bluuebunny/crossref_metadata_2025 huggingface dataset:
Thymus Dependence of Cells in Peripheral Lymphoid Tissues and in the Circulation Sensitive to Natural Thymocytotoxic Autoantibody in NZB Mice
Authors: Shirai Toshikazu , Yoshiki Takashi , Mellors Robert C.
Published: December 2022

The natural autoantibody against thymocytes of NZB mice was found to be cytotoxic in the presence of complement for some lymphocytes in the peripheral lymphoid tissues and in the circulation of C57BL/6J mice and phenotypically normal mice heterozygous for the recessive nude gene (nu/+). An extreme reduction or a total depletion in the number of autoantibody-sensitive lymphocytes was observed both in C57BL/6J mice thymectomized as newborns or as adults and in congenitally athymic nude mice homozygous for the nude gene (nu/nu). This observation suggests that the natural autoantibody against thymocytes of NZB mice has specificity for thymus-dependent cells. Congenitally athymic mice, although lacking autoantibody-sensitive lymphocytes, showed reactive antigen in brain tissue.
Studies on the Relative Synthesis and Distribution of IgA and IgG1 in Various Tissues and Body Fluids of the Cow
Authors: Butler John E. , Maxwell Charlotte F. , Pierce Carol S. , Hylton Martha B. , Asofsky Richard , Kiddy Charles A.
Published: December 2022

In vitro synthesis of bovine IgA was detected by a radioimmunoelectrophoretic assay in 17 of 20 different tissues obtained from cows and 2 of 6 different tissues obtained from a 1-week-old calf. Conclusions drawn from these qualitative studies are supported by the results of preliminary quantitative data. Synthesis of IgA was most pronounced in the adult ileum, duodenum, colon, lungs, lower nasal mucosa, oral pharyngeal mucosa, parotid gland, lacrimal gland and thymus and the calf parotid and lacrimal glands. Correspondingly, IgA, not IgG1, is the principal immunoglobulin in bovine tears and saliva. In comparison to other secretory tissues of the cow and the mammary glands of the rabbit, human and monkey, the bovine mammary gland shows moderate deficiency in the synthesis of IgA. This deficiency is reflected in the fact that IgA does not become the predominant immunoglobulin of normal bovine milk, although an increase in the IgA to IgG1 ratio does occur after parturition. The adult bovine thymus is an immunologically active secretory tissue, but the ileum of the 1-week-old calf appears to lack an IgA-producing system. The concentration of serum IgA is lower than in the human and is greater before calving than after. Most of the IgG1 synthesized in the mammary gland is eluted from Sephadex G-200 before 7S IgG1.
Identification of “J” Chain in a Homogeneous Canine IgA Immunoglobulin
Authors: Kehoe J. Michael , Tomasi Thomas B. , Ellouz Farielle , Capra J. Donald
Published: December 2022

A homogeneous IgA protein was isolated from the serum of a dog with myelomatous disease. Analytical ultracentrifugation showed that approximately 60% of this protein existed as an 11S component and the remainder as higher order polymers. The reactivity of the intact protein with an anti-human “J” chain antiserum implied that it contained a considerable amount of a “J” component. This was confirmed by the isolation of a highly acidic polypeptide by gel-filtration and ion-exchange chromatography from the 11S IgA after reduction. The amino acid composition of this polypeptide corresponded closely to that reported by others for human “J” components.
Myasthenia Gravis: Cross-Striational Fluorescence of Muscle Fibers Mediated by Fc Fragments
Authors: Aarli Johan A. , Closs Otto
Published: December 2022

The antiglobulin consumption test was performed by using human skeletal muscle tissue incubated with Fc fragments of γG globulins prepared from normal human serum. An increased consumption was found indicating binding of the Fc fragments to the tissue. The indirect immunofluorescence test was employed for localization of the binding. A cross-striational staining was found. The intensity was weaker, but the pattern otherwise indistinguishable from that observed when using a positive myasthenia gravis serum.
Genetics of the Immune Response
Authors: Di Pauli Raimund
Published: December 2022

The antibody response to Salmonella lipopolysaccharides was investigated at the cellular level by means of a hemolytic plaque test combined with inhibition. With these techniques the cross-reactivity of antibodies produced by single cells could be studied. A difference in the ability of mouse strains to produce typical specific antibodies was found. This strain difference resides in the process that recognizes the antigen and is not due to a lack of antibody-producing precursor cells. The role of receptors in the recognition of lipopolysaccharide antigens is discussed.
IgD-Bearing Human Lymphocytes
Authors: van Boxel John A. , Paul William E. , Terry William D. , Green Ira
Published: December 2022

IgD is a class of immunoglobulin described, thus far, only in humans and constituting approximately 0.2% of all serum immunoglobulin (1–2). Although antibody activity has been ascribed to the IgD class of immunoglobulin, the biologic function of these molecules is unknown (3–10). We now report that a surprisingly large fraction of human peripheral blood lymphocytes bear surface IgD. Thus, a mean of 2.7% of lymphocytes can be shown to have membrane-associated IgD. This is approximately 18% of all lymphocytes bearing surface immunoglobulin.

Materials and Methods. Heparinized venous blood from normal adult donors was sedimented in 6% dextran (Phamachem Corp., Bethlehem, Pa.) and the white cell-rich supernatant plasma incubated on rayon wool columns for 30 min at 37°C in an atmosphere of 95% air and 5% CO2. The erythrocytes in the effluent cell suspensions were lysed with ammonium chloride (11); the cells were then washed and resuspended in RPMI 1640 (Grand Island Biological Co., Rockville, Md.).
Intravaginal Immunization of Humans with Candida Albicans
Authors: Waldman R. H. , Cruz J. M. , Rowe D. S.
Published: December 2022

Ten women were immunized intravaginally with a Candida albicans vaccine. Antibody was measured by a radioactive single radial immunodiffusion technique, and antibody activity was expressed as the area of the precipitin ring. The mean rise in serum antibody was 41 to 66 mm2. The mean rise in cervicovaginal secretion antibody was from <12 mm2 to 74 mm2. The cervicovaginal secretion antibody was removed by absorption with anti-IgA, but not appreciably by anti-IgG or anti-IgM. These results suggest that cervicovaginal secretion IgA antibody is locally produced and can be stimulated by local application of antigen.
Polymer Formation and J Chain Synthesis in Mouse Plasmacytomas
Authors: Halpern Michael S. , Coffman Robert L.
Published: December 2022

Three out of four cloned mouse plasmacytoma cell lines examined synthesized and secreted polymeric IgA with covalently bound J chain, thus establishing that J is synthesized by the plasma cell. A fourth cell line synthesized and secreted only monomer (7S) IgA which contained no J chain. In the immunoglobulin secreted by the polymer-secreting lines, J was not bound to monomer and was added to polymer at or very near the time of polymerization. These results are consistent with the suggestion that polymer assembly is mediated by J chain.
Lymphocyte Classes in New Zealand Mice
Authors: Stobo John D. , Talal Norman , Paul William E.
Published: December 2022

Newborn through 1-year-old NZB mice demonstrate a 30 to 50% decrease in the frequency of κ-bearing splenic lymphocytes, compared to similarly aged BALB/c mice. In addition, the frequency of immunoglobulin-bearing cells among lymph node and spleen cell populations of 6-week-old NZB, NZW and (NZB × NZW)F1 mice is substantially decreased compared to five normal strains. In NZ animals, the immunoglobulin-bearing cells appear to be replaced by a nonthymus-derived lymphocyte which lacks detectable ϑ or κ chain determinants. Although the significance of these cells is yet uncertain, they may be an early manifestation of a basic immunologic defect in NZ animals.
Radiation Dose, Dose Rate, and Quality in Suppression of the Humoral Immune Response
Authors: Gottlieb Charles F. , Gengozian Nazareth
Published: December 2022

Radiation-induced immunosuppression was studied with special emphasis on the factors of dose rate and quality of the radiation. Fission neutrons, x-rays, and 60Co γ-rays at dose rates ranging from 2.8 to 95 rads/min were tested for their biologic effect. Data reported earlier from our laboratory were supplemented as necessary to allow intercomparisons to be made. The biologic systems in the mouse included: a) animal mortality, b) immune response capability of the irradiated animal, and c) antibody formation by irradiated spleen cells cultured in unresponsive hosts. The following empiric relationships were established: a) the three biologic responses were each related to the radiation dose by a probit-type analysis, b) the magnitude of the dose-rate effect was an exponential function of the linear energy transfer (LET), and c) the inverse cube root dose-rate relationship reported earlier was confirmed. Immunosuppression of the whole animal was related to mortality, but not in a simple manner: as the LET of the radiation used declined, the level of immunosuppression at the LD50 increased, indicating that mortality is not necessarily a measure of the level of immune activity. We present an empiric expression relating the radiation dose rate and quality (LET) to the expected biologic effect, anticipating the possible application of these data to clinical situations.
Complement-Unlike Hemolytic Activity in Lobster Hemolymph
Authors: Hall James L. , Rowlands David T. , Nilsson Ulf R.
Published: December 2022

Hemagglutinating and cobra venom factor (CVF)-activated hemolytic activities were found in the hemolymph of the lobster, Homarus americanus. The substances in hemolymph responsible for these two activities were separated and shown to be mutually independent. Hemolytic activity was due to the action of a low level of phospholipase A in the CVF preparation on lobster hemolymph lipoprotein. Lecithin was converted to lysolecithin. Phospholipase A activity was also demonstrated in a commercial preparation of CVF. Lecithin and human lipoproteins as well as lobster lipoproteins were suitable substrates for both CVF preparations.
Chemical Evidence for λ-Type Amyloid Fibril Proteins
Authors: Kimura S. , Guyer R. , Terry W. D. , Glenner G. G.
Published: December 2022

A group of proteins comprising the major component of human amyloid fibrils have been shown to have antigenic determinants in common with the amino terminal segment of immunoglobulin light polypeptide chains (1). On the basis of these immunochemical studies amyloid proteins of immunoglobulin origin have been designated as either of λ- or κ-type. Automatic amino acid sequence analysis has demonstrated that the κ-type amyloid fibril proteins are homologous with the amino terminal protion of a κ-Bence Jones (BJ)3 protein (2, 3).

Amyloid fibril proteins isolated from four patients have been fractionated by gel filtration to purity as defined by the presence of a single band on sodium dodecyl sulfate polyacrylamide disc gel electrophoresis (4). Immunochemical analysis of these four preparations showed reactions consistent with the presence of λ-light chains (1) and chemical analysis indicated that the polypeptide chains in these preparations had unreactive amino terminal residues (4).
Disappearance and Recovery of Human Monocyte IgG Receptor Activity After Phagocytosis
Authors: Schmidt M. E. , Douglas S. D.
Published: December 2022

Human monocytes were incubated with latex or formalin pre-treated SRBC and tested for IgG receptor activity. After 10 min, receptor activity could not be detected in 90% of phagocytizing cells; after 6 hr, 78 to 84% of the monocytes recovered IgG receptors. The kinetic data and the morphologic observation of selective sites of membrane binding suggest internalization followed by recovery of monocyte plasma membrane IgG receptor sites.
New Specificities in Australia Antigen Positive Sera Distinct from the Le Bouvier Determinants
Authors: Magnius Lars O. , Espmark J. Åke
Published: December 2022

Evidence for new antigenic specificities in Australia antigen positive sera, for one of which we have proposed the designation e, has been obtained in immunodiffusion tests according to Ouchterlony. These specificities co-occur with Au antigen and are distinct from the a, d, y and x determinants of the Au antigen complex according to Le Bouvier and occur on particles other than those carrying the a determinant. It was found in 18 out of 23 persistent carriers of Au antigen from hemodialysis units, in 6 out of 43 Au positive hepatitis cases but in none of 17 Au antigen-carrying blood donors. In the latter group, however, antibodies against the specificities described herein occurred in 13 out of 17 individuals. In five of these cases the antibody was directed against the e specificity. Some evidence is presented for the possible association of this antigen complex to contagiousness.
The Immune Capacity of Lymphocytes after Cross-Linking of Surface Immunoglobulin Receptors by Antibody
Authors: Katz David H. , Unanue Emil R.
Published: December 2022

Spleen cells from mice primed previously with keyhole limpet hemocyanin (KLH), horse erythrocytes (HRBC) or trinitrophenyl (TNP)-HRBC were incubated in vitro under appropriate conditions and with doses of anti-immunoglobulin antibodies known to cause partial or complete endocytosis of surface Ig-anti-Ig complexes. The effect of such treatment on the immune capacity of such cells was evaluated by both in vivo adoptive transfer secondary antibody responses and in vitro secondary antibody responses. These studies have shown that movement and endocytosis of surface Ig receptors by anti-Ig do not, per se, diminish or abolish the capacity of primed lymphoid cells to respond in a normal fashion to antigen subsequent to the reappearance of their receptors. Similarly, movement and endocytosis, per se, do not appear to trigger primed B lymphocytes to result in antibody formation in the absence of specific antigen either in vivo or in vitro. On the other hand, after reaction with anti-Ig, the efficiency of the antibody response of primed lymphoid cells in vitro is significantly increased upon subsequent antigenic stimulation.
The Immunologic Specificity and Biologic Activity of Heterologous Anti-Human Sera
Authors: Bachvaroff R. , Rapaport F. T.
Published: December 2022

Cultured human fibroblasts obtained from normal donors were used to produce heteroantisera in rabbits. The resulting antisera contained high titers of cytotoxic antibodies against three major categories of cell surface antigens: 1) species-specific antigens present on all human tissues tested; 2) species-specific antigens shared by man and subhuman primates; 3) fibroblast-specific antigens. In addition, rabbit antisera against human fibroblasts contained non-cytotoxic precipitating antibodies against soluble antigen(s) present in fibroblasts, lymphocytes and in the α1-glycoprotein fraction of normal human serum.
Effect of Anti-Mouse IgG1 on Some Complement-Requiring Alloantibodies of the Mouse
Authors: Harris T. N. , Harris Susanna
Published: December 2022

Ascitic fluid globulins of CBA mice previously injected with BALB/c spleen cells, containing alloantibodies which suppress hemolytic antibody plaque formation by BALB/c spleen cells, were treated by the addition of rabbit antimouse IgG1 serum and removal by high speed centrifugation of the resulting precipitate. The titer of suppressive antibody was found to be higher in the supernatants than in the original globulin. With increasing amounts of anti-IgG1 added, the suppressive titer rose progressively to a plateau level, at which it remained through further increases in the amount of anti-IgG1 added. The amounts of anti-IgG1 serum required to reach this plateau level varied between 0.1 and 0.3 ml/0.1 ml of the anti-BALB/c globulin pools. The supernatants were also examined by immunodiffusion to determine the endpoint for removal of all IgG1 from the globulin pools; this was found to coincide with that which brought the anti-BALB/c globulin pool to its maximal (plateau) level of suppressive titer. The extent of the increase in suppressive titer to its plateau level showed an association with the amount of anti-IgG1 required, but some overlapping was found.

Cytotoxic titers of these globulin pools also increased on addition of anti-IgG1, to a plateau level, and each globulin pool required the same amount of anti-IgG1 for attainment of plateau level as did the suppressive titer. The extent of the increase of the suppressive and cytotoxic titers, however, showed no relationship to each other. Titers of complement fixation against BALB/c spleen cell membrane fragments also showed such increases, again with the same relative amount of anti-IgG1 required to attain the plateau titer. Hemagglutination titers for BALB/c red blood cells (RBC) showed no change or a slight decrease on addition of anti-IgG1 and centrifugation.

These results indicate the presence in the anti-BALB/c globulin pools of complement-fixing antibodies, probably of IgG2 class, and noncomplement-fixing IgG1 antibodies of the same specificity which can compete with the IgG2 antibodies, as indicated by the increased titers after removing IgG1. The presence of such competing antibodies suggests that complement-requiring antibodies, in naturally occurring mixtures of IgG, could show titers substantially lower than their true level, or be entirely masked.
Cell Surface-Associated Gamma Globulins in Lymphocytes
Authors: Paraskevas F. , Orr K. B. , Lee S-T.
Published: December 2022

The reverse immune cytoadherence technique (RICA) which detects surface-associated γ globulins on lymphocytes was used to study the effect of antigenic stimulation on γ globulin-carrying lymphocytes. Six hours after administration of antigen in Freund's complete adjuvant there is a marked increase in γ globulin-carrying cells (by 8 to 10% of the spleen cells or 25% of γ globulin-carrying cells before immunization). A similar increase was produced in vitro by treating normal spleen cells with serum obtained 6 hr after antigenic stimulation and likely represents the attachment of a cytophilic γ globulin to cells previously not carrying surface γ globulin. Adjuvant is important for the induction of this increase by soluble antigens but particulate antigens in saline can induce similar changes. These changes are not related to the distinction of the antigens according to their degree of dependency on the thymus for an immune response. The number of γ globulin-carrying cells decreased dramatically by 24 hr and reached its lowest point at 15 days when the γ globulin-carrying cells decreased by 50% of the normal levels of γ globulin-carrying cells. The decrease of the γ globulin-carrying cells does not depend on the presence of adjuvant. It is suggested that this phenomenon may represent the loss of surface γ globulins from lymphocytes after the antigenic encounter. All plasma cells examined in this study by RICA showed no surface γ globulin.

According to the results presented here it is obvious that antigen affects a very large cell population.
Cell Surface-Associated Gamma Globulins in Lymphocytes
Authors: Lee S-T. , Paraskevas F.
Published: December 2022

Antigen in complete Freund's adjuvant injected intraperitoneally in mice induces large-scale changes of thymus-derived (T)-and bone marrow-derived (B)-cells in terms of surface-associated γ globulins as shown by reverse immune cytoadherence (RICA) and cytotoxicity. Six hours after antigenic stimulation there is an over-all increase of γ globulin-carrying cells. Exposure in vitro of normal spleen cells to serum collected 6 hr after antigenic stimulation reproduces the increase of the γ globulin-carrying cells observed in vivo. The increase is due to the acquisition of a cytophilic γG globulin by a T-cell. Such evidence is derived from the fact that concomitant to the 6-hr increase of γ globulin cells the number of T-cells detectable in the spleen by anti-θ serum decreases approximately by the same number. Furthermore anti-θ serum-treated normal spleen cells exposed to 6-hr serum do not show the increase and spleen cells from irradiated mice reconstituted with thymus cells show a similar to normal increase after challenge with antigen. In addition to these changes, in a significant number of the cells which carry γ globulin before immunization (B-cells), surface γ globulin is not detectable. Since the number of T-cells which take up γ globulin is larger than the number by which the B-cells decrease, the net result is an over-all increase of γ globulin-carrying cells at 6 hr.

After this time interval the T-cells return to normal levels within the 1st week, while the B-cells progressively decrease and reach the lowest point of 45% of the pre-immunization level 2 weeks after antigenic stimulation. Although the relationship of the phenomena described to other known phenomena of the immune response is at present obscure they nevertheless indicate that antigen affects a population of cells much larger than the antigen sensitive cells.
Antiantibody Enhancement of Hemagglutination Inhibition by Influenza Anti-Neuraminidase
Authors: Dowdle W. R. , Sarateanu D. , Reimer C. B.
Published: December 2022

Hemagglutination by influenza viruses can be inhibited by antibody to hemagglutinin or, under certain conditions, by antibody to neuraminidase. In the hemagglutination-inhibition (HI) test with antibody to hemagglutinin the HI titer is approximately proportional to the reciprocal of the virus concentration. In contrast, in the neuraminidase-hemagglutination inhibition (N-HI) test a 2-fold increase in virus dosage produced a nearly 7-fold decrease in antibody titer. The addition of antihuman IgG in most instances vastly increased the N-HI titers. The magnitude of enhancement was strongly dependent upon the combination of human sera, the virus dose and the particular lot of antihuman IgG. Fifteen of 21 commercial lots of antihuman IgG produced an enhancing effect. Greatest enhancement (up to a 1000-fold) was more often produced by antisera with the highest precipitating antibody potency (E-value) to human IgG. The enhancement of N-HI titers by antiantibody constitutes a highly sensitive test system. Each reactant is a potentially major variable which may appreciably alter the test results.
Reactions of Sensitized Guinea Pigs to Inhaled Antigens
Authors: Alexander H. L. , Becke W. G. , Holmes J. A.
Published: December 2022

Numerous efforts have been made to explain the underlying mechanism of bronchial asthma by attempts to reproduce similar symptoms in guinea pigs. Almost invariably the process has involved the introduction of antigenic substances into the respiratory tract of sensitized guinea pigs whose symptomatic and immunological behavior has then been noted. The results of these experiments, briefly summarized, are as follows:

When normal guinea pigs were exposed to suitable antigenic substances in the form of vaporous sprays, they apparently could be readily sensitized, for if subsequently injected intravenously with the antigen, they suffered anaphylactic symptoms. This was demonstrated first by Busson (1), and later by others (2) (3).

In contrast to this, guinea pigs that were sensitized no matter by what route, and later exposed to vaporous sprays of the sensitizing antigen rarely suffered anaphylactic symptoms on such contact, and then only when supplementary procedures were carried out.
Studies on the Dick Test and Natural Immunity to Scarlet Fever Among the American Indians
Authors: Sherwood Noble P. , Nigg Clara , Baumgartner Leona
Published: December 2022

Summary and Conclusions

Our experience at Haskell Institute as well as that of physicians at the other Indian Agencies would indicate that where epidemic diseases occur among the whites and exposure is possible, they develop also among the Indians. The one exception reported is scarlet fever. The American Indian apparently enjoys a high degree of natural immunity to scarlet fever. He is apparently exceedingly susceptible to measles, whooping cough, and fairly susceptible to diphtheria and Vincent's angina, as well as to the other infectious and contagious diseases. Very little evidence of furunculosis was obtained although streptococcus infections are quite common. Skin test would indicate that susceptibility to scarlet fever among the Indians is equal to that among the whites in the younger ages, but much less as maturity is reached. This work suggests some other mechanism supplementing antitoxic and perhaps also opsonic immunity to scarlet fever. The results indicate a certain lack of parallelism between the Dick test and natural immunity to scarlet fever.
Studies in Hypersensitiveness
Authors: Levine Philip , Coca Arthur F.
Published: December 2022

A quantitative study of the interaction between atopic reagin and its related atopen confirms the observation of Coca and Grove that the reagin is neutralized, that is, deprived of its sensitizing power by the admixture of the atopen, but that the activity of the latter is not lessened in any apprecible degree by the presence of its related reagin in the mixture. Confirming the observation of Coca and Grove, repeated reactions were obtained in the same sensitized site with the same concentration of the atopen. Such repeated reactions could be obtained even when the first “dose” of the atopen was mixed with the serum containing the reagin in vitro, that is, before its injection into the normal skin. The law of Coca and Kosakai regarding the fractional neutralization of precipitin applies in a modified form to the fractional “neutralization” of atopic reagin. After a passively sensitized skin site has been rendered insensitive, by repeated injections, to a certain concentration of the related atopen, a further reaction can be elicited with a stronger concentration, the ratio of the two concentrations being apparently constant with one atopic serum in the same skin.
Studies in Hypersensitiveness
Authors: Levine Philip , Coca Arthur F.
Published: December 2022

Two methods are outlined for studying quantitatively the reagins in the serum of hay fever patients. The reagin content of serum of patients with early hay fever was found to be proportional to the skin sensitivity in 27 of the 29 patients. With the method of serum dilution, the A sera have about four times the sensitizing power of the B sera, which, in turn, have about four times the sensitizing power of the C sera. The ratios are distinctly greater with the method of atopen dilution. In 2 cases with disporportion of reagin content and skin sensitivity, there was a loss of reagins from the serum with no corresponding drop of skin sensitivity. In each case, this decrease of reagins was associated with a gradual decrease in severity of the symptoms. Quantitative study of the reagins in 6 cases of late hay fever indicate that a similar proportion of reagin content and skin sensitivity exists in late hay fever.
Obscured Reactions in the Agglutination Test for Bacillary White Diarrhea
Authors: Mathews Frank P.
Published: December 2022

The agglutination test for bacillary white diarrhea is frequently obscured by a precipitate, the principal constituent of which is protein. Two cubic centimeters of a 2 per cent water solution of NaOH added to 100 cc. of E. sanguinaria antigen did not influence its agglutinability and eliminated 95 per cent of the “cloudy tests” when added just before setting up the test.
Carrier Function in Anti-Hapten Antibody Responses
Authors: Katz David H. , Paul William E. , Benacerraf Baruj
Published: December 2022

Guinea pigs primed with 2,4-dinitrophenyl (DNP)-ovalbumin (OVA) will develop markedly enhanced secondary anti-DNP antibody responses to the heterologous conjugate DNP-bovine γ globulin (BGG) provided that they have been supplementally immunized with appropriate amounts of BGG. This phenomenon reflects the enhancing influence of BGG-specific thymus-derived (T) lymphocytes on anti-DNP antibody production. The present studies demonstrate that such enhancing T cell influences can be abolished by the following manipulations: 1) simultaneous supplemental immunization with two unrelated proteins such as BGG and keyhole limpet hemocyanin (KLH) or glucose oxidase (GO) significantly diminished the secondary anti-DNP response upon challenge with a DNP-conjugate of one of the carriers employed; 2) the intraperitoneal injection of soluble BGG, in the appropriate dose range, 1 day before secondary DNP-BGG challenge completely abolishes the anti-DNP response regardless of whether BGG alone or BGG together with KLH had been used in the supplemental immunization; 3) a challenge with soluble KLH 1 day before secondary challenge with DNP-BGG inhibits the anti-DNP response provided KLH had been administered simultaneously with BGG in the supplemental immunization. The failure to observe similar suppression when KLH was replaced by a copolymer of d-glutamic acid and d-lysine (D-GL) which is nonimmunogenic for T cells indicates that this suppression is a reflection of a T cell-mediated influence.

We have interpreted these observations to indicate the production of soluble inhibitory mediators in phenomena such as antigen-induced suppression (“antigenic competition”) and, furthermore, that the elaboration of such mediators is most likely by T lymphocytes. Reasons for favoring the concept that enhancing or inhibitory influences on antibody production represent two ends of the spectrum of regulation exerted, perhaps, by the same T cell product are discussed.
Experimental Allergic Encephalomyelitis in Inbred and Outbred Mice
Authors: Levine Seymour , Sowinski Richard
Published: December 2022

Experimental allergic encephalomyelitis (EAE) was produced in 3 of 14 inbred and 3 of 4 outbred mouse strains. A single immunization with mouse spinal cord, mycobacterial adjuvant and pertussis vaccine produced clinical signs of EAE in most members of susceptible strains after 12 to 18 days. One apparently resistant strain was converted to susceptible by inoculations directly into lymph nodes. In one susceptible strain, inoculation into lymph nodes made it possible to produce EAE without pertussis vaccine. Thus, tests of footpad and lymph node inoculations, with and without pertussis vaccine, have exposed hierarchal levels of susceptibility among mouse strains, each of which may be under separate genetic control.
The First Component (C1n) of the Complement System of the Nurse Shark (Ginglymostoma Cirratum)
Authors: Ross Gordon D. , Jensen Joerg A.
Published: December 2022

Nurse shark C1 (C1n) was incompatible with rabbit IgG or IgM but could be hemolytically measured with sheep erythrocytes sensitized with natural nurse shark antibody (EAn). C1n was precipitated from nurse serum by dilution with 4.0 M urea to µ = 0.04 at pH 7.3 and 0°C. The precipitate was washed twice in µ = 0.15 Veronal-buffered saline (VBS++) and then dissolved in µ = 0.25 VBS++. The resulting C1n preparation had high specific activity but was still contaminated with nurse IgM. When optimally sensitized EAn were reacted for 20 min at 30°C with 90 effective molecules of C1n per cell in isotonic dextrose gelatin Veronal buffer (DGVB++) (µ = 0.12, pH 6.9), maximum reactivity of the resulting new intermediate cell (EAnC1n) was obtained. These cells could be specifically lysed with guinea pig serum devoid of C1 or whole guinea pig serum dilutions, since EAn did not react with guinea pig C1. C1n transfer from EAnC1n or the corresponding stroma to EAn was mainly dependent on the ionic strength. Antibody transfer could also be demonstrated, but antibody and C1n did not transfer as a unit. Mixed intermediate complexes: EAnC1n4gp, EAnC4gp could be formed.
Fibrillar Assemblage of Variable Segments of Immunoglobulin Light Chains: An Electron Microscopic Study
Authors: Shirahama Tsuranobu , Benson Merrill D. , Cohen Alan S. , Tanaka Akira
Published: December 2022

Bence Jones protein was enzymatically cleaved into its variable and constant segments, and then the variable segment was precipitated at neutral pH. The precipitate stained well with Congo red and showed green birefringence under the polarized light after such staining. High resolution electron microscopy of shadow-casted and negatively stained preparations revealed that they consisted of three types of fibrillar structures, respectively measuring 10 to 20 Å, 25 to 40 Å and 75 to 100 Å in width. The thinner fibrillar structures dominated the specimens from earlier stages of the precipitation procedure, while thicker ones predominated in the later samples. The sequential appearance of these structures and other observations suggested that they represented fibrils in different stages of development. These light and electron microscopic aspects of the precipitate have many points corresponding with those of the amyloid, although the identity between the two substances remains to be established. Moreover, the fibrillar structures could be produced in only 3 of 13 Bence Jones proteins treated in an identical fashion.
Serum Transmissibility of Immune Polioencephalomyelitis in C58 Mice
Authors: Sager Mark A. , Lawton John W. M. , Murphy William H.
Published: December 2022

The serum transmissibility of immune polioencephalomyelitis in C58 mice was characterized. The disease could be transmitted in C58 mice 10 or more months old but not in the BALB/wm, C3H/HeJ, C57BL/6J and AKR/J strains. The serum of both young and old mice was positive 24 hr after they were immunized with line Ib malignant leukocytes, reached a high titer (1:10,000) and remained positive for 11 to 15 days. Young mice remained free of disease. The active serum component was resistant to RNAse, DNAse and phosphodiesterase but was essentially inactivated by pronase. Sequential exposure of serum to RNAse or DNAse followed by pronase did not inactivate the serum factor more effectively than pronase alone. Transmission studies with purified immunoglobulins and immunoabsorption tests indicated that the serum factor was not an immunoglobulin. The active serum component was resistant to 37°C for 4 hr, repeated freeze-thaw, but was inactivated by exposure to 56°C for 45 min. Ultrafiltration studies showed that the active serum factor had a molecular weight between 64,000 and 165,000.
Effect of Cobra Venom Factor on the Local GVH Reaction
Authors: Ballow Mark , Day Noorbibi K. , Good Robert A.
Published: December 2022

A cytotoxic factor for rat lymphocytes present in cobra venom is described and partially characterized. This cytotoxic factor (CF) was isolated by gel filtration on Sephadex G-100 from anticomplementary cobra venom factor (CVF) that had been previously partly purified by DEAE chromatography. The CF elutes from G-100 later than does the anticomplementary CVF. Estimates indicate a molecular weight of about 13,000. While rat lymphocytes are very sensitive to this factor as indicated by a decrease in capacity to exclude trypan blue, erythrocytes and peritoneal leukocytes are more resistant. The activity of CF is temperature dependent.

Studies of the local graft-vs-host reaction revealed an inhibitory influence of the partially purified DEAE-CVF that was attributable to the new CF of cobra venom. The role of the two CVF in GVH disease and other cellular immune functions is discussed.
Differentiated Functions Expressed by Cultured Mouse Lymphoma Cells
Authors: Harris Alan W. , Bankhurst Arthur D. , Mason Sally , Warner Noel L.
Published: December 2022

Nineteen different radiation-induced thymomas originating in BALB/c, NZB and NZW mouse strains were tested for Ig synthesis by short-term culture with 14C-amino acids followed by radioimmunoelectrophoresis. Twelve were negative, six produced light (L) chains and one synthesized a protein similar to IgM. The IgM producer, WEHI-22, and one of the L chain producers, WEHI-105, were established as cloned cultured cell lines and shown to possess the lymphoid cell characteristics of susceptibility to inhibition by low concentrations of thymidine and of cortisol. Both were also shown to bear the θ antigen, a thymus-derived (T) lymphocyte marker. Cells of the WEHI-22 line also possessed surface immunoglobulin readily detectable by binding of labeled anti-Ig antibody and were able to bind mouse antibody-coated sheep erythrocytes forming rosettes, while WEHI-105 did neither. The specificity of the Ig receptor mediating rosette formation appeared from myeloma protein competition experiments to be very similar to that of the receptor described for non-thymus-derived (B) cells.

It was considered that WEHI-22 cells either possess a mixture of T and B cell characteristics or are neoplastic variants of T cells possessing surface IgM with antiglobulin activity.
Proportion of T and B Lymphocytes in Lesions of Marek's Disease: Theoretical Implications for Pathogenesis
Authors: Rouse B. T. , Wells R. J. H. , Warner N. L.
Published: December 2022

Cell preparations from visceral tumors and nerve lesions of chickens with Marek's disease (MD) were examined with antisera specific for avian T and B lymphocytes. In all instances examined, the large majority of lymphoid cells in the infiltrate were T lymphocytes, with only 3 to 10% of B lymphocytes present. It is suggested that the pathogenesis of this disease involves a T cell-mediated immunologic attack on virus-infected epithelial cells, analogous to that observed in lymphocytic choriomeningitis of mice.
Amplification of Thymus-Influenced Lymphocytes by Poly(A:U): Inhibition of Antigen Binding by Antiserum to Immunoglobulin Light Chain
Authors: Marchalonis John J. , Cone Robert E. , Rolley Ronald T.
Published: December 2022

Immunization of CBA mice with sheep erythrocytes (SRBC) plus a non-toxic adjuvant consisting of complexes of the homoribopolymers of polyadenylic acid and polyuridylic acid (poly(A:U)) induces the formation of a population of immunocytoadherent cells which is enriched in thymus-derived lymphocytes (T-cells). Four days after immunization, approximately 50% of specific rosette-forming cells (RFC) from mice given SRBC plus poly(A:U) bear the θ antigenic marker. In contrast, the number of θ-positive RFC in animals given SRBC alone does not constitute a significant proportion of the population. The capacity of both immune lymphocyte populations to bind SRBC is abrogated by treatment with antiserum specific for the light chain of normal mouse immunoglobulins. The inhibitory activity of this antiserum is completely blocked by addition of purified mouse γG immunoglobulin.

These observations are consistent with the hypothesis that immunoglobulin functions as the receptor for antigen on the surfaces of T-cells induced by antigen and poly(A:U).
Graft-Vs-Host Reactivity of Mouse Thymocytes: Effect of Cortisone Pretreatment of Donors
Authors: Tigelaar Robert E. , Asofsky Richard
Published: December 2022

The graft-vs-host (GVH) activity of thymocytes from BALB/c mice treated 48 to 72 hr previously with 2.5 mg cortisone acetate has been studied with both a spleen weight assay and a mortality assay. Although the cortisone-resistant (CR) thymocytes were 10 times as active as normal thymocytes in the spleen weight assay, they were only 4 to 5 times as active in the mortality assay, and the yield of thymus cells from cortisone-treated donors was only 1/25 that from normal donors: such pretreatment thus resulted in over 50% loss of total GVH reactivity recoverable from the thymus when measured by the spleen weight assay, and approximately 80% loss when measured by the mortality assay. In contrast to normal thymocytes, CR-thymocytes were unable to interact synergistically with normal peripheral lymph node cells; they were also unable to interact synergistically with normal thymocytes. The kinetics of cumulative mortality induced by CR-thymocytes were identical to those of normal thymocytes and strikingly different from those produced by various peripheral lymphoid cell populations. These results suggest that CR-thymocytes represent a unique population of thymus-derived cells and lend support to the concept that different expressions of cell-mediated immune reactions may be initiated by distinct cell types.
B-Cell Differentiation in the Splenic Environment: Acquired Susceptibility to the Helper Function of Irradiated T Cells
Authors: Ito Takaaki , Kino Toshiya , Cudkowicz Gustavo
Published: December 2022

The in vivo helper function of specific thymic inducer cells in anti-sheep hemolytic responses was retained after exposure to 1000 rads of γ-rays, but not after 3000 rads. A prerequisite for B-T cell interactions involving irradiated T cells was the residence (i.e., differentiation) of bone marrow-derived precursor cells outside the bone cavities, e.g., in the spleens of irradiated nonthymectomized mice. It is suggested that reproductive viability of T cells is not essential for inducing γM or γG responses in vivo, and that the properties acquired by B cells in the splenic environment confer susceptibility to the effects of nonantigen-specific T-cell mediators.
Antibodies against Sporozoites of Human and Simian Malaria Produced in Rats
Authors: Nussenzweig R. S. , Montuori W. , Spitalny G. L. , Chen D.
Published: December 2022

The various methods commonly used for the detection of antimalarial antibodies employ, in nearly all instances, the erythrocytic stages of these parasites as antigen source (1). The antigenic components of the different stages of development of the malaria parasites, however, differ considerably, in spite of the existence of some shared or common antigens (2, 3). Furthermore, the common antigens do not account for all of the antigenic components of the parasites, nor do they include the functional, i.e., protective, antigens of the various developmental stages. This is suggested by the finding that rodents immunized with attenuated sporozoites become totally resistant to an otherwise lethal sporozoite inoculum, but remain fully susceptible to challenge with erythrocytic stages of the same parasite strain (4).

Anti-sporozoite antibodies, i.e., antibodies directed against the infective stages of all malaria parasites, have previously been shown to occur in avian and rodent malaria. In both instances, these antibodies were observed upon immunization of the animals with attenuated, irradiated sporozoites.
A Measurement of the Specificities of Antibodies to Morphine-6-Succinyl-BSA by Competitive Inhibition of 14C-Morphine Binding
Authors: Wainer Bruce H. , Fitch Frank W. , Fried Josef , Rothberg Richard M.
Published: December 2022

Antisera reacting with morphine were produced in rabbits by immunization with morphine-6-succinyl-bovine serum albumin. The antibody assay employed ammonium sulfate precipitation of antibody-14C-morphine complexes. The specificities of the sera were measured by prior incubation of appropriate serum dilutions with increasing concentrations of various unlabeled opioids before the addition of 14C-morphine. Opioids differed in their ability to inhibit interaction of 14C-morphine and antibody; concentrations inhibiting binding of 88 pmol/ml of 14C-morphine by 50% were: morphine-6-hemisuccinate, 0.052 nmol/ml; heroin, 0.10 nmol/ml; morphine, 0.11 nmol/ml; codeine, 0.16 nmol/ml; hydromorphone, 0.50 nmol/ml; nalorphine, 2.1 nmol/ml; meperidine, 80.0 nmol/ml; naloxone, 30% inhibition at 1.0 × 103 nmol/ml. Variations in the ability to inhibit 14C-morphine binding were related to the nature of the structural dissimilarities between the competing compound and the homologous hapten. Differences in I50 values for the opioids studied were reflections of inhibition curves with differing slopes. Such observations allow the possibility of both qualitative and quantitative analyses in assay systems.
Allotype Preference in Human Rh Antibodies
Authors: Litwin S. D.
Published: December 2022

Gm(a) and Gm(f) genetic factors of human IgG1 heavy chains were quantitatively determined in Rh eluates isolated by the digitonin elution method. Thirteen Rh preparations from heterozygous subjects Gm(a+f+) showed a ratio of allotypes differing sharply, in many cases, from the individuals' own serum. Six eluates had twofold or greater differences in Gm allotype values; in five of these six, Gm(a) was the predominant genetic antigen.

Subpopulations of Rh antibody presumably selected for binding avidity were prepared by reacting progressively larger volumes of Rh sera with a fixed number of erythrocytes. Serial eluates prepared from single Rh sera showed stepwise changes in the proportions of Gm antigens. The most frequent pattern noted was an increase in Gm(a) concentration while Gm(f) remained stable.

The data indicated that Rh antibodies frequently showed allotype predominance with Gm(a) occupying a preferential but not exclusive position in Rh antibody bound to red cells under conditions of antibody excess. The results were interpreted as supporting an association between certain variable region genes determining Rh antibody and the Gma gene determining the constant region of IgG1 γ chains.
Variations in Complement Levels during Active and Adoptive Immunization
Authors: Rose Noel R. , Molotchnikoff Marie-F.
Published: December 2022

Active immunization of inbred Lewis rats with a foreign antigen (bovine serum albumin) or an autoantigen (rat thyroid extract) in complete Freund's adjuvant or Bordetella pertussis vaccine increased progressively the complement level to a maximum after 21 days. Active immunization with Freund's adjuvant and B. pertussis or Freund's adjuvant alone also raised the complement level. Adoptively transferred thyroiditis with lymph node cells from Lewis rats actively immunized with rat thyroid extract reduced the complement 7 days after the transfer. This drop of complement was not found when donors were adoptively immunized with bovine serum albumin.
Cross-Reactions of Hl-A Antibodies
Authors: Dorf Martin E. , Eguro Setsuko Y.
Published: December 2022

Cross-reactive HL-A antibodies were initially produced by subject BC in response to alloimmunization with leukocytes from a single donor. After six cycles of immunization with leukocytes from the original donor a second immunizing cell was substituted. A brisk anamnestic response resulted. The antibody response was primarily associated with antigens found on the original immunizing cells, but not present in the second donor.

Sera obtained after immunization with each donor were further compared. Both samples contained high titered cross-reactive HL-A3 antibodies and HL-A3 platelets could completely absorb cytotoxins from both serum samples. In addition, pH gradient elution studies indicated that the serum obtained after challenge with the second cell donor had a lower binding avidity for the HL-A3 antigen. These results extend the observations of the original antigenic sin phenomenon to include such responses with major histocompatibility antigens.
Rabbit Antiserum to Brain-Associated Thymus Antigens of Mouse and Rat
Authors: Peter Hans-Hartmut , Clagett James , Feldman Joseph D. , Weigle William O.
Published: December 2022

Immunization of rabbits with either mouse (CBA/ST) or rat (Le) brain homogenates results in the production of antisera which upon appropriate absorptions are T cell-specific for both mouse and rat. These antisera may be used effectively for direct cytotoxicity and detection of rat and mouse T cells by direct immunofluorescence. Furthermore, in the rat, it was demonstrated that antimouse brain serum, in the presence of complement, abrogates cell-mediated immunity in vitro, but does not affect antibody-forming cells.