bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Certain Properties of Naturally Occurring Low Molecular Weight γM and the γM Monomer Derived by Reduction and Alkylation of 19 S γM
Authors: Swedlund Harry A. , Gleich Gerald J. , Chodirker William B.
Published: December 2022

A naturally occurring low molecular weight γM protein (γMN) was isolated from the serum of a patient with type I dysgammaglobulinemia by preparative electrophoresis and gel filtration. This protein was compared to the macroglobulin (γM19) isolated from the patient's serum and to the γM subunit (γMS) prepared by reduction and alkylation of γM19. The results indicate that γMN and γMS are similar in size and have the same antigenic determinants. These observations support the concept that the γMN is a naturally occurring subunit of γM19 and is very similar to γMS, γM19, γMN and γMS were also prepared from the patient's serum after tetanus immunization and were found to bind radiolabeled tetanus toxoid. Most, but not all, controls did not show nonspecific binding of tetanus toxoid. These results suggest but do not conclusively establish the capacity of these γM proteins to bind antigen specifically.
Regulation of Antibody Synthesis Against Escherichia Coli Endotoxin
Authors: Britton Sven , Möller Göran
Published: December 2022

Cyclical fluctuations of cellular and humoral 19 S antibody synthesis were evoked by one single injection of heat-killed E. coli 055:B5 bacteria into CBA mice. The phenomenon was interpreted as involving feedback suppression of active antibody synthesis by 19 S antibodies. The biologically stable antigen would be prevented from stimulating antibody synthesis by reacting with the initially produced 19 S antibodies. In the absence of further stimulation 19 S-producing cells and serum antibodies would decay, leaving antigen free to initiate a second cycle of antibody synthesis. This hypothesis was supported by the finding that antiserum taken from the time of the first peak could suppress the appearance of a second peak.

Antigen and 19 S antibodies injected simultaneously delayed active antibody synthesis which eventually appeared spontaneously. Presumably this represents a more rapid catabolism of the blocking antibodies than of the antigen.

7 S antibodies were not detected against this antigen during the primary response but appeared after intense hyperimmunization. The most sensitive method for detection of 7 S antibodies was inhibition of antibody synthesis by passive transfer of purified 7 S fractions.

7 S antibodies were more potent in inhibiting active antibody synthesis than 19 S antibodies when equal quantities of hemagglutinins were injected.
Communications
Authors: Feldman Harry A.
Published: December 2022

Recently we demonstrated (1) that heparin-MnCl2 removes nonspecific rubella hemagglutinin inhibitor more effectively from serum than does kaolin. Mann et al. (2) previously had reported that the heparin-MnCl2 combination was superior to kaolin in precipitating the nonspecific serum inhibitor for reovirus hemagglutinin. Both of these nonspecific serum inhibitors are β-lipoproteins (1, 2) which kaolin adsorbs irregularly. Heparin-MnCl2 precipitates it uniformly. While kaolin may reduce the concentration of IgG substantially, heparin-MnCl2 does not. Kaolin also introduces a dilution factor which can be difficult to estimate with confidence.

This report is concerned with the extension of the heparin-MnCl2 system to the removal of the nonspecific measles virus hemagglutinin inhibitor (3) from human sera. As the data illustrate, this is accomplished as effectively as in the rubella system. In this investigation, the sera of 50 young children, which had been stored for several years at -20°C, were thawed and 1.0-ml amounts were removed from each.
The Reactivity of Long-Lived Lymphocytes to Typhoid Vaccine in situ in Rat Popliteal Lymph Nodes
Authors: Miller John J. , Cole Leonard J.
Published: December 2022

The cells of the popliteal lymph nodes of rats were labeled with tritiated thymidine for 4 days after primary or secondary injections of OT or after a secondary injection of typhoid vaccine. Thiry-one days after the last dose of tymidine, rats of each group were challenged with typhoid vaccine. Increased numbers of heavily-labeled large lymphocytes and mitotic figures were found in the popliteal nodes for 2 days after challenge with typhoid vaccine regardless of the antigen given prior to labeling. This in situ reaction to typhoid vaccine was demonstrated as long as 7 months after labeling. Reasons indicating that these large lymphoid cells were derived from labeled, long-lived small lymphocytes are discussed. We believe these results confirm the validity of the method of following tritiated thymidine-labeled lymphocytes for long periods of time.
Immune Response in Chiroptera to Bacteriophage øX174
Authors: Hatten Betty A. , Allen Rae , Sulkin S. Edward
Published: December 2022

The immune response of bats, guinea pigs and rabbits to a series of three primary injections and a booster injection of bacteriophage φX174 was studied. Antiphage activity developed more rapidly in bats maintained at 24°C and 37°C than in other animals, but the magnitude and duration of the primary response was less, particularly in 24°C bats. Deviations in the percentage of phage inactivated by bat plasma pools from the mean indicated indirectly that individual 24°C bats varied considerably in their response to φX174. Prolonged primary production of ME-sensitive antibody was observed in 24°C bats, and 37°C bats had a large proportion of ME-sensitive antibodies throughout the first 21 days. Kinetic studies of φX174 inactivation indicated that 37°C bat antibodies developed during the latter part of the primary response did not bind phage irreversibly. Some instability was also noted in interactions between a diluted 35-day guinea pig antiserum and φX174. A booster injection of φX174 enhanced the neutralizing capacity of antibodies produced in all three animal species. Approximately 40% of the antiphage activity in 10-day postbooster plasma pools from 24°C bats was due to ME-sensitive antibody. Guinea pigs, rabbits and 37°C bats had little detectable ME-sensitive antibody during the secondary response by the assay procedures used. While the rate and extent of phage inactivation by a 30-day postbooster plasma pool from 37°C bats greatly exceeded that obtained with a comparable pool from 24°C bats, bat antibodies did not inactivate φX174 as rapidly or to the same degree as 30-day post-booster guinea pig or rabbit antisera. From these results it was concluded that the primary and secondary immune response of bats to immunization with φX174 was quantitatively and qualitatively less than the response of rabbits and guinea pigs to the same stimuli.
Experimental Allergic Uveitis
Authors: Wacker W. B. , Lipton M. M.
Published: December 2022

Guinea pigs immunized with homologous retina in Freund's adjuvant developed both humoral and hypersensitive responses to retinal tissue, and were associated with production of experimental allergic uveitis in these animals. Serologic investigations indicated humoral antibody was made to two antigens of retinal specificity. One was extractable from retinal homogenate in saline, and the other was demonstrated in the particulate fraction of the ultracentrifuged homogenate. Antibodies to both antigens were produced by animals immunized with whole retinal emulsion, but a few of the animals made antibody to only one of the antigens. In these animals delayed hypersensitivity was elicited convincingly only to the extractable antigen.

Following immunization with either soluble or particulate fraction of retina, guinea pigs made humoral antibody only to the fraction used for immunization. Delayed hypersensitivity was demonstrated only in animals immunized with the extract.

The two antigens were limited in the guinea pig to retinal tissue, but similar antigens were demonstrated in the retinas of other species. Although humoral antibodies from guinea pigs immunized with homologous retina were reactive with heterologous retina, these animals showed delayed hypersensitivity only to guinea pig retina. Conversely, guinea pigs immunized with heterologous retina were not hypersensitive to homologous retina. These findings are correlated with previous observations that homologous, but not heterologous retina, was highly effective in production of experimental allergic uveitis in the guinea pig.
Further Studies on the Effect of Specific Antiserum on Induction, Maintenance and Termination of Immunologic Tolerance
Authors: Friedman Herman
Published: December 2022

Establishment of immunologic tolerance to soluble somatic antigens derived from Shigella paradysenteriae was prevented in neonatal mice by a single injection of either rabbit or mouse antiserum to Shigella. Serum dilutions less than 1:100 were generally necessary to demonstrate this effect, even when the sera had agglutinin titers greater than 1:5120. Injection of antiserum on the day of birth, or 1 day thereafter, readily interfered with establishment of tolerance. An interval of several days or more between injection of antiserum and SSA resulted in no demonstrable effect on tolerance induction.

γ-Globulin fractions derived either from rabbit or mouse antisera had similar effects in preventing tolerance induction. IgM and IgG rich fractions prepared by sucrose gradient centrifugation of γ-globulin prepared from pooled rabbit or mouse hyperimmune serum were also effective. However, IgG fractions prepared from “early” immune rabbit or mouse serum, which had low titers to Shigella, were ineffective.

Whole serum, γ-globulin, or IgM and IgG fractions pooled from serum specimens obtained from partially tolerant mice several months old also had little or no effect when injected into other mice at birth, together with SSA. Undiluted “tolerant” sera, even those with titers in the range of 1:256, were less effective in blocking establishment of tolerance than higher dilutions of “early immune” mouse or rabbit serum with lower agglutinin titers. Injection of specific antiserum or immunoglobulin fractions generally did not affect established tolerance in young adult mice. However, injection of such serum to tolerant mice several months of age often resulted in more rapid termination of tolerance.
Latency in Human Infections with Tric Agents
Authors: Hanna Lavelle , Dawson Chandler R. , Briones Odeon , Thygeson Phillips , Jawetz Ernest
Published: December 2022

Direct immunofluorescent staining of conjunctival cells is, at present, the most sensitive method for the detection of TRIC agents. Detailed evidence for the specificity of the method is provided. By means of immunofluorescent staining, TRIC agents can be detected in specimens from the eye of many individuals who do not exhibit current clinical activity of trachoma or inclusion conjunctivitis. Examples from spontaneously infected individuals and from experimental infection in volunteers support the belief that latent infection with TRIC agents is commonplace and may occupy an important role in the natural history of these infections which involve many millions of people. We propose that the clinical signs of activity in trachoma and inclusion conjunctivitis do not adequately reflect the presence of the infectious agent. Future considerations of diagnosis, treatment and control must include subclinical infection and latency of TRIC agents.
A Correlate of Human Delayed Hypersensitivity: Specific Inhibition of Capillary Tube Migration of Sensitized Human Lymph Node Cells by Tuberculin and Histoplasmin
Authors: Thor Daniel E. , Dray Sheldon
Published: December 2022

The migration of human monocytic-phagocytic sensitive cells from lymph node tissue culture suspensions was consistently and specifically inhibited by 10 µg/ml of PPD or 30 µg/ml of histoplasmin. Complete correlation of the inhibition of cell migration with the delayed hypersensitivity skin test was obtained in 27 patients sensitive to PPD, histoplasmin, or to neither or both of these antigens. For migration of these cells to occur, prior maintenance as tissue culture suspensions for 72 hr was necessary before placement in the capillary tubes for 36 hr. During tissue culture, a large proportion of the lymphocytes developed the ability to phagocytize microsized iron particles and this transformation is probably relevant to the development of the migrating cell population.

The application of the capillary tube cell migration method to man will facilitate the elucidation of factors important in human delayed hypersensitivity reactions and has implications for evaluating the role of delayed hypersensitivity in autoimmunity, contact sensitivity, infectious diseases and transplantation immunity.
Immunologic Studies of a Partially Purified Sheep Erythropoietin
Authors: Rioux Ernest , Erslev Allan J.
Published: December 2022

One-third of immune sera from rabbits immunized with a partially-purified sheep ESF were able to neutralize completely or partially the biologic activity of a given amount of sheep ESF. Stronger ESF-neutralizing immune sera were also able to suppress normal mouse erythropoiesis and to neutralize heterologous anemic sera. Weaker ESF-neutralizing sera did not significantly decrease normal mouse erythropoiesis and did not regularly neutralize heterologous anemic sera. Therefore a relative species-specificity of immune serum to sheep ESF is postulated. The similarity to insulin and growth hormone, two protein hormones capable of giving rise to antibodies in species in which they are biologically active, is stressed and possible causes of the antigenicity of sheep ESF in rabbits are briefly discussed.
Heterogeneity in Antibodies Specific for Aggregated Human γG-Globulin
Authors: Henney Christopher S. , Ishizaka Kimishige
Published: December 2022

Antibodies produced to aggregated human γG-globulin under autologous, isologous and heterologous conditions were compared by contrasting the specificity of antibodies present in rheumatoid arthritic sera, in the serum of a patient with acquired hypogammaglobulinemia and in guinea pig antisera. In each case antibody specific for the aggregated molecule, and exhibiting no affinity for its native form, was produced, and invariably the antigenic determinants eliciting antibody production were located in the Fc region of the aggregated antigen.

The antibodies produced under the different conditions were readily distinguishable by their hemagglutination and antigen-binding characteristics. Rheumatoid factor showed species cross reactivity, whereas the anti-isologous and anti-heterologous denatured γG-globulin antibodies were directed entirely against species-specific determinants.

Following aggregation of the Fc fragments of HGG, only a portion of the aggregated molecules (about 60%) possessed antigenic determinants capable of reacting with any of the antibodies. Although individual Fc aggregates showing reactivity with one group of antibodies were frequently shown to be antigenic for antibodies of the other groups, a portion of the aggregates reacted exclusively with each of the antibodies.

Evidence was presented to suggest that a correlation existed between the antigenic complexity of aggregated Fc fragments and their molecular size. Thus, small Fc aggregates (dimers and trimers) were found to lack antigenic determinants present in larger aggregates (hexamer and greater).

It was also shown that many, if not all, of the antigenic determinants revealed by nonspecific denaturation of HGG are also present on the γG-antibody molecule following combination with homologous antigen.
Difference in the Immunoglobulin Class of Polioantibody in the Serum of Men and Women
Authors: Ainbender Eugene , Weisinger Ruth Berger , Hevizy Magda , Hodes Horace L.
Published: December 2022

We have measured by radioimmunodiffusion (RID) the specific IgA and IgG polioantibody in the sera of 36 men and 36 women. We have found in 8 women the IgA polioantibody titer was equal to or greater than the IgG polioantibody titer. In 6 women, the IgA polioantibody was 50% of the IgG titer. No man was found to have an IgA polioantibody titer equal to 50% of his IgG polioantibody titer. In fact, 33 of the 36 men had an IgA polioantibody titer which was less than 20% of their IgG polioantibody titer. The other 3 men had an IgA polioantibody titer which was 25% of their IgG titer. These data show that the adult female population contains a significant number of women in whom the IgA polioantibody is equal to or greater than the IgG polioantibody. No such individuals were found among the adult male population. Thus we have demonstrated for the first time that there is a significant difference in the immunoglobulin pattern of the polioantibody in the serum of the adult male and the adult female.
Immunology in 1968
Authors: Horsfall Frank L.
Published: December 2022

It is gratifying to have, as a perogative of office, this opportunity again to speak to the members of the American Association of Immunologists and their guests. It occurs to me that some 33 years have passed since the first time I had the honor to present, with a considerably quickened pulse, a paper at a meeting of this Association.

In keeping with the long-established tradition that the Presidential Address may follow any desired course, I propose to speak of certain matters which may seem only distantly related but do support a single theme, the state of the discipline of immunology. The reasons for choosing this course are several, and chief among them is the belief that some of these matters very much need airing.

Probably only a few older members of the Association are aware that it was organized in New York City, shortly after 1914, largely as a result of the vision and vigor of one man, Dr. Arthur F. Coca.
Availability of Isoantigens to Circulating Antibodies
Authors: Witz Isaac , Yagi Yasuo , Pressman David
Published: December 2022

Iodinated and purified C57BL/6 anti-DBA/2 isoantibodies have been shown to exhibit in vivo localization in organs of DBA/2 mice when injected. Lung, spleen and liver fixed large proportions of the injected antibodies while kidney, thymus, lymph nodes, and heart did not fix large amounts of isoantibodies.

Only minute amounts of isoantibodies were fixed in the brain, but the localization was highly specific. There was essentially no localization of normal globulin in the brain.

No localization could be detected in organs of C57BL/6 mice which served as isoantibody donors. Some cross-localization was observed in the tissues of other inbred strains, depending on their genetic relation to the DBA/2 mice.

The degree of in vivo localization of isoantibodies does not represent the amount of the corresponding isoantigens in a certain organ, but depends mostly on the availability of these antigens to localizing antibodies.
Heterogeneity in the Ability of Rabbit 7 S and 19 S Neutralizing Antibodies to Differentiate Between Intratypic Antigenic Variants of Herpes Simplex Virus
Authors: Hampar Berge , Mage Michael G. , Keehn Mary Alice
Published: December 2022

The ability of early (7 day) and late (7 week) rabbit 7 S and 19 S antibodies to differentiate between two intratypic herpes simplex virus (HSV) antigenic variants was studied by carrying out neutralization kinetic tests. The early and late 19 S antibodies could differentiate between these HSV variants in the presence of complement (C′), and the late 19 S antibody could also differentiate between these variants in the absence of C′. However, neither the early nor the late 7 S antibodies could differentiate between these HSV variants in the presence of C′, but the late 7 S antibody could differentiate between these variants in the absence of C′. The ability of the late 7 S antibody to differentiate between these HSV variants in the absence of C′ was destroyed by treatment of the antibody with 2-mercaptoethanol (2-ME), although 2-ME treatment did not reduce the neutralization titers of the late 7 S antibody.
A Quantitative in Vitro Study of the Chromatographic Distribution and Immunoglobulin Characteristics of Human Blocking Antibody
Authors: Lichtenstein L. M. , Holtzman N. A. , Burnett L. S.
Published: December 2022

This report describes the immunoglobulin and chromatographic characteristics of human blocking antibody. Studies were carried out on a pool of serum from 20 allergic donors who had been immunized with ragweed antigen E as a form of therapy for ragweed hay fever. The serum and serum fractions were subjected to chromatography on DEAE-Sephadex, CM-cellulose, DEAE-cellulose and Sephadex G 200. Blocking activity was assayed by an in vitro technique: the inhibition of antigen E induced histamine release from isolated human leukocytes. This technique is more than 10 times as precise as the usual skin assay. Immunoglobulins were determined qualitatively by immunodiffusion against specific antisera and quantitatively by the Preer technique. Recovery of blocking activity was about 70%. In each fractionation procedure blocking antibody and IgG eluted together. Purified IgA had less than 1% the activity of IgG preparations and IgM antibody contributed less than 1% to the activity of the whole serum. Absorption of the serum with anti-IgA and treatment with 2-mercaptoethanol did not decrease its blocking titer, while absorption with anti-IgG caused a decrement of more than 97%. Circulating reaginic antibody appeared to account for less than 1% of the total serum activity. It was concluded that blocking activity is essentially a function of IgG molecules.
Differential Effect of Heterologous Anti-Lymphocyte Serum on Antibody-Producing Cells and Antigen-Sensitive Cells
Authors: Möller Göran , Zukoski Charles
Published: December 2022

Rabbit antiserum to mouse lymphocytes (anti-lymphocyte serum (ALS)) did not suppress the primary cellular 19 S or 7 S immune response to sheep red blood cells when given after the antigen. Furthermore, ALS failed to decrease the number of antibody-producing cells when injected into animals already hyperimmunized against sheep red blood cells, but had marked suppressing effect on the antigen-sensitive cells in these animals. This was investigated by a transfer system: hyperimmune spleen cells from ALS-treated and untreated donors, respectively, were mixed with sheep red blood cells and inoculated into irradiated (600 r) syngeneic, nonimmunized recipients. The number of 19 S and 7 S antibody-producing spleen cells was determined 7 days later. Transfer of spleen cells from ALS-untreated donors resulted in excessive cellular 7 S production, in the recipients. The total number of 7 S cells exceeded 106 per spleen and the proportion varied between 1 and 50% as a rule. Pretreatment of the immunized donors by ALS caused a reduction of more than 90% of the number and proportion of 7 S antibody-producing cells in the secondary hosts. Analogous results were obtained for 19 S production. The effect could not be ascribed to destruction of ALS-treated cells in the secondary recipients. The results suggest a differential effect of ALS on antibody-producing cells and antigen-sensitive cells.
The Synthesis of Ribonucleic Acid during Early Antibody Induction
Authors: Lazda Velta A. , Starr Jason L. , Rachmeler Martin
Published: December 2022

The early events in the primary antibody response of rats to flagella were characterized by a period of enhanced incorporation of radioactive nucleotides into RNA preceding antibody formation. During this period of apparently accelerated RNA synthesis, a rapidly labeled RNA was detected on spleen ribosomal aggregates, predominantly 2 and 3 to 4 ribosomal clusters, after a 1-hr P32 labeling. A large portion of the newly synthesized RNA extracted from the ribosomal aggregates sedimented as 29 S and 18 S ribosomal RNA. The RNA with the greatest specific activity however, was found as a polydisperse peak with sedimentation constants in the 6 to 12 S range, but with a sharp peak of high specific activity in the 18 S region. This broad range of sedimentation values of the RNA was peculiar to RNA extracted from immunized rat spleen preparations. The rate of RNA synthesis returned to normal by 5 days after immunization. The actual functioning of the newly synthesized RNA as messenger RNA for antibody synthesis was not demonstrated, but the kinetics of formation and the relationship of the RNA synthesis to the antibody response suggest that this might be its role.
The Metabolism of Messenger RNA Synthesized after Primary Immunization
Authors: Lazda Velta A. , Starr Jason L. , Rachmeler Martin
Published: December 2022

The synthesis of RNA in rat spleen cells was stimulated by immunization. Analyses of the RNA associated with ribosomes extracted from these cells which had been immunized 24 hr previously, revealed that during the 1st hr after injection of P32, the RNA synthesized in greatest amounts had messenger-like sedimentation characteristics. Over the next 24 hr, there was an extensive accumulation of stable ribosomal RNA, but the messenger RNA accumulated relatively slowly. The base composition of the 6 to 12 S RNA, measured from the P32 distribution in the various nucleotides, differed from the nucleotide composition of ribosomal and soluble RNA, and resembled more closely that of DNA in the GMP + CMP to AMP + UMP ratios. Particularly high UMP:AMP ratios also characterized this RNA. The base ratios of the messenger RNA which accumulated were different from those of the rapidly labeled but unstable 6 to 12 S RNA. On the basis of these results, it is apparent that the synthesis of at least two major species of messenger RNA are stimulated by immunization. One species is labile and may code for structural proteins and enzymes. One other is relatively stable and may be the message for antibody synthesis.
The Cell-Migration-Inhibition Correlate of Delayed Hypersensitivity
Authors: Thor Daniel E. , Dray Sheldon
Published: December 2022

When nonsensitive cells were incubated with an RNA extract from lymph nodes of human donors sensitive to tuberculin purified-protein-derivative, histoplasmin or both, the migration of these cells from capillary tubes was specifically inhibited by these antigens.

This RNA extract contained no detectable DNA and less than 3% protein and was inactivated by RNase but not by DNase or trypsin.
Significance of the Mast Cell Response to a Lysosomal Protein
Authors: Clark Junius M. , Higginbotham R. D.
Published: December 2022

The response of local tissue mast cells to the subcutaneous injection of relatively small amounts of cationic protein (or polypeptide) extracted from lysosomes of rabbit PMN has been examined and it was observed that 1) this lysosomal material (LCP) induced a rapid and rather explosive release of the heparin-containing granules from mast cells in a dose-response manner, 2) the shed granules formed relatively stable complexes with the cationic protein in vivo, and 3) the LCP-granule complexes were readily ingested by adjacent connective tissue cells.

It is suggested that this LCP-induced degranulation of mast cells may be a naturally-occurring event in the inflammatory process in that mast cells are characteristic constituents of the connective tissue and would, on an occasion of tissue injury, be exposed to this protein after its local release from PMN accumulating in the affected area. Inasmuch as PMN lysosomal substances may be involved in the production of inflammatory injury and heparin can interact with various biologically-active substances, the secretion of heparin-containing granules from mast cells may serve as a local means for the sequestration of these lysosomal proteins for subsequent ingestion by connective tissue cells and in this manner a) reduce the injury-producing potential of these proteins in the tissue and/or b) conserve the antibacterial and hydrolytic properties of these substances for reutilization by the recipient cells and thereby enhance their potential for dealing with phlogogenic stimuli in the tissue (e.g., bacteria).

The LCP-induced degranulation of mast cells may thus serve as a local mechanism for control of the inflammatory process and protection against the noxious effects of various cationic agents.
Neutralization and Sensitization of Herpes Simplex Virus with Antibody Fragments from Rabbits of Different Allotypes
Authors: Ashe Warren K. , Mage Michael , Mage Rose , Notkins Abner Louis
Published: December 2022

Incubation of herpes simplex virus (HSV) with papain-derived fragments (Fab) of rabbit anti-HSV γ globulin resulted in substantial virus neutralization. The infectious virus that survived incubation with the Fab fragments was found to exist in the form of an infectious virus-antibody complex (sensitized virus). Incubation of the sensitized virus with undigested sheep anti-rabbit γ globulin or the Fab fragments of sheep anti-rabbit γ globulin resulted in further virus neutralization. The specificity involved in the neutralization of sensitized virus by anti-γ globulin was shown by the fact that virus sensitized with undigested or papain-derived fragments of rabbit anti-HSV γ globulin of one allotype was neutralized by anti-γ globulin directed against that allotype but not by anti-γ globulin directed against a different allotype.
Relationship of Germinal Centers in Lymphoid Tissue to Immunologic Memory
Authors: Jacobson E. B. , Thorbecke G. J.
Published: December 2022

Cell suspensions, obtained from white and red pulp of rabbit spleens at various days after priming, were examined for their ability to respond, with increased proliferation, to reexposure to antigen. A comparison was made between the proliferative response and the secondary in vitro antibody response obtained with the same tissues.

A significant increase in mitotic activity in response to antigen was seen in white pulp as early as day 3 after priming. The maximum response was obtained on days 7 to 10. Neither of the antigens elicited a significant proliferative response in red pulp cells. However, in view of an unusually high background activity found in many of the red pulp suspensions, a limited stimulatory effect of antigen may have gone undetected.

A fairly good correlation was found between the proliferative and secondary antibody response of white and red pulp and a relationship to the development of germinal centers in the white pulp was suggested. The first striking responsiveness occurred at the time when germinal centers are beginning to form, and maximum responsiveness was noted at the time of their peak development.
Formation and Transfer of Antibodies in Congenital Murine Infections with a Type 2 Reovirus
Authors: Carruthers Mary M. , Lerner A. Martin
Published: December 2022

The formation and transfer of hemagglutinating inhibiting antibodies to reovirus, type 2 in congenital murine reovirus infections have been examined. Pregnant mice respond to reovirus antigen with active and persisting formation of antibody. Progeny are unresponsive. Antibodies in baby sera are passively transferred. Unresponsiveness in nursling mice is not a function of the quality or quantity of the antigen, but is induced by passively acquired specific immunoglobulin.

There is little demonstrable prenatal transfer of these antibodies. After delivery, suckling mice rapidly absorb homotypic antibody from their dam's colostrum, and later milk. Titers of hemagglutinating inhibiting antibody in the progeny are easily demonstrable by the 5th day of life. They equal those of their mothers 4 days later, and continue at this level to diminish by day 18. The system allows a critical characterization of maternal colostral antibody in the mouse.
Detection of γA Antibody-Releasing Cells to Erythrocyte and Lipopolysaccharide Antigens
Authors: Walters Carla S. , Jackson Anne L.
Published: December 2022

Following immunization of Swiss Webster mice with sheep erythrocytes or Escherichia coli lipopolysaccharide antigens, γA antibody-releasing cells were detected by a modification of the localized hemolysis-in-gel technique. When purified rabbit anti-mouse γA immunoglobulin was added to spleen cell suspensions before plating and enumerating, augmented numbers of antibody-releasing cells were detected. These “γAPFC” were found following primary and secondary injections of both antigens and were specifically inhibited by γA myeloma protein.
Staphylococcal Delayed Hypersensitivity in Mice
Authors: Taubler James H.
Published: December 2022

Tuberculin-type (delayed) hypersensitivity to staphylococci can be induced in mice by eight weekly subcutaneous injections of 103 viable staphylococci per injection. Such hypersensitive mice demonstrate a positive footpad reaction (swelling) when injected with a 200-µg dose of staphylococcal antigen. Hypersensitivity can also be transferred to normal recipient mice via lymphoid cells from sensitized donors. Such passively sensitized recipients also react positively when footpad tested. Delayed hypersensitivity cannot be passively transferred with plasma, nonviable cells or cell-free extracts from hypersensitive donors.
The Immunologic Response of Rabbits to Carrageenans, Sulfated Galactans Extracted from Marine Algae
Authors: Johnston K. H. , McCandless E. L.
Published: December 2022

Both κ and λ carrageenans, sulfated galactans, elicit formation of precipitating antibodies in rabbits. The carrageenan-anti-carrageenan system follows the kinetics of other well-known antipolysaccharide systems. Both λ and κ carrageenan show a high degree of immunologic specificity; namely, no reaction was observed between antigen and heterologous antibody. Molecular weight determinations of the κ carrageenan antigen according to the Boyd and Hooker equation agree with molecular weights determined by other investigators: a value of 350,000 is calculated for the λ fraction.
Rabbit Blocking and Binding Antibodies to Human Intrinsic Factor and Intrinsic Factor-B12 Complex
Authors: Samloff I. Michael , Turner Michael D.
Published: December 2022

Based upon studies of the relationships of blocking and binding antibodies to IF in patients with pernicious anemia, it has been hypothesized that the antigenic site on human IF for the blocking antibody may be a more potent immunogen than the corresponding site for binding antibody. The results of this study are in agreement with this hypothesis in that rabbits given a single injection of approximately 270 ng human IF were found to have low concentrations of blocking antibody but no detectable binding antibody in their serum.

Rabbits challenged with the same amount of IF complexed to B12 produced both blocking and binding antibodies. The concentration of blocking antibody in the latter animals was significantly higher than in the group immunized with IF, indicating that B12 enhances the immunogenic potencies of both antigenic sites on IF.

Binding antibody was detected in both the γM and γG classes of immunoglobulins. Blocking antibody was found to be predominantly γG.
Delayed Hypersensitivity to Myelin Basic Protein in the Passive Transfer of Experimental Allergic Encephalomyelitis
Authors: Falk George A. , Kies Marian W. , Alvord Ellsworth C.
Published: December 2022

Experimental allergic encephalomyelitis was passively transferred in strain 13 guinea pigs with lymph node cells from donors sensitized with either homologous spinal cord or myelin basic protein in Freund's complete adjuvant. Severity of EAE in cell recipients was proportional to the number of cells transferred. Evidence that disease in cell recipients was not due to inadvertent active sensitization was based on: 1) the significant decrease in induction time after cell transfer as compared to length of induction after active challenge; and 2) the almost complete inability of cells to transfer EAE after being heated to 60°C, a temperature which is known to damage cells but which has no effect on the encephalitogenic activity of the emulsion used for active challenge.

Delayed-type skin reactivity to myelin basic protein was correlated with severity of EAE in both cell donors and recipients, whereas circulating antibody to the encephalitogen was not detected in the majority of donors or in any recipient. This evidence strengthens the concept of EAE as a manifestation of delayed hypersensitivity to myelin basic protein.
Evidence of SV40-Specific Transplantation and Surface Antigens in Cells Transformed by Para-Adenovirus 12
Authors: Lausch Robert N. , Tevethia Satvir S. , Rapp Fred
Published: December 2022

The presence of viral determinants in tumor cells induced by a PARA-adenovirus 12 population carrying SV40 information has been investigated. The cells contained three markers specific for papovavirus SV40; the transplantation, surface and tumor antigens. Quantitative comparison with the SV40-transformed H-50 hamster cell line indicated the PARA-12 cells had a lower level of transplantation antigen but a higher level of T antigen. There was no evidence for any adenovirus markers, nor was infectious virus detected.
Calcium Requirements for Complement Dependent Hemolytic Reactions
Authors: Bryant Richard E. , Jenkins David E.
Published: December 2022

The calcium ion requirement for undiluted serum EAC′ hemolysis, PNH sucrose hemolysis and PNH acid hemolysis was re-examined using EGTA, a chelating agent with more than 100,000 times greater avidity for Ca++ than Mg++. At pH 7.6 undiluted serum EAC′ hemolysis and PNH sucrose hemolysis were markedly inhibited by MgEGTA indicating an absolute calcium ion requirement in these systems. At this same pH MgEGTA showed no such inhibition of PNH acid hemolysis suggesting that this reaction can occur in the virtual absence of calcium. No conclusions could be reached on the calcium ion requirements in these systems at pH 6.2 since EGTA is a much less effective chelator of calcium at the lower pH.
The Application of the Irradiated Hamster Test to the Study of Experimental Allergic Encephalomyelitis
Authors: Kornblum Joan
Published: December 2022

Lymph node cells taken from rats sensitized to guinea pig spinal cord produced delayed skin reactions when mixed with antigen and injected into irradiated hamsters. Node cells from normal unsensitized rats failed to elicit such lesions. The immunologic basis for the skin reactions was demonstrated by their specificity for the inducing antigen, the delay in appearance of responsiveness in the lymph node cells until 2 weeks following immunization of the donor (a time period corresponding to the lag prior to clinical symptoms in the donor), and finally by the failure of node cells taken from donors rendered neonatally tolerant to spinal cord to react when challenged with the antigen. It was shown in addition that sensitized lymphoid cells from a strain of rat genetically insusceptible to the expression of clinical EAE also failed to react against the antigen in the irradiated hamster test. This may reflect a deficiency in these cells of a chemical mediator of delayed hypersensitivity.
Immunogenicity and Specificity of Collagen
Authors: Timpl R. , Wolff I. , Wick G. , Furthmayr H. , Steffen C.
Published: December 2022

Rabbit antisera to acid-soluble calf collagen were used for cross-reaction studies with sheep, rat, guinea pig, rabbit and carp collagen in hemagglutination-inhibition tests. Advantage was taken of the use of three antibody fractions differing in specificity. One of them possessed a general collagen specificity, the others were species-specific and directed either to pepsin-stable or pepsin-labile determinants. Some of the antisera contained only one of the antibody fractions, in other cases they were separated on an immunoadsorbent.

The antibodies with general collagen specificity reacted with all the collagens, indicating a common antigenic determinant. Small but still significant differences observed in inhibition tests suggest, however, that these determinants are not identical but only similar in structure. The species-specific antibody fraction to pepsin-stable determinants cross-reacted with sheep and rat collagen or with sheep collagen only. The third antibody fraction, which in contrast to the others is directed to pepsin-labile structures of collagen, cross-reacted either with sheep collagen or showed no cross-reaction at all. The results were interpreted for the existence of at least five distinct antigenic determinants on calf collagen.
Spontaneous Delayed Iso-Hypersensitivity in Guinea Pigs
Authors: Battisto Jack R.
Published: December 2022

New data which allow the delayed-type dermal reactivity that guinea pigs manifest toward a homologous serum factor (SF) to be interpreted as a spontaneous delayed-type iso-hypersensitivity (IH) to an iso-antigen are presented. Histologic evidence has indicated the dermal reaction elicited by SF cannot be differentiated from that evoked by Old Tuberculin. A survey of the distribution of SF and the IH to it among guinea pigs of several strains has revealed an unequal occurrence of each. The earliest onset of spontaneous IH to SF observed, i.e., 4 to 8 weeks of age, corresponds to the earliest age at which guinea pigs can be made to show delayed cutaneous reactions to other antigens. The degree of delayed immunologic reactivity developed to a contact allergen by guinea pigs with and without spontaneous IH to SF was found to be equal. In addition, a cutaneously injected irritant, turpentine, elicited equal responses in animals of these two groups. SF was shown to be different from the permeability factors which elicit immediate type responses. Transfer of iso-hypersensitivity for SF to nonreactive closely related (F1) guinea pigs was accomplished by living lymphocytes. The occurrence in guinea pigs of natural delayed hypersensitivity toward xenogeneic antigens, the possible existence of spontaneous IH among species other than the guinea pig, and the possibility that certain recently reported phenomena may be interpreted as manifestations of spontaneous IH are discussed.
Adenovirus Type 12 Oncogenicity in Newborn Hamsters: The Effect of Pokeweed Mitogen
Authors: Haase Ashley T. , Kasel J. A. , Chessin L. N.
Published: December 2022

Pokeweed mitogen administered to newborn hamsters causes a marked reduction in tumor incidence when adenovirus type 12 is inoculated 72 hr after birth. Accelerated attainment of immunologic competence with subsequent tumor rejection is suggested as the explanation for the observed tumor inhibition.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Cooper N. R. , Müller-Eberhard H. J.
Published: December 2022

Previous work had raised the possibility of functional interdependence between C′5, C′6 and C′7; in the absence of C′6 and C′7, the C′5 reaction was inefficient and the reaction product was extremely labile at 37°C. Further analysis using isolated and 125I-labeled C′5 showed that formation of EAC′1a,4,oxy2a,3,5 from EAC′1a,4,oxy2a,3 has the following characteristics: 1) Formation began immediately on addition of C′5, increased with time to reach a maximum and then declined. 2) The product was unstable, i.e., the reactivity of cell-bound C′5 was lost with a half-life of 7 to 9 min at 30°C and 2 to 3 min at 37°C. 3) Loss of cell-bound C′5 hemolytic activity was not caused by release of bound C′5, which dissociated from the cell complex with a half-life of 2 to 3 hr at 30°C indicating that bound C′5 exists in active (C′5a) and inactive (C′5i) forms. 4) Dissociated C′5 was found to be of macromolecular size.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Rother K. O. , Rother U. A. , Philipps M. E. , Goetze O. , Thorbecke J. G.
Published: December 2022

Tissue cultures of rabbit liver produced C′6, as previously reported (Immunology, 14: 649, 1968). For further identification of the cell type involved, a tissue culture cell line, derived from a minimal deviation hepatoma (H4 II EC3) and consisting of parenchymal-type cells, was examined for the synthesis of complement components. For this purpose, the cells were cultured for 24 to 72 hr in a medium containing albumin but no other serum proteins in order to avoid contamination with extraneous complement factors. Titration of the media, using C′6 defective rabbit serum as a reagent, showed that these cells produced C′6. Production of C′9 activity was demonstrated, employing EAC′1–8 as the reagent. Evidence for production of complement factors by tissues other than the liver was also obtained. Post-irradiation chimeras, produced by injection of bone marrow from C′5 positive donors (B6AF mice) into C′5 negative recipients (A mice), showed a transient rise in overall C′ activity in their sera, indicating C′5 production by descendants of the grafted cells.
Abstracts of Papers Presented at the Third International Complement Workshop, Harvard Medical School, Boston, Massachusetts, June 3–5, 1968
Authors: Alper C. A. , Propp R. P. , Johnston R. B. , Rosen F. S.
Published: December 2022

It has been possible to identify seven codominant alleles for human C′3 by agarose electrophoresis of fresh sera. In Caucasians, there are two common alleles, S (slow) and F (fast), with approximate gene frequencies of 0.75 and 0.25. The F gene is less common in American Negroes and rare in Orientals. There are rare variants of C′3 in the three major races which, as a group, have an incidence of about 2 to 3%. These were named according to electrophoretic mobilities with reference to the S allotype: F1, F0.8, F0.5, S0.6 and S1. In heterozygotes, the two gene products are of approximately equal concentration. As judged by assays for hemolytic complement and immune adherence, all allotypes of C′3 thus far identified are functionally normal. In a kindred with members having one-half the normal concentration of C′3 inherited as an autosomal codominant trait, C′3 typing revealed that in affected individuals, only one allele is expressed.
In Vitro Studies on the Mechanism of Macrophage Migration Inhibition in Tuberculin Sensitivity
Authors: Heise E. R. , Han S. , Weiser R. S.
Published: December 2022

The mechanism of macrophage migration-inhibition was studied with alveolar macrophages obtained from BCG-sensitized guinea pigs. Sensitivity to migration-inhibition was conferred upon macrophages from normal guinea pigs or upon trypsinized macrophages from sensitized guinea pigs by incubation with either serum or heat eluates prepared from macrophages of BCG-sensitized animals. The migration of passively sensitized macrophages was inhibited only in the presence of specific antigen. Mixtures of PPD and immune serum or macrophage eluates were cytophilic for macrophages but were not demonstrably cytotoxic for mouse L cells. In contrast, supernatants from cultures of antigen-stimulated lymphocytes derived from sensitized guinea pigs were not strongly cytophilic for macrophages but were cytotoxic for L cells. Supernatants from similar cultures of macrophages were less active in inhibiting the migration of normal macrophages. Immunoglobulin was detected in the Sephadex G 200 fractions of macrophage eluates and immune sera which were active in the migration-inhibition test. On the basis of these results it is suggested that macrophage migration-inhibition may involve cytophilic Ab as well as a cytotoxic factor produced by lymphocytes.