bluuebunny/crossref_metadata_2025 huggingface dataset:
INTERFERENCE WITH IMMUNE HEMOLYSIS BY GLYCOPROTEIN ANTIGENS
Authors: Arquilla E. R. , Hamlin J. , Hamashige S. , Miller A.
Published: June 2004

1. The titer of an individual insulin antiserum measured by hemagglutination agrees favorably with the titer of the same antiserum as measured by immune hemolysis.

2. In contrast, a marked decrease is noted in the immune hemolysis titers relative to hemagglutination titers of antisera prepared against three different sialic acid-containing proteins (human chorionic gonadotropin, rabbit transferrin, and human transferrin).

3. The lower immune hemolytic titers of glycoprotein antisera are apparently not due to a lack of complement-fixing γ2-antibodies.

4. The glycoprotein antigens in solution do not interfere with hemolysis in the insulin immune system.

5. By contrast, marked inhibition of insulin immune hemolysis occurs when cells are sensitized with both glycoprotein and insulin.

6. Cells treated with neuraminidase (to remove cell surface sialic acid) lyse in the presence of C'a alone.

7. If neuraminidase-treated cells are sensitized with sialic acid-containing protein, the lysis of these cells by complement is inhibited.

8. It is, therefore, postulated that during some initial phase of immune hemolysis, a sialic acid-containing substrate is cleaved from the cell surface, rendering the cell susceptible to lysis. If this removal is interfered with, i.e., by sensitization of the cell with competitive sialic acid-containing antigen, then the lytic portion of immune hemolysis cannot proceed.
STUDIES OF TUBERCLE BACILLUS-HISTIOCYTE RELATIONSHIPS
Authors: Fong Jacob , Chin Dennis , Elberg Sanford S.
Published: June 2004

Comparison of the Brucella-immune and the BCG-immune histiocyte, each of which is resistant to necrotization by either Brucella or mycobacteria, has revealed a number of dissimilarities in their behavior. The Brucella-immune histiocyte was found to be incapable of transferring its resistance to the cells of normal animals; it was also unable to achieve attenuation of virulent tubercle bacilli. In contrast, the BCG-immune histiocyte and certain of its subcellular components (ribosomes and ribosomal RNA) were effective in inducing cellular resistance in normal animals against both Brucella and mycobacteria. When RNA was used, only immune ribosomal RNA was effective; when intact ribosomes were used, both immune and recipient ribosomes proved active.

These investigations have also shown that the resistance of the BCG-immune histiocyte against Brucella and mycobacteria was of long duration and not readily dissociable.
DISTRIBUTION, INHERITANCE, AND PROPERTIES OF AN ANTIGEN, MUB1, AND ITS RELATION TO HEMOLYTIC COMPLEMENT
Authors: Cinader B. , Dubiski S. , Wardlaw A. C.
Published: June 2004

An antigen, MuB1, present in the sera of some mice, can elicit a precipitating antibody in certain other strains of mice. An antibody to the antigen MuB1 can also be elicited in rabbits. 99 strains and substrains of inbred mice were tested for the presence of MuB1; the antigen was found in the sera of 44 strains (61 per cent) and 14 DBA substrains (52 per cent). Evidence is presented indicating that mice lacking MuB1 do not make a modified antigen, corresponding to MuB1, but are genetically deficient in synthetic ability at this site.

By reaction with antibody to MuB1 an antigen corresponding to MuB1 was found in 13 of the 15 orders of mammals, and in 63 of 85 mammalian species tested, including man and guinea pig.

The quantity of the antigen MuB1 is always greater in the serum of male than in the serum of female mice. The concentration of MuB1 increases with age; this increase is more marked in male than in female mice.

By means of backcross experiments it was shown that the inheritance of MuB1 is unifactorial, is independent of the inheritance of the gamma globulin allotype MuA2, and is qualitatively independent of the sex of the parents.

The antigen MuB1 is found in the euglobulin fraction of serum; it loses its ability to precipitate with antibody after heating at 56°C, but not after treatment with ammonia or hydrazine. By gel filtration, MuB1 is separated with a fraction containing molecules of molecular weight ≈ 150,000.

An empirical correlation was observed between the presence or absence of MuB1 in the sera from inbred mice and the presence or absence of hemolytic complement (Hc), as measured by a test using a high concentration of rabbit hemolysin. In backcross experiments also, a correlation between hemolytic complement and the presence of MuB1 was demonstrated. As with MuB1, male mice had a higher hemolytic complement level than females. The particular component of complement which may be identical with MuB1 has not been identified.
THE ROLE OF COMPLEMENT IN THE PASSIVE CUTANEOUS REACTION OF MICE
Authors: Ben-Efraim S. , Cinader B.
Published: June 2004

Intradermal injection of mice with ribonuclease antibody, followed by intravenous injection with ribonuclease, resulted in permeability increase, demonstrable by "blueing." The size of the blued area depends on the quantity of antibody injected and on the interval between the two injections. If antigen was injected first and antibody was injected subsequently, a similar increase in permeability was observed in animals having a complete complement system (MuB1-positive) and in animals which have a deficient complement system (MuB1-negative). Marked differences in response were observed between these two types of mice if antigen was injected some hours after the antibody. In MuB1-negative mice, a blueing reaction was not observed at intervals between injections (2½ hours if 3 µg N antibody and 15 hours if 25 µg N antibody were injected intradermally) at which MuB1-positive animals showed a marked permeability increase. At these intervals, blueing did occur in MuB1-negative animals if they were injected with the serum of MuB1-positive mice or with fresh guinea pig serum. Blueing was not induced if the serum of MuB1-negative mice or heated guinea pig serum was injected. The occurrence of two distinct phases of the cutaneous reaction, of which only one involves the complete hemolytic complement system, was deduced from these observations.
EVIDENCE FOR SPECIES' DIFFERENCES IN THE EFFECT OF SERUM γ-GLOBULIN CONCENTRATION ON γ-GLOBULIN CATABOLISM
Authors: Sell Stewart
Published: June 2004

The fractional rates of catabolism of isotopically labeled mouse, human, bovine, and guinea pig γ-globulins and human serum albumin were determined in mice and in guinea pigs whose serum γ-globulin and serum albumin levels were elevated by immunization or by injections of exogenous serum proteins. These serum proteins were also followed in mice with different serum γ-globulin levels due to different bacterial environments. The fractional rates of catabolism of the labeled γ-globulins from all species tested were markedly increased in mice with elevated γ-globulins due to immunization; to injections of human, mouse, guinea pig, or rabbit γ-globulins; to exposure to supra normal numbers of bacteria in the environment. Injections of bovine γ-globulin were only partially effective, and injections of human serum albumin had no effect. The γ-globulin catabolic rates were decreased in mice with subnormal serum γ-globulin levels (germfree mice). The catabolic rate of human serum albumin was essentially the same in all mice in spite of differences in serum γ-globulin levels. In contrast, elevation of the serum γ-globulin levels by injections of exogenous γ-globulins or by hyperimmunization with keyhole limpet hemocyanin produced no change in the fractional catabolic rates of the isotopically labeled γ-globulins and labeled albumin in guinea pigs. Thus, a feedback mechanism for the control of the serum γ-globulin concentration appears to be operative in the mouse, but not in the guinea pig.

Guinea pigs immunized with antigens in complete Freund's adjuvant or a saline suspension of killed E. coli had an increase in the catabolic rates of all labeled proteins tested including human serum albumin. Evidence is presented that the mechanism of this increase in catabolism is not the same as that seen in mice with elevated serum γ-globulin levels.
STUDIES ON ANTIBODY PRODUCTION
Authors: Fecsik Alfonz I. , Butler William T. , Coons Albert H.
Published: June 2004

As the interval between two antigenic stimuli to mice is lengthened, the magnitude of the response to the second dose increases up to approximately 40 days; thereafter it remains at a fairly constant, high level.
ENDOSYMBIOTIC RELATIONSHIP BETWEEN ANIMAL VIRUSES AND HOST CELLS
Authors: Fernandes Mario V. , Wiktor Tadeusz J. , Koprowski Hilary
Published: June 2004

RE cultures infected with a fixed rabies virus were studied. The virus can propagate itself in these cells for an indefinite period of time without interfering with cell growth. The present study characterizes this truly endosymbiotic relationship.

Virus-specific antigen was detected in the cytoplasm of each cell by fluorescein-labeled antirabies serum but only 4 to 5 per cent of the cells released infectious virus. All cells undergoing division showed viral antigen throughout the mitotic process. Also, the growth rate, plating efficiency, and morphological characteristics of both the infected and control cultures were identical. No difference was detected between the RE and the RE-CVS cell populations by RNA and DNA labeling experiments, using H3-thymidine, and H3-uridine. Although antirabies serum effectively inhibited the spread of extracellular virus, it did not interfere with cell-to-cell transmission of the virus during mitosis, in the course of 9 cell transfers during 53 days. RE-CVS cells, when exposed to fresh antirabies serum, lysed completely but inactivated serum had no lytic effect. The addition of fresh hamster complement to the inactivated serum restored its cytolytic properties.

The serially passaged RE-CVS virus gradually became less virulent for mice and displayed a weak antigenicity in the mouse protection test.

Another feature of the RE-CVS cell system is its resistance to infection with homologous and heterologous viruses despite the apparent absence of an interferon-like substance.
TRANSPORT OF GLOBIN BY THE RENAL GLOMERULUS
Authors: Menefee Max G. , Mueller C. Barber , Bell Allen L. , Myers Joseph K.
Published: June 2004

Purified human globin injected into rats forms aggregates which are identifiable by their characteristic appearance in thin sections in the electron microscope and by their positive autoradiographs when the globin is tritiated before injection. Globin is taken up by endothelial cells of glomerular capillaries and is transported across the cell within the limits of a surrounding membrane. Globin is rarely seen to pass through fenestrations. Globin is also taken into the stalk region where it is seen usually within the sponge fibers and only occasionally within stalk cells. Globin is seen in all stages of passage through the basement membranes and sponge fibers, which are not deformed by its passage. On the basis of the findings presented here and by others, it is postulated that the basement membrane and sponge fibers consist of a thixotrophic gel.

After traversing the basement membrane, the globin passes between foot processes of the epithelial cells. The slit membranes are deformed by this passage and thus appear to be distinctive structures. The globin is next found free in Bowman's space; the earliest aggregates are seen there within 1 minute after injection.

Globin taken up in the stalk region is slowly discharged and very little is found there 6 hours postinjection.
EXPERIMENTAL STUDIES IN ACUTE RENAL FAILURE
Authors: Menefee Max G. , Mueller C. Barber , Miller Tracy B. , Myers Joseph K. , Bell Allen L.
Published: June 2004

When purified human globin is injected intravenously into rats it produces acute renal failure characterized by tubular casts and oliguria. The globin is identifiable within vesicles and channels in the cytoplasm of the proximal tubules, through which it passes from lumen to basal side with no apparent serious effect on the cells. When a very minimal amount of globin is taken up by cells of the distal limb of Henle's loop or distal tubules (lower nephron), a markedly deleterious effect is apparent and the cells die within a short time. The mixture of cell debris and precipitated globin forms plugs within the confines of the basement membranes of the former distal limbs and distal tubules. After a number of lower nephrons are plugged a disruption of proximal tubules is found, which apparently results from the effect of back pressure in the obstructed nephrons.

We suggest that any amount in excess of a low threshold of globin, either alone or combined with heme or related material, has a toxic effect on lower nephron cells. Once initiated, the toxic effect is not reversible and the resulting plug of debris and precipitate will occlude the lumen. If a sufficient number of nephrons are made non-functional the animal becomes anuric; otherwise it is oliguric. A high rate of urine flow will protect against the excess absorption of material and thus against acute renal failure.
THE IN VITRO DESENSITIZATION OF SENSITIVE CELLS BY TRYPSIN
Authors: David John R. , Lawrence H. S. , Thomas L.
Published: June 2004

Peritoneal exudate cells from animals exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific antigen. This inhibition is completely abolished by pretreatment of the sensitive cells with trypsin. The action of trypsin is prevented by soybean trypsin inhibitor. The results of experiments with mixtures of normal and sensitive cells suggest that trypsin alters an immunologic capacity of the sensitive cells. Trypsinized sensitive cells are capable of passively transferring delayed hypersensitivity and peritoneal cells taken from recipient animals are inhibited from migrating in vitro by specific antigen. These results suggest that the cells rapidly resynthesize the material removed by trypsin. The possible nature of the material removed by trypsin is discussed.
ACTIVITY OF DISSOCIATED AND REASSOCIATED 19S ANTI-γ-GLOBULINS
Authors: Schrohenloher Ralph E. , Kunkel Henry G. , Tomasi Thomas B.
Published: June 2004

19S anti-γ-globulins were isolated in a high state of purity from the sera of two patients with rheumatoid arthritis. Following reduction with ethyl mercaptan and alkylation by iodoacetamide, fragments were produced which retained the capacity to combine with 7S γ-globulin.

The fragments from one of the 19S anti-γ-globulins agglutinated red cells coated with incomplete anti-Rh antibodies. This activity was shown by density gradient ultracentrifugation to be associated with low molecular weight fractions. The agglutination of the coated red cells by the fragments was strongly inhibited by normal and myeloma 7S γ-globulins and showed a greater specificity than the parent 19S material.

Analytical ultracentrifuge experiments demonstrated that the fragments from either of the 19S anti-γ-globulins formed complexes with 7S γ-globulin.

Reassociation of the dissociated fragments through reformation of disulfide bonds resulted in the formation of fast sedimenting molecules having properties similar to those of the untreated 19S material in respect to precipitation with aggregated γ-globulin and agglutination of coated red cells.
HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT
Authors: Rowley Donald A. , Fitch Frank W.
Published: June 2004

Passive immunization of rats with homologous anti-sheep erythrocyte serum markedly inhibited the primary antibody response to various doses of sheep erythrocytes. Inhibition was "specific" and apparently produced by either "19S" or "7S" antibody to the antigen. Passive immunization inhibited splenic hyperplasia associated with the primary antibody response. Passive immunization 24 hours after active immunization effectively inhibited the primary antibody response.

The markedly suppressive effect of specific antibody on the primary antibody response contrasted sharply with the absence of this effect on the secondary response. Antigen-antibody complexes formed in vitro elicited no measurable primary antibody response but did elicit a high secondary response. Exposure of normal spleen cells to the antibody in vivo or in vitro suppressed their response to the antigen in x-irradiated recipients. In contrast, cells from previously immunized animals transferred to x-irradiated animals produced antibody in the presence of passively given antibody. Thus, "potential antibody-forming cells" from normal animals were unresponsive to the antigen in the presence of specific antibody, while "antibody-forming cells" from previously immunized animals responded to the antigen in the presence of antibody. Presumably, antibody actively produced in small quantities by a few antibody-forming cells might inhibit antibody formation by potential antibody-forming cells. Confirmation of this suggestion was obtained by showing that some animals initially injected with small doses of antigen failed to produce measurable antibody to subsequent injections of larger doses of the antigen. Low doses of antigen capable of inducing unresponsiveness produced no measurable circulating antibody, but these doses did produce increased numbers of plaque-forming (antibody-releasing) cells in spleens of rats. Thus, the formation of specific antibody may provide a homeostatic or "feed-back" mechanism which controls or limits production of specific antibody to the portion of the antibody-forming system previously stimulated by the antigen. This mechanism may account in part for immunological unresponsiveness produced in certain other related experimental systems.
THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Cohn Zanvil A. , Benson Belinda
Published: June 2004

The in vitro differentiation of homogeneous populations of monocyte-like cells from the unstimulated mouse peritoneal cavity is described. Under the conditions employed, a progressive increase in cell size occurs without significant cell division. This process is characterized morphologically by the accumulation of phase-dense and neutral red-positive granules, mitochondria, and lipid droplets. The phase-dense granules react strongly for acid phosphatase. Biochemical determinations indicate marked increases in the total content and specific activity of acid phosphatase, cathepsin, and ß-glucuronidase. The production of acid phosphatase is more rapid and extensive than that of the other two hydrolases. From these data it appears that the conversion of a monocyte-like cell to a mature macrophage is accompanied by the formation of increased numbers of lysosome-like cytoplasmic organelles.

Mouse peritoneal phagocytes stimulated in vivo with a bacterial lipopolysaccharide undergo a similar series of morphological and biochemical events.
A NEW CLASS OF HUMAN IMMUNOGLOBULINS
Authors: Rowe David S. , Fahey John L.
Published: June 2004

The unique myeloma protein from S. J., a patient with multiple myeloma, was isolated and characterized. It resembled other myeloma proteins in many respects. The S. J. myeloma protein migrated in a distinct peak in the slow ß-globulin region on zone electrophoresis, appeared as a single band on starch gel electrophoresis, and sedimented at 7.04S in the ultracentrifuge. Papain and cysteine treatment produced Fc (fast) and Fab (slow) fragments. Reduction and alkylation of the myeloma protein produced heavy and light chains in a ratio of approximately 3:1. The S. J. myeloma protein had type L (type II) light chains. These were antigenically similar to the Bence Jones protein also found in this patient.

The S. J. myeloma protein was unique in the properties of its heavy chains. The myeloma protein (and its heavy chains and Fc pieces) did not contain antigenic determinants specific for IgG, IgA, or IgM. The myeloma protein (and its heavy chains), however, did contain antigenic determinants which are characteristic of a new class of immunoglobulin. The S. J. myeloma protein was unusual also in its effect on the metabolism of normal IgG and in the electrophoretic mobility of the Fc fragment produced by papain digestion.

No evidence was obtained to indicate that the entire heavy polypeptide of the S. J. protein was a grossly abnormal product of malignant cell metabolism. The unique properties of the S. J. myeloma protein (and its heavy chains) are believed to represent, in large measure, properties to be found in a small part of the normal immunoglobulin population.
A NEW CLASS OF HUMAN IMMUNOGLOBULINS
Authors: Rowe David S. , Fahey John L.
Published: June 2004

A new class of immunoglobulin, IgD, was identified in normal human serum by immunochemical technics. Antiserums prepared against the unique S.J. myeloma protein facilitated recognition of the related normal protein. IgD was shown to possess type K (I) and type L (II) light chain determinants, similar to those present in other classes of immunoglobulins. IgD does not possess determinants which are specific to IgG, IgA, or IgM. The IgD proteins possess their own specific antigenic determinants. IgD migrates in the fast γ-region on immunoelectrophoresis. The properties on sephadex gel filtration and DEAE cellulose chromatography are described.

IgD was found to have a median level of 0.03 mg/ml in 100 normal serums. The range of concentrations found in individual normal serums is much wider, however, than that of other classes of immunoglobulins. IgD, on the average, accounts for less than 1 per cent of the normal serum immunoglobulins.
BOUND COMPLEMENT AND IMMUNOLOGIC INJURY OF BLOOD VESSELS
Authors: Ward Peter A. , Cochrane Charles G.
Published: June 2004

Rats and guinea pigs were depleted of complement (C') by treatment with heat aggregated human γ-globulin (agg HGG), zymosan, anti-ß1C globulin, and carrageenan. Although antigen and antibody were bound to vascular structures, Arthus reactions were inhibited. This inhibition was characterized by the lack of C' binding to walls of vessels, the lack of polymorphonuclear (PMN's) cellular infiltrates, and the lack of significant vascular damage. When the same animals were followed for several hours thereafter, levels of serum C' began to rise, C' was bound in tissues, PMN infiltrates appeared, and immunologic vasculitis developed. Blood counts, chemotaxis of PMN's induced by lysates of PMN granules, together with studies on motility and phagocytosis by PMN's obtained from C' depleted rats, failed to establish any abnormality in these cells which would account for inhibition of Arthus reactions.

The specificity of C' depletion in terms of effects in the first four reacting components of guinea pig C' was studied. Treatment with agg HGG led to loss of activity in all components, whereas zymosan and anti-ß1C globulin predominately affected the third component (C'3c). Carrageenan mainly affected the first two reacting components of C'. Thus, the availability of the 3c component, or a subsequently reacting component, correlated with the attraction of PMN's to immune reactants in vivo.

Various antibodies with different C' fixing capacities in vitro were tested for their ability to induce immunologic vasculitis in normal animals. In rats, only those antibodies which fixed C' in vitro possessed biological activity, whereas in guinea pigs, all antibodies tested, regardless of C' fixation in vitro, induced Arthus reactions. For a given antibody in rats the vasculitis-inducing property was reflected in its ability to bind C' in vascular structures.

Rats depleted of circulating PMN's by specific antibody were tested for Arthus activity. Although concentrations of immune reactants and C' were readily detected in vascular structures, no PMN infiltration occurred and significant vascular damage was averted.
PLATELETS AND THE SHWARTZMAN PHENOMENON
Authors: Levin Jack , Cluff Leighton E.
Published: June 2004

Studies are reported on the effect of immunologically induced thrombocytopenia upon the local and generalized Shwartzman phenomena. Intravenous injection of antiplatelet serum to rabbits produced profound but transient thrombocytopenia unaccompanied by significant changes in circulating leucocytes. Platelet antiserum alone given to rabbits prepared with thorotrast produced renal lesions characteristic of the Shwartzman reaction. Thrombocytopenia induced by platelet antiserum did not inhibit the cutaneous hemorrhagic lesion of the local Shwartzman phenomenon produced by sequential injections of endotoxin intracutaneously and intravenously. The implications of these observations in the pathogenesis of the local cutaneous and generalized Shwartzman reaction are discussed.
ANTI-DNA ANTIBODIES IN HYPERIMMUNIZED RABBITS
Authors: Christian Charles L. , DeSimone Arthur R. , Abruzzo John L.
Published: June 2004

Complement-fixing anti-DNA antibodies were detected in a minority of sera of rabbits hyperimmunized with killed Gram-negative bacteria. The C'-fixing property of DNA was lost after DNase treatment. Preferential reactivity with denatured DNA was observed. The antisera reacted with DNA preparations derived from rabbit bone marrow and thymus, calf thymus, pneumococci, salmon sperm, and Escherichia coli. E. coli DNA was less effective than preparations of mammalian and salmon sperm DNA in fixation of C'. Inhibition of DNA C' fixation by nucleotides and nucleosides was observed. The bulk of anti-DNA activity was associated with the low molecular weight antibody fraction.
IMMUNOGLOBULIN ISOANTIGENS (ALLOTYPES) IN THE MOUSE
Authors: Herzenberg Leonard A. , Warner Noel L. , Herzenberg Leonore A.
Published: June 2004

Eight antigens of 7S γ2-immunoglobulins controlled by alleles at a single locus Ig-1, have been identified in mice. This locus has previously been shown to determine antigenic specificities on the F fragments of 7S γ2a-globulins. The reactions of these antigens with various isoantisera have shown that the antigens all cross react with one another.

New methods for the analysis of antigenic specificities of soluble proteins are presented in detail. A sensitive method for detecting in the order of 0.01 µg of these isoantigens has been developed, based on the quantitative inhibition of precipitation of I125-labeled antigen.

Cross-reactions of the antigens were analysed in inhibition assays and the data is compatible with the existence of a minimum of eight antigenic specificities. Each of the antigens is composed of different combinations of these specificities, with only one antigen having a specificity not present in any other.

Sixty-eight mouse strains have been tested with specific isoantisera, and on the basis of the results, have been placed into the eight allele groups.

Evidence for close genetic linkage of the Ig-1 locus and 11 chromosome markers has been sought and not found.
HISTOCHEMICAL STUDIES OF LYSOSOMES AND LYSOSOMAL ENZYMES IN VIRUS-INFECTED CELL CULTURES
Authors: Allison A. C. , Mallucci L.
Published: June 2004

The appearance of lysosomes and the distribution of lysosomal enzymes have been studied in a number of cell cultures exposed to viruses. Lysosomes were shown by fluorescence microscopy after vital staining with aminoacridines and light microscopy after vital staining with neutral red. The lysosomal enzymes studied histochemically in unfixed and fixed cells were acid phosphatase and 5-bromo-4-chloro-indoxyl acetate esterase.

Activation of lysosomal enzymes was found to take place in three stages. The first is characterized by permeability of lysosomal membranes without release of enzymes. This is demonstrable by staining of lysosomal enzymes in unfixed cells and by increased uptake of aminoacridine fluorochromes and neutral red into lysosomes. In cell sheets initially stained with neutral red this gives rise to red plaques. This stage can be fully reversible; cells infected with, and yielding, the red-plaque strain of NDV, recover fully afterwards.

In the second stage lysosomal enzymes are released into the cytoplasm, the cells round up and there is decreased uptake of aminoacridines and neutral red into lysosomes. In cell monolayers this results in the formation of white plaques. In the third stage, not usually seen in cell cultures, lysosomal enzymes are released from or inactivated in the cells and are not seen in either fixed or unfixed preparations.

The possible roles of lysosomal enzymes in production of cytopathic effects, polykaryocytosis and malignant cell transformation are discussed.
QUANTITATION OF TRANSPLANTATION IMMUNITY
Authors: Najarian John S. , Feldman Joseph D.
Published: June 2004

A technique for in vivo quantitation of transplantation immunity has been presented. Known numbers of H3-thymidine-labeled lymphoid cells were injected intravenously into isologous or homologous recipients. The total radioactivity in host spleens was counted at different time intervals. The rate of isotope disappearance from the spleen was exponential to 0.5 per cent of the dose or less. In isologous recipients, the calculated half-life of labeled cells was 82 hours; in homologous recipients it was 40 hours; and in presensitized homologous hosts it was 18 hours. The technique is a highly reproducible, precise, and sensitive measure of transplantation immunity.
THE EXPRESSION OF HISTOCOMPATIBILITY ANTIGENS ON CELLULAR AND SUBCELLULAR MEMBRANES
Authors: Herberman Ronald , Stetson Chandler A.
Published: June 2004

The mouse isoantigens determined at the major histocompatibility locus known as H-2 have been found to be closely associated with the cellular surface membranes, with the membranes of the endoplasmic reticulum, and probably with those of the lysosomes as well. Mitochondrial membranes, on the other hand, show little or no H-2 antigen activity. Membrane material prepared from certain tissues, including brain and muscle, have no detectable H-2 antigenic activity. Evidence is presented which indicates that all of the H-2 antigens of the genome are expressed as a unit, supporting the hypothesis that the complex H-2 genetic locus consists of a single cistron. It is postulated that these histocompatibility antigens form some structural or functional unit in the membranes of cells.
INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS
Authors: Grey Howard M. , Mannik Mart , Kunkel Henry G.
Published: June 2004

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled γ-globulin and for the localization of these determinants on the γ-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of γ-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum.

The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined.

After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains.

These studies on myeloma proteins furnished evidence concerning the portions of the γ-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Bentwich Zvi , Harris T. N.
Published: June 2004

The relationship of the streptococcal hemolysin which is recognized on incubation of RBC with streptococcal cells (cell-bound hemolysin, CBH), to RNA hemolysin, a representative of oxygen-stable hemolysin (streptolysin S) has been studied. A number of similarities have been found in the conditions for optimal production of each of these hemolysins, a requirement for cysteine, Mg++, and glucose; maximal production by streptococci in the stationary phase; similar curves of pH-dependence. In both systems, the production of hemolysin was inhibited by certain antibiotics, by ultraviolet irradiation, and by sonic disruption and was absent in the same streptococcal mutant strain. The hemolytic activity of both systems was inhibited by lecithin, trypan blue, and papain. Similarities were also found in relative susceptibilities to the two hemolytic systems of erythrocytes of a number of animal species.

These data support a suggestion advanced in an earlier study that a streptococcal hemolytic moiety, which can be induced by, and carried on, a number of diverse agents to comprise the group of oxygen-stable hemolysins, serves, in its original attachment to a component of the streptococcal cell, to produce the hemolytic effect recognized as the cell-bound hemolysin.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Harris T. N.
Published: June 2004

In studies of the mechanism of lysis of red blood cells by washed streptococci with hemolytic activity (cell-bound hemolysin, CBH) no components released spontaneously by RBC or streptococci, or by interaction between these cells, could be found to induce the formation of soluble hemolysin by the streptococci. It was also found that separation of RBC from streptococci even by Millipore filter or a very thin layer of agar could prevent their hemolysis.

By means of cellulose columns it was possible to separate RBC from streptococci after a short incubation. RBC thus separated from streptococci with which they had been incubated underwent hemolysis on subsequent incubation at 37°C. By varying the period of incubation prior to separation it was possible to demonstrate the transfer of increasing amounts of hemolysin from streptococci to RBC with increasing periods of incubation. A considerable part of this appeared to be at a constant rate.

A theory is presented on the relationship between the streptococcal cell-bound hemolysin and the group of oxygen-stable streptococcal hemolysins, in terms of a transferable hemolytic moiety and binding sites for this moiety on the streptococcal cell, on various molecular species which can act as inducers of the oxygen-stable hemolysins, and on the RBC, with the affinity of the respective binding sites for the hemolytic moiety increasing in that order.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Unanue Emil R. , Dixon Frank J.
Published: June 2004

A direct correlation between the amount of kidney-fixing antibody and the degree of associated renal injury was demonstrated for rabbit and duck nephrotoxic antibodies. No evidence for a qualitative difference among nephrotoxic antibodies of a given type was obtained. It appeared that duck nephrotoxic antibody was directed against a wider spectrum of rat renal antigens than was rabbit nephrotoxic antibody. In order to produce immediate proteinuria an amount of rabbit or duck gamma-2 kidney-fixing antibody capable of occupying approximately 45 per cent or more of the capillary filtration surface was needed. For immediate proteinuria an amount of rabbit gamma-2 kidney-fixing antibody capable of reacting with more than one-half of the available antigenic sites was needed. Less than twice that amount of rabbit antibody completely saturated available antigenic sites in the kidney. Virtually all nephrotoxic antibodies in hyperimmune rabbit nephrotoxic sera were of the gamma-2 variety while nephrotoxic antibodies in comparable duck nephrotoxic sera were found in gamma-2 (with 5.8 and 7.4S sedimentation coefficients) and gamma-1M fractions.

Gamma-1M duck nephrotoxic antibody was 60 times more potent a nephritogen than gamma-2 duck nephrotoxic antibody on a molecular basis. Mercaptoethanol abolished the nephrotoxicity of gamma-1M duck antibody and reduced that of gamma-2 duck antibodies but had no effect on rabbit gamma-2. In no case did mercaptoethanol treatment have an effect on the kidney-fixing properties of the antibodies involved.

After injection of nephrotoxic antibodies there appeared to be a prompt fixation of a majority of the antibody to tissue antigens primarily in the kidney. However, a small amount of potentially kidney-fixing antibody remained in the circulation for a considerable period apparently reflecting a dissociation of less avid antibodies with an equilibrium between fixed and free antibody. The role of this more easily dissociable antibody in the progression of nephrotoxic nephritis is not certain but it is possible that it could play a role in the early progression of the disease.
LYSOSOMAL ACID HYDROLASES IN MICE INFECTED WITH BCG
Authors: Saito Kazuhisa , Suter Emanuel
Published: June 2004

Experiments are reported dealing with the increase of lysosomal acid hydrolases induced by BCG infection. Acid hydrolases were determined quantitatively in peritoneal MP, liver homogenate, and plasma of normal and BCG-infected mice. A significant increase of acid phosphatase, ß-glucuronidase, and cathepsin was found in MP and liver homogenate of BCG-infected mice. In plasma also a significant increase of acid phosphatase and ß-glucuronidase was noticed. The results of the determination of the enzymes in centrifugally separated subcellular fractions of liver homogenate indicated clearly that the acid hydrolases associated mainly with the "large granular" fraction, which consists of mitochondria, lysosomes, and microsomes and that infection with BCG caused significant increase of the enzymes specifically in this fraction. Differences in the pattern of location among centrifugally separated fraction of liver homogenate were observed between acid phosphatase and the other two acid hydrolases. MP cultured in vitro doubled their acid phosphatases content within 24 hours, whereas ß-glucuronidase rather decreased in the same cells.
LYSOSOMAL ACID HYDROLASES AND HYPERREACTIVITY TO ENDOTOXIN IN MICE INFECTED WITH BCG
Authors: Saito Kazuhisa , Suter Emanuel
Published: June 2004

Experiments are reported dealing with the correlation between activities of lysosomal acid hydrolases and hyperreactivity to endotoxin induced by BCG infection. Acid hydrolases were determined quantitatively in peritoneal MP, liver homogenate, and plasma of normal and hyperreactive mice. Mice infected with BCG not only exhibited a hyperreactive state to lethal effect of endotoxin, but also responded to endotoxin by rapid increase of acid hydrolases, especially of ß-glucuronidase, in the plasma; whereas control mice responded to endotoxin by almost no change in plasma acid hydrolases. The extent of increase of ß-glucuronidase in plasma of hyperreactive mice was shown to correlate fairly well with the degree of hyperreactivity to the lethal effect of endotoxin. Desensitization of such animals with endotoxin was found to cause a decreased response of plasma ß-glucuronidase parallel with decreased mortality. A large amount of PPD exerted the similar effect to that of endotoxin in hyperreactive mice. Furthermore, the effect of PPD was decreased by desensitization of such animals with endotoxin, a fact which suggests contamination of PPD with endotoxin.
C'1 ESTERASE EFFECT ON ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF THE FOURTH COMPONENT OF COMPLEMENT
Authors: Müller-Eberhard Hans J. , Lepow Irwin H.
Published: June 2004

Highly purified C'1 esterase of human serum is capable of inactivating isolated fourth component of human complement (ß1E-globulin). Inactivation is accompanied by changes in electrophoretic and ultracentrifugal properties of ß1E-globulin. If non-sensitized sheep erythrocytes are present during the action of C'1 esterase on ß1E-globulin, a complex is formed consisting of cells and cytolytically active fourth component (EC'4). Thus, inactivation of ß1E-globulin by C'1 esterase appears to be preceded by a state of activation enabling ß1E-molecules to combine with cell membrane receptors. Acceptor groups appear to be present also in 7S γ-globulin and in ß1E-globulin itself, since C'1 esterase can induce the formation of ß-ß and of ß1E-7S γ-globulin complexes.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Greisman Sheldon E. , Woodwards William E.
Published: June 2004

Bacterial endotoxins were administered by continuous intravenous infusions at constant rates to normal man and rabbits. An initial progressive febrile reaction was followed by progressive defervescence to baseline. The resulting pyrogenic refractory state was characterized as follows: (a) reticuloendothelial blockade with thorotrast neither prevented nor reversed its course; (b) passive transfer was unsuccessful with refractory phase plasma; (c) infusions of normal plasma or fresh whole blood failed to restore responsiveness; (d) a minimum of 4 hours of continuous endotoxin infusion was required for full development of unresponsiveness; (e) circulating antibody titers to endotoxin remained unaltered; (f) peripheral leukocytosis appeared; (g) infusion of febrile phase plasma reevoked an immediate, monophasic fever; (h) endotoxinemia could be demonstrated by pyrogen bioassay; (i) 10-fold increases in endotoxin infusion rates reevoked fever; (j) impaired responsiveness extended to heterologous endotoxins; (k) dermal inflammatory responses to endotoxin were suppressed in man while tuberculin reactivity remained unimpaired; dermal inflammatory responses to endotoxin were enhanced in rabbits; and (l) pyrogenic reactivity to endotoxin reappeared within 24 hours in man; refractoriness persisted in rabbits.

It is concluded that the pyrogenic refractory state reflects an inability of the host to continue to mobilize endogenous pyrogen during sustained endotoxinemia. Such observations, together with previous studies, are consistent with two distinct immunologic mechanisms of resistance to endotoxin pyrogenicity: (a) desensitization at the cellular level; and (b) elaboration of circulating antibodies which assist reticuloendothelial clearance and destruction of endotoxin. Whereas both such mechanisms may contribute to pyrogenic tolerance, the characteristics of the pyrogenic refractory state suggest the participation only of the former.
ANTIGENS IN IMMUNITY
Authors: Nossal G. J. V. , Ada G. L. , Austin Caroline M.
Published: June 2004

Flagellar antigens from S. adelaide bacteria were labelled with carrier-free 125I so as to achieve a substitution rate of 0.1 to 2.1 radioactive iodine atoms per flagellin molecule. Lymph nodes from rats injected with small amounts of these antigens were teased into a single cell suspension. Single antibody-forming cells were identified and submitted individually to autoradiography so as to measure their content of iodine 125I. The study was confined to the 7S phase of the primary response.

Grain counts over 216 single antibody-forming cells were no higher than counts over equivalent background areas in the emulsion. This finding suggested that the cells contained little or no macromolecular antigen, and it was considered very unlikely that there were sufficient macromolecules of antigen in a plasma cell to act as a direct template on polysomes for the formation of antibody. The question of the possible presence, in such cells, of fragments of antigen was considered. This possibility, while not supported by the present results, cannot be excluded at present.
ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL
Authors: Möller Göran , Wigzell Hans
Published: June 2004

The suppressing activity of passively transferred antibodies on antibody synthesis against sheep red cells was investigated at the cellular level by the agar-plaque technique developed by Jerne. Humoral antibodies injected prior to the antigen suppressed the appearance of plaque-forming spleen cells producing 19S antibodies completely. Antibodies given during the first 4 days after antigen injection also showed such action, but only after a latency period of 40 hours. The inhibiting efficiency of 7S antibodies was about 100 to 200 times greater than that of 19S antibodies. The results support the conclusion that humoral antibodies inhibit the immune response by removing the stimulus for the proliferation of the antibody producing cells and not by directly depressing antibody synthesis in already committed cells.

Passively transferred antibodies inhibited the 7S response if given prior to, or 24 hours after the antigen injection, in analogy with previous results concerning 19S response. In contrast to these previous results on 19S synthesis, antibody transfer had no detectable effect during the early exponential phase of 7S production (5 to 7 days after antigen injection). Only limited inhibition was observed 3 days after the antigen. One possible explanation of this difference is that 7S-producing cells do not divide, or divide at a slow rate. Antigen injection would stimulate the proliferation of 19S-producing cells. Subsequently these would switch to the synthesis of 7S antibodies. These would inhibit the initiation of new 19S-producing cells by combining with the antigen. They would thus suppress the recruitment of their own precursors. A steady state of 7S antibody production by cells with a long lifetime would be the result. This hypothesis ascribes an important regulatory function to 7S antibodies. They would be parts of a feed-back system preventing excessive cell multiplication in response to a single antigen.
STRUCTURAL STUDIES OF HUMAN IMMUNOGLOBULINS
Authors: Frangione Blas , Franklin Edward C.
Published: June 2004

1. Comparison of peptide maps of the Fc fragments of normal G immunoglobulins and 11 G myeloma proteins of the We (b) type showed them to be very similar except for differences associated with the Gm type. Some additional differences were noted, however, in the Fc fragments of three Vi (c) myeloma proteins.

2. Peptide maps of heavy chains from the same G myeloma proteins differed from each other and from normal heavy chains. In general, the myeloma chains contained a larger number of well defined spots; some of these were common to normal heavy chains while others were unique to each protein. Others, present in normal heavy chains, were lacking in the myeloma proteins.

3. Comparison of the heavy chains and Fc fragments from the same protein suggests that much of the variability of different myeloma proteins and, presumably, antibodies resides in the Fd fragment.

4. Further support for this is given by the finding that the antigenic specificity of 3 myeloma proteins also appeared to reside in the Fd fragments.