bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunity to Transplantable Tumors Following Viral Oncolysis
Authors: Lindenmann Jean , Klein Paul A.
Published: January 2023

The intraperitoneal LD50 of Krebs 2 (K-2) and Sarcoma 180 (Sa-180) ascites tumors for inbred A2G mice was below 100 cells/mouse. Mice that had been inoculated with 106 Ehrlich ascites (EA) cells and 4 to 6 days later with WSA influenza virus underwent oncolysis and were subsequently resistant to challenge with all three tumors. This resistance could be transferred to normal A2G mice with serum or peritoneal exudate. The levels of active and passive immunity were comparable when measured with either EA or Sa 180 challenges, but definitely ower when measured with K-2.

Postoncolytic EA-immune sera from A2G mice agglutinated saline cell suspensions from all three tumors to similar titers. In addition, certain sera obtained after various challenge schedules gave a precipitation line in double diffusion tests with aqueous extracts from the three tumors. These sera and tumor extracts could also be used to induce passive cutaneous anaphylaxis in guinea pigs.
Lack of Correlation between Infectivity, Serologic Response and Challenge Results in Immunization with an Avian Infectious Bronchitis Vaccine
Authors: Raggi Livio G. , Lee George G.
Published: January 2023

White Leghorn chickens of two different ages and sources were vaccinated with diluted and undiluted infectious bronchitis (IB) vaccine. Statistical evaluation of the results showed: Incubation period was prolonged by the presence of congenital passive antibodies, and by using a vaccine that was diluted 100-fold.The combined factors of age and dose level affected vaccination reaction in that per cent of infectivity was highest and reactions were most severe in older birds receiving undiluted vaccine.Congenital passive immunity interfered with the development of active antibodies in that geometric mean serum neutralization titers peaked lower and later in birds having maternal antibodies than in birds from a susceptible source.Per cent of resistance on two challenge dates (7 weeks and 6 months after vaccination) was higher in the older birds vaccinated with the undiluted vaccine.There was no difference between immune and susceptible sources in immunity over the long run (at 6 months) in chicks vaccinated against IB within their 1st week of life.None of the six groups of birds showed any correlation between infectivity and serologic responses, between infectivity and challenge results, or between serologic responses and challenge results.
Phagocytosis and Intracellular Fate of Pasteurella Tularensis
Authors: Thorpe Bert D. , Marcus Stanley
Published: January 2023

Host mechanisms of resistance to Pasteurella tularensis infections in white mice, guinea pigs and rabbits were studied by using passively transferred phagocytic cells and sera to protect the challenged animals. Homologous and heterologous cells and sera from normal and previously immunized (recovered) animals were used. Three strains of the pathogen, varying in virulence for the three animal species, were used as challenge organisms. It was found that specific antibodies, whether from a homologous or heterologous source, were capable of increasing the survival times of challenged animals, while phagocytes from immune animals (homologous and heterologous) increased the survival times and decreased the mortality rates. This latter phenomenon was also evident using normal cells from a naturally resistant species to protect a naturally susceptible species. It was concluded that cellular factors were of critical importance in acquired immunity to tularemia while specific antibodies per se were of less significance.
The Flocculation Test and the Law of Mass Action
Authors: Levine Leo , Wyman Louise
Published: January 2023

Experiments are presented which show that flocculation time in both the Ramon and Dean-Webb methods is the resultant of two different interacting variables which affect the velocity of precipitation. One is the independent variable of interest, namely, the equivalence ratio. The other is the mass-law effect, that is, the variation from tube to tube of the product of the concentrations of the reactants which is a necessary consequence of keeping one reactant constant. A new, equally simple method is proposed which eliminates the mass-law effect by maintaining a constant product of concentrations. Comparisons of all three methods are presented in both the diphtheria and tetanus systems.
Studies on Histoplasmosis
Authors: O'Hern Elizabeth M.
Published: January 2023

Results of two tests of experimental histoplasmosis in hamsters showed that infections induced by i.d. inoculation progressed to a somewhat slower, less extensive dissemination and to an earlier clearance of organisms from the tissue than infections induced by s.c. inoculation.

The Histoplasma inhibitory factor (HIF) was demonstrated in 30% of the animals (66% of those infected more than one week) with infections of moderate intensity induced by i.d. inoculation of 10,000 yeast cells; whereas, in infections resulting in early and extensive dissemination, induced by either i.d. or s.c. inoculation of 50,000 Histoplasma yeast cells, little or no HIF was demonstrable.

HIF activity could be demonstrated in portions of liver and in saline extracts of liver tested against in vitro grown organisms of the homologous and two heterologous strains of Histoplasma. No HIF activity was demonstrable against a variant strain derived from the homologous strain organism.

Heated liver extracts, aqueous suspensions of alcohol soluble material and heated fractions thereof also exhibited HIF activity.

No HIF activity could be detected against the mycelial form of Histoplasma in initial cultures of infected tissue or in tests using in vitro grown organisms.

The inadequacies of the present methods of testing for HIF are discussed and suggestions are made for following the production of the inhibitor in the living animal.
Role of the Posterior Hypothalamus in Mediating the Lethal Action of Bacterial Endotoxin in the Rat
Authors: Porter Philip J. , Kass Edward H.
Published: January 2023

The LD50 of endotoxin is approximately twice as great when given intracardially as when given into the carotid artery. Elevation of ambient temperature increases the body temperature of rats and decreases the LD50 strikingly. Rats maintained at elevated temperatures respond to endotoxin with hyperthermia rather than the usual hypothermia. In hyperthermic animals, the intracarotid route is still about twice as lethal as the intracardiac. Stereotactic ablation experiments, performed to localize the site of unusual sensitivity to endotoxin in the brain, indicated that lesions in the paraolfactory area, superior colliculus or lateral hypothalamus had no effect on the lethal action of endotoxin. However, lesions in the posterior hypothalamus protected rats against an otherwise lethal dose of endotoxin, and did so in the absence of significant alterations in body temperature. Lesions in the anterior hypothalamus produced hyperthermia and were associated with decreased resistance to the lethal action of endotoxin. It is concluded that there are graded sites of sensitivity to endotoxin, and that the posterior hypothalamic area is the most sensitive so far discerned. The lethal action of endotoxin is therefore manifested, in part at least, through the mediation of the posterior hypothalmus. No conclusions are drawn as to whether the action of endotoxin is direct or indirect, or related to hypersensitivity.
Radiosensitivity of the Immune Response to Sheep Red Cells in the Mouse, as Measured by the Hemolytic Plaque Method
Authors: Kennedy J. C. , Till J. E. , Siminovitch L. , McCulloch E. A.
Published: January 2023

γ-Ray survival curves have been obtained for the capacity of adult male mice to respond to the injection of sheep erythrocytes by the production of hemolytic plaque-forming cells (11, 12). When antigen was given within 2 hr after irradiation of the mice, the survival curve was found to be a simple negative exponential, with a D37 of 80 rads. No significant change in this curve was found when an interval of 10 days separated radiation and antigen injection, indicating that radiation-induced damage to the immune system was not repaired during this interval. The capacity of plaque-forming cells to form plaques was found to be much less sensitive to radiation than was the capacity of the animals to produce plaque-forming cells. No decrease in the capacity of plaque-forming cells to form plaques was found for doses of radiation up to 2 kilorads.

On the basis of these survival curves, it is suggested that the spleens of normal mice contain a minimum of 103 cells which do not themselves produce hemolysin, but respond to the injection of antigen by proliferation and differentiation into hemolysin-producing cells. Further, when these cells, which may be termed antigen-sensitive cells, are rendered incapable of proliferation by radiation they are not replaced to a significant degree for a period of at least 10 days.
Immunologic Response to Subarachnoid and Intracerebral Injection of Antigens
Authors: Panda J. N. , Dale H. E. , Loan R. W. , Davis L. E.
Published: January 2023

Antibody response in rabbits was measured after canine red blood cells (RBC) and Brucella antigen were injected s.c., i.v., into the cisterna magna (i.c.m.), and into the substance of the brain (i.c.). The following average agglutinin titers were observed after injection of RBC: s.c., 1:320; i.v., 1:5,120; i.c.m., 1:30,000; and i.c., 1:160. The following average hemolysin titers were observed after injection of RBC: s.c., 1:10; i.v., 1:16; i.c.m., 1:28; i.c., 1:8. After injection of Brucella antigen, agglutinin titers were s.c., 1:200; i.v., 1:900; and i.c.m., 1:2,560.

In splenectomized rabbits agglutinin and hemolysin titers after s.c. injection were similar to titers after s.c. injection in normal rabbits. After i.v. injections in splenectomized rabbits, titers were similar to those attained after s.c. injection. Titers after i.c.m. injection in splenectomized rabbits were similarly lower than titers produced by i.c.m. injection in normal rabbits.

Magnitude of the antibody response was thought to be related to the distribution of antigen in the body; the extremely high titers after i.c.m. injection, to a “slow leak” of antigen from the cerebrospinal fluid into the blood.
The Suppressive Role of Mouse Peritoneal Phagocytes in Agglutinin Response
Authors: Perkins Eugene H. , Makinodan T.
Published: January 2023

In an attempt to determine the possible role of peritoneal phagocytes in the initiation of agglutinin response to RBC, bio-assay curves were first constructed to assess the immunogenicity of the test antigen by culturing in vivo varying numbers of sheep RBC with 107 primed mouse spleen cells. This number of spleen cells, when optimally stimulated, synthesized as much antibody as an intact mouse. Observations made at varying time intervals after culture of RBC with fixed or varying numbers of phagocytes revealed that immunogens or immunogen-like substances were neither released nor stored by phagocytes actively engaged in phagocytosis in either in vitro or in vivo conditions. Furthermore, when fixed or varying numbers of peritoneal phagocytes were cultured in vivo together with a fixed number of spleen cells and RBC, they were shown to be destructive competitors rather than “symbionts” of spleen cells undergoing either a primary or secondary antibody response. Finally, non-opsonized and opsonized RBC were injected into glycogen-treated and untreated mice by the intraperitoneal and intravenous routes, and the results showed that minimum response was obtained when opsonized RBC were injected i.p. into glycogen-treated mice, and maximum response when nonopsonized RBC were injected i.v. into untreated mice. These results show that peritoneal phagocytes respond to foreign RBC as scavenger cells and are not essential for the initiation of antibody response.
Role of Sialic Acid Receptors in Adsorption of Influenza Virus to Chick Embryo Cells
Authors: Haff Richard F. , Stewart Richard C.
Published: January 2023

Treatment of CE cell monolayers with neuraminidase produced 2.5- to 4.7-fold inhibition of plaque formation with different myxoviruses on subsequent infection. Continued incubation in the presence of neuraminidase failed to increase appreciably the extent of inhibition. In contrast, neuraminidase at 800-, 4000- and 500-fold lower concentrations modified receptors for virus on RBC and released sialic acid from mucin and N-acetyl neuramin-lactose, respectively, under comparable conditions. Thus, a large proportion of virus receptors on CE cells were refractory or relatively resistant to enzyme action.

Evidence is presented that plaque reduction which was observed was probably attributable to the neuraminidase component of the enzyme preparation. On the other hand, the action of neuraminidase on virus infection could be distinguished from that on RBC by pH effect and by lack of competitive inhibition with N-acetyl neuramin-lactose. A difference between CE and RBC receptors for the same virus was further indicated by release of significant quantities of sialic acid from CE cells by concentrations of neuraminidase which produced hemagglutination inhibition but no reduction in infectious centers.

Extent of plaque inhibition by neuraminidase was reflected by decrease in virus adsorption to the cells.
Cryptococcus Neoformans Polysaccharide: Studies of Serologic Properties and Role in Infection
Authors: Bennett John E. , Hasenclever H. F.
Published: January 2023

A complement fixation test for polysaccharides of Cryptococcus neoformans was found to detect concentrations of as little as 0.25 to 1.0 µg/ml, depending on the preparation of polysaccharide. The test was less sensitive toward other polysaccharides but did react with those from Hansenula minuta, Hansenula capsulata, Cryptococcus laurentii and Diplococcus pneumoniae. The test was used to demonstrate that cryptococcal polysaccharide injected intracisternally into rabbits disappeared rapidly from the cerebrospinal fluid but appeared and persisted for weeks in the bloodstream. Cryptococcal polysaccharide injected i.v. into rabbits or mice also persisted in the bloodstream for weeks. The inability of mice to clear this foreign antigen from their bloodstream was felt to help account for the high titers of cryptococcal polysaccharide found in the mice infected with C. neoformans. An i.v. injection of polysaccharide into mice caused no gross toxicity but hastened mortality if the mice were infected subsequently with a large inoculum of C. neoformans.
Dinitrophenylated Bacitracin A as an Antigen in the Guinea Pig
Authors: Abuelo J. G. , Ovary Zoltan
Published: January 2023

Bacitracin A and its dinitrophenylated derivatives were investigated for antigenicity because they offer several unusual characteristics: a) they are small molecules composed of twelve amino acids; b) they have well-defined structures; c) the dinitrophenyl hapten groups couple to the bacitracin A molecule at known positions and d) bacitracin and its dinitrophenylated derivatives may be obtained in a highly purified state. These properties make bacitracin A and its derivatives suitable for use in the investigation of the nature and characteristics of antigenicity and the homogeneity of the antibody population obtained after immunization with a relatively simple antigen.

Materials and Methods. Animals. Hartley strain albino guinea pigs weighing about 400 g, obtained from the same dealer but not from an inbred colony, were used for immunization.

Antigens. Bacitracin A (Fig. 1) (1) was coupled to 2,4-dinitrophenyl groups according to the method of Craig, Konigsberg and Hill (2), and the products were purified by countercurrent distribution.
Blood Groups in the Rabbit
Authors: Cohen Carl , Tissot Robert G.
Published: January 2023

Two new isoantibodies have been prepared which detect the antigenic products for the heretofore immunologically undetectable alleles at two blood group loci of the rabbit. Three of the five known blood group systems of the rabbit can now be completely identified. Both antibodies are of the 19 S variety and will agglutinate the corresponding red blood cells in saline. The anti-L is a good dosage serum, and the L antigen is much stronger than the antigenic product of its allele. The L antigen does not play a role in fetal-maternal isoimmunization, nor is it an effective histocompatibility antigen. The reaction of anti-M with its corresponding erythrocytic antigen is not strong, as is also characteristic of the reaction of the antibody to the antigen controlled by its allele.
Fluorescent Antibody Staining
Authors: Wood B. T. , Thompson S. H. , Goldstein G.
Published: January 2023

A rapid method of preparing bright and specific staining fluorescent antibodies is described. The method is discussed emphasizing a) the need for chromatographically homogeneous antibody globulin, b) the importance of pH in the coupling reaction and c) the advantages of fractionating the fluorescent antibody reaction mixture on DEAE-cellulose.
Improved Measurement of Influenza Virus Hemagglutinin Titer
Authors: Miller Gail Lorenz
Published: January 2023

An improved procedure for measurement of hemagglutinin titer of influenza virus has been developed. Interference due to inhibitors was minimized through the use of a longer period of incubation of the virus-red blood cell mixtures; that due to enhancing agents, by incorporation of gelatin into the diluent medium. Protective action against loss of hemagglutinin was also afforded by the gelatin. The kinetics of the hemagglutinin titration, as revealed by the relationships between long virus dilution and percentage of transmission of the mixtures of virus and red cells, are described for different strains of the virus, and the implications of the findings with regard to meaningful application of the method are discussed.
Single Lymph Node Cells Producing Heteroclitic Bacteriophage Antibody
Authors: Mäkelä O.
Published: January 2023

Fractions of antibody could be isolated from anti-T2 sera by using adsorption onto and elution from T4 phage, which inactivated T4 more effectively than T2. Corresponding aberrant (heteroclitic) fractions were isolated from anti-T4 sera with the aid of T2. Few single lymph node cells from rats and mice immunized with T2 phage were found to liberate antibody heteroclitic for T4 or T6. Heteroclitic serum antibody could be the product of a relatively small number of such cells. These cells are thought to form the tail of a continuous distribution of anti T2 cells producing different degrees of cross-reaction with T4 or T6.
Surface Properties of the Egg and Mouse Lines of A1 Influenza Virus
Authors: Borecký L. , Lackovič V. , Rathová V.
Published: January 2023

Changes in the surface properties of a viral population were studied in the course of adaptation of A1/Moscow/1949 influenza virus to mouse lung. The mouse line virus (Em2), as compared with egg line virus (Em1), was found to be non-sensitive to both α and β inhibitors. Heating at 56°C for 30 min converted the Em2 virus to the “indicator” state, while heating at 62°C caused complete destruction of its hemagglutinating ability. The hemagglutinins of mouse virulent virus (Em2) were highly sensitive also to treatment with trypsin or papain. On the other hand, the immunogenicity and antibody-binding capacity of Em2 virus were higher and were independent of the presence of thermolabile components in sera which seem to be necessary for the reaction of egg line virus (Em1) with early antibodies in hemagglutination-inhibition tests. The two lines of virus differed also in their ability to agglutinate bovine erythrocytes at room temperature. Some of these markers were tested in various other strains of myxovirus. Attempts were undertaken to obtain “pure” populations of the Em1 and Em2 lines by passaging the egg line virus in the presence of trypsin and the mouse line virus in the presence of normal sera in eggs. The results of these studies are discussed.
Reactivity of Rheumatoid Factor with Rabbit γ-Globulin
Authors: McDuffie Frederic C. , Oikawa Tatsuro , Nishi Ichiro
Published: January 2023

Studies with subunits (papain-digestion) of 7 S RγG have confirmed that the major reactivity of rheumatoid factor is directed against subunit III. In tests with tanned sheep cells coated with subunits I and II and sensitized sheep cells coated with subunits I and II of digested rabbit antibody, it was found that part of the specificity of rheumatoid factor is directed against the part of RγG represented by these subunits. The reaction of rheumatoid factor and of sheep or goat anti-RγG with subunits I and II is less easily inhibited by the subunits in soluble form or by 7 S RγG than is the comparable reaction with subunit III. Whether this difference is due to an alteration of subunits I and II when they combine with antigen on the test cells or whether there are other differences between the reaction of these subunits with antibody and that of subunit III has not yet been determined.
Effect of Hypothermia on Systemic Anaphylaxis: Limitations of Cold Protection
Authors: Bloch Kurt J. , Lane Joseph M. , Austen K. Frank
Published: January 2023

Hypothermia protected actively sensitized guinea pigs against anaphylactic shock elicited by a dose of antigen approximately five times as large as that producing fatal anaphylaxis at normal body temperature. Protection may be attributed to decreased histamine release and increased tolerance for circulating histamine. It is also dependent upon the relationship between circulating and tissue-bound antibodies.

Following initial challenge under hypothermia with a fixed dose of antigen, “lightly immunized” guinea pigs were refractory to subsequent challenge for several days, whereas hyperimmunized animals were refractory to rechallenge 3 hr but not 24 hr later. The most likely explanation for the rapid return of susceptibility to anaphylactic shock in the latter group is that the enzymes mediating histamine release are reconstituted after several hours or that mast cells remaining intact after initial challenge are sensitized by transferred or recently synthesized anaphylactic antibodies.
Destruction of Splenic Transplantation Antigens by a Factor Present in Liver
Authors: Mandel Mark A. , Monaco Anthony P. , Russell Paul S.
Published: January 2023

Intact liver tissue implanted subcutaneously or liver cell suspensions injected subcutaneously sensitized recipient animals to subsequent appropriate skin grafts. Two standardized methods for the preparation of cell-free transplantation antigens, as assayed by accelerated skin graft rejection, were employed for the extraction of antigens from C57BL/6 spleen and liver. Both methods resulted in active sensitizing material from splenic tissue; however, no active antigen could be extracted from hepatic tissue. Incubation of active C57BL/6 splenic antigen for 1 hr at 37°C with C57BL/6 whole liver homogenate destroyed the ability of splenic antigen preparations to sensitize to subsequent skin grafts. Heating the whole liver homogenate to 80°C (10 min) prior to incubation destroyed the ability of the homogenate to inactivate the splenic antigen. Treatment of the liver homogenate with a chelating agent and dialysis of the liver homogenate failed to inhibit its ability to inactivate splenic antigen preparations. These experiments suggest that liver cells apparently contain a material which is capable of destroying the sensitizing ability of the transplantation antigens extracted from splenic tissue. These results further suggest an explanation for the frequently observed inability to prepare from hepatic tissue antigenic material capable of sensitizing to a subsequent skin allograft.
Characteristics of Herpes Zoster and Varicella Viruses Propagated in Vitro
Authors: Gold Eli
Published: January 2023

The agents of varicella and herpes zoster grown in cultures of human amnion retain infectivity only when associated with viable cells. Conditions which lead to cell death as measured by the eosin Y dye exclusion test result in concomitant loss of infectivity. Using a plaque assay method without agar overlay, the optimum conditions for virus absorption, propagation and release have been investigated. The preparation of cell-free infectious varicella virus from infected primary human thyroid cultures has been confirmed.
Comparative Immune Diffusion at Gelatin-Agar Interfaces: A Presumptive Test for Protein and Acidic Polysaccharide Antigens
Authors: Dudman W. F.
Published: January 2023

Analysis of a range of antigens by comparative immune diffusion, from wells located at the interface between gels containing 0.75% agar and 3% gelatin respectively, suggests that the formation of immune precipitates in gelatin is selective and restricted to protein and acidic polysaccharide antigens while immune precipitation in agar is not selective and not restricted to any class of antigens.

The antigens examined included ferritin, dextran, bacterial polysaccharides, bacterial toxins, snake toxins and tobacco mosaic virus. Tobacco mosaic virus and its protein were the only protein antigens found to behave atypically by not producing bands in gelatin although bands were formed in agar.

The mechanism of the selective nature of immune precipitation in gelatin was investigated. Methylation or acetylation of gelatin had no effect on the phenomenon but hydrolysis with pronase destroyed the ability of gelatin to interfere with immune precipitation.

The effect of temperature was critical. At 37°C gelatin did not interfere with immune precipitation in gel diffusion or quantitative precipitin reactions with antigen-antibody systems inhibited by gelatin in the gel state at 2°C.

In the gel state, gelatin is postulated to combine reversibly with antibody and antigen molecules. The outcome of competition between these nonspecific interactions and the antigen-antibody reaction is thought to determine whether or not immune precipitation will occur in gelatin gels.
Some Observations on the Behavior of Vaccinia Virus Particles with Antiserum, Particularly Their Agglutination
Authors: Galasso G. J. , Sharp D. G.
Published: January 2023

The growth curve of antiserum-treated vaccinia virus in cultures of L cells resembles that from smaller inocula of untreated virus. Except when used in high concentration, the serum does not change the ultimate yield of new virus. The antibody-absorbing powers of virus preparations of high and low plaquing efficiency, as well as of those inactivated by UV, are closely related to the number of particles present, not to the number of plaque-forming units. Kinetic studies of the agglutination of vaccinia virus by antiserum, via electron microscopy, show serum strengths which are proportional to those obtained in plaque suppression experiments. Virus particles agglutinated by strong sera are often enmeshed in an amorphous cloud of unresolved structure, possibly composed of globulin molecules, which is not seen among particles agglutinated by other means.
Enhancement of the Replication of Measles Virus by Mitomycin C
Authors: Rapp Fred , Vanderslice Darlena
Published: January 2023

The replication of both virulent and attenuated strains of measles virus in BSC-1 cells is enhanced by mitomycin C. This enhancement results in larger virus yields, the formation of larger plaques and a decrease in the latent period of the virus in the cells employed. Other inhibitors, including actinomycin D, iododeoxyuridine and cytosine arabinoside, failed to stimulate or inhibit synthesis of the virus. The action of mitomycin C, therefore, does not appear to be due to repression of interferon production but is more likely a secondary consequence of the effect of the antibiotic on the metabolism of the host cells.
The Immunoglobulins of Mice
Authors: Barth Werner F. , McLaughlin Carla L. , Fahey John L.
Published: January 2023

Serum levels of 7 S γ2-, 7 S γ1-, γ1A- and γ1M- globulins and of hemagglutinating antibody were determined in 10 strains of mice immunized with hemocyanin and ferritin.

The effect of five factors on the response to immunization were investigated: a) difference between single and repeated injections of antigen, b) differences between antigen administration in saline and in adjuvant, c) effect of different time intervals between first and second administration of antigen, d) effect of adjuvant alone and e) mouse strain differences.

A single injection of antigens in saline produced no appreciable change in the serum immunoglobulin levels. After a single injection of antigen emulsified in Freund's adjuvant, the levels of the 7 S γ1-globulins showed a two- to five-fold increase. After a second injection of the antigens in adjuvant, 7 S γ1-globulins showed a 10- to 30-fold increase. The absolute and relative changes in the other three immunoglobulins (7 S γ2, γ1A(IgA) and γ1M(IgM)-globulins) following primary and secondary challenge were not as marked as the increase in 7 S γ1-globulins. Repeated injections of antigen in saline produced a greater increase of γ1M(IgM)-globulins than did several injections of antigen in Freund's adjuvant.

The response of specific immunoglobulins to antigenic challenge is strain dependent. The most notable strains were a) the C57BL mice, which showed marked increase of γ1M(IgM) and γ1A (IgA)-globulins and b) the white Swiss (GP) mice, which showed very little increase in γ1M-(IgM)- and γ1A(IgA)-globulins while developing the highest levels of 7 S γ1-globulin.

Injection of adjuvant without antigen had no notable effect except in C57 strains of mice, where marked increases of γ1M(IgM)-globulins occurred.
Synthetic Polypeptide Metabolism
Authors: Papermaster David S. , Gill Thomas J. , Anderson W. French
Published: January 2023

A wide variety of synthetic polypeptide antigens bind to serum proteins. There is no evidence for an in vivo binding mechanism, since the binding patterns are the same whether the antigens are injected into the rabbit or mixed with serum in vitro. The glutamic acid-rich polymers bind to more serum proteins than the lysine-rich polymers and a polymer containing equal amounts of glutamic acid and lysine shows a binding pattern intermediate between those of the glutamic acid-rich and lysine-rich polymers. There is no optical determinant to binding, because both the D- and L-enantiomorphs of a synthetic polypeptide show identical binding patterns under a wide variety of conditions.

The conclusions concerning the binding patterns of synthetic polypeptides to serum proteins are consistent over a wide range of electrophoretic conditions (pH 5.5–10.6) in a given animal species and among several different species (rabbit, dog, guinea pig, and ox).
Attempts to Induce Early-Type (“Jones-Mote”) Delayed Hypersensitivity in Mice
Authors: Crowle Alfred J. , Hu C. C.
Published: January 2023

Unlike guinea pigs and man, mice injected with minute quantities of purified protein antigen under conditions especially favoring induction of delayed hypersensitivity developed immediate hypersensitivity more readily than delayed hypersensitivity. In these mice immediate hypersensitivity appeared first, developed more frequently, lasted longer and could be induced with less antigenic stimulus than was needed to induce delayed hypersensitivity. No early (“Jones-Mote”) form of delayed hypersensitivity was evident in these mice. Our results suggest that delayed hypersensitivity is not a necessary precursor of immediate hypersensitivity, and that mice differ from guinea pigs and man in the quality and timing of immunologic response to protein antigens.
Skin-Sensitizing Activity Related to γ-Polypeptide Chain Characteristics of Human IgG
Authors: Terry William D.
Published: January 2023

Human G-myeloma proteins differ in their ability to sensitize guinea pig skin for reverse passive cutaneous anaphylaxis. Skin-sensitizing activity correlates with γ-chain antigenic characteristics of these molecules. Positive RPCA tests were obtained with 21 γ2b-, 8 γ2c- and 5 γ2d-myeloma proteins. Fourteen γ2a-myeloma proteins were unable to sensitize guinea pig skin for this reaction.

Inhibition experiments suggest that γ2a-molecules are incapable of producing reverse passive cutaneous anaphylaxis because they fail to combine with a critical tissue receptor site.

The Fc (fast) fragment produced by papain digestion of some G-myeloma proteins contains the portion of the molecule both necessary and sufficient for the sensitization of guinea pig skin. Neither Fab (slow) nor F(ab′)2 (pepsin) fragments of G-myeloma proteins have skin-sensitizing activity.

“Heavy-chain disease” proteins, which are very similar to enzymatically produced Fc fragments, also sensitize guinea pig skin for RPCA.
The Role of Lysosomes in Hypersensitivity Reactions: Tissue Damage by Polymorphonuclear Neutrophil Lysosomes
Authors: Golub Edward S. , Spitznagel John K.
Published: January 2023

Injection of isolated polymorphonuclear neutrophil (PMN) granules into the skin of normal rabbits causes a local leukocytosis and increase in vascular permeability. The permeability increase is dose dependent and maximal at 2 hr. Activity is not affected by dialysis but is almost completely lost after heating at 85°C for 30 min. The granule preparations do not cause contraction of an isolated segment of smooth muscle nor are they affected by doses of cyproheptidine which inhibit the action of histamine and serotonin.

Pretreatment of normal recipient rabbits with 5 mg/kg body weight of cortisone-acetate abolishes the vascular response to intact granules, but not lysed granules. It is concluded that cortisone prevents in vivo lysis of the granule by membrane stabilization.

All of the permeability increasing properties were located in the 20% ethanol precipitable fraction of PMN granules. This fraction was shown to contain little cathepsin-like protease activity. The majority of the cathepsins were located in the 45 and 80% ethanol precipitable fractions. The active fraction was found by electrophoresis to be the most cationic.

The vascular permeability increasing activity of intact or lysed granule preparations was not reduced by the general protease inhibitors phenylmethylsulphonyl fluoride or soybean trypsin inhibitor.

It was concluded that the vascular permeability altering properties of PMN granules might not be due to the presence of the cathepsins. The possibility that activity is due to electrostatic charge is presented.

The histology of the granule-induced lesions is similar to the histology of the Arthus reaction. There is edema, an accumulation of PMN and vasculitis in both cases, but the granule induced histologic alterations appear at an earlier time after injection than do comparable changes in the Arthus reaction.

A possible mechanism for the Arthus reaction is presented.
Anaphylatoxin Formation by Purified Human C′1 Esterase
Authors: da Silva W. Dias , Lepow Irwin H.
Published: January 2023

Incubation of purified human C′1 esterase with guinea pig or rat plasma or serum produced a smooth muscle stimulating activity with the following properties: a) contraction of guinea pig ileum which was made unresponsive after a few applications and which did not then respond to agar-anaphylatoxin; b) failure to contract guinea pig ileum previously desensitized to agar-anaphylatoxin or treated with an antihistaminic drug; c) degranulation of mast cells and release of histamine from guinea pig tissues; d) failure to contract rat uterus. These findings indicated that the activity liberated by C′1 esterase is related to anaphylatoxin. Generation was prevented by inactivation of C′1 esterase with DFP or partially purified serum inhibitor of C′1 esterase, prior heating of the serum at 56°C, the presence of salicylaldoxime or phlorizin, or by selective chelation of Mg++. A correlation between the formation of anaphylatoxin and complete consumption of hemolytic complement was also observed. These observations suggested that C′1 esterase generates anaphylatoxin by interaction with the complement system.
Influenza Virus Growth and Antibody Response in Amantadine-Treated Mice
Authors: Davies W. L. , Grunert R. R. , Hoffmann C. E.
Published: January 2023

Amantadine (1-adamantanamine), a symmetrical primary amine, reduces the mortality rate and increases the survival time of mice infected with influenza A viruses. Virus production, although not completely prevented, is considerably diminished in treated mice. Treated survivors are generally resistant to challenge with homologous virus when the primary infecting virus inoculum is high. With a low primary virus dose a small percentage of treated mice escape an immunizing infection.
Cellular Kinetics of Phagocytic Cells in Immunized X-Irradiated Mice
Authors: Muramatsu Shigeru , Morita Toshiteru , Sohmura Yasunobu
Published: January 2023

A large number of phagocytic cells were found in clusters in the water-in-oil emulsion injected into mice subcutaneously. Studies on the effect of x-radiation indicated that the migratory capacity of phagocytic cells was not affected by irradiation but the proliferation of these cells was depressed, and that the phagocytosis appeared to be enhanced transiently. The radiosensitivity of the antibody response seems likely to be related to the reduction of the total amount of antigen ingested by phagocytic cells.
Systemic Anaphylaxis Produced in Guinea Pigs by Soluble Bovine Serum Albumin-Antibody Complexes
Authors: Litt Mortimer
Published: January 2023

Systemic anaphylaxis was induced in normal unsensitized guinea pigs by intravenous injection of soluble bovine serum albumin (BSA)-antibody complexes, prepared with rabbit immune serum under conditions of antigen excess. The importance of using sufficiently large numbers of guinea pigs, when studying anaphylaxis, is emphasized. The severity of the anaphylactic response showed a linear dependence on the log dose of antibody in the complex. No effect of the concentration of complex was detected. Doses of antibody N (in complex) as small as 250 µg Ab N caused death, and doses as little as 10 µg Ab N caused definite signs of respiratory embarrassment. Effective doses could be administered in minute volumes, e.g., 0.005 ml. Optimum effects were produced by complexes which were prepared at five times antigen excess. A prior injection of antigen had no influence on the severity of the reaction caused by a subsequent injection of soluble antigen-antibody complexes. The results suggest that certain soluble antigen-antibody complexes per se are effective mediators of systemic anaphylaxis in guinea pigs.

Parallel studies of passive systemic anaphylaxis, using the same pool of antiserum, confirmed earlier findings that the severity of anaphylaxis is proportional to the dose of antibody employed for sensitization and to the duration of the latent period before the antigen is administered. The degree of response was similar whether the reagents were administered simultaneously and complex formation occurred in vivo, or whether similar amounts of reagents were equilibrated in vitro prior to injection. However, substantially augmented responses occurred when a period of only 5 min elapsed between the injection of antibody and antigen.
Radioimmunoelectrophoretic Study of Rabbit Anti-Protein Antibodies during the Primary Response
Authors: Freeman M. J. , Stavitsky A. B.
Published: January 2023

Radioimmunoelectrophoretic analysis disclosed similar primary antibody responses to several protein antigens. Discrete γ2 and γ1M antibodies were also demonstrated after fractionation of pooled, early antiserum by several physicochemical methods.

The indirect method of radioimmunoelectrophoretic analysis, i.e., addition of I* antigen in inert carrier after removal of unreacted, soluble proteins following development of precipitin arcs with anti-rabbit protein sera, appeared to provide the clearest demonstration of the two antibody activities.

Both γ2 and γ1M antibodies appeared simultaneously, usually 6 to 7 days after immunization, and had begun to decrease by 21 days. Other immunologically active, antigen-binding globulins were not observed.

These data indicate that the concept of sequential synthesis of 7 S γ2 and 19 S γ1M antibodies previously postulated must be reexamined.
Studies on the Mechanisms of Hypersensitivity Phenomena
Authors: Lichtenstein Lawrence M. , Osler Abraham G.
Published: January 2023

Normal human serum can enhance the rate and extent of immune histamine release from ragweed-sensitive leukocytes under specified experimental conditions. The quantitative expression of this potentiation is governed largely by the amount of antigen in the reaction system, being most marked when the release process is limited in this respect. The enhancing effect diminishes with higher antigen levels, becoming entirely inapparent with amounts of antigen which suffice for a maximal response.

The potentiating activity of serum is retained after heating at 56°C and treatment with ammonium hydroxide. Serum so treated is shown to be markedly depleted with respect to C′1, C′4, and over-all complement activity. Moreover, this depletion was not offset by a contribution of C′1 from the leukocytes.

Two inhibitors of complement activity, diisopropylfluorophosphate and salicylaldoxime, rendered the leukocytes incapable of a response to antigen. Since the inhibition was manifest even after the cells were washed and resuspended in optimal buffer, it cannot be decided whether these compounds act to derange homeostasis in the leukocyte or to suppress a reaction step specific to the histamine release process.
Esterase, Peptidase, and the Enhancement of Guinea Pig Complement
Authors: Amiraian Kenneth , Purcell James D.
Published: January 2023

The complement-enhancing property of bovine carboxypeptidase A is lost when the enzyme is treated with acetylimidazole. Bovine carboxypeptidase B is as effective in enhancing guinea pig complement as carboxypeptidase A when used at five times the molar concentration as the latter. These data suggest that the peptidase, and not the esterase, activity of carboxypeptidase A is associated with the complement-enhancing property. Bovine procarboxypeptidase A, inert in immune hemolysis, will, when treated with trypsin, enhance guinea pig complement.
The Immune Response to Circulating Autologous Hepatocellular Antigens
Authors: Sargent A. U. , Myers J. , Richter M.
Published: January 2023

The injection of thioacetamide into rats resulted in the release of hepatocellular-specific antigens into the systemic circulation. These hepatic proteins remained in the circulation for 1 to 2 days. Circulating autoantibodies, directed to autologous liver antigens, were detected about a week later in the sera of only 2 of the 20 rats.
The Effect of the Scorbutic State on Tuberculin Hypersensitivity in the Guinea Pig
Authors: Zweiman Burton , Schoenwetter William F. , Hildreth Eugene A.
Published: January 2023

An attempt to characterize the previously noted depression of tuberculin skin reactivity in the scorbutic guinea pig was made, utilizing cell transfer techniques. Scorbutic guinea pigs manifested markedly reduced tuberculin skin responses after receiving complete Freund's adjuvant. This was accompanied by an almost completely absent mononuclear inflammatory response. The inflammatory response to 1% benzyl alcohol, an irritant, was likewise reduced in these animals. In the majority of experiments, pooled cells from these scorbutic animals were able to transfer tuberculin hypersensitivity to normal recipients. By contrast, equal numbers of cells from tuberculin-sensitive donors did not transfer tuberculin hypersensitivity to scorbutic recipients.
Agglutinins for Human Erythrocytes in Mollusks
Authors: Boyd William C. , Brown Rebecca , Boyd Lyle G.
Published: January 2023

A number of mollusks have in their expressed body fluids substances that react with human erythrocytes. The snail Otala lactea contains a powerful and specific anti-A agglutinin that precipitates promptly and specifically with blood group A substance prepared from hog gastric mucin.
Weight Estimates of Rabbit Anti-Human Serum Albumin Based on Antigen-Binding Capacity
Authors: Mulligan James J. , Osler Abraham G. , Rodriguez Eugene
Published: January 2023

A quantitative technique is described for weight estimations of anti-human serum albumin (HSA) based on the primary union of the specific reactants rather than on the formation of insoluble aggregates. Trace-labeled I125·HSA is added, in quantities adequate to supply a great excess of antigen, to a series of tubes containing a constant volume of rabbit anti-human serum albumin. The globulins are precipitated and washed with half saturated ammonium sulfate, and assayed for I125·HSA. These values are converted to weight units of HSA, after appropriate correction, and are in turn used to calculate the absolute amount of antibody in the serum.

The results obtained in these assays are relatively insensitive to such variables as pH, duration of antigen-antibody incubation, and the presence of ethylenediaminetetraacetic acid.

A recovery assay with sheep anti-rabbit γ-globulin serum gave results similar to those obtained by mABC and by quantitative precipitin analyses.

The specificity of the assay system has been investigated with rabbit antisera to egg albumin, bovine serum albumin, human γ-globulin, and pneumococcus polysaccharide Type VI.
Biologic Properties of 19 S and 7 S Mouse Isoantibodies Directed against Isoantigens of the H-2 System
Authors: Möller Göran
Published: January 2023

Various immunologic properties of 19 S and 7 S isoantibodies directed against mouse H-2 isoantigens were investigated in vitro and in vivo. 19 S antibodies prepared in strains A.SW, A.BY, C57BL and B10.5M against strain A were more efficiently hemolytic and cytotoxic than 7 S antibodies, but less potent in agglutination tests. Antisera prepared in strain A.CA were exceptional, however, since 19 S and 7 S antibodies were equally efficient in hemolytic, cytotoxic and agglutination tests. The number of lysed red cells or killed nucleated cells decreased slowly with increasing dilutions of 19 S antibodies, whereas there was a rapid decrease with 7 S antibodies.

7 S antibodies were more efficient in eliminating H-2 incompatible red cells than 19 S antibodies in spite of equal agglutinin titers, but were less competent to induce the change to hemolytic resistance characteristic for mouse red cells after contact with antibodies in vivo. Passive transfer of 7 S antibodies induced immunologic enhancement of tumor homografts and inhibited the secondary immune response, whereas 19 S antibodies had no detectable effect in any of the tests.

It is suggested that these results are caused by quantitative differences between 19 S and 7 S antibodies. The 19 S antibodies are presumably more efficient on a molecular basis in various serologic tests in vitro, but less competent in tests requiring the participation of a minimum number of antibody molecules, such as immunologic enhancement and inhibition of the immune response.