bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Human Serum and Nasal Hemagglutinating Antibody to Francisella Tularensis
Authors: Bellanti J. A. , Buescher E. L. , Brandt W. E. , Dangerfield H. G. , Crozier D.
Published: January 2023

The presence of specific antibody associated with the γA-immunoglobulins in nasal secretions was studied during the course of human respiratory tularemia in volunteers. Subjects immunized percutaneously with an attenuated tularemia vaccine 3 months previously, possessed detectable hemagglutinating antibody in both secretions and serum at the time of aerosol challenge with virulent organisms; nonimmunized subjects had none. Following aerosol challenge with 2500 virulent organisms, three of four previously immunized men withstood the challenge; all of the nonimmunized subjects and immunized individuals challenged with 25,000 organisms developed overt illness. Serum and nasal antibody persisted without significant change in titer in the immunized and became detectable in serum and nasal secretions of the nonimmunized subjects within 14 days after challenge. In both groups, serum antibody was associated primarily with the γM-immunoglobulins. Antibody in nasal secretions was found exclusively with the γA-immunoglobulins even though γG-immunoglobulins were detected in some secretions in both groups. Respiratory antibody activity to F. tularensis thus is found in the same immunoglobulin fraction which has been shown previously to possess antiviral activity.
Radioiodination of Antibodies Adsorbed to Insoluble Antigens
Authors: Day Eugene D. , Lassiter Sylvester , Fritz Robert B.
Published: January 2023

A method for radiolodinating antibody adsorbed to an insoluble antigen was developed. Antifibrin antibody as measured by its adsorption to fibrin was found to be sensitive to iodination. Antifibrin adsorption activity was preserved if iodination was carried out while the antibody was adsorbed to fibrin. Subsequent elution and readsorption showed little loss in activity. A fibrinophilic factor from normal globulin with a relatively high adsorption capacity was insensitive to iodination and was therefore unlike antifibrin antibody. A naturally occurring fibrinophilic protein, readily iodinated and elutable, was disclosed by the technique for labeling insoluble components.
Reversal of Post-Thymectomy Wasting Disease in Mice by Multiple Thymus Grafts
Authors: Stutman Osias , Yunis Edmond J. , Martinez Carlos , Good Robert A.
Published: January 2023

Reversal of post-thymectomy wasting in mice has been achieved by subcutaneous (s.c.) or intraperitoneal (i.p.) grafting of five thymuses from syngeneic, hemiallogeneic or allogeneic donors. The i.p. route was more effective in salvaging the wasted animals. In some instances a single i.p. graft proved to be effective. The reconstituted animals were able to reject skin homografts from third party strains. When syngeneic thymus donors were used, the spleen cells of restored animals had significant graft-vs.-host capability. When hemiallogeneic or allogeneic donors were used, the pattern of immunologic reconstitution varied with the strain combination and the site of thymus implants. If skin of the donor strain was rejected, the thymus grafts were usually not viable at autopsy, and the graft-vs.-host reactivity was appreciable and of host type. When skin of the donor strain was accepted, viable thymus grafts were noted at autopsy, and graft-vs.-host reactivity of host type was significant but reduced, presumably a reflection of the chimeric state. In certain allogeneic combinations, both donor and host components were detected in discriminating spleen assays.
Quantitative Hemadsorption, a New Assay Technique
Authors: Finter N. B.
Published: January 2023

A modification of the hemadsorption-inhibition method for measuring serum neutralizing antibodies to appropriate viruses is described. The extent of hemadsorption is measured indirectly on a spectrophotometer. The method described is sensitive and gives results which are reproducible and are obtained in 20 to 24 hr.
Suppression by Antihistamine of Passive Cutaneous Anaphylaxis Produced with Anaphylactic Antibody in the Guinea Pig
Authors: Movat Henry Z. , Di Lorenzo Nancy L. , Taichman Norton S. , Berger Sam , Stein Howard
Published: January 2023

Summary and Conclusions

Passive cutaneous anaphylaxis (PCA) was induced in guinea pigs with guinea pig anaphylactic (γ1) anti-egg albumin. The γ1 antibody was isolated by diethylaminoethyl cellulose chromatography or starch block electrophoresis. The PCA reactions could be significantly suppressed by the antihistamines mepyramine maleate and triprolidine hydrochloride.

These findings are in contrast to those obtained with heterologous γ2 antibody. PCA produced with the latter can be partially suppressed by rendering the animals leukopenic, but antihistamines have little suppressive effect. On the basis of these and of ultrastructural findings reported elsewhere, it is concluded that there are two mechanisms underlying the PCA reaction, depending on the type of antibody used for sensitization. Whereas PCA induced with γ2 antibody seems to be mediated primarily by release of lysosomal material from polymorphonuclear (PMN) leukocytes, PCA elicited with anaphylactic (γ1) antibody is probably mediated by release of histamine from sensitized mast cells.
An Antigen Common to Mouse Cells and Salmonella Typhimurium
Authors: Boyle William
Published: January 2023

The existence of a common antigen of mouse cells and virulent Salmonella typhimurium, as postulated by Rowley and Jenkin, has been confirmed. It has been shown to be the C-antigen, shared by mouse tissue cells and erthrocytes. The The antigen was detected by mixed agglutination between these cells using rabbit anti-erythrocyte sera or pig normal sera. This reaction was abollished by prior absorption of the sera with S. typhimurium, without concurrent reduction of the direct mouse hemagglutination titer of the sera. Rowley and Jenkin hypothesized that mice were susceptible to S. typhimurium infection because they recognized the common antigen as a “self” component and, so, failed to make an immune response against the bacterium. However, the C-antigen has been found in two strains of mice which differ by 1000-fold in their susceptibility to S. typhimurium and also in rats which are highly resistant to the bacterium.
Studies Concerning the Importance of Mononuclear Cells in the Development of Experimental Hepatitis
Authors: Scheiffarth F. , Warnatz H. , Mayer K.
Published: January 2023

Transfer of lymphocytes from C57B1 inbred mice with experimentally induced liver damage was made into normal isologous mice. Transferred lymphocytes may lead to infiltration of the periportal fields with mononuclear cells, and to an increase of Kupffer cells in the livers of recipients in a rather high percentage. No significant difference could be observed between animals treated with lymphocytes of mice poisoned with carbon tetrachloride or treated with lymphocytes from mice that had been sensitized to homologous liver extract given in Freund's adjuvant. Controls which had received lymphocytes from normal animals showed no liver injury as determined histologically.
Suppression of the Primary and Secondary Immune Response of the Mouse by Phytohemagglutinin
Authors: Spreafico Federico , Lerner Edwin M.
Published: January 2023

The effect of phytohemagglutinin on the immune response of mice to sheep erythrocytes has been investigated by measuring the 19S and 7S antibody-producing capacity of isolated spleen cells.

The administration of phytohemagglutinin (PHA) simultaneously with, or prior to, the injection of sheep red blood cells induced a marked depression of both the primary and secondary immune response. On the other hand, PHA given after the antigen led to no modification of the antibody response. The observed immune suppression was transient, and disappeared within 4 days after PHA administration; thereafter a normal response to antigenic challenge was observed. The magnitude of the immune suppression was dose-dependent and no effects were detected when heat-inactivated PHA was used.
Synthesis of Human Immunoglobulins in Germinal Centers of Lymphoid Organs
Authors: Burtin Pierre , Buffe Denise
Published: January 2023

Fluorescein and rhodamine labeled monospecific antibodies to IgG, IgA and IgM immunoglobulins and to K and λ light chains were used to investigate their localization in lymphoid follicles of human tonsils, spleens and lymph nodes. With few exceptions, only one immunoglobulin, and one light chain was detected in individual germinal centers. These findings support the hypothesis that at a given time, only one immunoglobulin, and one type of light chain is synthesized by cells in an individual germinal center.
Immunochemical Study of Influenza Virus and Associated Host Tissue Components
Authors: Howe Calderon , Lee Lucille T. , Harboe Arild , Haukenes Gunnar
Published: January 2023

The relation of chicken tissue antigens to influenza viruses propagated in chicken embryos has been investigated by immunochemical analysis of viral vaccine concentrates, in which egg albumin and other normal chicken tissue components have been identified. An acid mucopolysaccharide (host factor) (HF) which is extractable from chorioallantoic fluid, and antibody to which combines specifically with viral hemagglutinin, has been identified in vaccine preparations and in crude extracts of chorioallantoic membrane. Further evidence is presented to support the conclusion that HF forms part of the viral envelope, in intimate association with but distinct from hemagglutinin and neuraminidase.
Anti-Pasteurella Pestis Factor from Mice and Guinea Pigs
Authors: Eisler Daniel M. , Hill Beverly , Von Metz Eleanor K. , Chang Wei-Jen , Heckly Robert J.
Published: January 2023

The anti-Pasteurella pestis factor (APF) from the organs of mice and guinea pigs contained 75 to 87% protein, 1% or less of carbohydrate and phosphorus and from 2 to 12% of cold chloroformsoluble substances. Amino acids constituted 51 to 84% of the proteins, the remainder being unidentified. The chief amino acids were arginine, leucine, lysine, glutamic and aspartic. Since the activity of APF was destroyed by lipase and a chloroform-soluble fraction alone retained activity, the activity appeared to be associated with a lipid. Chloroform-soluble substances contained 1% or less of cholesterol esters, 3 to 10% triglycerides and 18 to 58% fatty acids. The fatty acids were chiefly caprylic, lauric, myristic, stearic, oleic and linoleic. The protein, though apparently inactive against P. pestis, served to solubilize the active lipids and thus facilitate their action in vitro.
Nonspecific Agglutination of Tanned Sheep Erythrocytes by Heat-Inactivated Mouse Serum Collected from Diluted Blood
Authors: Munoz J.
Published: January 2023

Mouse plasma collected from diluted blood, when heated at 56°C for ½ hr, produces agglutination of tanned sheep erythrocytes to high titers. The nonspecific agglutination can be removed by absorption of the sera with tanned cells but not with washed erythrocytes. Five minutes at 56°C is sufficient to activate the substance responsible for nonspecific agglutination, but heating at 35°C for ½ hr did not produce a significant increase of nonspecific titers.

Exclusion of complement did not increase nonspecific agglutination. When mouse blood was allowed to clot, the nonspecific agglutination by serum did not take place either before or after heating the serum, indicating that substance involved in the clotting mechanism was responsible for the nonspecific agglutination. This substance might be mainly fibrinogen. Human fibrinogen solutions, when heated at 56°C for ½ hr, produced agglutination of tanned sheep erythrocytes. This agglutinating capacity could be removed by absorption with tanned but not with washed erythrocytes. Similar nonspecific agglutination of tanned sheep erythrocytes was also observed in human and rabbit plasma but not in guinea pig plasma.
Interaction of Rabbit Anti-Human H Chain Sera with Denatured Human γ-Globulin and its Subunits
Authors: Hirose Shun-Ichi , Osler Abraham G.
Published: January 2023

Rabbits immunized with H polypeptide chains of human γ-globulin develop specific antibodies for both the clear and turbid (polymerized) preparations. The reactivity for the latter was relatively transient and barely detectable within 4 weeks after a single injection. The rabbit antisera resembled the human rheumatoid factors in demonstrating interaction with antigenic determinants induced by conformational changes in human γ-globulin or its subunits. These determinants were detected in polymerized H chains, the Fab fragments and in the intact γ-globulin molecule denatured by treatment with 6 M urea or heat.
Studies on the Effect of Interferon on the Formation of Antibody in Mouse Spleen Cells
Authors: Mazzur Scott R. , Ellsworth Barbara , Paucker Kurt
Published: January 2023

A method for the maintenance of mouse spleen cells in vitro by means of a rabbit kidney cell feeder layer has been described. Measuring cell viability by trypan blue exclusion, survival of spleen cells after 24 hr in culture was improved from approximately 50% to greater than 90%. Functional integrity of spleen cells cultured during that time interval was unimpaired as measured by the production of interferon and synthesis of antibody on transfer to x-irradiated recipient mice. However, the ability to form antibody plaques on agar was reduced, though not abolished, by incubation of spleen cells in vitro.
Studies on the Effect of Interferon on the Formation of Antibody in Mouse Spleen Cells
Authors: Mazzur Scott R. , Paucker Kurt
Published: January 2023

The effect of interferon on three types of antibody response has been studied. The formation of primary sheep red cell-hemolyzing antibody was examined in the antibody plaque assay of Jerne. Primary sheep red cell agglutinin production and the induction of the secondary Shigella agglutinin antibody response were investigated by transfer of interferon-treated spleen cells to x-irradiated recipient mice.

In no case did interferon exert any effect on the synthesis of antibody. However, antibody production could be depressed by exposure to the PR8 strain of influenza A virus. Since this effect of PR8 could be prevented by pretreatment of the cells with interferon, it is concluded that antibody-producing cells are susceptible to the action of interferon. These data indicate that interferon has no general effect on host cell protein synthesis in the uninfected antibody-producing cell.
Neutralizing and Hemagglutination-Inhibiting Activity of Nasal Secretions Following Experimental Human Infection with A2 Influenza Virus
Authors: Alford Robert H. , Rossen Roger D. , Butler William T. , Kasel Julius A.
Published: January 2023

Nasal washes from eight volunteers experimentally infected with A2 influenza virus were collected at frequent intervals prior to and following infection. Total protein and IgA concentrations increased following infection and remained elevated for 3 weeks. An early increase in protein concentration was associated with markedly increased nonspecific HI activity presumably related to the presence of mucoprotein inhibitor. Increased neutralizing activity for the infecting virus strain appeared 10 days following inoculation concurrently with the appearance of serum neutralizing antibody. Specific nasal wash neutralizing antibody was also related to total protein concentration but was consistently demonstrated only after serum neutralizing antibody had increased to significant titers. The presence of nasal wash neutralizing activity to strains not related to the infecting virus was almost associated with elevated nasal secretion protein and IgA concentrations. No serum antibody titer changes to these strains occurred. Nasal secretion A2 influenza neutralizing and HI activities were present following infection in association with 11S IgA predominantly and also 7S immunoglobulins.
Studies on the Biophysical Characteristics of Antibodies Produced in Birds and Mammals in Response to Experimental Chlamydial Infection (Psittacosis)
Authors: Page L. A. , Patterson Judith M. , Roepke M. H. , Glaser F. O.
Published: January 2023

Circulating complement-fixing and agglutinating antibodies—produced in turkeys, pigeons, sheep, rabbits and a calf at early and late stages of experimental infection with agents of the genus Chlamydia (psittacosis group)—were analyzed by sucrose gradient centrifugation and electrophoretic methods. All species, except pigeons, produced antibodies of the fast sedimenting type early in the course of experimental infection and slow sedimenting type in the later stages. Only slow sedimenting antibodies were found in pigeons. Both molecular types were readily detectable in turkey serums using the indirect complement fixation (ICF) method and in the other species using the direct complement fixation method. Agglutinating antibodies detected by the capillary tube method of Mason were principally of the fast sedimenting type.

Electrophoretic patterns of whole serums and gradient separated fractions confirmed that the antibodies were of the γ-globulin type. Inactivating serums at 56°C or 65°C caused a marked shift in the electrophoretic mobility of serum albumin, and 65°C inactivation reduced the γ2-globulin content.

The serologic activity of fast sedimenting antibodies produced in the calf was eliminated by 65°C heating (as was previously shown by others). However, heating the serums or gradient fractions thereof from turkeys or sheep not only inactivated the fast sedimenting antibodies but also reduced the titers of slow sedimenting antibodies.
Immunoglobulins of the Rhesus Monkey (Macaca Mulatta)
Authors: Lakin James D. , Patterson Roy , Pruzansky Jacob J.
Published: January 2023

Macaca mulatta monkeys immunized to bovine serum albumin and the dinitrophenyl antigenic determinant demonstrated immediate type skin reactivity and a 24-hr reaction of cutaneous necrosis. The serum of three of the four monkeys immunized transferred immediate type skin reactivity. Precipitating antibody, migrating in the γ-globulin region was synthesized in response to both DNP and BSA determinants. Anti-BSA antibody of the IgA and two specificities of IgG types were demonstrated by radioimmunoelectrophoresis. Anti-BSA IgM was detected in purified and concentrated pooled hyperimmune anti-BSA serum. Anti-DNP antibody of the IgM and IgG types was detected. The precipitating capacity of the sera was measured by the direct radioactive antigen precipitin technique; and the formation of soluble antigen-antibody complexes in antibody excess was found in the DNP-anti-DNP system. The formation of soluble complexes was shown to be more marked when DNP-BGG of a lower degree of haptenization was reacted with the anti-DNP serum. Equilibrium and dilution factors were measured and found to contribute little to the formation of soluble complexes. Classical quantitative precipitin types of curves were constructed. Anti-BSA precipitated in combination with antigen around a 3:1 ratio on a molar basis, with a sharp zone of equivalence. Anti-DNP combined with a broader zone of equivalence, than was observed in the BSA-anti-BSA system.
Duck Immunoglobulins
Authors: Grey Howard M.
Published: January 2023

Investigation of the sera from three species of duck has demonstrated the presence of two major low molecular weight γ-globulins, a 7.8S and a 5.7S protein. The 7.8S protein shows similarities to mammalian γG-globulins when products of reduction and enzymatic cleavage were investigated.

The 5.7S γ-globulin had several interesting characteristics. It lacked certain antigenic determinants of the Fc fragment that were present on the 7.8S protein, yet had no detectable unique antigens to suggest it contained structural components that differed significantly from those found on the 7.8S protein. Gel filtration of the peptide chains indicated that the 5.7S protein had a smaller heavy chain than that of the duck 7.8S γ-globulin or mammalian γG-globulin. Also, reduction in the absence of denaturing agents caused a decrease in S rate from 5.7S to 3.5S. These data suggested that the duck 5.7S immunoglobulin lacked a considerable segment of the Fc fragment of the heavy chain. As a result of this, inter-H chain non-covalent bonds were sufficiently small in number so that reduction of the inter-H chain disulfide bond(s) lead to the formation of half molecules.
Duck Immunoglobulins
Authors: Grey Howard M.
Published: January 2023

Studies of the metabolism of duck 7.8S and 5.7S γ-globulins indicated that the 5.7S protein was present in large quantities in fresh duck serum and that there was no detectable in vivo conversion of the 7.8S protein into the 5.7S protein. It was concluded from this that the 5.7S protein was a de novo synthesized protein. Anti-bovine serum albumin (BSA) was 75 to 85% 5.7S γ-globulin after the 3rd week of immunization and 15 to 25% 7.8S.

Reduction of the 5.7S and 7.8S duck antibodies led to a 75% decrease in the half dissociation time of preformed antigen-antibody complexes whereas rabbit antibody was not affected by this treatment. Reduction also decreased the antigen binding capacity of the 5.7S antibody but had little effect on the 7.8S antibody. Passive hemolysis of BSA-coated sheep erythrocytes indicated that only the 7.8S antibody was able to fix duck complement. Also, the 7.8S antibody and not the 5.7S antibody was capable of eliciting a passive cutaneous anaphylaxis reaction in duck skin.
The X-Y-Z Scheme of Immunocyte Maturation
Authors: Dowden Stanley J. , Sercarz Eli E.
Published: January 2023

Mice receiving a total of 16 to 18 mg of bovine serum albumin (BSA) during the first 3 weeks of life, including 2 mg of alum-precipitated BSA as a last injection, displayed so-called “spontaneous escape.” A very small percentage of animals receiving only soluble BSA exhibited this phenomenon during the time course of these studies. Spontaneous escape was delayed in animals which were challenged 1 or 2 weeks postregimen. Spontaneous escape was hastened in animals which were challenged 3 or 4 weeks postregimen by means of alum-precipitated BSA. After the administration of a supposedly hyperimmunizing series of injections from the 2nd to the 6th week postregimen, paralysis was prolonged with respect to onset of response and the level of antibody produced. From these studies it is concluded that one important route of “spontaneous escape” involves a sequence of paralysis, the generation of memory cells, and contact of these cells with endogenously retained antigen, followed by extensive antibody formation. A dualistic view of escape was supported in the discussion toward which both reversibly paralyzed X cells and virgin competent immunocytes make a contribution.
The X-Y-Z Scheme of Immunocyte Maturation
Authors: Sercarz Eli E. , Byers Vera S.
Published: January 2023

It is shown that the capacity for rapid and augmented recall of cellular IgM antibody production (“IgM memory”), in the sheep red cell system of the mouse, can be detected as early as 1 day after an initial dose of 2 × 106 SRBC, and reaches a peak concomitant with the peak of the IgM response. The transitory nature of this capacity is indicated, firstly, by its eight-fold decrease 1 month after priming. Secondly, if the net excess secondary response is induced 1 day or 1 month following priming, rather than at the optimal time, the “memory” increment falls to zero quickly.

These findings have given rise to an altered view of the heterogeneity of the Y or memory cell which is discussed at length.
Uptake by Mononuclear Phagocytes of Protein-Coated Bentonite Particles Stabilized with a Carbodiimide
Authors: Carpenter Robert R. , Barsales Petronilo B.
Published: January 2023

The rate of phagocytosis and digestion of inert particles by cultured mononuclear phagocytes can be conveniently measured with bentonite particles which are readily coated with antigenically defined, iodine-125 labeled protein. Reaction of the protein coat with 1-ethyl,3-(3-dimethylaminopropyl) carbodiimide limits release of protein from particles in cell suspensions. The mechanism by which the carbodiimide stabilized the particle coat is not certain.

Large mononuclear phagocytic cells developed within 7 days in cultures of guinea pig splenic leukocytes in isologous serum. These cells phagocytized protein-coated particles more slowly than did freshly isolated polymorphonuclear leukocytes. The per cent of particles phagocytized depended upon the nature of the particle coat. Particle uptake by cells cultured on a glass surface was difficult to demonstrate in the absence of opsonin. Uptake was stimulated by nonspecific heat-labile opsonins of normal serum and by specific, heat-stable opsonins of immune serum. Evidence is presented that isolated antibovine γ-globulin antibody obtained from an immune adsorbent, is such a specific opsonin. The nonspecific opsonins of normal serum shared several properties of the serum complement system.

Within 60 min, 10-2 M sodium iodoacetate, sodium fluoride or sodium azide inhibited phagocytosis by cultured guinea pig mononuclear phagocytes.
An Alteration of Secreted Immunoglobulin in Serum
Authors: Kölsch Eckehart
Published: January 2023

Microsomal and cell-sap antibody titers in the spleen were compared with serum antibody levels for 18 days following the intravenous injection of sheep erythrocytes into rabbits. The microsomal fraction was isolated from individual spleens, sonicated and treated with DOC to release antibody. Both released and unreleased microsomal antibody was titrated. Titers were determined by a modification of the standard, 50% photometric assay for hemolytic antibody.

As compared with the serum hemolysin response, the response measured on the subcellular level displayed a marked shortening of the interval between antigen injection and rise in titer. This interval was 4 days in the serum, 3 days in the microsomal fraction and 1 day in the cell-sap fraction. Subsequently, the subcellular antibody levels increased logarithmically, reached peak titers between days 6 and 12 and then declined. The data suggest an earlier peak titer in the cell sap and a more rapid titer decline in both the cell-sap and microsomal fractions than in the serum.

The apparently earlier titer rise in the subcellular fractions than in the serum may be attributed to the masking effect of natural hemolysin levels in the serum, while the earlier appearance of antibody in the cell sap as compared with the microsomal fraction suggests the existence of an antibody pool in the soluble phase of the cytoplasm.
Ontogeny of the Immune Response
Authors: Kim Yoon Berm , Bradley S. Gaylen , Watson Dennis W.
Published: January 2023

Colostrum-deprived, germfree piglets devoid of all known immunoglobulins and antibodies have varying amounts of a serum component designated X; this component has an electrophoretic mobility and ion exchange characteristics identical to 7SγG but is antigenically distinct from all known immunoglobulins including γG, γA and γM. The electrophoretic mobility of X is modified by treatment with 2-mercaptoethanol and its concentration remains constant regardless of antigenic stimulation. Evidence is presented and discussed to support our previous concept that antibody globulins are 19SγG and 7SγG immunoglobulins synthesized sequentially during ontogenic development which is initiated only by specific antigenic stimuli; in contrast, X as well as γM has no antibody activity and may arise spontaneously without antigenic stimulation.
The Behavior of Autologous Thyroglobulin in the Circulation of Rabbits Immunized with Either Heterologous or Altered Homologous Thyroglobulin
Authors: Weigle William O. , High Gloria J.
Published: January 2023

Injection of adequate doses of NaI131 into iodine deficient but otherwise normal rabbits results in disruption of thyroid structure with release of I131 thyroglobulin into the circulation. In these rabbits, the I131 thyroglobulin is eliminated at an exponential rate with a half-life of 2.3 days. The release of autologous I131 thyroglobulin in rabbits previously immunized with either arsanil-sulfanil-thyrogobulin (homologous) or a heterologous thyroglobulin causes a secondary stimulation resulting in an immune elimination of the I131 thyroglobulin and production of antibody to native rabbit thyroglobulin. Complexes formed between the circulating I131 thyroglobulin and the newly synthesized antibody deposit along the glomerular basement membrane of the kidney resulting in mild glomerular inflammatory changes and proteinuria.
“Protein A” from Staphylococcus Aureus
Authors: Gustafson G. T. , Sjöquist J. , Stålenheim G.
Published: January 2023

Arthus-like reactions in rabbits are produced by the interaction of human γG-globulin and a cell wall protein (protein A) from Staphylococcus aureus. The skin lesions are produced either by intradermal injection of preformed protein A-γ-globulin precipitates or by intradermal injection of protein A into rabbits that had previously received human γG-globulin intravenously. The skin reaction is regarded as not due to an antigen-antibody reaction but rather to a pseudo-immune reaction between protein A and human γG-globulin.
Experimental Streptococcal Glomerulonephritis in Rats
Authors: Lindberg Lois H. , Vosti Kenneth L. , Raffel Sidney
Published: January 2023

The induction of experimental glomerulonephritis was attempted by exposing female Sprague-Dawley rats to intraperitoneal diffusion chambers containing viable hemolytic streptococci of group A, types 1, 6, and 12 and of groups C and G for 60 days.

Only two of the seven strains of streptococci used in these studies were associated with significant proteinuria at the termination of the experiment. A strain of group A, type 12 (A12n) which had been demonstrated clinically to be “nephritogenic” for man, induced significant proteinuria in 21 of 33 rats. In most instances proteinuria was correlated with the presence of bound γ-globulin and M protein in the region of the basement membrane of renal glomeruli. Two of four rats exposed to a strain of group C streptococci also had significant proteinuria. Three of these animals had fixed γ-globulin in the glomeruli, but none had demonstrable bound streptococcal antigen.

Although histologic evidence of glomerular disease was not found at 60 days, other similarities of the disease suggest that this may provide a useful model for studying the pathogenesis of poststreptococcal glomerulonephritis.
Studies on the Induction of Immunologic Unresponsiveness
Authors: Golub E. S. , Weigle W. O.
Published: January 2023

The time course of the inhibition of establishment of immunologic unresponsiveness to human γ-globulin (HGG) in adult mice by endotoxin (ET) has been studied. ET prevents the establishment of unresponsiveness in C57BL/6J and A/J mice only if given up to 2 days after injection of HGG. ET given before or 3 or more days after HGG is ineffective. The effect of ET on induction of unresponsiveness is apparently independent of the granulopectic activity of the reticuloendothelial system (RES), as measured by clearance of colloidal carbon from the circulation, since ET is effective when the activity of the RES is either elevated or depressed. One dose of ET before HGG eliminates the ability of the ET given after HGG to prevent the establishment of immunologic unresponsiveness, although the granulopectic activity of the RES is elevated. The amount of HGG associated with spleen cells is comparably elevated above controls in animals treated with ET before or after HGG. The effect is not the result of complex formation between ET and HGG. Cortisone given at the time of ET does not alter the effect of ET.

Phytohemagglutinin (PHA) induces an intense proliferation of spleen cells in vivo as measured by incorporation of tritiated thymidine and increase in cell number, but has no effect on the induction of immunologic unresponsiveness.

Neither ET nor PHA affect the unresponsive state which has been induced in neonatal life.
Antigenic and Immunogenic Studies on Purified Tetanus Toxoid
Authors: Nielsen P. A. , Ablondi F. B. , Querry M. V. , Gussoni Cecilia , Cooper M. S.
Published: January 2023

Tetanus toxoids were prepared by two different methods. Toxoid produced in a protein-free medium did not differ in its basic qualities from that produced in a medium containing considerable quantities of protein. When the toxoids were purified by alcohol fractionation and diethylaminoethyl (DEAE)-cellulose column chromatography, specific activities of 2500 Lf/mg of nitrogen (infusion medium toxoids) and 2630 Lf/mg of nitrogen (protein-free medium toxoids) were obtained. It was demonstrated that no statistically significant antigenic difference was obtained with toxoid of approximately 2320 Lf/mg of nitrogen as compared with toxoid of 1330 Lf/mg of nitrogen. There was no loss of ability to induce a satisfactory immune response after purification to a high degree. The involvement of toxoids purified to varying degrees in the production of hypersensitivity is discussed.
Antibody Production by Mice Repopulated with Limited Numbers of Clones of Lymphoid Cell Precursors
Authors: Trentin J. , Wolf N. , Cheng V. , Fahlberg W. , Weiss D. , Bonhag R.
Published: January 2023

Lethally irradiated (850 r) CBA mice were given intravenous injections of 105 bone marrow cells from normal adult (CBA × T6)F1 donors. Four to 13 discrete colonies, assumedly of clonal origin, developed in their spleens. The colonies were composed of cells of the several hemopoietic cell lines and of a small number of undifferentiated precursor cells; typical lymphoid cells were not seen in the early colonies.

The spleen-colonies were removed on the 10th day after irradiation and repopulation, at a time when immunologically competent cells could not be demonstrated in the spleen by the Jerne technique. Cell preparations derived from the colonies were used to repopulate secondary irradiated CBA mice. The myeloid and lymphoid tissues of some of these hosts were then employed for the repopulation of a third group of lethally irradiated CBA animals (tertiary hosts).

Secondary and tertiary host mice surviving more than 30 days were challenged with sheep red blood cells, bovine serum albumin and killed organisms of a strain of S. typhosa. They produced antibody to these antigens just as well as did appropriate nonclonal control mice. The hemopoietic and lymphoid systems of such clonally repopulated mice were of donor origin as indicated by the presence of the T6 marker chromosome in 100% of the mitotic cells of the bone marrow, spleen and mesenteric lymph node of most of the mice.

The findings are discussed with reference to the question of the nature of the genetic control of immunoglobulin specificity.
Studies on Antigenic Structure of Bovine Aortic Intima
Authors: Milgrom Felix , Intorp Hans W. , Witebsky Ernest
Published: January 2023

Antisera were prepared by immunization of rabbits with a suspension of bovine aortic intima incorporated into complete Freund adjuvant. By means of such antisera, several antigens characteristic for intima of aorta as well as for intima of other large vessels and for the endocardium were identified. The major antigenic component was a lipid-containing protein with fast electrophoretic mobility. Upon more careful analysis, this antigen was shown to be composed of two molecular species, one which resisted heating at 100°C and the other which was thermolabile. It was further demonstrated that the thermoresistant component does not belong to the previously described category of thermostable, ethanol-insoluble tissue antigens (BE antigens). However, subsequent studies performed by means of anti-BE sera showed that the BE fraction of aortic intima also contains tissue-specific antigenic components. The relation of these components to antigens detectable in plain intima extract has been discussed.
Some Effects of Antigen-Antibody Complexes Prepared from Heterologous and Homologous Antibody on the Immune Response of Rabbits
Authors: Patterson Roy , Suszko I. M.
Published: January 2023

The rate of passive immune elimination of soluble antigen-antibody complexes and the subsequent active antibody response in rabbits varied with the source of the antibody used for preparation of the complexes. Chicken complexes were retained in the circulation in the initial passive phase but were eliminated more rapidly than rabbit complexes in the second active phase of complex elimination. The chicken complexes stimulated an earlier, higher and more prolonged antibody response, similar to a secondary type of immune response. The antibody response which followed the injection of rabbit complexes in rabbits occurred earlier than that following antigen alone, but was otherwise similar.

No differences in types of immunoglobulins resulting from the different stimuli were observed.
The Role of Antibodies in the Ingestion of Aldehyde-Treated Erythrocytes Attached to Macrophages
Authors: Rabinovitch M.
Published: January 2023

Erythrocytes treated with glutaraldehyde (GRC) were bound to macrophages in saline medium and their subsequent ingestion was quantitatively estimated. Dose-dependent stimulation of GRC ingestion was obtained with antisera against red cell antigens or against bovine albumin or ovalbumin. In the last two instances the GRC were treated with the antigens before attachment to macrophages. Tests with red cells of different species as well as absorption experiments indicated that the stimulatory effect was immunologically specific. Ingestion was stimulated when the antisera were: 1) added to the incubation medium after GRC attachment, or 2) used to treat GRC prior to their attachment to macrophages. In the latter case ingestion proceeded in the absence of serum.
Preparation and Properties of Antibody Directed Specifically Against the Neuraminidase of Influenza Virus
Authors: Webster R. G. , Laver W. G.
Published: January 2023

Antiserum was prepared against a recombinant influenza virus possessing A0 (NWS strain) type hemagglutinin and A2 (RI/5+) type neuraminidase. This antiserum was absorbed sequentially with NWS and A2 viruses and antibody directed against A2 type neuraminidase was then dissociated from the A2 virus.

This antibody had no activity against the hemagglutinin activity of A0, A1 and A2 influenza viruses or against the infectivity of A0 and A1 viruses. It neutralized the enzyme activity of A2 but not A0 or A1 type influenza viruses.

Anti-enzyme antibody caused apparent neutralization of the infectivity of influenza viruses possessing A2 type neuraminidase providing that the antibody was allowed to remain in contact with the cells during the test period. This antibody did not prevent infection of susceptible cells but apparently prevented the release of detectable levels of hemagglutinin. It had no effect on the infectivity of an A2 type recombinant virus that lacked neuraminidase activity.
Immune Hemolysis: A Simplified Method for the Preparation of EaC′4 with Guinea Pig or with Human Complement
Authors: Borsos Tibor , Rapp Herbert J.
Published: January 2023

The intermediate product of immune hemolysis EAC′4hu was prepared by a new, simplified and rapid method. This stable reagent can be used to titrate the first component of human and guinea pig complement and after conversion of EAC′4hu to EAC′1a4hu can be used to titrate human or guinea pig C′2. The intermediate product EAC′4gp can also be prepared by this new method. Evidence is presented for the existence of two different kinds of SAC′4 both of which are capable of interaction with C′2 but only one of which can be converted to S*.
Dengue Virus Identification by the Plaque Reduction Neutralization Test
Authors: Russell Philip K. , Nisalak Ananda
Published: January 2023

A method for identification and serologic classification of dengue viruses using a plaque reduction neutralization test and monkey immune serum is described. Results of typing 40 strains confirm the usefulness of this method for classification of low passage strains. Adaptation of the isolates to suckling mice or tissue culture was not required and strains within each of the four dengue serotypes were readily identified.

Cross neutralization tests using monkey antiserum confirmed the results of the one-way neutralization test using antiserum to reference dengue strains and also indicated antigenic variation within serotypes 1, 2 and 4.
False Positive Radio-Immunoautograph Lines Associated with Immunoglobulins from Normal Sera
Authors: Minden Percy , Grey Howard M. , Farr Richard S.
Published: January 2023

Radio-immunoelectrophoresis and radio-immunodiffusion are practical methods to detect antigen binding in immunoglobulins and immunoglobulin sub-units. The lower limit of sensitivity of radio-immunodiffusion was 0.003 µg N anti-BSA/ml. The advantages of these sensitive procedures may be limited at times by the occurrence of positive reactions which are not specific, and experiments are described that account for some of these reactions. Recommendations to prevent some nonspecific reactions and to enhance the proper interpretation of positive results are presented.
Induction, Maintenance and Termination of Immunologic Unresponsiveness to Bovine Thyroglobulin in Rabbits
Authors: Nakamura Robert M. , Weigle William O.
Published: January 2023

Rabbits were rendered unresponsive with periodic injections of very small doses of bovine thyroglobulin starting on the day of birth. All of the animals receiving periodic injections of 0.25 mg (total 6.0 mg), 62% of rabbits given 0.05 mg injections (total 1.2 mg) and 29% of rabbits given 0.025 mg injections of bovine thyroglobulin (total 0.6 mg) were unresponsive. In the latter group, the amount of bovine thyroglobulin in the blood at the time of challenge was below that detectable by a sensitive serologic technique. After no further antigen injection, the induced unresponsive state to bovine thyroglobulin lasted at least 3 months; however, there was a gradual loss of the unresponsive state which began 3 to 4 months after the last injection.

Similar mechanisms appear to be involved in the termination of the acquired unresponsive state to bovine thyroglobulin and production of experimental autoimmune thyroiditis. The unresponsive state to bovine thyroglobulin was readily terminated by injections of a serologically related human thyroglobulin, and simultaneous injections of bovine thyroglobulin inhibited this termination.
Factors Affecting the Reactivity of Human Lymphocytes in Vitro
Authors: Moorhead John F. , Connolly John J. , McFarland William
Published: January 2023

Summary and Conclusions

Quantitative studies of immunologically stimulated blood leukocytes in vitro show that DNA synthesis is affected by variations in cell number, duration of culture and area of the surface on which the cells are cultured. Of particular interest is the demonstration in both mixed leukocyte and antigen-stimulated cultures that as cell proximity increases the synthesis of DNA increases proportionally. It is suggested that this increase in DNA synthesis is the result of recruitment of otherwise nonreactive lymphocytes through the previously demonstrated mechanism of uropodapsis.
A Comparison of the Antigenic Properties of Nucleus Pulposus and Cartilage Protein Polysaccharide Complexes
Authors: Pankovich Arsen M. , Korngold Leonhard
Published: January 2023

Protein-polysaccharide complexes and their light fractions (PP-L) from human nucleus pulposus (H-NP), steer and dog nucleus pulposus (S-NP, D-NP) and articular cartilage (S-AC, D-AC) were compared. These preparations were used in their native form and also after digestion with hyaluronidase. Antisera obtained by immunization of rabbits with H-NP, S-NP and S-AC were tested with all PP-L preparations by double diffusion in agar, by microdiffusion in agar and by immunoelectrophoresis. PP-L preparations were also examined by analytical ultracentrifugation, by moving boundary electrophoresis, and were stained by alcian blue 8GS stain after electrophoresis in agar. The results of this study clearly show that 1) PP-L from nucleus pulposus is antigenic in the rabbit. 2) PP-L from nucleus pulposus contains at least two antigenic determinants common to all species tested and, in addition, at least one species specific antigenic determinant. These antigenic determinants appear on at least two separate antigens. 3) PP-L from nucleus pulposus and cartilage are closely related if not identical. 4) Hyaluronidase digestion increases the rate of diffusion of PP-L preparations, and possibly uncovers some new determinants.
Purification by Starch Block Electrophoresis of Renal Antigen that Induces Nephrotoxic Antibody
Authors: Shibata Seiichi , Naruse Takuji , Nagasawa Toshihiko , Takuma Takehide , Miyakawa Yuzo
Published: January 2023

Further purification of the antigenic substance in the supernatant substance of trypsin-digested rat kidney cortex homogenate (TR-KH) was achieved using starch block electrophoresis.

Almost all the antigenic activity responsible for the production of nephrotoxic antibody was found in fraction -3, which was free of nucleic acid. Rats receiving a single injection of antiserum against fraction -3 showed distinct clinical and histologic changes of typical proliferative glomerulonephritis. Moreover, severe chronic glomerulonephritis (so-called contracted kidney) was induced in rats killed 7 to 9 weeks after a single injection. Studies using the fluorescent antibody technique showed that this purified antigen (fraction -3) is derived from the glomerular basement membrane.

This fraction was more highly purified as a single peak by gel-filtration using Sephadex G 200.

Fraction -3 is probably a polysaccharide-protein complex, and the results of chemical analysis suggest strongly that the active principle of this antigenic substance is closely related to the polysaccharide moiety.
Cumulative Changes in the Antigenic Properties of Herpes Simplex Virus from Persistently Infected Cell Cultures
Authors: Hampar Berge , Keehn Mary Alice
Published: January 2023

Reciprocal neutralization kinetic studies were carried out between the virus isolated at different times from persistent herpes simplex virus (HSV) infected cell cultures and their respective antisera. The results indicated that the virus acquired new antigenic determinants with time, while still retaining the determinants of the antecedent virus. The serologic relationship between the HSV variants isolated from these persistent infections was similar to that observed by others between HSV and herpes B virus, but not previously noted with strains of HSV.
Evaluation of Light Chain Antigen Binding by Radioimmunoelectrophoresis
Authors: Minden Percy , Grey Howard M. , Farr Richard S.
Published: January 2023

The ability of radioimmunoelectrophoresis to demonstrate specific antigen binding directly by isolated antibody light chains was evaluated using BSA as the antigen. Radioactive arcs and specific I*BSA binding were readily demonstrated by light chain preparations which did not contain detectable amounts of heavy chains when tested by gel diffusion.

The arcs observed, however, could not be interpreted as evidence for I*BSA binding by isolated light chains because: 1) as little as 0.19 µg/ml of isolated antibody heavy chains were sufficient to detect I*BSA binding using radioimmunoelectrophoresis whereas 544 µg/ml of the isolated light chains were required; 2) when hybrid molecules made by mixing normal light chains with small amounts of antibody heavy chains were tested, a radioactive are developed that was qualitatively similar to the arc produced by the antibody light chain preparations; and 3) the amount of antibody heavy chains required to produce radioactive arcs when mixed with light chains was less than the amount of antibody heavy chain that could have been detected in the antibody light chain preparation.