bluuebunny/crossref_metadata_2025 huggingface dataset:
Species-Specific Antigens from the Cell Walls of the Agents of Meningopneumonitis and Feline Pneumonitis
Authors: Jenkin Howard M. , Ross Martin R. , Moulder James W.
Published: January 2023

When cell walls were prepared from the agents of meningopneumonitis and feline pneumonitis by treatment first with deoxycholate and then with trypsin, the group-specific antigens were found in the deoxycholate extract whereas the species-specific antigens remained in the cell walls. Group-specific antigens were demonstrated by complement fixation, whereas the presence of species-specific antigens was shown by both complement fixation and absorption of infectivity-neutralizing antibody. The deoxycholate extracts contained periodate-sensitive and periodate-resistant group antigens. The specific complement-fixing antigens of the cell walls resembled previously described specific antigens in being resistant to periodate but differed from them in not being destroyed by heating at 100°C. Unlike intact particles, the cell walls were not toxic for mice upon intravenous injection. The possible application of these findings to practical serology of the psittacosis group was discussed.
A Colorimetric Neutralization Test for Herpes Simplex, with Observations on Neutralizing and Complement-Fixing Antibody Levels in Human Sera
Authors: Schmidt Nathalie J. , Lennette Edwin H.
Published: January 2023

Discussion and Summary

The colorimetric neutralization test for herpes simplex described in this report is considerably easier to conduct than neutralization tests in mice or embryonated eggs, and lends itself to large-scale studies. Also, the constant virusvarying serum technique, widely regarded as more sensitive than the constant serum-varying virus method for detecting differences in levels of neutralizing antibody, is utilized.

As a tool for epidemiologic and diagnostic purposes, the neutralization test was found comparable to the complement fixation test in its ability to demonstrate 4-fold or greater titer rises. It would appear that either the complement fixation or colorimetric neutralization test would be adequate for diagnosis of primary herpetic infections, and that little would be gained diagnostically by the use of both tests except in instances where equivocal results were obtained with one test. Only 2 of 31 4-fold or greater rises in antibody titer were detected by the neutralization test, but not the complement fixation test, and only 3 of the 31 antibody rises were detected by the complement fixation test, but not the neutralization test.

Although the neutralizing antibody titers tended to be somewhat higher than the complement-fixing antibody titers, they both increased at approximately the same rate in cases of primary herpetic infections. This is in contrast to the antibody response in many other viral diseases in which neutralizing antibodies appear long before complement-fixing antibodies, and may even reach their maximal titer by the time of onset of the illness, e.g., poliomyelitis (19).

The neutralizing antibody titers detected by the colorimetric method showed good correlation with the complement-fixing antibody titers for the same sera (r = 0.82). This correlation between complement-fixing and neutralizing antibody titers was noted for individuals in all age groups studied, and it would appear, on the basis of the limited amount of data available, that production of both types of antibody is stimulated by recurrent herpetic infections, or that complement-fixing antibody persists for as long after primary infections as does neutralizing antibody.
The Anamnestic Antibody Response to Japanese Encephalitis Virus in Monkeys and its Implications Concerning Naturally Acquired Immunity in Man
Authors: Lee H. W. , Scherer W. F.
Published: January 2023

Primary and anamnestic antibody responses to infectious Japanese encephalitis (JE) virus were studied in monkeys. The intradermal anamnestic dose of virus in suspensions of Japanese mosquitoes collected in nature was small, essentially equal to the intradermal infectious dose for susceptible monkeys, and well within the range of virus which vector mosquitoes might inoculate. Anamnestic antibody responses were uniformly measurable by hemagglutination-inhibition (HI) tests, usually detectable by complement fixation (CF) tests, but only infrequently demonstrable by virus-dilution neutralization tests. That anamnestic antibody responses resulted merely from virus antigen inoculated intradermally and did not depend on multiplication of virus in blood, skin or superficial tissues of previously infected monkeys was evidenced by a) lack of measurable viremia and virus proliferation in skin or superficial tissues and b) the ability of noninfectious, ultraviolet-irradiated virus to stimulate anamnestic antibody responses as readily as infectious virus. The fact that small amounts of infectious virus stimulated anamnestic antibody responses in previously infected, nonviremic monkeys, whereas large amounts of virus were available in viremic, susceptible monkeys to evoke primary antibody responses is compatible with the increased sensitivity of hosts to small “booster” injections of antigens; it does not necessarily infer that anamnestic antibody responses occur as a result of virus multiplication in previously infected hosts.

Upon extrapolation to humans these findings suggest that a single endemic arthropod-borne virus can, upon transmission by vector mosquitoes, repeatedly stimulate anamnestic antibody responses in man and thus maintain detectable antibody levels and immunity throughout life. Moreover, in areas such as the Kanto Plain near Tokyo, Japan, where JE virus is the only known group B arthropod-borne virus, seasonal rises in HI and CF antibody titers to JE virus in persons with preseasonal homologous neutralizing (N) antibody need not imply that another group B virus exists in the same geographic region.

HI, CF and N antibodies remained detectable in monkeys for at least 11 months after primary inapparent infection. HI and CF anamnestic antibody responses to large doses of JE virus were not significantly inhibited by high, preexisting HI, CF or N antibody levels in serum of hyperimmunized monkeys, but the effects of high antibody levels on anamnestic antibody responses to subsequent small virus doses were not conclusively ascertained.
Immunologic Properties of Weak Histocompatibility Genes
Authors: McKhann Charles F. , Berrian James H.
Published: January 2023

The antigens determined by individual histocompatibility genes differ in ability to induce transplantation immunity. Those of the H-2 locus are effective in all tissues of an individual and induce immunity rapidly. Those of the H-3 locus are antigenically less effective in some tissues than in others and permit longer graft survival. Using coisogenic strains of mice a further comparison has been made between antigens of H-2 and H-3 genes with respect to: a) the time required to induce immunity, b) the time when immunity can first be demonstrated, c) the effect of variations in graft dose, and d) adoptive transfer of immunity with lymph node and spleen cells.

It was found that in both H-2 and H-3 strains immunity can be induced by 4 days contact with a skin graft but that additional time must elapse before immunity can be demonstrated. This additional time requirement was greater in H-3 than in H-2. The effects of variations in graft dose were equivalent and minimal. H-2 immunity was adoptively transferred by lymph nodes and spleen cells. H-3 was transferred best by nodes that had been exposed to skin grafts for 24 days. Nodes that were stimulated by H-2 and H-3 antigens from the same grafts transferred immunity against H-2 only.
Studies on the Role of Serotonin and Mast Cells in Anaphylaxis of the Mouse Produced with Soluble Antigen-Antibody Complexes
Authors: Tokuda Seikichi , Weiser Russell S.
Published: January 2023

The influence of various treatments on the anaphylactic response of the Swiss-Webster mouse to challenge with a soluble antigen-antibody complex composed of bovine serum albumin-antibovine serum albumin was studied.

Protection against anaphylaxis was afforded by prechallenge treatment with either reserpine, epinephrine, norepinephrine, dopamine, histamine and sodium salicylate or with the “serotonin antagonists” lysergic acid diethylamide, its bromine analogue and chlorpromazine. The antihistamine agent, pyrilamine maleate, was without effect.

The protective effect of reserpine can be abolished with 5-hydroxytryptophan but not with 3,4-dihydroxyphenylalanine. Histamine or sodium salicylate did not affect the response to intravenous challenge with serotonin or histamine. Prechallenge treatment with 5-hydroxytryptamine or 5-hydroxytryptophan increased the susceptibility of the animals to anaphylaxis.

The highly sensitive pertussis-vaccinated mouse was protected against anaphylaxis by prechallenge treatment with epinephrine but not by prechallenge treatment with reserpine, the bromine analogue of lysergic acid diethylamide or dopamine.

The refractory state induced by prior sublethal doses of antigen-antibody complex was not reversed by the administration of mouse complement or 5-hydroxytryptophan or a combination of both substances.

Mice of the DBA/2 strain show only mild symptoms of anaphylaxis following doses of antigen-antibody complex three times those necessary to produce fatal anaphylaxis in a high percentage of Swiss-Webster mice.

Examination of various tissues following anaphylactic death produced with the complex gave no indication that morphologic changes in mast cells accompany anaphylaxis.
Antigenic Activity of Various Tissues in Transplantation Immunity
Authors: McKhann Charles F. , Berrian James H.
Published: January 2023

Using coisogenic strains of mice differing by a single, weak histocompatibility gene at the H-3 locus, it was shown that various donor tissues differed greatly in ability to induce transplantation immunity. Skin grafts, epidermal cells, and renal epithelial cells were antigenically effective. Lymphoid cells injected intraperitoneally failed to induce immunity. Similar lymphoid cells gave marginal immunity when administrered by other routes and, when injected into newborn mice, rendered them highly tolerant of later skin grafts. It was concluded that the tissues studied may contain identical complements of transplantation antigens and that the basis of the different abilities of the various tissues to induce immunity may reside in the location of antigens within the cells, and in the interaction between grafted cells and the host.
Effect of Antiserum and Antibiotics on Persistent Infection of HeLa Cells with Meningopneumonitis Virus
Authors: Galasso G. J. , Manire G. P.
Published: January 2023

The effect of antiviral agents on a persistent infection of HeLa cells with meningopneumonitis virus has been studied. Antiserum does not appear to have a significant effect. Penicillin, even when treatment is prolonged for 3 ½ months, causes a drop in titer but does not completely remove the virus. Chloramphenicol treatment for 21 days and tetracycline for 14 days are sufficient to remove all traces of virus. Tetracycline appears to have an in vitro effect on the virus.
Inhibition of Immune Phagocytosis of Diplococcus Pneumoniae by Human Neutrophiles with Antibody against Complement
Authors: Jeter W. S. , McKee Albert P. , Mason Rachel J.
Published: January 2023

Treatment of normal human blood with rabbit antibody against human complement completely blocks the phagocytosis by the neutrophiles of Diplococcus pneumoniae in the presence of its type-specific antibody. The effect is observed whether the incubation period of blood with organisms is as short as 15 min or as long as 4 hr. The addition of fresh, untreated serum to cells from treated blood does not reverse the inhibition, nor does the addition of fresh complement-containing serum in amounts 4 times that of the original serum present. Bactericidal studies indicate that antipneumococcal serum is capable of the destruction of the organism even when the complement is inactivated by anticomplement and the phagocytes appear to be inactive.
Studies of Lymphocytic Choriomeningitis in Mice
Authors: Weigand Heribert , Hotchin John
Published: January 2023

This study comprises an investigation of mice surviving inoculation with LCM virus during first few days after birth. Such animals harbor the virus at high titers for long periods of time and have been designated as suffering from persistent tolerated infection (PTI) with LCM virus. These animals survive rechallenge with virus and can be considered as immune; however, two types of immunity have been described. One type is designated “tolerant immunity” and is defined as the state in which the mice do not exhibit any detectable immunological response to the presence of the virus, i.e., there is no antibody production and no virus suppression. The immunity of mice with PTI is of this type. A second type of immunity to LCM has been defined as resulting from peripheral nonlethal inoculation of adult animals. This type has been called “active immunity” and refers to immunity which involves a response by the immune mechanism of the host evidenced by an ability to suppress virus infection. High titer virus has been found in mice as long as 235 days after the original inoculation. When this was done during the first few days after birth, mice resisted challenge with homologous or heterologous LCM viruses and complement-fixing antibody could not be demonstrated in their sera. The offspring of such PTI female mice, born as long as 144 days after the original intracerebral inoculation of the mother, proved to have PTI also, with high titers of virus in their brains and blood. Adult mice could be hyperimmunized with virus by giving the first dose of live virus subcutaneously. Subsequent inoculations, either intraperitoneally or intracerebrally, failed to kill the mice which produced complement-fixing antibody and suppression of virus in their brains. No significant amount of neutralizing antibody was found in any of the mice tested irrespective of which type of immunity they possessed. The results are discussed in terms of concepts of immunological tolerance to viruses and the nature of immunity to LCM virus.
The Persistent Production of Small Quantities of Infectious Newcastle Disease Virus in Grossly Unaltered L and U12 Strain Cells
Authors: Mason Earl J. , Kaufman Nathan
Published: January 2023

Inapparent infections of L and U12 cell strains by Newcastle disease virus are described in which low concentrations of virus were persistently elaborated by the cells. Detectable amounts of infectious virus were found more frequently in L strain cultures and appeared to be associated with the cell fractions in slightly greater quantities. Even though they contained virus, the carrier cell lines were as susceptible as previously uninoculated stock cell cultures to the toxic effect of large virus inocula.
Significance of the Blocking Antibody in Experimental Brucellosis
Authors: Glenchur Harry , Zinneman Horace H. , Hall Wendell H.
Published: January 2023

Hyperimmunization of rabbits with heat-killed Brucella abortus called forth blocking antibodies which appeared late and only if the antigenic dose was very large. The blocking antibody was shown to have a shifting electrophoretic mobility in rabbit and human serum proteins, varying with the duration of antigenic stimulation. Early, the blocking phenomenon appeared in the slow moving γ-globulins; with continued stimulation, the blocking antibodies migrated in the serum proteins with the mobility of the β-globulins. The blocking phenomenon in a B. abortus hyperimmunized rabbit disappeared 14 weeks after the cessation of heavy antigenic stimulation. It reappeared after a single injection of the same antigen. These findings suggest that in the rabbit blocking antibody indicates continued antigenic stimulation or active infection by Brucella.
In Vitro Formation of 7S and 19S γ-Globulins by Tissues from Normal Subjects and Patients with Rheumatoid Arthritis
Authors: Levene Howard I. , Franklin Edward C. , Thorbecke G. Jeanette
Published: January 2023

The incorporation of radioactively labeled amino acids into 7S and 19S γ-globulins by human lymph nodes and splenic tissue in vitro has been studied. De novo formation of 7S γ-globulin has been demonstrated in 13 of 26 tissue culture tubes prepared with tissue obtained from 13 normal patients, and in five of nine tubes prepared with tissue obtained from three patients with rheumatoid arthritis. Formation of 19S γ-globulin has been found only in cultures prepared with tissues from patients with rheumatoid arthritis.

Attempts to demonstrate the production of serologically active rheumatoid factor have been unsuccessful.
Retention of Rabbit Antibody Activity during Acetylation
Authors: Pressman David , Stelos Peter , Grossberg Allan
Published: January 2023

Although acetylation destroys the ability of rabbit anti-BSA to form a precipitate with BSA it was found here that it still combines with BSA to form soluble complexes. The combination was studied by electrophoretic and ultracentrifugal methods. Acetylation of 96% of the amino groups of anti-BSA γ-globulin resulted in a preparation that could still form soluble complexes with BSA. Normal rabbit γ-globulin, however, when acetylated to 86% of its amino groups, did not form soluble complexes with BSA.

The failure of acetylated antibody to form a precipitate with its antigen is attributed to electrostatic repulsion effects between antibody molecules.
Immune-Adherence with Leptospira Antigens
Authors: Linscott William D. , Boak Ruth A.
Published: January 2023

A procedure has been presented by means of which Leptospira antigens have been tested in the immune-adherence (I-A) system. Extensive re-adherence was found to occur after mechanical disruption of the I-A bond, although it diminished in completeness when disruption was repeated several times. In the presence of a great excess of antiserum, complement fixation by antigen-antibody-complexes was found to occur at 1–5°C. Antigen-antibody-complement complexes formed in this manner, after being washed in the cold, were capable of adhering to erythrocytes in the absence of additional antiserum or complement. Antigen-antibody-complement complexes were prevented by normal serum from adhering to erythrocytes at low temperature, but not at 37°C. In the presence of a high concentration of antiserum, I-A was demonstrated to occur in the presence of fresh guinea pig or human complement diluted as much as 1:5120. The I-A reaction was found to be sufficiently sensitive that humoral antibodies against leptospirae could be detected within 40 hr after the initial injection of a rabbit with the homologous antigen.
The in Vivo Production of Penicillinase by Hemolytic Staphylococcus Aureus
Authors: Dineen Peter
Published: January 2023

The production of staphylopenicillinase has been demonstrated in vivo. The sterilized homogenate of mouse kidneys when placed in wells on agar plates seeded with Sarcina lutea showed penicillinase activity. This activity was seen only in strains that were naturally penicillin resistant. This was not an adaptive enzyme, as it was present in the absence of penicillin exposure. Penicillinase was not present immediately after infection in mouse kidneys, but required time for production.
The VI Antigens of the Enterobacteriaceae
Authors: Whiteside Roberta E. , Baker Edgar E.
Published: January 2023

Vi antigens and deacetylated Vi antigens from P. ballerup, E. coli and S. typhosa, strain Ty2 were tested with antisera prepared against various Vi producing microorganisms by the agar diffusion precipitin test. Differences in type of reaction were noted between deacetylated antigen preparations reacted with antisera prepared with P. ballerup or S. paratyphi C bacilli and deacetylated Vi antigens reacted with antisera prepared with S. typhosa or E. coli organisms. It appeared that serologic differences exist in Vi antigens of the various bacilli used for preparation of antisera which become evident when these antisera are reacted with degraded Vi antigens. It has been shown that these differences are not differences in basic specificity of Vi antigen and its antibody.
Agar Precipitation Reactions between Human Serum Albumin and Hemoglobin in Human Tissue Extracts
Authors: Metzgar Richard S. , Grace James T.
Published: January 2023

Normal human and animal sera gave agar precipitation reaction with certain human tissue extracts. The serum component reacting with the human tissue extracts had an electrophoretic mobility corresponding to albumin. The constituent in the human tissue extracts which interacted with albumin had an electrophoretic mobility corresponding to that of an α-2 globulin and appeared to be hemoglobin or a hemoglobin product. The precipitate formed was soluble in hemoglobin excess and the density of the precipitate was dependent upon the albumin concentration. The agar precipitation reactions were not demonstrable by other serologic techniques. A cautious interpretation of immunologic reactions in an agar medium was advised.
Studies on Rickettsial Toxins
Authors: Wisseman Charles L. , Pazourek Lawrence , Boccuti Anthony , James Herbert , Oldstone Michael B. A.
Published: January 2023

Comparison of the action of toxic viable Rickettsia mooseri with that of a Boivin type endotoxin from Escherichia coli in mice revealed striking differences. One LD50 of the endotoxin caused a prompt depression in total leukocyte count followed by leukocytosis, whereas 1 LD50 of the toxic rickettsial suspension failed to cause a significant shift in total leukocyte count toward a comparable response pattern. Reticuloendothelial blockade with colloidal iron saccharate markedly increased the susceptibility of mice to the lethal action of the endotoxin, but failed to alter their susceptibility to the toxic action of the rickettsiae. Moreover, mice rendered tolerant to endotoxin remained as susceptible to the rickettsial toxin as normal control mice. It is concluded that the mouse lethal toxin of R. mooseri and classic bacterial endotoxin differ significantly in several important properties.
Development and Application of New Parenteral Adjuvants
Authors: Woodhour Allen F. , Jensen Keith E. , Warren Joel
Published: January 2023

The relative antigenic potencies of influenza vaccine emulsified in various oils have been compared using a guinea pig assay system. Primary antibody responses were significantly elevated with 50% W/O emulsions of the plant oils, peanut, sesame and chaulmoogra, whereas preparations with poppyseed and safflower were without noticeable effect. In contrast, all oils tested were effective in elevating a secondary response, indicating that some degree of antigenic sensitization occurred even in the absence of any primary adjuvant effect. Maximal titers were obtained with mineral oil (Drakeol) emulsions, while intermediate responses were noted with a synthetic oil, ethyl oleate, and an animal oil preparation, lantrol. Addition of hexadecylamine to emulsions did not produce a synergistic effect.
The Immunologic Response of Rabbits to Homologous and Heterologous Corneal and Uveal Tissue
Authors: Wacker Waldon B. , Dodd Matt C.
Published: January 2023

Naturally occurring antibody for uvea, but not cornea, was demonstrable in normal rabbit sera by the complement fixation test, and is apparently the same as that previously found by Kidd and Friedewald to be reactive with other rabbit tissues. In addition, a naturally occurring agglutinin for tanned red cells treated with rabbit corneal extract was found in rabbit, chicken, guinea pig and human sera. This agglutinin may be a nonantibody substance.

The injection of rabbits with homologous cornea or uvea failed to produce convincing evidence of an immune response either by the criteria of serology or hypersensitivity. However, a reaction between rabbit sera and uvea was noted in the complement fixation test and was associated with natural antibody and anticomplementariness of immune sera.

Cross-reacting, or organ specific, antigens were found in the corneas and in the uveas of different species. By the use of these antigens from a heterologous species, it was possible to stimulate the production of antibody in the rabbit for rabbit cornea or uvea. The failure of these antigens to sensitize the homologous species suggests that they are haptens which owe their antigenicity to attachment to proteins of foreign species. These organ specific antigens from the uvea, like the Kidd-Friedewald antigen present in various animal tissues, were found to be quite labile.

Although naturally occurring and acquired antibody for cornea and uvea were present in these animals, gross pathology of the eye tissues was not found.
Laboratory and Field Investigations of Bovine Myxovirus Parainfluenza 3 Virus and Vaccine
Authors: Ketler A. , Hamparian V. V. , Hilleman M. R.
Published: January 2023

Comparison was made of the properties of the bovine SF-4 and the human HA-1 strains of Myxovirus parainfluenza 3 virus. Both grew abundantly in tissue cultures of bovine and monkey renal epithelium, causing characteristic cytopathic change. Antigenic difference between the strains was demonstrated in serum neutralization, CF and HI tests. The SF-4 strain generally appeared to have an antigenic composition more broad than that of the HA-1 virus. The two strains also differed in that the SF-4 antigen agglutinated chicken erythrocytes at room temperature but the HA-1 virus failed to do so. Tests for presence of nonspecific inhibitors of hemagglutination in human, bovine and rabbit antisera against Myxovirus parainfluenza 1 and 3 viruses were negative. It was concluded that nonspecific inhibitors for the parainfluenza viruses tested were either absent entirely or of such low titer as to be without consequence in serodiagnostic and sero-epidemiologic studies with these agents. Complete correspondence in the diagnostic results of paired sera from cases of SF-4 virus infection in calves was obtained using the serum neutralization, CF and HI techniques.
Effect of Antibiotics on Intracellular Salmonella Typhosa
Authors: Showacre Jane L. , Hopps Hope E. , Du Buy Herman G. , Smadel Joseph E.
Published: January 2023

Observations by phase microscopy showed that Salmonolla typhosa located within L929 mouse fibroblast cells multiplied at the same rate as extracellular organisms; i.e., they divided about every 30 min.

Multiplication of S. typhosa ceased promptly when streptomycin, chloramphenicol, penicillin or synnematin was added to infected tissue cultures. Moreover, division of extra- and intracellular organisms stopped simultaneously. Thus, for the first time it was demonstrated directly that antibiotics which penetrate mammalian cells retain their biologic properties.

Penicillin and synnematin induced spheroplast formation in those bacilli situated extracellularly but not in those located within healthy L cells. Intracellular spheroplast formation was observed in dying cells or in cells the permeability of which was irreversibly altered by addition of saponin. Chloramphenicol and streptomycin did not exert a marked effect on morphology of the bacilli.
Experimental Isoimmunization to Hemoantigens in Man
Authors: Stern Kurt , Goodman Harold S. , Berger Maya
Published: January 2023

Expanded data have been presented and analyzed concerning interference of ABO incompatibility with formation of Rh antibodies in Rh-negative men injected with Rh-positive blood. ABO-incompatible Rh-positive blood appeared to be also less capable of stimulating secondary responses to Rh antigen. Forty per cent of the men who had failed to form Rh antibodies after injection with ABO-incompatible blood did form Rh antibodies after subsequent injection of ABO-compatible blood. Injection into A Rh-negative recipients of A Rh-positive blood coated in vitro with anti-A was an efficient stimulus for formation of Rh antibodies. Injection into O Rh-negative men of O Rh-positive blood coated in vitro with Rh antibodies was completely ineffective in inducing Rh antibodies. Subsequent injection of such recipients with noncoated Rh-positive blood led to the development of Rh antibodies in 50%. These data were interpreted as compatible with the hypothesis of “clonal competition for antigen,” namely, that presence of large numbers of antibody-forming cells for one red cell factor may interfere with antibody response to another blood factor contained in the same red cell. On the basis of preliminary experiments the possibility was considered that, even without preformed antibody in the host, presence of more than one difference in blood factors between recipient and donor may lessen likelihood for isoimmunization in certain circumstances.
Immunological Paralysis and Adoptive Immunity
Authors: Brooke Marcus S. , Karnovsky Morris J.
Published: January 2023

Utilizing the adoptive technique of Mitchison, it has been shown that spleen or lymph node cell suspensions of paralyzed mice do not protect normal mice from subsequent challenge with the homologous pneumococcus, suggesting that there are no antibody forming cells in the donated suspensions. Paralyzed mice can be protected by the transfer of spleen or lymph node cells from immunized mice. Immune mice, injected with a paralyzing dose of SSS, are no longer immune.
Antibody Synthesis by Transplanted Heterologous Chimera Spleen Cells in Irradiated Recipients
Authors: Gengozian N. , Carter R. , Peterson W. J.
Published: January 2023

Lethally irradiated mice treated with heterologous rat bone marrow (950-r RBM chimeras) were either splenectomized or sacrificed for spleens at various intervals after treatment. Injection of these chimera spleen cells into lethally irradiated recipients resulted in the production of antibody to rat RBC antigen detectable in the serum 7 days after transfer. Under the appropriate experimental conditions this antibody-forming activity was attributable to the chimera spleen, and not the irradiated recipient, which served primarily as an in vivo tissue culture for the cells. In contrast, injection of the chimera spleen cells into midlethally (800 r) irradiated rats did not result in agglutinin formation to mouse RBC antigen when the serum of the recipients was tested at intervals from 3 to 10 days after transfer. These data support the thesis that in the heterologous chimeras there exists an immunologic reaction of the irradiated host against antigens of the foreign graft, and this in vivo antigen-antibody reaction is the underlying mechanism of the secondary disease syndrome observed in these animals. Evidence for graft reactivity against the host was not apparent in this experimental design.
Organ Specificity of the Heart
Authors: Gery Igal , Davies A. Michael
Published: January 2023

Rabbits were immunized with preparations of rabbit heart with adjuvant. Only 4 of 20 animals responded with high titers of hemagglutination antibodies. No response was obtained without adjuvant. In the tanned cell hemagglutination test, antisera showed cross-reactions only with hearts of other species and the organ specificity was confirmed by inhibition and neutralization tests. Other serological methods failed to demonstrate this. Reactions of antisera to homologous heart are compared with those of antisera to heterologous hearts. The importance and possible mechanism of production of organ specific autoantibodies in animals and humans are discussed.
Quantitative Hemagglutination Inhibition Studies of Blood Group Substances
Authors: Gibbs Mary B. , Collins William S. , Akeroyd Joseph H.
Published: January 2023

A quantitative hemagglutination inhibition technique for the precise determination of the relative effectiveness of the inhibitory strength of substances possessing blood group A activity has been developed. The method was shown to be highly reproducible and valid for blood group A substances from a variety of sources. A reversible equilibrium existing among the components of the system comprised of A substance, group A1 cells and human anti-hog A serum was demonstrated.
Biological Activity of Aggregated γ-Globulin
Authors: Ishizaka Teruko , Ishizaka Kimishige , Borsos Tibor
Published: January 2023

Aggregated human γ-globulin, obtained by heating, inactivated C′1 and/or C′4, as well as C′2 and C′3. With respect to the successive steps of the complement inactivation, the aggregated γ-globulin fixed C′1,4, followed by inactivation of C′2. Inactivation of C′3 in whole complement by the aggregated γ-globulin was inhibited in the presence of EDTA, due to blocking of the preceding steps. The similarity in the mechanism of complement fixation by antigen-antibody systems and by aggregated γ-globulin was discussed.
Interaction of Rickettsiae and Phagocytic Host Cells
Authors: Wisseman Charles L.
Published: January 2023

Purified preparations of yolk sac-grown virulent (Breinl strain) and attenuated (Madrid E strain) Rickettsia prowazeki and the Wilmington strain of Rickettsia mooseri were found to exert a positive chemotactic effect upon migrating human polymorphonuclear leukocytes in an in vitro test system. Normal yolk sac material failed to influence leukocyte migration.
Characterization and Purification of Ferritin-Antibody Globulin Conjugates
Authors: Borek Felix , Silverstein Arthur M.
Published: January 2023

Investigation of a number of agents for the conjugation of ferritin with antibody globulin showed m-xylylene diisocyanate to be the only satisfactory reagent examined by us thus far.

Conjugates of ferritin with fractionated rabbit antiovalbumin, antibovine γ-globulin, and antisouthern bean mosaic virus sera were prepared and characterized.

Taking advantage of electrophoretic mobility differences, we fractionated the crude conjugates by means of continuous-flow paper electrophoresis. Purified conjugates were obtained, free of uncoupled ferritin and uncoupled globulin.
Biological Properties of the Cross-Reactions between Anti-BSA and Heterologous Albumins
Authors: Weigle William O.
Published: January 2023

The in vivo reaction between rabbit anti-BSA and cross-reacting serum albumins produced systemic anaphylaxis, passive cutaneous anaphylaxis, and the Arthus phenomenon. In some situations, the biological effects produced by the cross-reactions were comparable to the biological effects produced by the homologous reaction, provided that the amount of cross-reacting antibody involved in the cross-reactions was the same as the amount of antibody involved in the homologous reactions. To obtain biological effects with the cross-reactions of severity comparable to the effects obtained with the homologous reaction, larger amounts of the cross-reacting antigens were required than of the homologous antigen. As judged by the in vitro and in vivo properties of the BSA-anti-BSA reaction and the cross-reactions, it appeared that the cross-reactions were usually less avid than the homologous reaction.
Studies on the Immune Response of Guinea Pigs to the Envelope Substance of Pasteurella Pestis
Authors: Walker Richard V.
Published: January 2023

According to fluorescent antibody study of the distribution and fate of Fraction I, it may be absorbed by a variety of fixed tissues, such as endothelium of blood vessels, dead striated muscle or reticular tissue in spleen and lymph nodes. It may be absorbed by fibroblasts, fixed reticulum cells in lymph nodes and bone marrow and fat cells. It may be transported by one of two means: A large portion may flow freely in lymph or plasma, or it may be adsorbed as a thick coating on circulating erythrocytes or phagocytes. It is ingested by few mobile macrophages or microphages in quantity detectable with this method. Its presence in Bowman's capsule and convoluted tubules suggests elimination in urine. Its last site of appearance in antibody-producing organs is the germinal centers of Flemming. Its prolonged presence as a thick coating or lining in various structures suggests numerous areas of local excess that might absorb circulating antibody for a prolonged period, thus explaining the long-delayed immunity in guinea pigs given an excess of Fraction I in oil adjuvant.
Studies on the Immune Response of Guinea Pigs to the Envelope Substance of Pasteurella Pestis
Authors: Walker Richard V.
Published: January 2023

Given a weight-adjusted dose, mice excreted an excess of Fraction I two to three times faster than guinea pigs, which explains former difficulties in detecting immunounresponsiveness in mice.

The rapidity of elimination of further Fraction I by immunounresponsive guinea pigs 90 days after a primary excess in oil may prevent further stimulation of antibody production in some animals, thus resulting in partial, rather than complete, immunity.

Hyperimmune animals were not easily made immunounresponsive. Immunity to Fraction I once established was solid and not easily overwhelmed.

Serologic response of guinea pigs to graded doses of Fraction I approaching excess 21 days after injection or over a long period after a single large excess indicates a limited plateau of antibody production to excess Fraction I.

This and previous studies indicate immunounresponsiveness of guinea pigs to excess Fraction I in oil adjuvant to be a temporary long delay in immunity resulting from a prolonged blockade of elements of the RES by finely divided state of the antigen, producing a saturation of a limited plateau of antibody production by this system. These inhibiting factors are partially overcome 3 to 6 months later by a gradually appearing antibody excess stimulated from within or by booster inoculation from without. Complete immunity was not obtained because of the rapidity of excretion of later immunizing doses, appearing slowly from the encapsulated injection site or as booster injections.
Application of a Microtechnique to Viral Serological Investigations
Authors: Sever John Louis
Published: January 2023

A microtechnique (modified Takatsy) is described which can be applied to complement fixation, hemagglutination, hemagglutination inhibition and metabolic inhibition tests. The system permits an 8-fold saving of reagents and rapid performance of microdilutions. The specific methods and modifications of equipment necessary to obtain reliable results are presented in detail. Comparative data obtained with the micro- and standard systems establish the reliability and validity of the microsystem.
Differences in Trypsin Susceptibility Among Influenza Viruses and Relationship of the Susceptibility to the Antigenic Type of Subtype of the Virus
Authors: Sugg John Y. , Cleeland Roy
Published: January 2023

The effect of crystalline and of crude trypsin on the hemagglutinins of 35 strains of influenza A and B and one strain of swine influenza virus has been determined under different test conditions. The swine influenza virus was completely resistant in all tests. The susceptibility of the strains of human origin varied with the medium in which the virus and enzyme were contained and with the kind of trypsin preparation employed. Under the most favorable conditions the hemagglutinins of all human strains were at least partially inactivated. By proper selection of test conditions patterns of trypsin-sensitivity were established which, in general, corresponded to the antigenic type or subtype of the virus.

With the exception of PR8, the pattern of trypsin-sensitivity of the A strains isolated before 1937 was, on a group basis, indistinguishable from that of the A1 or A-prime strains, and the pattern of PR8 and the A strains isolated from 1940 to 1945 was similar to but readily distinguishable from that of the A2 or Asian strains.
Antibody Production by Hypogammaglobulinemic Patients
Authors: Baron Samuel , Nasou John P. , Friedman Robert M. , Owen George M. , Levy Hilton B. , Barnett Eugene V.
Published: January 2023

Some properties of the viral neutralizing activity in the serums of hypogammaglobulinemic patients were studied. The neutralizing activity was sometimes detected by standard viral neutralization tests but was more often detected by extremely sensitive tests; neutralization of virus was time-dependent and was not reversed by dilution; the activity was stable at 56°C for 30 min; neutralizing activity was located almost exclusively in the 7S γ-globulin fraction of serum; poliovirus neutralizing activity appeared or was stimulated following inoculation of poliomyelitis vaccine; and the maximum neutralization titer observed, following strong antigenic stimulation, was very low. The neutralizing activity in the serums of “agammaglobulinemic” patients neutralized virus directly; was not reversed by dilution; and was heat stable. The results suggest that hypogammaglobulinemic and “agammaglobulinemic” patients are able to produce antibody to a variety of antigens but only in abnormally small amounts.
Immunologic Studies of Heart Tissue
Authors: Kaplan Melvin H. , Meyeserian Mary
Published: January 2023

Injection of rabbits with whole homogenates of heterologous heart from beef or rat, incorporated in aluminum hydoxide gel adjuvant, induced antibodies strongly reactive with saline extracts of normal rabbit heart by precipitation and complement-fixation tests. These antisera were not reactive in precipitation tests with extracts of other rabbit organs except for occasional weak reactions with skeletal muscle. Absorption tests with skeletal muscle indicated antigenic activity specific only for heart tissue. In two-dimensional complement-fixation tests with antisera to heterologous heart, rabbit heart extract showed far higher titers of reactive antigen than extracts of other rabbit organs. This heart-related antigenic material was sedimentable at high speed (56,500 × G) as determined by both precipitation and complement-fixation, and its cellular localization was correlated, as determined by immunofluorescent staining, with material in myocardial cells distributed between myofibrils. These observations are consistent with origin of the above antigen or antigens from sarcoplasmic reticulin or mitochondria.

Separate heterogenetic organ-related antigenic activity of rabbit skeletal muscle was demonstrated with rabbit antisera to heterologous skeletal muscle from beef or rat by precipitation tests. Complement fixation tests were inconclusive. This skeletal muscle antigen was not sedimented following centrifugation at 56,500 × G and could not be localized with certainty in tissue sections, presumably because of its solubility.
Weak Histocompatibility Genes: The Effect of Dose and Pretreatment of Immunizing Cells
Authors: McKhann Charles F.
Published: January 2023

In coisogenic strains of mice differing by a single histocompatibility gene at the H-3 locus it was found that the immune response to intraperitoneally (i.p.) injected spleen cells was influenced by the dose of cells injected. Small doses induced immunity to subsequent skin grafts, large doses gave prolonged graft survival, and intermediate doses had no effect on the duration of graft survival. The effectiveness of intermediate doses was increased by pretreating the spleen cells with trypsin or by using spleen cells specifically immunized against the recipient. Similarities between the prolonged graft survival following large doses of spleen cells and “enhancement” of tumor homografts is discussed.
Cell Culture Reactivity to Diphtheria, Staphylococcus, Tetanus and Escherichia Coli Toxins
Authors: Gabliks Janis , Solotorovsky Morris
Published: January 2023

Cell cultures derived from host species sensitive and resistant to diphtheria toxin were submitted to reaction with the toxin. Primary kidney cultures of rabbit, guinea pig, dog, monkey and human were susceptible, as were the human HeLa, HEp #2, HE-76 and rabbit kidney cell lines. Mouse kidney, rat kidney, and mouse L strain were unaffected by high concentrations of toxin. All embryonic rat cultures tested were resistant and all embryonic chicken cultures tested were sensitive. These results indicated that cells in primary and established cultures, used in this study, maintained the sensitivity or resistance observed for whole animal. The level of comparative cell susceptibility is indicated and the effective concentrations of diphtheria toxin extends from 0.0003 MLD for primary human or guinea pig cells to 0.3 MLD/ml for human HE-76 cells. It was also evident that established cell strains are less sensitive than primary cultures derived from the same species, and may even become completely resistant.

Staphylococcus alpha toxin destroyed cell cultures derived from susceptible species, mouse, rabbit and man. Tetanus exotoxin did not show any observable cytopathogenic effect against cultures derived from mouse, rat, guinea pig, rabbit, chicken, dog, monkey and man. E. coli endotoxin was not toxic for cell cultures derived from mouse, rat, guinea pig, rabbit, chicken and man.
The Action of Various Snake Venoms and Their Chromatographic Fractions on Animal Cells in Culture
Authors: Gaertner Clara , Goldblum Natan , Gitter Simon , de Vries Andre
Published: January 2023

The effect of various snake venoms and their chromatographic fractions was tested on different animal cells in vitro. A broad range of susceptibility of the various cell lines to the destructive effect of the venoms was observed.

Minute amounts of the venoms of Vipera palestinae and of Walterinnesia aegyptia caused destruction of chick and mouse embryonic cells, whereas no cytopathic activity was observed on monkey kidney cells. Echis colorata venom showed a similar effect on the former two cell types, exerting, in addition, a pronounced cytopathic effect on monkey kidney cells. The venom of Pseudocerastes fieldii exhibited no cytopathic effect on any of the cells.

The susceptibility of cell cultures to the destructive action of the venoms of Vipera palestinae and Echis colorata was a hundred times higher than that of mice in toxicity tests.

The cytopathic effect of the chromatographic fractions of Vipera palestinae and Echis colorata venoms on cells in culture was correlated with their hemorrhagic activity and their in vitro proteolytic activity, more so with the latter.
Quantitative Analyses by Diffusion Column Reactions
Authors: Glenn William G.
Published: January 2023

Of 100 lines resulting from regression of diffusion (mm) onto √min for SD columns of fraction (II, V)-antifraction homologous reactions, 91% could be adequately expressed by a linear equation (y = K√min + a) when tested for good-of-fit (F-ratio test) over a wide range of antibody concentrations. At specific reactant concentrations, diffusion (mm) vs √min had 57% and 100% reproducibility for two series for Fractions II and V homologous SD reactions respectively (Table I). Analyses of standard curves with slope m, resulting from K regressed on the logarithm of wide ranges of antigen or antibody concentration, indicated that 19 out of 40 (47%) could be adequately expressed by a linear equation (K = m (log concentration + b)) (Table II). Considering only standard curves that gave adequate straight line fits and using stored SD columns, the resulting slopes m had good reproducibility (89%) even on only duplicate series of titrations (Table II).
The Serologic Sequelae of an Influenza A-2 Epidemic Modified by Intercurrent Vaccination in an Insular Eskimo Population Group
Authors: Reinhard Karl R.
Published: January 2023

An epidemic of Influenza A-2 virus infection occurred in an isolated Eskimo population in November of 1957. This was studied serologically, using pre- and postepidemic sera from 183 of the people involved. Approximately 40% of the population had been given a small dose of A-2 influenza vaccine after onset of the epidemic. The general quantitative serologic reaction found post-epidemically in the vaccinated group was significantly lower than that found in unvaccinated, naturally infected individuals. The data did not prove that intercurrent vaccination prevented infection, but did suggest strongly that it altered the morbidity rate and also that it interfered with serologic response to the epidemic virus.