity with H agglutinins was present for a longer period, sometimes more than 20 days.

Although antigen could be shown to be present on fetal colon cells in tissue culture, exposure of the culture, in the presence of fresh guinea pig serum, to sera from patients with ulcerative colitis did not lead to any visible cytotoxic damage. In order to investigate the possible cytotoxic effect of the sera with a more sensitive technique, freshly explanted fetal colon was dispersed by trypsinization and the cells labeled with 32P-orthophosphate. Subsequently, these cells were exposed to sera, in a final concentration of 30 per cent, from patients or healthy controls in the presence of fresh guinea pig serum (final concentration 15 per cent). Approximately 20 per cent of the cellular isotope was released into the medium within 150 minutes of incubation, but the release was the same in the samples treated either with patients' sera or normal control sera. Thus, under the present conditions, the patients' sera did not exert any specific cytotoxic action on colon cells.
ACTIVATION OF LYSOSOMAL ENZYMES IN VIRUS-INFECTED CELLS AND ITS POSSIBLE RELATIONSHIP TO CYTOPATHIC EFFECTS
Authors: Allison A. C. , Sandelin K.
Published: June 2004

Activities of the enzymes ß-glucuronidase, acid phosphatase, acid DNAase, acid RNAase, and acid protease have been measured in the lysosomal and supernatant fractions of mouse liver cells and monkey kidney cells before and after infection with mouse hepatitis virus and vaccinia virus, respectively.

In the infected cells there was easily measurable release of lysosomal enzymes into the supernatant fraction. Evidence was presented that this is not an artefact of homogenization and precedes cell degeneration demonstrable histologically.

It is suggested that release of lysosomal enzymes may explain some of the biochemical changes found in infected cells and may contribute to the cytopathic effects of some viruses.
SEQUENCES OF SYNTHESIS OF γ-1 MACROGLOBULIN AND γ-2 GLOBULIN ANTIBODIES DURING PRIMARY AND SECONDARY RESPONSES TO PROTEINS, SALMONELLA ANTIGENS, AND PHAGE
Authors: Bauer D. C. , Mathies M. J. , Stavitsky A. B.
Published: June 2004

The nature of the antibodies produced by the rabbit during the primary and secondary responses to T2 phage, proteins, and the O and H antigens of Salmonella typhosa has been determined. Immune sera have been fractionated by zone electrophoresis, sucrose density ultracentrifugation, and anion exchange chromatography. The resulting fractions have been assayed by phage neutralization or hemagglutination (antisera to proteins) or bacterial agglutination. In confirmation and extension of earlier work from this laboratory, the primary response to these antigens, with the exception of the O antigen of the Salmonella, included the early synthesis of 19S, γ-1 globulin antibody, and the later synthesis of 7S, γ-2 globulin antibody. The primary response to the O antigen consisted of the synthesis of only a macroglobulin agglutinin. The secondary response to the proteins, including the H antigen of the Salmonella, comprised the early synthesis of large amounts of the 7S γ-2 globulin antibody to the same level attained during the primary response. The secondary response to the phage consisted in the synthesis of 7S, γ-2 globulin antibody alone. Treatment of the macroglobulin phage-neutralizing antibody with mercaptoethanol resulted in complete loss of its neutralizing activity.

A working hypothesis to explain these observations was presented. A salient feature of this hypothesis was the suggestion that different cells synthesized the two distinct molecular forms of antibody. The significance of the sequential synthesis of the two forms of antibody is not known. It was proposed that the system for synthesis of macroglobulin antibody is an auxiliary system for antibody synthesis, perhaps the first to develop phylogenetically and ontogenetically. It is felt that the present observations indicate a clear-cut qualitative distinction between the primary and secondary responses to immunization whereby these responses might be identified in various experimental situations. It is also felt that these findings with the primary and secondary responses to various antigens in the rabbit may be of widespread occurrence in nature among a variety of species.
PROPERTIES OF GUINEA PIG 7S ANTIBODIES
Authors: Benacerraf Baruj , Ovary Zoltan , Bloch Kurt J. , Franklin Edward C.
Published: June 2004

Guinea pigs hyperimmunized with single protein antigens or hapten conjugates emulsified in complete adjuvants produced two types of precipitating antibodies with different electrophoretic mobilities. "Slow" migrating antibody generally appeared earlier and "fast" migrating antibody later in the course of immunization. Animals initially immunized by the intraperitoneal route with hapten conjugates without adjuvants produced primarily fast migrating antibody. Purified guinea pig antibodies were also separable into slow and fast migrating components by electrophoresis in supporting media. Using suitable antisera prepared in rabbits hyperimmunized with guinea pig serum, it was demonstrated that slow and fast antibodies have both common and distinct antigenic determinants. Analytical ultracentrifugation disclosed that both antibodies have sedimentation coefficients of approximately 7S. These antibodies have been designated guinea pig 7Sγ1 and 7Sγ2.
PROPERTIES OF GUINEA PIG 7S ANTIBODIES
Authors: Bloch Kurt J. , Kourilsky François M. , Ovary Zoltan , Benacerraf Baruj
Published: June 2004

Guinea pig 7Sγ2 antibodies were demonstrated to fix complement in the presence of antigen and to sensitize antigen-coated, tanned erythrocytes for lysis in the presence of complement; guinea pig 7Sγ1 antibodies did not participate in these reactions. Gamma-2 antibodies were more efficient in provoking hemorrhagic necrosis in reverse passive Arthus reactions than equal amounts of non-complement-fixing gamma-1 antibodies. Unlike anaphylaxis in the guinea pig, both guinea pig 7Sγ1 and 7Sγ2 antibodies provoked passive cutaneous anaphylactic reactions in the rat.

Efficient hemolytic activity attributable to 7S guinea pig anti-sheep erythrocyte antibodies migrated faster than the peak of complement-fixing activity, but slower than the peak of PCA activity in starch block electrophoresis. It is uncertain whether this activity is a function of a third type of antibody produced in response to the particulate property of the antigen or whether it is due to the antigenic heterogeneity of the erythrocyte cell membrane.
STRUCTURE AND SPECIFICITY OF GUINEA PIG 7S ANTIBODIES
Authors: Edelman G. M. , Benacerraf B. , Ovary Z.
Published: June 2004

Additional evidence has been obtained to show that different guinea pig anti-hapten antibodies differ in the structure of their L polypeptide chains. Antibodies from animals immunized with the same hapten conjugated to different carrier proteins gave similar starch gel electrophoretic patterns after dissociation of their chains. In a study of fine differences of specificity, cross-reacting antibodies were found to have some L chains with the same electrophoretic mobility. The multiplicity of L chain bands found in the characteristic starch gel electrophoretic patterns of dissociated anti-DNP antibodies was shown to be a reflection of the heterogeneity of antibodies of slightly different specificities. Reduction and alkylation of the active fragment produced by digestion of antibodies with papain yielded starch gel electrophoretic bands corresponding in mobility to L chains.

The results are consistent with the notion that L chains are involved in the acquisition of immunologic specificity.
ISOLATION OF GRANULES FROM EOSINOPHIL LEUCOCYTES AND STUDY OF THEIR ENZYME CONTENT
Authors: Archer Gordon T. , Hirsch James G.
Published: June 2004

Eosinophils were separated from other types of cells in horse blood or rat peritoneal fluid by centrifugation in concentrated albumin solutions. Eosinophils did not appear to be damaged by this separation procedure.

A technique was also devised for isolation of cytoplasmic granules from eosinophils, thus allowing studies on enzyme content of the granules.

Granules from both horse and rat eosinophils contained a number of hydrolytic enzymes, similar in variety and in concentration to those previously found in granules of rabbit polymorphonuclear leucocytes. Eosinophil granules differed from those of the rabbit granulocyte in their high content of peroxidase and the absence of lysozyme and phagocytin. On disruption of eosinophil granules by repeated freezing and thawing in saline, cathepsin, ribonuclease, arylsulfatase and beta glucuronidase were released into solution, but phosphatases were partially and peroxidase completely bound to the insoluble granule residue. Peroxidase could be extracted from the granule residue with weak acid.

Eosinophil granules thus are lysosome-like structures.
THE CELLULAR ORIGIN OF HUMAN IMMUNOGLOBULINS (γ2, γ1M, γ1A)
Authors: Mellors Robert C. , Korngold Leonhard
Published: June 2004

A study was made of the cellular origin of human immunoglobulins (γ2, γ1M, γ1A). The results indicated that two closely related families of cells form immunoglobulins in human lymphoid tissue: germinal (reticular) centers and plasma cells. Thus their cellular origin in addition to their known antigenic relations further justifies placing the immunoglobulins in one family of proteins.

Immunoglobulins were also formed to a small extent in primitive reticular cells which resembled those of germinal centers but were separated from them. Possibly such cells were undergoing transition to the much more numerous plasma cells with which they were commonly associated.

The mantles of small lymphocytes which surrounded germinal centers did not contain detectable quantities of immunoglobulins.

While in general only one type of immunoglobulin was present in an individual cell or germinal center, γ2- and γ1M-globulin were identified on occasion in the same plasma cell and germinal center.

A peculiarity of the fetal thymus gland was the presence of immunoglobulin, mainly γ1M, in a small number of cells of small and intermediate size and primitive reticular appearance and in Hassall's corpuscles.
THE ATTENUATION OF THE VIRUS OF EPIZOOTIC HEMORRHAGIC DISEASE OF DEER BY ITS SERIAL PASSAGE IN THE BRAINS OF NEWBORN MICE
Authors: Shope Richard E. , MacNamara Lester G. , Mettler Norma E.
Published: June 2004

Serial passage through the brains of newborn mice markedly attenuates the New Jersey strain of EHD virus. Deer inoculated with this attenuated virus show no clinical evidence of illness, but do develop virus-neutralizing antibodies in their sera. They also become solidly immune to infection with the regularly fatal unattenuated virus.
STUDIES ON THE RELATIONSHIP OF ALLOTYPIC SPECIFICITIES TO ANTIBODY SPECIFICITIES IN THE RABBIT
Authors: Rieder Ronald F. , Oudin Jacques
Published: June 2004

Purified antibodies against three different antigens and haptens (ovalbumin, dinitrophenol, and Type II pneumococcal polysaccharide) were prepared from specific precipitates from the antisera of several rabbits. The reactions of these preparations with antisera against the allotypic specificities carried by each of the animals forming the antibodies were used to compare the relative concentrations of molecules bearing each specificity in the different solutions of antibodies from each rabbit. These relative concentrations appeared to vary greatly from one preparation to another, although all the allotypic specificities carried by each animal were found in all the preparations of antibodies from that animal. The interpretation of these results is discussed.
HOMOLOGOUS DISEASE IN THE ADULT RAT, A MODEL FOR AUTOIMMUNE DISEASE
Authors: Stastny Peter , Stembridge Vernie A. , Ziff Morris
Published: June 2004

The cutaneous lesions of adult rats with homologous disease are described, and evidence is presented to indicate that they have an immunologic basis. The skin changes included erythema, purpura, edema, and a variety of inflammatory lesions. In the more active lesions, dermal infiltration, hydropic degeneration, acanthosis, and atrophy of the epidermis with hyperkeratosis and follicular plugging were present. In some cases, ulceration and sloughing were also observed. More chronic lesions were characterized by atrophy of the epidermis and collagenization of the dermis with disappearance of the skin appendages.

Rejection of autografts was observed simultaneously with acceptance of homografts. The histologic appearance of autografts undergoing rejection was similar to that of the spontaneous skin lesions, suggesting that the latter, too, had an immunologic basis. In favor of this, also, was the specificity of the dermatitis for the skin of the host, with sparing of neighboring homograft tissue.

There was a histologic similarity between the spontaneous skin lesions of homologous disease and those of lupus erythematosus on the one hand, and scleroderma on the other, thus supporting the possibility that the cutaneous lesions of these connective tissue diseases of man may also have an immunologic basis.

It was concluded that the adult rat with homologous disease may furnish a model for human autoimmune disease.
STUDIES OF TUBERCLE BACILLUS-HISTIOCYTE RELATIONSHIPS
Authors: Fong Jacob , Chin Dennis , Vickrey Herta M.
Published: June 2004

Immunization of mice or guinea pigs with BCG rendered all or most of the histiocytes of these animals resistant to necrotization by virulent H37Rv; this cellular resistance was mediated by immune serum.

Immune mouse histiocytes (from BCG-immunized animals) were able to induce cellular resistance in normal homologous and heterologous (rabbit) animal species; mouse histiocytic ribosomes were also tested in the homologous species and found to be active.

Immune guinea pig histiocytes (from BCG-immunized guinea pigs) were ineffective in transferring cellular resistance to either homologous or heterologous (mouse and rabbit) animal species.

Immune rabbit histiocytes were capable of inducing cellular resistance in mice and guinea pigs; rabbit histiocytic ribosomes were also tested in normal mice and found to be active in induction of cellular resistance.

Recipient guinea pig histiocytes (from guinea pigs inoculated with immune rabbit histiocytes) were capable of inducing cellular resistance in normal guinea pigs and rabbits.

Cultivation of lysed immune histiocytes of all three animal species on glycerol-blood agar medium failed to reveal any viable BCG; this provided one additional bit of evidence against the idea that induction of cellular resistance is due to viable bacilli.
RHEUMATOID FACTOR PROPERTIES OF HYPERIMMUNE RABBIT SERA
Authors: Christian Charles L.
Published: June 2004

The rheumatoid factor-like substance (RFLS) induced by hyperimmunization of rabbits with bacteria was consistently and exclusively associated with the macroglobulin fraction of the sera studied. The RFLS is separable from the bulk of serum proteins by zone centrifugation, DEAE cellulose chromatography, and gel filtration. Partially purified preparations of the RFLS were studied by immunoelectrophoretic analysis and analytical ultracentrifugation. Certain RFLS sera demonstrated selective reactivity with one or more rabbit isohemagglutinin antibodies. Pepsin treatment of rabbit γ-globulin removed or greatly diminishes its capacity to react with the RFLS.
THE EFFECT OF 6-MERCAPTOPURINE AND AMINOPTERIN ON EXPERIMENTAL IMMUNE THYROIDITIS IN GUINEA PIGS
Authors: Spiegelberg Hans L. , Miescher Peter A.
Published: June 2004

The influence of 6-mercaptopurine and aminopterin was studied on immune response and immune thyroiditis in guinea pigs immunized with thyroid extract.

1. Both compounds depressed delayed hypersensitivity to thyroglobulin and immune thyroiditis.

2. Antibody formation to thyroglobulin was strongly depressed by aminopterin but not significantly influenced by 6-mercaptopurine.

3. Immune response and thyroiditis were suppressed as long as the compounds were administered; after discontinuation of treatment, immune response and thyroiditis appeared in the same time intervals as observed in control animals after initiation of immunization.

4. Treatment with 6-mercaptopurine and aminopterin 10 days after immunization lead to suppression of delayed hypersensitivity and thyroiditis.

5. Treatment with 6-mercaptopurine of animals after onset of thyroiditis lead to suppression of delayed hypersensitivity and disappearance or diminution of round cell infiltration in the thyroid.

6. The results are discussed in terms of the pathogenesis of experimental immune thyroiditis, the mode of action of these antimetabolites on this experimental immune disease, and in view of the potential value of these compounds in human diseases.
STUDIES ON THE ROLE OF THE THYMUS IN IMMUNOBIOLOGY
Authors: Dalmasso Agustin P. , Martinez Carlos , Sjodin Kenneth , Good Robert A.
Published: June 2004

The immunologic competence of spleen cells of mice, as assessed by their graft versus host capabilities, increases to 35 days of age and beyond. Thymectomy at any point along this continuum of development produces "immunologic arrest;" the peripheral lymphoid tissues of such mice do not show significant increases in activity as the animals mature, nor is there appreciable loss of activity up to 6 months after surgery.

Adult spleen cells from mice thymectomized at 1 to 24 hours of age have a greatly reduced ability to induce runt disease. Five million spleen cells from immunologically mature animals will uniformly cause fatal runt disease in neonatal recipients, but this same number of cells from neonatally thymectomized animals produces almost no runt disease. When the dosage of cells from neonatally thymectomized C57Bl mice is increased to 20 million, about half of the A recipients develop runt disease. Thus, the defect is a quantitative one.

Spleen cells from neonatally thymectomized mice will induce tolerance of skin grafts from the donor strain. In one recalcitrant strain combination, C57Bl to A, use of spleen cells from neonatally thymectomized donors as the tolerance-inducing inoculum permits survival of the recipients, which usually die with severe runt disease, but does not induce tolerance.

Cell free extracts of spleen and thymus tissue, including "promine" of Szent-Gyorgyi et al., did not affect the runting syndrome or the immunologic reactivity of neonatally thymectomized mice.

When syngeneic thymic tissue is grafted into neonatally thymectomized mice, or the animals are given viable syngeneic spleen or thymus cells, the majority of the animals escape the early mortality characteristic of this group. Administration of syngeneic spleen cells from adult donors and grafting of syngeneic neonatal thymus provide restoration of homograft immunity and graft versus host reactivity of the peripheral lymphoid tissues in most of the neonatally thymectomized animals. Thymus cells rarely provide significant restoration of these parameters.

Allogeneic thymus grafts also restore neonatally thymectomized mice. Such animals are chimeric: the immunologically competent cells of their peripheral lymphoid tissues are chiefly of host origin as determined by the discriminant spleen assay, but in many instances a significant donor component is also demonstrable in this system. These chimeric animals accept skin grafts from both donor and host strains.

A degree of reconstitution has also been attained by grafting of allogeneic adult spleen in neonatally thymectomized animals. The discriminant spleen assay indicates that cells of the donor strain predominate in the peripheral lymphoid tissues of such mice.
THE CATABOLISM OF PROTEIN ANTIGENS IN THE NEWBORN AND MATURING RABBIT
Authors: Robbins John , Eitzman Donald V. , Smith Richard T.
Published: June 2004

The rate of degradation, organ deposition, and blood clearance of SBSA, SRSA, and IRSA has been measured in the newborn, 6-, and 30-day-old rabbits. When the animals were injected with a weight-graded dose of the 3 proteins, differences in their catabolism in the newborns were demonstrable as compared to the 6-, and 30-day-old animals.

The capacity to degrade the azo compounds was shown to be incompletely developed at birth. At 6 days of age, however, the rabbits catabolized these proteins much at the same rate as the 30-day-old animals. Addition of the benzenesulfonate moiety determined the rate of degradation organ deposition and excretion rather than the carrier protein when the azo compounds were injected.

The biosynthetically labeled S25 rabbit serum albumin (IRSA) was catabolized at a slower rate than the azoproteins in all age groups. Very little difference in the metabolism and organ deposition of the IRSA was shown to exist between the newborn and maturing animals.

A dosage schedule, therefore, designed to test the immunological capacity of developing animals may not be valid when calculated upon body weight. The low level of activity of enzyme systems present at birth which degrade anti-genic material may serve as an explanation as to why this period of development is so vulnerable to the induction of tolerance rather than immunity when compared to the adult.
EFFECTS OF ACIDIC AZOPROTEINS ON PLASMA TRIGLYCERIDE LEVELS AND ON THE HEPARIN-ACTIVATED CLEARING SYSTEM
Authors: Broome J. D.
Published: June 2004

When injected into the rabbit 3 acidic azoproteins produced marked changes in the blood triglyceride levels. 4-Arsonophenylazoproteins, which were found to act similarly in 2 other mammalian species, produced a gross and prolonged hyperlipemia. 4-sulfono- and 4-carboxyphenylazoproteins in the rabbit produced an initial elevation and later lowering in blood triglyceride levels. The correlation between these changes and the action of the azoproteins on clearing factor lipase provides further evidence for the importance of this enzyme in fat transport mechanisms. 4-Arsonophenylazoprotein is powerfully inhibitory to the lipase. 4-Carboxy- and 4-sulfonophenylazoprotein in vivo initially inhibit the enzyme and later produce a heparin-like activation.
STUDIES ON HUMAN ANTIBODIES
Authors: Allen James C. , Kunkel Henry G. , Kabat Elvin A.
Published: June 2004

Human antibodies against dextran, teichoic acid, blood group A substance, levan, tetanus toxoid, and nuclei were isolated and analyzed for their content of Gm(a), Gm(b), and Inv(a) γ-globulin genetic factors. The majority of these antibodies contained all the genetic factors determined in the donor's whole γ-globulin, but in many antibodies at very different concentrations. In a few instances specific factors could not be detected despite their presence in the individual's whole γ-globulin. Different antibodies isolated from the serum of the same individual showed different relative concentrations of genetic factors. The distribution of genetic factors seen in certain isolated human antibodies appeared to approach the selective occurrence of these factors in myeloma proteins.
SINGLE CELL STUDIES ON 19S ANTIBODY PRODUCTION
Authors: Nossal G. J. V. , Szenberg A. , Ada G. L. , Austin Caroline M.
Published: June 2004

Rats were immunized with Salmonella adelaide flagella. By zone centrifugation of serum samples in sucrose gradients, it was shown that, as in many other systems of antibody formation, the first response was the formation of 19S, mercaptoethanol (ME)-sensitive antibody. This was quickly replaced by 7S, ME-insensitive antibody. Popliteal lymph node cell suspensions were prepared, and cells with antibody on their surface were identified by the method of bacterial adherence. By micromanipulation such cells were washed, placed into microdroplets, examined under high-power phase contrast and broken to release intracellular antibody. These droplets were then studied in either of two ways. In the first method, each droplet was halved and one half treated with ME. Then both halves were titrated for immobilizing antibody through serial twofold dilution of the half microdroplets. Droplets showing destruction of antibody by ME were classified as 19S; those showing no reduction in titer as 7S; and those showing significant (>1 log2) reduction as double producers; i.e., cells containing both 7S and 19S antibodies. In the second method, droplets were divided into 4 equal quarters, for testing after treatment with either ME, or a specific rabbit anti-rat 7S globulin serum, or both. In these experiments, cells showing some remaining antibody after treatment with either reagent, but not after treatment with both reagents, were classified as double producers.

Of 144 cells tested, 123 contained readily detectable amounts of antibody. These comprised 42 19S cells, 64 7S cells, and 17 double producers. The double producers were frequent at times when the switchover from 19S to 7S antibody production was occurring. All except 4 of the cells in the study could clearly be identified as members of the plasma cell series. Though 7S cells became more frequent as the cell population matured, no clear-cut correlation between cell immaturity and 19S production could be obtained. In the primary response many fully mature plasma cells contained only 19S antibody; conversely, in the secondary response many blasts contained 7S antibody. No morphological difference between 19S and 7S cells could be found.

The results suggested that many cells or cell clones go through a sequence whereby each forms first 19S and later 7S antibody with identical combining sites.
THE REGENERATION OF F1 HOST CELL SPLEEN AND THYMUS AT ECTOPIC SITES IN F1 ANIMALS INDUCED BY IMPLANTATION OF PARENTAL SPLEEN AND THYMUS
Authors: Green Ira
Published: June 2004

The ability of parental to F1 spleen grafts to regenerate was equal to that of parental to parental or to F1 or F1 spleen grafts. Cytotoxicity analysis of parental to F1 spleen and thymic grafts indicated that these "regenerated grafts" were composed of F1 lymphocytes. Regenerated parental to F1 spleen grafts were incapable of producing runt disease in newborn F1 animals.
THE MACROMOLECULAR NATURE OF THE FIRST COMPONENT OF HUMAN COMPLEMENT
Authors: Naff George B. , Pensky Jack , Lepow Irwin H.
Published: June 2004

Kinetic and ultracentrifugal experiments demonstrated that the previously described subcomponents of human C'1, designated C'1q, C'1r, and C'1s, interacted with each other in liquid phase to form a macromolecule which was then capable of converting sensitized erythrocytes (EA) to the state EAC'1. The apparent sedimentation constants of C'1q, C'1r, and C'1s and of the macromolecular product of their interaction were approximately 11S, 7S, 4S, and 18S respectively. Association of C'1 subcomponents was prevented and dissociation of macromolecular C'1 was effected by Na3HEDTA and Na2MgEDTA but not by Na2CaEDTA. The rate of formation of macromolecular C'1 was a function of concentration of subcomponents and temperature of interaction, with an apparent energy of activation of 21,000 calories per mol.

Ultracentrifugal studies further indicated the macromolecular nature of C'1 in normal human serum. In the absence of EDTA, C'1 sedimented with the serum macroglobulins and C'1 subcomponents were not detected. Conversely, in the presence of EDTA, macromolecular C'1 was not demonstrable and individual C'1 subcomponents could be measured in lighter fractions.

The significance of these observations in relation to previous studies on C'1 subcomponents, the role of Ca++ in C'1 function, and the subunit structure of Enzymes has been discussed.
GAMMA GLOBULIN METABOLISM IN RABBITS DURING THE ANAMNESTIC RESPONSE
Authors: Catsoulis Evangelos A. , Franklin Edward C. , Oratz Murray , Rothschild Marcus A.
Published: June 2004

1. Gamma globulin metabolism and distribution were studied employing rabbit gamma globulin (RGG)I131 24 times in 13 control rabbits. Similar studies were performed before and during the ananmestic response in 4 rabbits previously sensitized with a polyvalent pneumococcal vaccine.

2. During the ananmestic response, gamma-globulin levels increased from 1.0 to 6.0 gm/100 ml, and the gamma-globulin pool increased from 0.7 to 4.7 gm/kg. There was no change in the intravascular-extravascular partition of gamma globulin.

3. Gamma globulin degradation increased from 0.06 to 0.33 gm/kg/day during the 28 days of the immunization period while gamma globulin synthesis increased even further to average 0.47 gm/kg/day. Following the attainment of elevated gamma globulin levels the fractional rate of RGG-I131 turnover increased from 8.0 to 12.5 per cent/day.

4. No differences were noted in the metabolism of homologous or autologous gamma globulin regardless of the allotypic specificities.
SEPARATION OF TEICHOIC ACID OF STAPHYLOCOCCUS AUREUS INTO TWO IMMUNOLOGICALLY DISTINCT SPECIFIC POLYSACCHARIDES WITH α- AND ß-N-ACETYLGLUCOSAMINYL LINKAGES RESPECTIVELY
Authors: Torii Mitsuo , Kabat Elvin A. , Bezer Ada E.
Published: June 2004

Human sera were found to contain antibodies precipitating with each of two samples of teichoic acid of Staphylococcus aureus prior to immunization; these antibodies were probably formed as a result of contact or infection with this microorganism. Injection of teichoic acid into two individuals resulted in a rise in circulating antibody to teichoic acid; a third subject probably had a primary response to α-teichoic acid. Quantitative precipitin and agar diffusion studies revealed the presence of two distinct antibodies in the sera and showed that each specimen of teichoic acid was a mixture of two polymers an α-linked N-acetylglucosaminyl-ribitol polymer and a ß-linked N-acetylglucosaminyl-ribitol polymer, termed α- and ß-teichoic acids respectively. The α-teichoic acid anti-α-teichoic acid system was inhibited best by α-linked glucosaminides and the ß-anti-ß-teichoic acid system was inhibited best by a ß-linked glucosaminide. The α- and (ß-teichoic acids could be separated from each other by specific precipitation under appropriate conditions and recovered from the washed specific precipitates. The existence of two distinct teichoic acid polymers raises important questions as to cell wall structure and the biosynthesis of the teichoic acids.
A STUDY OF THE DISTRIBUTION OF INCOMPLETE RHESUS ANTIBODIES AMONG THE SERUM IMMUNOGLOBULIN FRACTIONS
Authors: Dodd Barbara E. , Wilkinson P. C.
Published: June 2004

Sera containing Rh antibodies were taken from Rh-negative women at intervals during pregnancy and postpartum. A selection of these was fractionated on DEAE cellulose and by density gradient ultracentrifugation.

The distribution among the immunoglobulin fractions γSS, γ1A, and γ1M of Rh antibodies in the sera of Rh-negative women during pregnancy was analysed by these fractionation procedures and also by treatment with 2-mercaptoethanol and by testing with rabbit antisera prepared against purified immunoglobulin fractions.

The experiments showed that incomplete Rh antibodies occurred in the 7SS-, γ1A-, and γ1M-globulin fractions, although the bulk of the antibody was in the 7SS. In addition, evidence that the previously described (13) "papain-type" antibody is an incomplete γ1M-globulin is presented.
RECONSTITUTION OF ANTIPHAGE ANTIBODIES FROM L AND H POLYPEPTIDE CHAINS AND THE FORMATION OF INTERSPECIES MOLECULAR HYBRIDS
Authors: Fougereau M. , Olins D. E. , Edelman G. M.
Published: June 2004

Reconstitution of phage-neutralizing activity was observed after admixture of separated L and H polypeptide chains of purified antibodies obtained from single sheep or guinea pigs and directed against f1 and f2 phages. Hybrid mixtures of complementary chains of antiphage antibodies and γ-globulins of the same animal showed less activity than the homologous mixtures of chains from antibodies of the same specificity. 7S interspecies molecular hybrids could be formed between L or H chains of sheep γ-globulins and the complementary chains of guinea pig γ-globulins. In contrast to the results obtained within a single animal species, mixtures of L or H chains of antiphage antibodies from one species with the complementary chains of antibodies to the same phage from the other species showed slight or negligible potentiation of neutralizing activity.
THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS
Authors: Johnson Richard T.
Published: June 2004

The resistance to herpes virus encephalitis which develops with age was studied in mice using fluorescent antibody staining. Adult mice remained susceptible to intracerebral inoculation, and the infection of the central nervous system was identical with that found in immature mice. A "barrier" to the spread of virus inoculated extraneurally developed with maturation, and the limitation of spread appeared to coincide with the infection of peritoneal and tissue macrophages.

In vitro, suckling and adult mouse macrophages were infected with equal ease. However, suckling mouse macrophages infected other cells in contact with them, while infected adult mouse macrophages did not. Studies failed to reveal the nature of this change in macrophages which developed with age.

The role of macrophages in the pathogenesis of herpes virus encephalitis is discussed. The hypothesis is made that an alteration in the macrophages of the maturing mouse plays an important role in its development of resistance to herpes virus encephalitis.