bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Organ Specificity
Authors: Beutner Ernst H. , Witebsky Ernest
Published: January 2023

The interactions between human sera and human and monkey thyroid antigens were studied by the fluorescent antibody method, complement fixation, and tanned cell hemagglutination.

Three types of antibodies which stain human thyroids were demonstrated in human sera by the fluorescent antibody method. The antigens are characterized by staining of: a) thyroid colloid, b) cytoplasm of thyroid epithelium, and c) thyroid nuclei. Antibodies to thyroid colloid and to the cytoplasm of thyroid epithelium frequently occur together. Some sera appear to contain only antibodies to the cytoplasm of the thyroid epithelium. Antibodies to thyroid colloid and to the cytoplasm of thyroid epithelium were further differentiated by: a) differences in the chemical stability of the two antigens, b) selective removal of antibodies which stain thyroid colloid by adsorption with thyroglobulin. Sera which stained the cytoplasm of thyroid epithelial cells by the fluorescent antibody method also fixed complement with human thyroid microsome, to a lesser extent with human thyroid mitochondrial fraction and not at all with the nuclear fraction. Adsorption of sera, even with well washed microsomes, removed both the cell and the colloid staining antibodies. Immunofluorescent staining of the cytoplasm of thyroid epithelium occurred with the patient's own thyroid sections in three cases thus confirming the autoantibody nature of the reaction. All sera which stained thyroid colloid by the fluorescent antibody method also gave strong hemagglutination reactions. The converse was not always true. Hemagglutination occurred with the patient's own thyroid extracts in two cases thus confirming the autoantibody nature of this type of reaction. One of 17 sera studied stained all three thyroid consituents, the colloid, the cytoplasm of the epithelial cells, and the thyroid nuclei. Nuclear staining and colloid staining antibodies were removed by selective adsorption. Sera containing nuclear antibodies (mostly from patients with lupus erythematosus) stained no other component of thryoid sections but stained nuclei of all organs. Pathologic diagnosis and serologic findings were compared in 46 thyroidectomized patients. Thyroglobulin autoantibodies occurred in all chronic nonspecific thyroiditis cases. No other generalization could be made.
Studies on the Effect of Complement on Anaphylaxis in the Mouse
Authors: Frick Oscar L. , Stiffel Claude , Biozzi Guido
Published: January 2023

The reduction of hemolytic complement to 10% or less by human γ-globulin aggregates and antigen-antibody complexes in mice has no effect on passive cutaneous anaphylaxis induced by homologous antibody.

In general anaphylaxis in mice treated with Hemophilus pertussis the decomplementation by human α-globulin aggregates has no effect, whereas the antigen-antibody decomplementation produces a significant protection which is probably due to a shocking effect from this treatment.
Quantitative Studies on Surface Phagocytosis
Authors: Weaver R. E. , Seastone C. V.
Published: January 2023

Clotted human blood possessed greater phagocytic and bactericidal activity against encapsulated pneumococci and β-hemolytic streptococci than did heparinized blood, evidently a manifestation of surface phagocytosis. The effect of a fibrin surface on the efficiency of the phagocyte in the presence of specific opsonin, as measured by the bactericidal effect, varied with experimental conditions; this effect was not great in either direction.
A Study of Passive Sensitization of Guinea Pigs with Antigen-Antibody Complexes
Authors: Rosenberg Leon T. , Tachibana Dora K.
Published: January 2023

Passive cutaneous anaphylaxis was induced at sites sensitized with antigen-antibody complexes in antigen excess and a subsequent injection of antigen. Seventeen guinea pig antisera, seven rabbit antisera and one mouse antiserum to two antigens, egg albumin and bovine plasma albumin, were studied.

Sensitization of guinea pig skin sites occurred with complexes prepared with guinea pig antisera at various antigen excess ratios. Complexes prepared with either rabbit antisera or the mouse antiserum did not sensitize. A longer time of induction of PCA was required when antigen-guinea pig antibody complexes were employed than when equal amounts of free antibody were injected.

These results are interpreted to mean that antigen-guinea pig antibody complexes dissociate in vivo in guinea pigs. Rabbit complexes and mouse complexes appear not to dissociate in guinea pigs.
Detection of Antibodies in the α-2 and γ-Globulin Fractions of Human Tuberculous Sera
Authors: Allerhand Jona , Zitrin Charlotte M.
Published: January 2023

Human tuberculous and nontuberculous sera were fractionated by means of the continuous flow paper electrophoresis method. Precipitin tests were then performed, using the α-2 and γ-globulin fractions as the sources of antibody, with OT, PPD, and an unheated culture filtrate of tubercle bacilli as the sources of antigen. Both the tuberculous and control sera gave negative results before fractionation. After fractionation, the control sera remained negative. Of the 14 patients' sera, 12 became positive, 7 with both fractions, 3 with γ-globulin alone and 2 with α-2 globulin alone. The α-2 globulin fraction, in those cases where both were positive, generally precipitated earlier than the γ-globulin fraction.

In a comparison between the agar doublediffusion test with whole serum and the precipitin test with fractions of the same serum, the latter was positive in seven out of eight samples, whereas the former was positive in three out of the eight.
Demonstration of Gm 1(a) and Anti-Gm 1(a) Specificities by Tanned Cells Coated with Individual γ-Globulins
Authors: Epstein Wallace V. , Fudenberg Hugh
Published: January 2023

The detection of rheumatoid factors by human Rho cells coated with incomplete Rho antibody is based on a reaction determined by the genetic (Gm) specificity of the 7 S γ-globulin coating the cells. Both pooled human γ-globulin (Cohn Fraction II) and rabbit γ-globulin lack this specificity and thus are unable to distinguish the anti-Gm specificities of the several rheumatoid factors.

The present study demonstrated that 7 S γ-globulins isolated from normal human sera by chromatographic techniques and coated on tannic acid-treated sheep erythrocytes retain their Gm specificity. The Gm 1(a) character of several sera and their 7 S γ-globulin fractions and the anti-Gm 1(a) specificity of several rheumatoid sera were established by correlating the inhibitory capacity of a panel of sera with their Gm 1(a) positivity or negativity as established by the sensitized D cell test. Heating the isolated γ-globulin to 56°C before coating cells was usually necessary to provide test cells with Gm specificity, whereas preheating the γ-globulin to 63°C destroyed Gm specificity.

A major limitation of the Gm test system is the scarcity of anti-Rho sera capable of distinguishing rheumatoid factors of various anti-Gm specificities.

The described system eliminates the need for anti-Rho sera of Gm 1(a+) phenotype and permits the Gm 1(a) classification of normal sera, as well as the detection of rheumatoid factor of anti-Gm 1(a) specificity.
Cytotoxicity of Anti-Tissue Antibodies
Authors: Ehrlich G. , Halbert S. P. , Manski W.
Published: January 2023

Duck anti-adult rabbit lens sera demonstrated striking cytotoxicity against rabbit lens epithelium in tissue culture, whereas unimmunized duck serum was without effect. In addition, duck antisera to 26-day-old fetal rabbit lenses revealed similar cytotoxic effects. Duck antisera to rabbit sclera or cornea showed only minimal damaging effects on rabbit lens epithelium. These data confirm and extend earlier observations on the differences in specificity of cytotoxic antigens in various tissues from a single species. Homologous antisera prepared in the rabbit against pooled rabbit lenses, did not reveal cytotoxic effects on rabbit lens epithelium. Rabbit antisera against human, bovine, frog and marine fish (menhaden) similarly failed to damage rabbit lens epithelial cells, although all of the antisera contained numerous precipitating organ-specific antibodies active against rabbit soluble lens components. The data thus indicate that the antigens involved in organ specificity of the lens were not concerned in the cytotoxic reactions.
A Tissue Culture Assay for Variola Virus Based upon the Enumeration of Hyperplastic Foci
Authors: Pirsch James B. , Purlson Elliott H.
Published: January 2023

The observation of hyperplastic foci in monolayer cultures of HeLa cells infected with variola virus led to the development of a tissue culture assay for this virus. The specificity of the assay was demonstrated by the fact that heat inactivation or exposure to immune serum reduced the capacity of the virus to produce the areas of hyperplasia. The proliferative lesions can be counted as early as the second day of infection; formation of secondary foci has never been detected. A linear relationship has been demonstrated between the numbers of foci formed and the concentrations of variola virus present in the inocula. The precision of the assay was established with a series of parallel titrations of a standard suspension of variola virus both in tissue culture and on the chorioallantoic membranes of embryonated chicken eggs. Counts derived from the tissue culture assay were four times higher and showed consistently less variation than those obtained by the pock method. The new tissue culture assay is simple to perform and economical of time and equipment.
Histochemical and Biochemical Changes in the Chorioallantoic Membranes and Allantoic Fluids of Embryonate Eggs Infected with Influenza Virus
Authors: Kelly Richard , Greiff Donald , Anderson Doris
Published: January 2023

The endodermal cells of chorioallantoic membranes, from eggs infected with the PR8 strain of influenza virus, fixed and stained with alcian blue PAS stain 24 hr postinoculation, showed a diminution in the histochemical reaction for acid mucins; a negative reaction 48 and 72 hr postinoculation; stainable material reappeared at the 96th hr and increased up to 144 hr. Strongly positive reactions for the periods above were observed in the cells of membranes from noninfected eggs. Sections of membranes from infected and noninfected eggs stained with fluorescent PAS stain, acridine orange stain, and Bismarck brown stain showed histochemical changes similar to the above. The staining reactions of cells of membranes from eggs inoculated with virus inactivated by ultraviolet irradiation were similar to those from noninfected eggs. The reactions of membranes from eggs producing incomplete virus paralleled those of membranes from eggs inoculated with complete, active virus.

The staining reactions of the positive material of the endoderm was not altered by incubating sections of membranes from noninfected eggs with diastase or testicular hyaluronidase; sections incubated with Vibrio cholerae neuraminidase resembled those from infected eggs 48 hr postinoculation. These data suggested a possible alteration in the amounts of total, bound and free sialic acids in the allantoic fluids of eggs infected with influenza virus. The total sialic acid content of allantoic fluids from noninfected and infected eggs increased with time, the variations observed were not significant; bound sialic acid in fluids from noninfected eggs increased with time, the levels in fluids from infected eggs remained unchanged; the levels of free sialic acid in fluids from infected eggs were significantly higher than those in noninfected eggs.

The relationships between neuraminidase of viral origin, mucopolysaccharide, mucoprotein and inhibitor substance of allantoic fluid are discussed.
Antibody Formation in the Rat
Authors: Fitch Frank W. , Winebright James
Published: January 2023

The role of dose of antigen, the route of its injection, and the presence or absence of the spleen in the primary and secondary agglutinin response of the rat have been studied using purified, soluble flagellin from Salmonella typhosa as antigen. Within the range studied, injection of larger quantities of antigen generally resulted in higher circulating agglutinin levels in both the primary and secondary response. Compared with the results obtained when particulate flagella was used as antigen, the effect of splenectomy and the effect of route of injection were less marked. The general pattern of agglutinin response was also different after administration of the two forms of antigen. Possible reasons for these differences are discussed.
Human Hypersensitiveness to Whole Horse Serum or Serum Globulins Following Diphtheria Toxin-Antitoxin Injections—Its Importance
Authors: Park William H.
Published: January 2023

This preliminary communication is made at this time because of the interest aroused by Hooker's communication at the December meeting of the Society of American Bacteriologists.

He observed that a considerable percentage of adults who had some months previously received three injections of diphtheria toxin-antitoxin (3 L plus preparation) developed a skin sensitiveness to horse serum.

Two series of observations are here presented, one on children, the other on adults which confirm Hooker's conclusion, that a specific skin hypersensitiveness may be induced, in a moderate percentage of children and adults by the injection of the minute amount of horse serum globulins contained in the toxin-antitoxin injections. The results of tests on untreated persons and on those who had received larger amounts of serum globulins are also given as a comparison. As the antitoxin globulin solution is universally used to supply the antitoxin in the toxin-antitoxin, the globulin solution is used as the testing substances in most cases.
The Chemical Basis of Immunological Specificity
Authors: Wells H. Gideon
Published: January 2023

So remarkable are the manifestations of specificity, so exquisitely delicate are many of the immunological reactions exhibiting specificity, and so wonderfully minute are the traces of proteins that may suffice to demonstrate it, that it has commnly been assumed taht specificity must depend on chemical or physical differences far too slight to be detected by other than immunological methods. The most recent and extensive reference book on the subject of immunity (Zinsser's Infection and Resistance, 3d Edition, 1923, p. 86) makes the statement that the manifestation of specificity.

points to an exquisite chemical difference between the protein substances which constitute the bacterial cell bodies or their metabollic products.
Reactivity of Rheumatoid Arthritis Sera with Altered and Aggregated Human γ-Globulin
Authors: Oreskes Irwin , Singer Jacques M. , Plotz Charles M.
Published: January 2023

Fourteen commercial pooled human γ-globulin (HGG) preparations varied widely in their ability: a) to sensitize tanned sheep red cells for agglutination with rheumatoid arthritis serum (RAS), b) to precipitate with RAS, and c) to inhibit agglutination of sensitized tanned sheep red cells by RAS. The inhibitory power of any given γ-globulin preparation paralleled its sensitizing and precipitating capacity. There was little correlation between these reactions and the amount of aggregates present in the γ-globulin preparations.

Different preparations of aggregated HGG also varied in their inhibitory power and precipitating capacity but, when the aggregates were heated, their reactivity increased to about the same level in all cases.

The inhibitory power of purified aggregated HGG was found to increase with the heating time employed in their preparation. When the aggregates were dissolved in alkali, this effect was abolished and reactivity decreased to a uniform level.

Purified 7 S HGG, when denatured under conditions that avoided aggregation, was also found to be reactive with RAS.

From these results it has been concluded that reactivity of pooled HGG for serum rheumatoid factors is primarily due to denaturation. Subsequent aggregation of the denatured globulin enhances its reactivity, probably because of decreased solubility of the rheumatoid factor-γ-globulin complex.
A Comparison of Fluorescein-Labeled γ-Globulins Purified by Rivanol and Deae Chromatography
Authors: Frommhagen Laurence H. , Martins Mary J.
Published: January 2023

Preparations of fluorescein-labeled γ-globulins obtained by the Rivanol procedure were found to be comparable to DEAE γ-globulins in recovery of antibody and specificity of fluorescent staining. An application of these preparations was made to the fluorescent antibody analysis of the V antigens of influenza virus where it was necessary to use purified, labeled γ-globulins to achieve full specificity. However, in other virus-cell systems immune globulins prepared by ammonium sulfate precipitation, conjugated at low F:P ratios, and passed through a sephadex column were found to be comparable to the Rivanol and DEAE globulins in specificity and, at times, superior in stainability. In the reverse situation, where essentially no contaminating host materials are present, as with preparations of bacteria, the use of ammonium sulfate globulins conjugated at high F:P ratios seems to afford the greatest intensity of staining.
Adoptive Tolerance; Transfer of the Tolerant State
Authors: Argyris Bertie F.
Published: January 2023

Lymphoid cells from tolerant mice can be successfully transferred to a new environment without affecting their tolerant behavior. In such transfer, both the original host and donor cells are transferred, with the establishment of a chimeric state in the irradiated recipients. In addition to being mutually tolerant, the host and donor cells from the tolerant animal tolerate each other's type of skin grafts. This tolerance is not due to a general impairment of the immune capacity but to a specific inhibition of the immunologic response. The results suggest that the graft-versushost tolerance in the newborn C3H mouse injected with adult CBA strain spleen cells is not due to immunologic paralysis.
The Behavior of Escherichia Coli Endotoxin (Somatic Antigen) during Infectious Arthritis
Authors: Braude A. I. , Jones J. L. , Douglas H.
Published: January 2023

On the basis of an immunologic assay method developed with the Boivin endotoxin of E. coli O:113, the behavior of this endotoxin and its antigenic component was studied in animals with septic arthritis produced by the parent organism. A single inoculation of this strain of E. coli into the knee of rabbits established a severe septic arthritis that was accompanied by high spiking fever lasting 2 weeks. Somatic antigen was found in the blood of febrile animals in the absence of bacteremia; this observation indicated that endotoxin was released into the knee by living and dead bacteria in quantities exceeding those that appeared to be bound locally by the articular tissues. In addition to fever, circulating somatic antigen was accompanied by the hematologic changes and immunologic response characteristic of animals given purified endotoxin intravenously and intraarticularly.

E. coli was cultured from the knee for 2 weeks. The infectious arthritis was then replaced by a prolonged sterile progressive suppurative arthritis. Because E. coli somatic antigen was demonstrated in the sterile joint fluid and because a similar sterile arthritis with fever was produced by knee injections of endotoxin, it is possible that the endotoxin elaborated by living and dead bacteria was responsible for both the local tissue damage and the systemic effects that occurred during infection.

Specific antibody against circulating endotoxin reached its peak at 7 days, whereupon the fever began to decline and further antibody production was checked. Since antisera were found to neutralize both the pyrogenic and antigenic actions of endotoxin, the specific immune response may be partially responsible for interrupting these processes during the infectious arthritis due to E. coli.
Immunologic Unresponsiveness to Purified Proteins in Guinea Pigs
Authors: Gregg Michael B. , Salvin S. B.
Published: January 2023

Unresponsiveness to a purified protein was produced by intraperitoneal inoculation of antigen into guinea pigs in utero. This unresponsiveness embraced not only circulating antibody but also the delayed type of skin hypersensitivity. Unresponsiveness to a protein, such as hen egg albumin, conferred concomitant unresponsiveness to the same protein altered only by the addition of haptenic groups such as para-aminobenzoic acid. This unresponsiveness to the conjugate was demonstrated by the absence not only of detectable circulating antibody but also of detectable intracutaneous delayed hypersensitivity.
Effect of Prolonged Immunization on the in Vitro and in Vivo Immunologic Activity of Rabbit Anti-Mouse Erythrocyte Serum
Authors: Davidsohn I. , Lee C. L. , Panczyszyn O.
Published: January 2023

Summary and Conclusions

Twenty-eight normal and splenectomized rabbits were injected intravenously or intraperitoneally for from 7 to 14 courses of 4 biweekly injections with erythrocytes of BALB/c, C57B, and DBA inbred strains of mice. Antisera collected after each course of injections were examined for hemolysin and agglutinin titers as well as their ability to produce anemia in mice. Ability of the antiserum to hemolyze erythrocytes in vivo and in vitro (the hemolytic ratio) was compared. The three immunologic activities could not be detected in the serum of normal rabbits. They rose rapidly and significantly after the first two courses of injections. With few exceptions, the peaks of in vitro and in vivo reacting antibodies were reached after from three to four courses; thereafter, the in vivo activity decreased steadily, while the in vitro titers were maintained or increased. This dissociation pattern was less distinct or was absent in sera of intravenously injected splenectomized and previously immunized rabbits, and of intact rabbits injected intraperitoneally. Although the immunologic activity of antisera of rabbits injected with erythrocytes from different strains of mice was different in potency, the pattern of in vivo and in vitro dissociation was similar. Antisera of rabbits injected intraperitoneally showed much lower immunologic activity than those of intravenously injected rabbits and reached their peaks only after six courses of injections. After prolonged immunization, antisera of splenectomized rabbits showed a tendency to regain their in vivo potency while their in vitro activity was decreasing. Responses of previously immunized rabbits to a single reinjection of erythrocytes were determined by the intervals since the preceding series of immunization; they were totally unresponsive after 1 month, selectively responsive after 3 months, and showed a transient exaggerated response after 6 months. Hemolytic ratio which expresses numerically the differences in the relative activity of antisera in vivo as compared with in vitro illustrates clearly the similarities and differences in rabbits under different experimental conditions, and in different stages of immunization. It may be that differences in the distribution of cells and tissues which participate in the production of the various antibodies are a determining factor.
Immunologic Relation of Streptococcal and Tissue Antigens
Authors: Kaplan Melvin H.
Published: January 2023

Antisera prepared in rabbits against cell walls or M protein preparations of a group A type 5 strain of streptococcus have been found reactive by immunofluorescence and complement fixation with human heart tissue. The reactant in heart tissue was localized to cardiac myofibers of all heart specimens tested and in smooth muscle elements of vessel walls and endocardium of a proportion of heart specimens tested. Rheumatic and nonrheumatic hearts showed comparable reactivity. The reactant was also identified in human skeletal muscle and in heart and skeletal muscle of the rabbit.

In the streptococcus, the cross-reactive antigen was demonstrated in cell walls and in acid extracts of cell walls by immunofluorescent absorption tests. Following absorption of antisera with cell walls, antibody bound to cell walls could be eluted at pH 3.0, and shown to possess serologic reaction with heart.

Cross-reactive antigen was partially purified from acid extracts of cell walls by chromatography on DEAE- and CM-cellulose columns and reactive fractions were consistently found to contain M protein. However, the serologic activities of type-specific M protein and cross-reactive antigen could be distinguished by absorption tests.

Absorption tests were employed for screening acid extracts of 52 streptococcal strains for presence of cross-reactive antigen. Positive tests were obtained with four type 5 and two type 19 strains, and presumptively positive tests with two additional type 19 strains. Forty-four strains of various types of group A and of groups C, D and G were found negative by this procedure.

The immunologic relationship between streptococcal cell wall antigen and myofibers and smooth muscle of vessel walls is consistent with the hypothesis that bound γ-globulin observed in rheumatic hearts in these sites is derived from immune bodies.
The Effect of Horse Serum on the Quality of Vaccinia Virus Grown in L Cell Cultures
Authors: Galasso G. J. , Sharp D. G.
Published: January 2023

Vaccinia virus, inoculated at a multiplicity of 10 particles per L cell in closed tube cultures with media containing the serum of certain individual horses has produced progeny notably poor in plaque-forming efficiency (quality). The total virus particle yield from these cultures has been high and independent of the particular serum used. These differences were greatly reduced when the sera were heated at 56°C for 30 min. Possible reasons for these effects include indirect influence of a heat-labile serum component upon progeny virus quality through the agency of the cell.
Studies on the Role of Complement in the Immune Clearance of Escherichia Coli and Rat Erythrocytes by the Reticuloendothelial System in Mice
Authors: Spiegelberg H. L. , Miescher P. A. , Benacerraf B.
Published: January 2023

The role of C′ in the immune clearance of sensitized E. coli and sensitized rat erythrocytes by the reticuloendothelial system of the liver and spleen is demonstrated in mice: Decomplemented mice are no longer able to eliminate rapidly antibody coated E. coli and rat erythrocytes from the blood.In vitro incubation of sensitized E. coli (37°C) and rat erythrocytes (0°C) with fresh mouse serum as source of C′ leads to full opsonized particles which can be equally well phagocytized by normal and decomplemented mice.Pepsin and papain digestion of rabbit immune globulins resulted in loss of opsonic activity.
Multiplicity of Insulin Binding Antibodies in Human Sera
Authors: Yagi Yasuo , Maier Patricia , Pressman David , Arbesman Carl E. , Reisman Robert E. , Lenzner Alfred R.
Published: January 2023

Insulin-binding antibodies in human sera were studied with respect to their immunoelectrophoretic and chromatographic properties. The reagents used for developing precipitate arcs in immunoelectrophoresis were mixtures of a trace amount of I131 insulin and rabbit antiserum against particular components of human serum. Arcs formed by reaction of rabbit antibody and insulin-binding components of human serum fix I131 insulin and can be revealed by radioautography. The method is simple and extremely sensitive. In addition, the nature of insulinbinding components can be readily identified by comparing the radioautograph with the stained slide. Fifteen out of 18 sera from diabetic patients under insulin treatment contained detectable amounts of insulin-binding components, presumably antibodies. (Three negative sera had been obtained from patients receiving less than 30 units insulin daily.) Sera from three insulin-allergic patients also contained insulin-binding antibodies. None of the sera from normal donors and diabetic patients who had never received insulin showed such components. In the majority of the sera tested, the insulin-binding activity was found only in the γ-globulin. However, a serum from an insulin-allergic patient had the activity in the β2A- and β2M-globulins in addition to the γ-globulin. Another serum from an insulin-insensitive patient (requiring 90 units daily) also showed the detectable activity in the β2A-globulin. Antibodies of the γ-globulin type were further separated into two distinctly different fractions by chromatography on diethylaminoethyl cellulose. These two fractions differed in their electrophoretic mobility (migrating in the γ1- and γ2-globulin regions respectively), but reacted in an identical manner against rabbit antiserum. The binding characteristics of these fractions to I131 labeled bovine zinc insulin were quite similar to each other.
Production of Neutralizing Antibody by Mice Injected with Actinophage
Authors: Bradley S. Gaylen , Watson Dennis W.
Published: January 2023

The sera of adult BALB mice showed increased neutralizing activity within 6 hr after the intraperitoneal injection of 1010 actinophage MSP8. Moreover, as few as 2 × 105 phage particles were sufficient to elicit a measurable immune response. Because most serum samples from normal mice contained detectable, specific antibody for coliphage T2, coliphage øX174 or actinophage MSP8, the observed increase in neutralizing activity after injection of phage was not considered a primary response. Sera from animals receiving a single antigenic stimulation displayed phage-neutralization kinetics different from hyperimmune sera. Activity of both early and late sera was in the γ-globulin fraction.
The Effect of Ionic Strength on the Formation, Stability and Lysis of Persensitized Erythrocytes (EAC′142)
Authors: Walker Harold G. , Wardlaw Alastair C.
Published: January 2023

Summary and Conclusions

This investigation has shown that at least two of the intermediate reactions in the over-all process of immune hemolysis are strongly influenced by ionic strength and proceed optimally at values in the region of 0.07 to 0.08 rather than at the physiologic ionic strength 0.155. The reactions so influenced are a) the formation of EAC′142 from EA, and b) the lysis of EAC′142 by C′3. The former reaction has a sharper optimum than the latter.

In contrast, two other reactions were found to be quite unaffected by changes in ionic strength over the wide range 0.035 to 0.3. These were a) the initial sensitization reaction in which EA is formed, and b) the decay reaction of EAC′142 to EAC′14. The ionic strength independence of the latter suggests that the foward reaction in which EAC′414 is converted to EAC′142 may also be indifferent to ionic strength. Hence the dependence on ionic strength in the formation of EAC′142 from EA probably resides in either or both of the previous steps in which EAC′1 and EAC′14 are successively formed.

These observations help to explain the previously reported finding (1) that the optimum ionic strength for the over-all process of immune hemolysis is close to 0.08.
The Resistance of A2G Mice to Myxoviruses
Authors: Lindenmann Jean , Lane Christine A. , Hobson Derek
Published: January 2023

Inbred A2G mice were found to be more resistant than other laboratory mice with respect to the following viral infections: neurotropic influenza A virus given intracerebrally (strains NWS, WSNF and Neuro-Kunz) and intranasally (strains NWS and WSNF); pneumotropic influenza A virus given intranasally (strains Swine, WS and PR8); and Sendai parainfluenza 1 virus given intranasally. Two mouse-adapted strains of Asian influenza (A/Singapore/1/57) were the only myxoviruses studied to which there was no difference in susceptibility between A2G and control animals.

Not many more virus particles were required to initiate neuro-infection in A2G mice as compared to control mice. Virus titers reached in the brains after inoculation of neurotropic influenza virus were 100 times lower in A2G mice; similarly, 100 times less virus was recovered from lungs of A2G mice inoculated with Lee influenza B virus of low mouse virulence.

No differences were found in the susceptibility to the toxic action of influenza A virus between A2G and control animals. After comparable inocula of influenza A virus given intranasally, A2G mice developed lower levels of hemagglutination-inhibiting and complement-fixing antibodies than did surviving controls.

A2G and control mice proved equally susceptible to the following viruses: Yellow Fever 17 D, West Nile, EMC, Polio type 2 (mouse-adapted), Herpes simplex and ECHO type 9.
Antibody, Lysozyme and Complement Levels in Animals Chemically Protected against X-Irradiation
Authors: Hook William A. , Toussaint Andre J. , Muschel Louis H.
Published: January 2023

Various chemicals have been found to protect animals against the lethal effects of x-rays when administered before irradiation. Substances creating anoxia and chemicals containing sulfhydryl (-SH) groups are among those discovered to be capable of protecting against doses of the LD50 to LD100 range (2). The effect of x-rays on the immune mechanism of mice given a protective chemical containing -SH groups was studied by Makinodan et al. (3) who found that the rate of recovery of the antibody forming mechanism in animals given 950 r and protected with 2-mercaptoethylguanidine hydrobromide (MEG) was approximately equivalent to the rate for mice given 475 r without protection. Their results indicated that -SH compounds such as MEG do not specifically protect antibody forming cells but aid the animal by acting as “dose reducing” agents. Irradiation has been shown also to cause a decline in levels of natural hemagglutinins (4), natural hemolytic antibodies (5), and bactericidal constituents of serum (6, 7).
Infectious Ribonucleic Acid of Japanese B Encephalitis Virus: Optimal Conditions for Its Extraction and for Plaque Formation in Chick Embryo Cell Monolayers, and Some Biologic Properties
Authors: Nakamura Masahiro , Ueno Yoshie
Published: January 2023

Optimal conditions for obtaining infectious RNA from mouse brains infected with JBE virus were three phenol extractions followed by more than three ether treatments for removing the excess phenol contained in the aqueous phase. Maximum number of plaques in chick embryo cell monolayers were formed either when the RNA preparation was diluted in 1.0 M NaCl solution, or when the cell layer was washed with 1.0 M NaCl solution prior to seeding with the RNA preparation. RNA required approximately 5 to 10 minutes to initiate maximum infection of chick embryo cell cultures. RNA was quite stable to acid compared to intact JBE virus, and was about as sensitive to heat as intact virus. Ether, chloroform, and n-butanol had no influence on the infectivity of JBE RNA, whereas the intact virus was promptly inactivated by these reagents. RNA was much more resistant to sodium desoxycholate than was intact virus.
The Inheritance of Hemolytic Complement Activity in CF-1 Mice
Authors: Tachibana Dora K. , Ulrich Marian , Rosenberg Leon T.
Published: January 2023

The presence or absence of hemolytic complement activity in CF-1 mice is determined by a single Mendelian factor. Complement deficiency occurs as a recessive character. The majority of CF-1 mice are deficient in hemolytic complement.
Studies on Complement Effects in a New Immune System
Authors: Davis John S. , Hurt John O. , Bollet Alfred Jay
Published: January 2023

NADH oxidase was markedly inhibited by dilute antimitochondrial antibody in the presence of a serum factor found in man, guinea pigs and rabbits. Little or no inhibition occurred when the additional serum was from mice or was treated with ammonia, EDTA, zymosan, or immune precipitates, or was heated to 56°C for 30 min. The factor which potentiates enzyme inhibition by antibody thus has all the properties of the hemolytic complement system. NADH-cytochrome C reductase, succinate-cytochrome C reductase, and cytochrome oxidase were markedly inhibited by the antimitochondrial serum. This inhibitory effect was overcome on addition of a complement source. Addition of small amounts of cytochrome C to the NADH oxidase system reversed the inhibitory effect of complement in the presence of antibody. Added cytochrome C did not serve as a terminal “trap” for electrons. These observations are consistent with the interpretation that antibody alone blocks access sites for the oxidation and reduction of exogenous substrate cytochrome C, while sparing the endogenous enzymatically functioning hemeprotein. On addition of complement, however, binding sites for exogenous cytochrome C are “revealed”, whereas endogenous cytochrome C is inactivated. This suggests specific effects of complement on the binding sites for cytochrome C. These effects of complement are analogous to the action of certain detergents and snake venom phospholipase A on electron transport particles, except that cytochrome C could not be recovered in the supernatant solutions.
The Effect on Antigenic Specificity of Changes in the Molecular Structure of Ribonuclease
Authors: Mills John A. , Haber Edgar
Published: January 2023

Antigenic determinants of proteins apparently involve considerable lengths of the amino acid chain (1). Because of molecular folding, chemical groups on the surface of the molecule which might constitute an antibody binding site could be widely separated in the amino acid sequence. Changes in the three dimensional configuration of a protein, by altering the topography of such binding sites, should interfere with its immunologic specificity. The availability of a method for altering the spacial configuration of a purified protein, ribonuclease, to new and reasonably stable three dimensional structures without chemically changing the amino acid residues, offered an opportunity for testing this hypothesis.

Procedures which grossly denature proteins are known to result in a loss of antigenic specificity (2, 3), but the molecular changes caused by such methods are ill-defined. They probably involve covalent changes in a number of amino acid residues.
Anti-Bovine Serum Albumin Formation by Transferred Hyperimmune Mouse Spleen Cells
Authors: Mark Raymond , Dixon Frank J.
Published: January 2023

Antibody formation by transferred hyperimmune spleen cells has been studied with bovine serum albumin as antigen and inbred mice as donors and recipients. It has been shown that isologous adult and neonatal hosts support antibody formed in neonatal hosts was less than that in adult recipients. Antibody was not formed in homologous adult or newborn recipients and this is most likely because of rejection of the transferred cells prior to their formation of antibody. The host vs. graft reaction could be suppressed by prior x-irradiation of recipients with consequent antibody formation by transferred homologous cells. Further, if isologous recipients were irradiated prior to cell transfer, the antibody response was found to be greater than that in nonirradiated isologous hosts. Transferred cells appeared to survive in the isologous recipients for a prolonged period of time with continuing formation of antibody.
Antigen Penetration into the Thymus
Authors: Sainte-Marie G.
Published: January 2023

Bovine serum albumin was injected intramediastinally in rats. It was found that part of the injected antigen reached the mediastinal lymph nodes as well as the adjacent thymus where it penetrated the medulla and some areas of cortex. In both thymic regions, the antigen was seen on and/or in the cytoplasm of lymphocytes. It is concluded that there exists no barrier to prevent the penetration of antigens into the thymic parenchyma, and that antigens which normally drain into the mediastinal nodes also penetrate the thymic parenchyma. This suggests that the failure of the thymus to yield antibody forming cells does not result from its nonpenetration by antigens.
The Effect of X-Radiation and Passive Antibody on Immunologic Tolerance in the Rabbit to Bovine Serum Albumin
Authors: Weigle William O.
Published: January 2023

Whole body x-radiation as employed in the above studies did not result in the termination of immunologic tolerance to BSA induced in rabbits by neonatal injection of BSA. The doses of x-radiation which were administered were 450 r and 1000 r. Passive anti-BSA and a combination of passive anti-BSA and x-radiation also had no effect on the BSA tolerant state. The relation of these results to both a theory of antibody production and the mechanisms involved in immunologic tolerance is discussed.
Protection of a Complement-Sensitive Enzyme System by Rheumatoid Factor
Authors: Davis John Staige , Bollet Alfred Jay
Published: January 2023

A factor in rheumatoid euglobulin can protect an enzyme-anti-enzyme system from the inhibitory effects of serum complement. The enzyme-protection effect correlated with the γ-globulin-coated latex particle agglutination titer. This factor could be adsorbed onto sensitized sheep cells and was presumed to be rheumatoid factor. The factor blocks complement fixation, resulting in recovery of complement in the supernatant fluid in active form. There is no evidence for direct inactivation of complement by rheumatoid factor.
Immunologic Unresponsiveness to Heterologous Serum Proteins Induced in Adult Mice and Transfer of the Unresponsive State
Authors: Dietrich Felix M. , Weigle William O.
Published: January 2023

Complete tolerance to HGG, TGG and partial tolerance to BSA was induced in adult C57B1/6 mice by injecting small amounts of soluble protein before an injection of antigen incorporated into Freund's adjuvant.

Minimal doses required to induce tolerance in mice lasting for a given period of time were compared to the amounts of protein left 20 days after injection. The results suggested that persistence of antigen per se is not the determining factor for maintaining the tolerant state.

“Adoptive tolerance” to HGG was induced in lethally irradiated recipients following injection of spleen cells of HGG tolerant donors. Spleen cells obtained from mice rendered tolerant either after birth, or later in adult life, were effective
Decreased Immunogenicity of a Transplantation Antigen in Hosts Sensitized to Other Isoantigens of its Cellular Vehicle
Authors: Elkins William L.
Published: January 2023

Accelerated rejection of male skin isografts by C57BL/6 female mice occurs as a consequence of previous injection of 20 million male CBA spleen cells by either the i.p. or i.v. route. However, if the test mice are immunized against CBA isoantigens from female donors 20 days before inoculation of the male CBA cells, rejection of the test grafts is significantly delayed. The inhibitory effect of prior CBA isoimmunization on sensitization to the male factor does not occur when isologous male cells are mixed with CBA female spleen cells and inoculated. These results are interpreted as evidence that the secondary response to the CBA isoantigens is capable of blocking access of the male antigen to those sites in which the primary response can be initiated.
Blood Group Antigens and Cross-Reacting Antibodies in Primates including Man
Authors: Wiener Alexander S. , Moor-Jankowski J. , Gordon Eve B.
Published: January 2023

Rabbits immunized with human blood of type N. He responded by producing antisera from which reagents of specificities anti-N, anti-He and anti-Me could be prepared. From the sera of rabbits immunized with blood from chimpanzees and baboons anti-M reagents have been prepared which give reactions almost identical with those of anti-M reagents prepared in the usual way from sera of rabbits immunized with human type M blood. These observations provide further evidence of the multiplicity of blood factors characterizing agglutinogens in general, and agglutinogen M in particular.
Streptococcal Related Glomerulonephritis
Authors: Markowitz A. S. , Lange Charles F.
Published: January 2023

Soluble fractions obtained from pooled human glomeruli and the cell membrane of nephritogenic streptococci were shown to be immunologically cross-reactive. One of the components present in the glomerular extract was shown to be unrelated to the streptococcal cross-reactive material but related to a component present on all human red cells tested. Chemical and physical analysis of soluble fractions obtained from isolated human glomeruli and streptococcal cell membranes indicated that they are low molecular weight glycoproteins. The glomerular extract has approximately 78.9% protein and 13 to 15% carbohydrate whereas the streptococcal extract has 80% protein and 7% carbohydrate. The glomerular fraction contains 1.5 to 2% sialic acid but no appreciable phosphorous whereas the streptococcal fraction has no sialic acid but 3.7% phosphorous.
Persistence of Acquired Tolerance in Cells Transferred to an Antigen-Free Environment
Authors: Stastny Peter
Published: January 2023

Lymph node and spleen cells of rats tolerant to sheep erythrocytes were transplanted into isologous, lethally irradiated recipients. Growth of lymphoid cells in these animals, which were presumably free of antigen, did not result in termination of the tolerant state during a period of up to 6 weeks before initial challenge with antigen. Antibody response to another antigen was normal. The state of tolerance induced in the donor animals was not permanent as demonstrated by antibody production after 6 months in the tolerant donor controls. At this time, however, irradiated recipients of tolerant lymph node and spleen cells remained tolerant. The failure of lymphoid cells from spleen and lymph nodes to lose tolerance more rapidly in the absence of antigen suggests that other factors may be required for this change.
γ-Globulin and Antibody Formation In Vitro
Authors: Thorbecke G. J. , Jacobson E. B. , Asofsky R.
Published: January 2023

The effect of whole body irradiation, administered on days 8 or 21 after a primary intravenous injection of BGG, on the ability to respond to a subsequent booster injection given at various intervals was studied in rabbits. It was found that late irradiation was followed by a permanent partial inhibition of the booster response, whereas early irradiation resulted in inhibition followed by a rapid recovery during the following week. This recovery was correlated with the destruction and reappearance of secondary nodules in the white pulp of the spleen. The cellular aspects of the various parameters of the irradiation effects are discussed.
Use of β-Propiolactone in Preparation of Inactivated Arbovirus Serologic Test Antigens
Authors: French George R. , McKinney Robert W.
Published: January 2023

The results of experimentation designed to develop procedures for preparing noninfectious arthropod-borne virus antigens are presented. Noninfectious serologic antigens have been prepared for the viruses of VEE, WEE, EEE, and TP-21 strain Langat virus and found to be comparable or superior in every respect to nontreated control antigens. Preliminary data are presented for Mayaro and YF viruses. The immediate HA titers of group A arbovirus BPL-treated antigens were usually 32- to 64-fold greater than those of nontreated preparations. A similar but less dramatic difference in titer was found with the group B virus agents tested. Concurrently, the pH range of agglutination is broader for BPL-treated HA antigens. BPL-treated CF antigens were usually equal in titer to nontreated controls and not anticomplementary. BPL-treated antigens may be stored in identical fashion to nontreated antigens and are equally stable. Recommendations are presented for preparing noninfectious HA and CF antigens for the six viruses tested.
the Nature of the Antigenic Relationship between Trichinella Spiralis and Salmonella Typhi
Authors: Weiner Lawrence M. , Neely Joann
Published: January 2023

The existence of a heterogenetic reaction between Salmonella typhi and Trichinella spiralis has been confirmed. The major antigen responsible is the somatic 12 antigen of S. typhi. A secondary role for the 9 antigen and an as yet uncharacterized antigen common to many Salmonella is also indicated.

The somatic antigens of Salmonella typhi successfully immunize mice and rats against experimental infection with larvae of Trichinella spiralis. The protective effect is directed primarily against the larval maturation process rather than the reproductive abilities of the adult forms. The flagellar antigens of the organism are not involved in the heterogenetic response.