bluuebunny/crossref_metadata_2025 huggingface dataset:
Agglutination by Antibody of Erythrocytes Sensitized by Virus Hemagglutinin
Authors: Lim K. A. , Pong W. S.
Published: January 2023

When goose erythrocytes are treated with HA of Japanese encephalitis, dengue or Langat viruses, at the optimum pH for hemagglutination, the washed erythrocytes are agglutinable by antibody at pH 7.6.

HA is rapidly adsorbed and the sensitized erythrocytes under optimum conditions of preparation may be stored for many days. Nonspecific inhibitor causes slipping of agglutination of sensitized erythrocytes at low serum dilutions. This can be avoided by treatment with kaolin although it is not essential to do so.

The sensitized erythrocyte agglutination test is at least as specific as the CF or HAI tests. Diagnostic tests on human sera suggest that the SEA test may have a higher degree of specificity especially if 1-day-old chick erythrocytes are used for preparing antigens.
Inhibition of Immediate and Delayed Hypersensitivity in the Rabbit by 6-Mercaptopurine
Authors: Borel Yves , Schwartz Robert
Published: January 2023

Six-mercaptopurine (6-MP) was shown to exert both central and peripheral actions on immune reactions. Its central effects were inhibition of humoral antibody formation and suppression of delayed hypersensitivity. The antimetabolite also blocked the peripheral manifestations of immunity (skin reactions to antigens) without affecting the immune status of the animal. These various actions of 6-MP were brought out under selected conditions of timing, dosage and mode of antigen administration. The processes leading to the development of delayed hypersensitivity were found to be very sensitive to 6-MP; a 4-day course of the drug suppressed this response without inhibiting humoral antibody production or inflammatory responses. The suppression of skin reactions in hyperimmunized rabbits was presumably due to an anti-inflammatory effect of 6-MP; inhibition of the local passive Arthus reaction by 6-MP was a function of the amount of antibody in the test serum. Leukopenia or inanition could not explain these actions of 6-MP.
A Serum Inhibitor in Animal and Human Sera of Bovine Enteroviruses
Authors: Klein Morton , Evans George , Deforest Adamadia , Kleger Bruce
Published: January 2023

A serum factor having neutralizing activity against bovine enteroviruses is described. It is significantly inactivated by trypsin, sodium periodate and neuraminidase, stable at 56°C for 30 min, and present in the sera of man and other species. Neutralizing activity is best demonstrated using a minimal viral challenge, at 37°C for a relatively long period of contact. The level of the inhibitor does not vary with age or illness. Part of the activity is associated with serum Fraction V. Although the neutralizing activity is relatively specific against viruses the inhibitor is widely reactive and combines with tissue homogenates and certain bacteria. The relationship of this inhibitor to other inhibitors is discussed.
The Relationship between Rheumatoid “Factor” and Serum Desoxyribonucleic Acid
Authors: Gray J. D.
Published: January 2023

A series of experiments undertaken to elucidate the identity of the rheumatoid “factor” present in the serum of rheumatoid arthritics have shown that this substance closely resembles desoxyribonucleic acid.

In vitro DNA appears to complex with a Cohn IV-4 globulin and a Cohn Fraction III globulin. The latter in very small amounts inhibits the ability of both rheumatoid factor and DNA to agglutinate sensitized sheep cells.

Electrophoretic patterns of normal and rheumatoid serum stained by the Fuelgen reaction demonstrates Fuelgen-positive material consisting of a γ tail, a band at β and a further small concentration in the α region. There is no detectable difference in the patterns given by either serum.

The concentration of DNA in serum measured by the diphenylamine reaction of a Schneider extract gives a range of 7 to 14.1 mg/100 ml. The results do not differ materially in either the rheumatoid or normal cases.
The Influence of Degree of Aggregation and Virus Quality on the Plaque Titer of Aggregated Vaccinia Virus
Authors: Galasso G. J. , Sharp John , Sharp D. G.
Published: January 2023

The degree of aggregation among the particles of a suspension of virus is one of the parameters upon which the plaque titer depends. Careful workers have always recognized this fact and they have employed various means to insure maximum dispersion of virus on which critical plaque titrations were to be made. Still, we are not aware of any published work which sets out clearly in experimental or theoretical form the relationship between plaque titer and degree of particle aggregation. Our first effort (1) in this direction provided evidence that vaccinia virus, which was released from infected L cells by the freeze-thaw procedure, as well as virus that had been pelleted one or more times in a centrifuge, was highly aggregated. It showed that the plaque titer of such preparations could be increased by treatment of the virus with 9-kc sonic waves.
Immunity to Transplantable Tumors Following Viral Oncolysis
Authors: Lindenmann J.
Published: January 2023

The intraperitoneal LD50 of an Ehrlich ascites tumor (EA) for inbred A2G mice was close to 10 cells per mouse. Mice which had been inoculated with 106 EA cells and 6 days later with WSA influenza virus underwent oncolysis and were subsequently resistant to challenge with 106 to 107 EA cells (postoncolytic immunity). This resistance could be transferred to normal A2G mice with 5 × 106 to 5 × 107 spleen cells (adoptive transfer) or with plasma, serum or ascitic fluid from immune mice. Postoncolytic EA immune sera from A2G mice were protective only when tested in A2G mice and not when tested in ICR mice.

Sera which were protective in vivo agglutinated EA cells in vitro. Upon fractionation of hyperimmune serum by sucrose gradient ultracentrifugation or by column electrophoresis the agglutinin titer in vitro of the various fractions paralleled their protective power in vivo; both seemed to be associated with 7 S γ-globulin.
Duration of Some Cutaneous Hypersensitivities in Mice
Authors: Crowle Alfred J. , Hu C. C.
Published: January 2023

The courses of development, maintenance, and eventual loss of immediate (humoral) and delayed (cellular) skin hypersensitivities in mice to chicken ovalbumin, bovine and human serum albumins, and tuberculoprotein as well as delayed hypersensitivity to 1-chloro-2,4-dinitrobenzene were followed.

The durations of primary hypersensitivities to the two serum albumins and 1-chloro-2,4-dinitrobenzene were easily determined and were similar, extending over approximately 12 to 16 weeks. Decline of primary hypersensitivity to the serum albumins was followed by resurgence of hypersensitivity, apparently as a secondary response to intrinsic antigenic stimulation from the original depots of emulsified antigen. The time spans of primary hypersensitivities to ovalbumin and tuberculoprotein could not be determined, because these hypersensitivities merged with secondary reactivities due to such internal restimulation.

Various data obtained suggest that the proteins used can be arranged in the following decreasing order of allergenicity in CF1 mice: ovalbumin, tuberculoprotein, bovine serum albumin, human serum albumin. Distinctions in relative antigenicity were especially obvious in capabilities for inducing delayed hypersensitivity, the last antigen being unable to do so in half the mice tested unless injected in Freund's complete adjuvant. The significance of these findings in the comparative mechanisms of immediate and delayed hypersensitization in mice and guinea pigs is discussed.
Antinuclear Factor in Mice
Authors: Norins Leslie C. , Holmes Margaret C.
Published: January 2023

The natural incidence of antinuclear factor (ANF) has been examined in several mouse strains using a standard fluorescent anti-globulin technique. NZB mice with autoimmune disease had an ANF incidence of about 40%, whereas the normal strains C3H and C57/Bl showed delayed onset of about 15% incidence. F1 (NZB × C3H) showed a distinctive sex difference, females eventually showing about the NZB incidence and males the C3H incidence. The apparently normal Hall Institute “outbred” mice showed a steady increase to an ANF incidence of about 85%. The murine ANF appeared to be all or mainly a 7 S γ-globulin with nucleoprotein specificity. In NZB mice, an increased ANF incidence was associated with severe renal disease, early splenectomy in males, partial or complete thymectomy, and receipt of a thymus graft, whereas a decreased ANF incidence was associated with late splenectomy in females.
The Blood Groups of Mink
Authors: Saison Ruth
Published: January 2023

An A-like antigen on the red blood cells of some mink can be detected by the use of high titer, incomplete pig anti-A sera. This antigen is not present on the red cells at birth but is acquired by the kits between 8 and 15 weeks of age.

It was not possible to determine by coating experiments whether the A antigen is a soluble serum substance which coats the cells. However, the inhibition test demonstrated that A-like substance is present in the serum of group A mink.

Absorption of pig anti-A serum with mink A cells did not remove all the antibodies to pig group A cells from this serum. This would indicate that the mink A antigen resembles the A of pigs but does not wholly conform to the same configuration. Absorption with mink A cells removes only those antibodies which react to the portion of the pig A antigen present on mink A cells.

By the use of pig anti-A serum, mink red blood cells can be classified as group A or group O. The expression of these two characters is believed to be controlled by a pair of allelic genes, giving rise to two phenotypes, A and O, and three genotypes, AA, AO and OO. No antibody to either of these antigens has been found in the sera of mink lacking the corresponding antigen.
Viral Leukocyte Interrelationships
Authors: Nahmias André J. , Kibrick Sidney , Rosan Robert C.
Published: January 2023

The replication of herpes simplex virus in human leukocyte cultures has been demonstrated in several ways. A consistent decrease in viral titer was observed over the first few days, usually followed by an increase in titer. Virus was demonstrable in such cultures for as long as 26 days. A viral inoculum of at least 103 TCD50 per 0.2 ml of culture was found necessary to initiate infection.

Viral replication did not occur in the leukocyte cultures in the absence of phytohemagglutinin. However, viral multiplication was not affected by certain variations in technique of leukocyte culture preparation or incubation, or by age of the culture at time of viral inoculation.

The kinetics of herpes simplex virus replication in human leukocyte cultures are discussed.
Distribution and Properties of Anaphylactic and Venom-Induced Slow-Reacting-Substance and Histamine in Guinea Pigs
Authors: Middleton Elliott , Phillips Gerald B.
Published: January 2023

A striking parallel between the capacity of specific antigen and cobra venom to give rise to slow-reacting-substance activity in tissues of sensitized guinea pigs was demonstrated. By either method of treatment lung was the major source of slow-reacting-substance. Aorta, ileum, spleen and uterus showed considerably less capacity to form slow-reacting-substance. Antigen and venom showed significant differences in their ability to cause histamine release from various tissues. Both materials caused histamine release from lung, but venom produced considerably more histamine release than antigen from heart, kidney and diaphragm.

Of several tissue lipid extracts examined, only lung lipid extract produced SRS on treatment with venom. Typical SRS activity was found to be present in untreated lipid extracts of brain and small intestine.

Histamine was found in lipid extracts of lung and was dialyzable.

Anaphylactic SRS was not dialyzable until it had been extracted into 80% ethanol in water. SRS formed from chopped lung treated with venom, however, was found to be dialyzable without extraction into ethanol. On the other hand, SRS prepared from lung lipid extract treated with venom was not dialyzable before or after ethanol extraction.

The distribution of ethanol extracted anaphylactic SRS between ether and water at different pH values showed that it was not completely extractable into ether even at pH 2 to 3. Gasliquid chromatography of anaphylactic SRS preparations following methanolysis did not show a pattern of fatty acids different from control samples. On the basis of these observations anaphylactic SRS does not appear to be a fatty acid.

Four metabolites of histamine, N-acetylhistamine, imidazole-acetic acid, methylhistamine and methylimidazole-acetic acid, as well as histamine incubated with venom, failed to show SRS activity.
Neutralizing Activity of Fragments Obtained by Papain Digestion of Viral Antibody
Authors: Cremer Natalie E. , Riggs John L. , Fujimoto Frances Y. , Hagens Shirley J. , Ota Margaret I. , Lennette Edwin H.
Published: January 2023

When pure by Ouchterlony and immunoelectrophoretic analyses, 3.5 S Fractions I and II from anti-poliovirus γ-globulin and anti-WEE virus γ-globulin neutralized their respective viruses in the metabolic inhibition test, while 3.5 S crystalline Fractions III with trace contamination of Fraction II gave minimal (with poliovirus) or no neutralization (WEE virus).

Pure, 3.5 S Fractions I and II from anti-WEE virus γ-globulin did not give significant neutralization of WEE virus in the mouse, while 3.5 S Fraction III with trace contamination of Fraction II gave significant neutralization (NI ≧ 2).
An Anti-Mycobacterial Principle of Peritoneal Mononuclear Cells
Authors: Ramseier Hansruedy , Suter Emanuel
Published: January 2023

The anti-mycobacterial substance found in guinea pig peritoneal mononuclear cells is heat labile. Heating at 56°C for 30 min at pH 6.3 destroyed its activity completely.

It was found that peritoneal mononuclear cells contained approximately 0.2 × 10-6 µg of lysozyme/cell. This observation, together with the facts that lysozyme is heat stable and that only relatively high concentrations of the enzyme inhibit virulent tubercle bacilli, led to the conclusion that the inhibitory material is distinct from lysozyme.

The anti-mycobacterial activity was shown to be associated with the nuclear cell fraction. Nuclei of normal and immune cells inhibited tubercle bacilli to about the same degree. The activity of the nuclear fraction proved to be heat sensitive.

The anti-mycobacterial activity of nuclear preparations was susceptible to a variety of hydrolases. Observations on the mode of action of the inhibitor suggest that it is bactericidal rather than bacteriostatic.
The Immunologic Behavior of Baby Pigs
Authors: Locke R. F. , Segre D. , Myers W. L.
Published: January 2023

Low molecular weight (6.6S) diphtheria and tetanus antibodies of ovine origin were absorbed relatively efficiently through the intestine of newborn, colostrum-deprived pigs, whereas high molecular weight (18S) antibodies were absorbed poorly or not at all.

Antibodies contained in 750 mg of purified 6.6S ovine globulin, administered orally and intraperitoneally, were eliminated from the circulation of newborn pigs at a constant exponential rate. The 6.6S globulin did not stimulate the production of anti-sheep globulin by the recipient pigs. Intraperitoneal administration of 750 mg of crude ovine globulin, containing antibodies in both the 6.6S and 18S fractions, resulted in an immune-type elimination of the passive antibodies by the recipient newborn pigs. This treatment resulted in the production of anti-sheep globulin by the recipient pigs.

Dilute 6.6S ovine antitoxin, premixed with toxoid and injected intraperitoneally into 3-week-old, colostrum-deprived pigs, induced the production of relatively large quantities of tetanus and diphtheria antibodies by the recipient pigs. Dilute 18S antitoxin plus toxoid, under the same circumstances, failed to stimulate diphtheria antibody formation but resulted in the production of high titers of tetanus antibodies.
Studies of the L Chains of Guinea Pig and Rat Anti-2,4-Dinitrophenyl Antibodies
Authors: Benacerraf Baruj , Merryman Carmen , Binaghi Ruben A.
Published: January 2023

The electrophoretic patterns in starch gel in 8 M urea of the L chains of dissociated guinea pig and rat anti-DNP antibodies were investigated. Guinea pig anti-DNP antibodies isolated from weekly bleedings of individual animals or from pooled guinea pig antisera yielded 5 L chain bands in urea starch gel. Rat anti-DNP antibodies also showed bands in the zone of L chain migration, but their pattern differed from that of guinea pig antibodies.

Guinea pig γ1 and γ2 anti-DNP antibodies yielded the same 5 L chain bands.

A study of the fractions of guinea pig or rat anti-DNP antibodies separated by zone electrophoresis at pH 8.6 revealed that different L chains are obtained from antibodies with different electrophoretic mobilities.
Identification of Hemagglutinins in Chicken Blood Sera Following Homografting
Authors: Gleason Ray E. , Fanguy Roy C.
Published: January 2023

A study of hemagglutinins in blood sera following skin homografting was made using 245 Single Comb White Leghorn chicks from a partially inbred population. Homografts were made between full-sibs which were either compatible or incompatible for alleles of the B, D or E blood group system. Donor-host incompatibility at the B and E blood group loci resulted in a significantly greater number of host birds which produced donor-cell hemagglutinins than when donor and host were of compatible blood type. No such increase was noted when donor and host were incompatible at the D locus.

Hemagglutinins specific for the B2, B7, B8, E1 and E2 antigens were identified in host sera following skin homografting. There was some indication that specific D system antibodies are also produced following skin homografting.

Data from host birds showing nonspecific hemagglutinins indicate that there is no relationship between these agglutinins and skin graft survival.

Hemagglutinins resulting from skin homografts were found to form a weaker antigen-antibody complex with erythrocyte antigens than do hemagglutinins resulting from isoimmunizations with erythrocytes. This suggests the skin tissue antigens are similar to but not identical with the red cell antigens.

Repeated skin homografts from the same donor appear to result in increased antibody titer as evidenced by increased mean red cell sediment pattern scores following the first two grafts. After this, the titer apparently levels off and shows a slight decline after rejection of the fourth graft.
Interaction of Rickettsiae and Phagocytic Host Cells
Authors: Wisseman Charles L. , Tabor Harry
Published: January 2023

In contrast to the focal perivascular collections of mononuclear cells which constitute the classical basic lesion seen in persons dying of typhus fevers, the initial cellular response in man to the presence of typhus rickettsiae, as revealed by the skin window technique, consisted of a typical acute inflammatory reaction. Polymorphonuclear leukocytes appeared within 1.5 hr after introduction of the organisms and increased in numbers during the first 24 hr. Although mononuclear cells began to appear in the lesions between 6 and 12 hr, the polymorphonuclear leukocyte remained the dominant cell throughout the 24-hr observation period. The main difference between the responses of susceptible and immune subjects lay in the more intense polymorphonuclear reaction in the immune subjects. In vivo phagocytosis of living and dead rickettsiae was demonstrable with both polymorphonuclear and larger mononuclear cells in immune as well as nonimmune subjects. The experimental conditions employed reproduced closely the conditions which obtain at the time of natural infection. The implications of these findings with regard to host defense reactions against typhus rickettsiae are discussed.
Biologic Activity of Soluble Antigen-Antibody Complexes
Authors: Ishizaka Kimishige , Ishizaka Teruko , Banovitz Jay
Published: January 2023

Soluble antigen-antibody complexes composed of ε, α-DNP-L-lysine and rabbit anti-DNP antibody induced increased permeability of guinea pig skin capillaries, whereas ε-DNP-L-lysine did not form skin reactive complexes with the same antibody. The divalent hapten-antibody complexes, but not the monovalent hapten-antibody complexes, fixed guinea pig complement. An equimolecular mixture of ε,α-DNP-L-lysine with antibody contained a 9.7 S component, which was lacking in an ε-DNP-lysine antibody mixture. By increasing the hapten/antibody ratio in the ε,α-DNP-lysine-antibody mixture, both the 9.7 S component and the biologic activities, such as skin reactivity and complement-fixing properties, decreased. Essential properties of antigen and minimum size of antigen-antibody complexes for the induction of the biologic activities were discussed.
Studies on Species Specificity
Authors: Milgrom Felix , Tuggac Z. Maide , Witebsky Ernest
Published: January 2023

Species-specific antigens were described which are present in fractions of mammalian tissues prepared by extraction at 100°C. followed by precipitation by ethanol (BE fractions). Interspecies cross-reactions were rather weak; they were more pronounced in closely related species, e.g., man and Rhesus monkey, than in distant species.

Rabbit antisera to BE fractions of human, bovine, porcine and equine origin were used as reagents for identification of the species origin of various blood, urine and tissue specimens. Specimens to be studied were at first processed to obtain the BE fractions, and then they were tested against the antisera. Correct identification of the species origin could be made in testing autoclaved blood, decayed tissues and blood, and processed food products. The antigens under investigation were not destroyed by digestive enzymes and could be demonstrated in the feces of rats fed with bovine and porcine liver.

The possible application of the described methods in forensic medicine was discussed.
The Specificity of the Cytolytic Effect of Sensitized Lymphoid Cells in Vitro
Authors: Rosenau Werner , Moon Henry D.
Published: January 2023

BALB/c mice were inoculated with L cells (strain 2071), C3H, or C57BL mouse spleen cells. The effect of splenic lymphoid cells of these BALB/c mice on various cell lines was studied in vitro. Cell lines derived from the same mouse strain as the cells used for sensitization were lysed by the sensitized lymphoid cells. Cell lines derived from other mouse strains or heterologous cells in general were not destroyed. The studies provided further evidence of the specificity of cytolytic reaction between lymphoid cells and homologous target cells.
Cellular Activities in Hypersensitive Reactions
Authors: Rauch Helene C. , Raffel Sidney
Published: January 2023

A basic protein of small molecular weight isolated from bovine nerve tissue induces allergic encephalomyelitis in guinea pigs when injected in small amount in Freund's adjuvant. This protein has been shown to reside in the myelin sheaths of the animal of origin as well as of guinea pigs and man. The responses which follow the administration of nerve tissue to guinea pigs include a specific reactivity of lymphocytes of nodes and spleen for this purified antigen and delayed skin reactivity to it, in the absence of circulating antibodies detectable by ordinary serologic methods. The relationship of lymphocytic and skin reactivity and of disease induction to a purified protein antigen of the myelin sheath strongly suggests a contingency of the lesions upon the reactivity of the cells. However, the intervention of cell-bound or cell-produced antibodies cannot yet be excluded as a basis for the pathologic process.
Effects of the Rheumatoid Factor and Antigen-Antibody Complexes on the Vessels of the Rat Mesentery
Authors: Baum John , Stastny Peter , Ziff Morris
Published: January 2023

The localization and vascular effects of rheumatoid factor, and of antigen-antibody complexes, have been studied in the exposed, living, rat mesentery following intravenous injection of fluoresceinated and unfluoresceinated preparations of these agents, both alone and in combination. Following injection of rheumatoid euglobulin, thrombosis and hemorrhage were observed in the exposed mesentery. Following injection of a chromatographically separated, fluoresceinated 19 S γ-globulin fraction of rheumatoid serum, the vascular changes described were accompanied by a visible layer of fluorescence along the intimal surface of vessel walls. These changes did not occur after injection of a fluoresceinated preparation of Waldenström's macroglobulin.

Although soluble antigen-antibody complexes produced no gross vascular changes, a persistent layer of fluorescence was observed along the intimal surface of vessel walls after injection of fluorescent preparations of such complexes. This localization of fluorescence was prevented by prior injection of normal euglobulin, but not rheumatoid euglobulin.

When rheumatoid euglobulin preparations and fluorescent antigen-antibody complexes were injected together, the injected fluorescent complexes appeared to be bound in the resulting thrombus, as indicated by fluorescence of the thrombus. Fluorescence due to complexes was not observed in a thrombus produced by application of local mechanical pressure on a vessel.

The results described indicate that soluble antigen-antibody complexes and rheumatoid factor, when injected either alone or in combination, are localized at the intimal surface of the vessels of the exposed mesentery. Localization of the complexes is blocked by euglobulin obtained from normal serum but not by rheumatoid euglobulin. These findings suggest that rheumatoid factor and antigen-antibody complexes may play a role in the development of the vascular abnormalities observed in some patients with rheumatoid arthritis.
The Nature of Antibodies Following Experimental Arbovirus Infection in Guinea Pigs
Authors: Bellanti Joseph A. , Russ Sudie B. , Holmes George E. , Buescher Edward L.
Published: January 2023

Following experimental infection of guinea pigs with Japanese encephalitis and Russian spring-summer encephalitis viruses, complement-fixing (CF), hemagglutination-inhibiting (HI) and neutralizing (N) antibodies are regularly formed by the 7th to the 10th days. Characterization of these antibodies at various times over a 4-month period revealed that CF antibody was invariably associated with a 7 S γ2-globulin; there was no evidence of an early 19 S complement-fixing antibody. The earliest detectable HI and N antibodies at 7 to 10 days were largely associated with a 19 S γ-globulin; after 14 days, these activities were found in the 7 S γ1 and γ2-globulin moieties.

These data are interpreted to indicate that following experimental infection with these arboviruses, antibody is produced with different physicochemical properties which may account for the temporal dissociation of antibody responses seen following infection.
The Nature of the Antigen-Antibody Complexes Which Initiate Anaphylactic Reactions
Authors: Levine Bernard B.
Published: January 2023

Several nontoxic univalent benzylpenicilloyl (BPO) haptens, a toxic univalent BPO hapten, a divalent BPO hapten and a multivalent BPO hapten were quantitatively compared in regard to their abilities to evoke passive cutaneous anaphylactic (PCA) reactions in guinea pigs sensitized by intravenous injection of rabbit anti-BPO sera.

It was found that the four nontoxic univalent haptens were incapable of evoking PCA, that the toxic univalent hapten could evoke only faint PCA reactions, and that the divalent and multivalent haptens evoked equally intense PCA reactions in animals sensitized with antibodies of comparatively high binding affinities, whereas the divalent hapten was a less effective elicitor than the multivalent hapten in animals sensitized with antibodies of comparatively low binding affinities. Evidence was obtained which demonstrates that the divalent hapten did indeed function as a divalent hapten, and not as a toxic univalent or as an aggregated multivalent hapten.

These results are interpreted as indicating that, at least in this system, for the effective elicitation of PCA reactions mediated by comparatively high binding affinity antibodies, the elicitor must contain at least two haptenic groups per molecule. For effective elicitation of PCA reactions mediated by antibodies of comparatively low binding affinity, the elicitor must contain more than two (possibly in the range of three to six) haptenic groups per molecule.
Immunization of Mice to Coccidioides Immitis: Dose, Regimen and Spherulation Stage of Killed Spherule Vaccines
Authors: Levine H. B. , Kong Yi-Chi M. , Smith C. E.
Published: January 2023

Mice immunized intramuscularly with killed spherules of Coccidioides immitis showed an intranasal LD50 > 3000 arthrospores compared to approximately 50 arthrospores in control animals. The immune response was dependent upon factors pertaining to both the host and the vaccine. As early as 7 days postvaccination, the host survived challenge with 85 arthrospores. However, an additional 19 days were required for the induction of immunity to 1000 arthrospores and the development of optimum immunity required more than 30 days. Removal of the footpad vaccination site prior to 30 days impaired the immune response. The extent of the response to intramuscular vaccination was dose-dependent over a 4-fold range and immunity was augmented by administering the vaccine to multiple sites. Injection of baker's yeast resulted in an increased survival of arthrospore-challenged mice but, compared to specific immunization, the protection was slight.

The magnitude of the immune response was also influenced by the stage of spherulation. Vaccines prepared from mature spherules were superior to those prepared from immature spherules or endospores. Evidently the spherule walls, previously shown to be the primary locus of the immunogens, increased in immunogenicity concomitantly with maturation of the spherules.

Immunity induced by spherules of an old laboratory stock culture and that induced by spherules of a newly isolated strain were comparable in mice challenged intranasally with arthrospores of the homologous or heterologous strains.
The Relative Heat Stability of Antibodies in Chromatographic Fractions of Rabbit Antisera to Various Antigens
Authors: Pike Robert M. , Schulze Mary Louise
Published: January 2023

Chromatographic fractions containing, on the one hand, predominantly 7 S, mercaptoethanolresistant antibody and on the other, 19 S, mercaptoethanol-sensitive antibody were prepared from rabbit antisera to the H and O antigens of Salmonella typhosa, Leptospira grippotyphosa, bovine serum albumin, and sheep erythrocytes. Agglutinins in the 7 S fractions were found to be more resistant to inactivation by heat than the agglutinins in the 19 S fractions. A similar difference in resistance to heat was demonstrated for the hemolytic activity of 7 S and 19 S antibodies to sheep erythrocytes and to the somatic antigens of S. typhosa. The observed differences in heat inactivation could not be accounted for by the formation of complexes between antibody and other serum proteins as a result of heating. The relative heat resistance of 7 S antibody as compared to 19 S appears to explain the well known difference in the susceptibility of somatic and flagellar agglutinins to inactivation by heat.
Induction of Mitosis in Macrophages by Endotoxin
Authors: Forbes Ian J.
Published: January 2023

A subcutaneous dose of 12 µg of lipopolysaccharide from Escherichia coli BV caused a peritoneal reaction which culminated in mitosis of free macrophages in the peritoneal fluid. The mitosis was preceded by a pronounced fall in the number of free macrophages. The appearances suggested, but did not prove, that macrophages were irreversibly damaged by the endotoxin or by products of its metabolism, and that new macrophages arose by transformation from lymphocytes and subsequent mitosis.
Extent of Antigenic Variation of A2 Influenza Viruses from Prototype Strains
Authors: Weinberger H. L. , Buescher E. L. , Edwards V. M.
Published: January 2023

Application of the cell culture neutralization (N) test demonstrates that representative strains of the 1963 A2 variant are antigenically homogeneous. Reaction patterns of individual antisera clearly show the differences between the 1957 strain and the current family of A2 viruses. None of these differences could be demonstrated by hemagglutination-inhibiting (HI) test alone. The analysis of the patterns of incidence of N antibody in recruit populations lends laboratory support to the epidemiologic descriptions of the progression of the 1963 epidemic across the United States. Despite the presence of considerable N antibody to both the 1957 and 1963 strains of virus, 47 cases of A2 virus infection were confirmed in 1963. The tenuous correlation between humoral antibody to influenza and immunity has been discussed.
Quantitative Determination of Serum Immunoglobulins in Antibody-Agar Plates
Authors: Fahey John L. , McKelvey Eugene M.
Published: January 2023

The antibody in agar plate test has proved valuable for the quantitative measurement of individual serum immunoglobulins. With this technique, specific antiserum is mixed uniformly in an agar gel plate. Antigen containing solutions are placed in small antigen wells cut in the agar. A concentric ring of antigen: antibody precipitate forms around the antigen well. By graphically comparing the ring diameters with those of appropriate standards, the protein concentration of the test sera can be determined. The probable error in measurement of normal serum immunoglobulins is ±10%. This procedure has been used to quantify protein concentrations as low as 0.003 mg/ml. Multiple samples can be easily tested and less than 0.1 ml of sample is required.

The mean immunoglobulin levels in 20 normal human sera were found to be 12.4 mg/ml for IgG (7 S γ2-globulins); 2.8 mg/ml for IgA (γ1A or β2A-globulins) and 1.23 mg/ml for the IgM (18 S γ1M-globulins). Type K (I) and Type L (II) immunoglobulins were similarly determined. The results by the antibody-agar plate method are similar to those obtained by the isotopic immune inhibition technique, except for the serum IgA and Type K (I) and Type L (II) immunoglobulin levels. With each of these proteins the values obtained by the isotopic immune inhibition test are higher than those found by the antibody-agar plate test. The basis for this difference is discussed.
Hydrolytic Enzymes of Rabbit Mononuclear Exudate Cells
Authors: Carson Margaret E. , Dannenberg Arthur M.
Published: January 2023

Oil-induced peritoneal mononuclear cells from rabbits were assayed for lysozyme with Sarcina lutea. They had about the same activity per cell as glycogen-induced peritoneal polymorphonuclears and about one seventh the activity of pulmonary alveolar macrophages. Rabbits inbred for resistance and susceptibility to tuberculosis showed no consistent differences in the lysozyme activities of their mononuclears (MN). However, the lysozyme activities of MN from rabbits immunized by active tuberculosis were elevated about 1.4 times. Previous studies have indicated that their MN lipase, proteases and esterases were not elevated. The elevation of lysozyme may be in part responsible for the increased capacity of MN in immunized animals to destroy the tubercle bacillus.
The Specificity of Blood Group A-B Cross-Reacting Antibody
Authors: Schiffman Gerald , Howe Calderon
Published: January 2023

A subject of group O was found to produce A-B cross-reacting antibody in response to the injection of a preparation of blood group B substance free of blood group A activity. Both anti-A and anti-B could be precipitated from the serum with either blood group A or B substance, and precipitation of either A or B substance could be inhibited by dialyzable oligosaccharides from either antigen. Evidence is presented to indicate that the specificity of the cross-reacting antibody is directed against structural features common to the oligosaccharides which determine blood group A and B specificity. The possible antigenic sites involved in the cross-reaction are discussed.
Prevention of Immunologic Tolerance by Lymphoid Cell Transplants
Authors: Friedman Herman
Published: January 2023

Transfer of spleen cell suspensions from normal neonatal donor NIH mice into newborn recipient NIH mice injected with Shigella soluble antigen (SSA) prevents the establishment of immunologic unresponsiveness to Shigella. The optimal time interval between injection of cell suspension and antigen for maximum interference of tolerance was found to be less than 48 hr after birth. Transfer of cells 4 to 7 days after neonatal injection of antigen resulted in partial interference. Transfer of cells 14 days or longer after birth had no detectable effect. Transfer of large numbers of spleen cell suspensions was found to be more effective in interfering with tolerance than transfer of smaller numbers of cells. Intravenous and intraperitoneal administration of cell suspensions were found to be the most effective routes for preventing tolerance induced by the i.p. injection of Shigella antigen. Transfer of lymph node cell suspensions was nearly as effective as transfer of spleen cell suspensions. Thymus cells were also capable of preventing tolerance, but were not as effective as spleen cells. Transfer of peritoneal exudate cells was much less effective, whereas buffy coat leukocytes and bone marrow cells were essentially negative. Injection of larger concentrations of Shigella antigen necessitated transfer of larger numbers of spleen cells for comparable interference of tolerance. Transfer of spleen cells from young mice, 1 to 21 days of age, which were themselves tolerant to Shigella following injection of SSA at birth, to other newborn mice receiving SSA also resulted in prevention of tolerance. These observations suggest that transfer of various lymphoid cell suspensions into SSA-injected newborn mice may interfere with establishment of unresponsiveness by increasing the ratio of available lymphoid cells to antigen, and thus reduce the concentration of SSA per cell below a postulated threshold level necessary for establishing and maintaining tolerance.
Effect of Ionic Strength on the Reaction between Nucleoprotein and Antinuclear Factors
Authors: Laffin Robert J. , Baumstark John S. , McCarthy John S.
Published: January 2023

It has been demonstrated that at low ionic strength nucleoprotein removes greater quantities of antinuclear factors from serum. These factors can be dissociated from nucleoprotein and obtained in fairly pure form by increasing the ionic strength of the system.

A study of these preparations has showed that they contain principally 6.6 S γ-globulin and lesser amounts of β2-macroglobulin and β2A-globulin. Antinuclear factor (ANF) activity has been demonstrated by positive indirect fluorescent antibody tests.

In a random sample of 10 normal sera, 6.6 S γ-globulin-ANF has been detected in levels ranging from 0.51 to 0.73 mg/ml.
Enterovirus Antibodies in Mouse Ascitic Fluids after Immunization
Authors: Fabiyi Akinyele , Wenner Herbert A.
Published: January 2023

High-titered complement-fixing (CF) antibodies to coxsackieviruses A3, 5, 19 and 21 have been produced in mouse ascitic fluids. Ascites was induced by a series of injections of antigen-adjuvant (complete Freund's) mixture followed by Ehrlich's ascites tumor cells. The CF antibodies in the mouse ascitic fluids were of the same level as, and sometimes higher than, those in the sera from the same animal. Neutralizing antibodies in mouse ascitic fluid for coxsackievirus A21 were less potent than those obtained in the homologous monkey antiserum. Mouse immune ascitic fluids were found to be very stable in antibody level if kept frozen at -20°C, but repeated freezing and thawing produced considerable loss in CF antibody titers.
The Immunogenicity of Hapten-Polylysine Conjugates
Authors: Parker C. W. , Thiel J. A. , Mitchell S.
Published: January 2023

The immunogenicity of L and D polylysines substituted with penicilloyl, dinitrophenyl and tosyl groups has been evaluated in random-bred Hartley strain guinea pigs. The L polylysine derivatives produced an immunologic response in about 20% of animals. Of a total of 106 guinea pigs immunized with D polylysine conjugates, in no instance was there evidence for antibody formation.
β1C-Globulin: an “Acute Phase” Serum Reactant of Human Serum
Authors: Hornung Maria , Arquembourg Renee Cornille
Published: January 2023

Acute phase human serum from various sources was found to contain elevated levels of β1C-globulin. Experiments designed to establish the relationship between this globulin and complement showed that, although β1C-globulin had physicochemical characteristics associated with both C′3 and C′4, serum lacking this globulin showed undiminished hemolytic complement activity. The serum fraction used for the isolation of C′4 contained no β1C, and similarly some serum fractions having concentrated C′3 activity (as this is customarily defined) contained no β1C. Neither red cells of other species nor incompatible human red cells removed this globulin from normal human serum. However, β1C-globulin was selectively affected by antigen-antibody complexes, Mycobacterium tuberculosis, Neisseria meningitidis and cortisone. The results suggest that β1C-globulin plays a part in physiologic response to stress.
Inhibition of Antibody Formation by Homologous Tissue Factors
Authors: Thompson Richard , Fishel Charles W.
Published: January 2023

Volumes of normal mouse tissue extracts, containing 40 mg of protein, when injected intraperitoneally into mice 24 hr before the intraperitoneal injection of sheep red blood cells, significantly inhibited the production of hemolysins. Fifty per cent ammonium sulfate selectively precipitated and concentrated (2 ×) the active factor(s). Acetone precipitated the active factor(s).

In control experiments, in which bovine serum albumin, bovine γ-globulin, human fibrinogen and polystyrene particles of several sizes were injected, in amounts equivalent to or greater than the effective amounts of tissue factors, little inhibition of hemolysin formation was produced. Trypsin (crystallized 0.3 mg; 1–300 1.5 mg) produced significant inhibition. Crystallized lysozyme produced significant inhibition but was somewhat less active than equivalent amounts of tissue precipitates.

Tissue extracts and their precipitates produced no inhibition when injected at any time after the antigen, nor did trypsin or lysozyme. Bovine serum albumin, bovine γ-globulin and polystyrene particles sometimes produced similar insignificant amounts of inhibition when given after the antigen as before it.

Normal mouse serum and 50% ammonium sulfate precipitates of serum produced no inhibition.

The inhibiting activity of tissue extracts was destroyed by exposure to 56°C but not to 37°C.
Reactions of Human Sera with Mammalian Cell Cultures
Authors: Kano Kyoichi , Milgrom Felix , Barron Almen L. , Witebsky Ernest
Published: January 2023

The mixed agglutination reaction with kidney cell cultures was employed to study pathologic and normal human sera. Positive results were obtained with 29 of 88 sera from patients with viral infections and with 6 of 30 sera from patients with bacterial infections. Only 1 of 65 normal sera gave a weak reaction. An increase of the reaction titer in the course of virus disease was observed in all of 10 patients whose sera obtained early and late in the disease were tested. Reactions with cell cultures of bovine kidney were in general much stronger than reactions with kidney cultures of other species origin.

The possibility was discussed that the serum factor under study is an antibody whose production was stimulated by antigens which were exposed or created in a patient's own tissues as a result of a morbid process.
Studies on the Adjuvant Action of Bacterial Endotoxins on Antibody Formation
Authors: Merritt Katharine , Johnson Arthur G.
Published: January 2023

Experiments designed to test the hypothesis that the adjuvant action of endotoxins might be mediated through cell damage, release of nucleic acids, and subsequent stimulation of division of potential antibody forming cells, are reported. When given to the inbred mouse, BALB strain, with, or up to 14 hr after, a single injection of bovine γ-globulin (BGG), 5 fluoro-2-deoxyuridine (FUDR) enhanced the antibody response. In contrast, FUDR, given 18 hr or more after antigen, inhibited the synthesis of antibody, unless endotoxin had been given with the antigen. In the latter instance, the antibody response was not only permitted, but accentuated.

The postulated intermediates, nucleic acids, were shown to decrease the induction period and enhance the level of anti-BGG when given with antigen. Digestion of the nucleic acids with nucleases did not affect their adjuvant action unless low molecular weight products were removed by dialysis. The latter, when concentrated from the dialysate by lyophilization, were shown to have retained adjuvant activity.
Pseudoglobulin Rheumatoid Factors
Authors: Heimer Ralph , Nosenzo Carlo J.
Published: January 2023

Although the rheumatoid factors (RF) are believed to be relatively insoluble in dilute salt solutions, considerable RF activity in pseudoglobulin fractions was encountered on examination of certain sera of persons having rheumatoid arthritis. Evidence was furnished that pseudoglobulin RF, rather than being laboratory artifacts, represent discrete molecular species.

Pseudoglobulin RF were isolated from a number of sera and shown to resemble euglobulin RF with respect to their belonging to the γ1M-immunoglobulin class and with respect to a number of physicochemical parameters, including behavior on ion-exchange chromatography and sedimentation coefficient. Two of the sera examined contained unusual RF, which sedimented considerably more slowly than the usual 19 S globulins, lacking also the antigenic characteristics of γ1M-globulins. One of the serum samples contained one or two RF which were neither related to γ1M- or γ2-globulins, withstanding reduction by mercaptoethanol without loss of biologic activity.

On direct comparison of pseudoglobulin RF and euglobulin RF of the γ1M-globulin type from the serum of a person with Waldenstrom's macroglobulinemia, no difference could be detected in their immunologic and serologic behavior. The euglobulin RF, however, appeared to differ some-what from its pseudoglobulin counterpart with respect to sedimentation coefficient, aggregative behavior and amino acid content.
The Suppression of Anti-Bovine Serum Albumin Production in Rabbits by Acriflavine Hydrochloride N. F.
Authors: Farr Richard S. , Samuelson Joel S. , Stewart P. Brian
Published: January 2023

The primary immune response of rabbits was greatly suppressed by acriflavine HCl N.F. given 2 days before and continued for 13 days after the i.v. injection of bovine serum albumin (BSA). Two such courses of acriflavine HCl N.F. and BSA induced a degree of immune paralysis to subsequent injections of BSA. Acriflavine HCl N.F. started 10 min after the injection of antigen also depressed the immune response but was not as effective as when acriflavine was given prior to the antigen. Acriflavine HCl N.F. treatment in the dosage of 4 mg/kg for 7 days had minimal effect upon the secondary immune response once a primary response was established in the absence of acriflavine. In contrast to other immunosuppressant agents, the limiting toxicity of acriflavine HCl N.F. was not caused by apparent damage to granulopoiesis and lymphopoiesis. Serum γ-globulin levels were also unaltered. Rabbits given immunosuppressant doses of acriflavine HCl N.F. appeared healthy except for a slight elevation in the blood urea nitrogen and a slight depression in the hematocrit. Toxic doses of acriflavine HCl N.F. damaged the distal convoluted tubules of the kidney to produce a renal acidosis and nephrocalcinosis. Acriflavine HCl N.F. interfered with antibody production in a manner which appeared to be different from those of other immunosuppressant agents, but the mode of action remains unknown.