bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperimmune Response to a Protein and a Polypeptide Antigen Coated on Pneumococcus R36A
Authors: McDonald H. C. , Odstrchel G. , Maurer P. H.
Published: December 2022

Bacterial stimulation of the immune response is a well known but incompletely understood phenomenon (1). The most successful method used to enhance the immunogenicity of protein and polypeptide antigens has been the use of complete Freund's adjuvant. However, the levels of antibody generally produced in rabbits are far below those reported for carbohydrate antigens when they are part of a formalinized suspension of whole bacteria (vaccine). Intensive intravenous (i.v.) immunization of rabbits with either streptococcal or pneumococcal vaccines often results in levels of 5 to 20 mg of antibody/ml serum which is directed mainly against the surface polysaccharides (2–4). An explanation for this vaccine effect is that the bacterial cell serves as the “carrier” for bacterial polysaccharide which can be considered a hapten attached to the bacterial surface.

We have examined the possibility that a bacterial cell might serve as a nonspecific carrier for antigens adsorbed onto the cell surface.
Macrophage Proteinase and Inflammation: The Production of Chemotactic Activity from the Fifth Component of Complement by Macrophage Proteinase
Authors: Snyderman Ralph , Shin Hyun S. , Dannenberg Arthur M.
Published: December 2022

When the activation of complement proceeds through its fifth component (C5), a chemotactic fragment (C5a) is released (1–3) which attracts both macrophages and polymorphonuclear leukocytes (PMN).4 Proteolytic enzymes such as trypsin and PMN neutral proteinase also release C5a from C5 (2–4). This report shows that an acid-acting proteinase from both macrophages and lung (a tissue rich in macrophages) (5–7) could do likewise. It therefore describes what is possibly an important mechanism by which leukocytes accumulate in chronic inflammatory areas, namely, that macrophage proteinase could, from C5, produce C5a which attracts more macrophages and PMN to the site.

Two sources of macrophage proteinase were used in these experiments. The acid-acting proteinase was partially purified from beef lung by the method of Dannenberg and Smith (5, 6), and further purified on CM-Sephadex columns. Homogenates of either peritoneal or pulmonary macrophages from rabbits also served as a source of this proteinase (7).
Structural Studies of Human J Chain
Authors: Meinke Geraldine C. , Spiegelberg Hans L.
Published: December 2022

Primary structural studies on J chain from human IgA and IgM indicated that the NH2-terminus was blocked. The isolated NH2-terminal peptide differed from known NH2-terminal peptides of heavy and light chains. Its amino acid composition was Glx, Asx and S-carboxymethylcysteine in a molar ratio of 2:1:1. Four additional half-cysteine containing peptides also differed from analogous heavy and light chain peptides. A glycopeptide with an amino acid composition, Asx-(Arg, Asx, CHO) (Asx, Glx, Ser2, Thr, Ile, Leu, Pro) was isolated from subtilisin digests of both IgA and IgM J chain. The glycopeptide differed from known IgA and IgM heavy chain glycopeptides. These data support the hypothesis that J chain represents a unique polypeptide chain which is present in IgA polymers and IgM macroglobulins and which differs in its primary structure from heavy and light chains.
Studies on Brain Antigens
Authors: Yo Sui-Lan , MacPherson Catherine F. C.
Published: December 2022

A highly immunogenic spinal cord protein (SCP) has been extracted from bovine spinal cord (BSC) with 0.1 M sodium chloride. Immunodiffusion analyses of the subcellular fractions of BSC homogenates separated by differential centrifugation revealed that the antigen was located in the soluble fraction. SCP occurs in bovine peripheral nerve but has not been detected in extracts of other bovine organs and has a regional distribution in the bovine central nervous system (CNS); it composes about 5% of the total protein of extracts of BSC but accounts for only 0.2% of the total protein of extracts of cerebral white matter. SCP is distributed in similar fashion in the CNS of the human, rat and rabbit.

Immunoelectrophoretic analyses revealed that SCP occurred in two molecular forms having the electrophoretic mobilities of a β1 globulin (β1-SCP) and a γ globulin (γ-SCP) respectively. The more basic form of the antigen also existed as a peptide which was separated from the other proteins by filtering BSC extracts through dialysis tubing. Similar amounts of the peptide were obtained when BSC was homogenized and extracted in the presence of cupric ions to inhibit protease activity. About 6% of the total SCP activity was found in the peptide form. The molecular forms of the antigen retained by dialysis tubing, β1-SCP and γ-SCP, were estimated by gel filtration chromatography to have molecular weights of 18,000 and 12,000 respectively. The SCP peptide had a molecular size approaching 5000.

β1-SCP that was purified by batch absorption of bovine cord extracts with DEAE Sephadex A-50 and CM-cellulose chromatography formed one band when analyzed by polyacrylamide gel electrophoresis at pH 8.9. Although β1-SCP is not an acidic protein, the dicarboxylic amino acids, glutamic and aspartic, comprise 20% of the total amino acid content.
The Infectiousness of Antigenic Competition: Conferrability of Nonreactivity upon Allogeneic T-Cells
Authors: Menkes Jeffrey S. , Hencin Ronald S. , Gershon Richard K.
Published: December 2022

The effects of antigenic stimulation upon graft-vs-host (GVHR) activity were studied in mice lethally irradiated between the time of immunization and subsequent inoculation of allogeneic thymocytes. The GVHR (measured as DNA synthesis in lymphoid tissue) was depressed in preimmunized animals, more so in secondarily immunized mice than in those that responded primarily. The suppression after secondary immunization was as pronounced in femoral lymph nodes as it was in the spleen, although all inoculations of antigen were intraperitoneal.

The findings illustrate that nonreactivity may be conferred upon normal allogeneic thymus-derived (T)-cells introduced into a milieu of antigenic competition. The concept of a body-wide, radiation resistant negative feedback factor appearing after antigenic stimulation is supported.
Anamnestic Secretory Antibody Response in Respiratory Secretions of Intranasally Immunized Mice
Authors: Gerbrandy J. L. F. , van Dura E. A.
Published: December 2022

Respiratory antigen administration by inhalation, or by intranasal (i.n.)1 or intratracheal (i.t.) instillation, is known to induce a marked antibody response in a variety of animals including man (1–3). Respiratory immunization has further gained special interest by its induction of secretory IgA antibodies, which play a role as a local barrier against various human respiratory virus infections (4, 5).

Evidence is accumulating that this secretory 11S IgA is produced by plasma cells, located in the nasal and bronchial submucosae (6, 7), in a similar way as the well-known IgA production by plasma cells in the intestinal submucosa after oral antigen administration (8). Less known aspects of the secretory immunologic response of the respiratory tract are, however, its relation to the systemic immune response, and the existence of a distinct anamnestic secretory IgA response (9–11).
Humoral and Cellular Responses to Trypanosoma cruzi Infection
Authors: Yanovsky Jorge F. , Albado Emilia
Published: December 2022

Cell-mediated immunity is a subject of intense interest in parasitology. Experiments with animals and observations on humans suggest that cell-mediated immunity is involved in protozoal infections (1). The inhibition of leukocyte migration has proved a suitable method for the in vitro study of cellular immunology.

Søborg and Bendixen (2, 3) have successfully used this test with human peripheral leukocytes; Rosenberg and David (4) have shown it applicable to soluble antigens. In the present work we have attempted to obtain an in vitro test of the immune mechanisms in American trypanosomiasis. We observed the in vitro migration of peripheral leukocytes from patients with positive serology for Trypanosoma cruzi infection against soluble antigen.

Materials and Methods. Blood. Two samples from each of 30 human adults were drawn: one, with heparin (Abbott 5000 U/ml with benzyl alcohol preservative) for the migration test, the other for the serologic tests.
Sequestration of Pha-Responsive Cells (T-Lymphocytes) in the Bone Marrow of Leukemic Children Undergoing Long-Term Immunosuppressive Therapy
Authors: Borella Luis , Green Alexander A.
Published: December 2022

Although data from experimental models suggest that certain immunocompetent units are preferentially inhibited by drugs, the suppressive effects of chemotherapy upon various cell compartments in man have not been characterized. In this study we compared the effect of long-term combination chemotherapy upon T-lymphocytes in the bone marrow and peripheral blood of children with acute lymphocytic leukemia (ALL) in remission. The “in vitro” response to phytohemagglutinin (PHA) was used as index of T-lymphocyte function. After 2 to 3 years of immunosuppressive therapy, in half of the patients the response to PHA was significantly greater in bone marrow than in peripheral blood cultures. This contrasts with the results obtained after cessation of chemotherapy when 14 of 15 patients had greater response in peripheral blood than in bone marrow. We conclude that in some children with ALL in remission, long-term immunosuppressive therapy produces a relative increment of a PHA-responsive cell population in bone marrow, possibly by a selective sequestration of T-cells in this compartment.
Production of Antibody to Homologous α-Fetoprotein in Rabbits, Rats and Horses by Immunization with Human α-Fetoprotein
Authors: Nishi Shinzo , Watabe Hiroyuki , Hirai Hidematsu
Published: December 2022

Rabbits, rats, horses and a dog were immunized with purified human α-fetoprotein. High titered antibodies were produced except in the case of the dog. The rabbit, rat and horse antibodies cross-reacted with their own homologous α-fetoprotein. Attempts to produce antibody with homologous α-fetoprotein in rabbits, rats and dogs were not successful.
Immunocytology of Cultured IgM-Forming Cells of Mouse
Authors: Namba Yuziro , Hanaoka Masao
Published: December 2022

An attempt was made to gain an established culture cell line of murine IgM myeloma cells (MOPC-104E). The growth of the tumor cells could be maintained for more than 10 months in tissue culture by adding a factor obtained from the culture medium of tissue macrophages (histiocytes) or spleen phagocytic cells of mouse. The factor is protein in nature and has a molecular weight of about 5 × 104 daltons. Without this factor the tumor cells stopped growing at G1 stage and did not continue the cell cycle; however, the synthesis of IgM and its subunit was unaffected. The factor reinitiated DNA synthesis almost synchronously with a lag of about 90 min. The factor was also found in mouse serum and its activity increased remarkably after the injection of Freund's complete adjuvant. Adenosine 3′:5′-cyclic monophosphate could substitute for the factor in a range of 0.3 µg/ml to 1.0 µg/ml. The immunologic role of the factor is discussed.
Comparative Studies of Vertebrate Immunoglobulins
Authors: Mehta P. D. , Reichlin M. , Tomasi T. B.
Published: December 2022

IgG and IgM were isolated from 10 different species (human, monkey, horse, dog, cow, sheep, rabbit, chicken, rat and guinea pig) by a combination of starch block electrophoresis and Sephadex G-200 gel filtration. The patterns of heavy and light chains were studied in urea starch gel electrophoresis at pH 3.0 after reduction and alkylation. With the exception of the chicken 7S immunoglobulin, the electrophoretic patterns of IgG from the different species were remarkably similar. However, when IgM preparations from these species were compared, marked differences in mobility of the µ chains were seen. The immunologic cross-reactions of the IgG and IgM proteins from these same species were studied by quantitative complement fixation with three rabbit antisera specific for human γ chains and three specific for human µ chains. The nonprimate IgG cross-reacted weakly (5 to 30%) compared with nonprimate IgM preparations which cross-reacted strongly (30 to 55%). In accordance with the electrophoretic studies, the chicken 7S protein was uniquely different from the other IgG fractions and did not cross-react at all with various antihuman γ chain sera while chicken IgM showed good cross-reactivity.
Mouse Antibodies to Group a Streptococcal Carbohydrate; Use of Idiotypy to Detect Inbred Strain Specificity and to Monitor Spleen Cell Transfer in Syngenetic Mice
Authors: Briles David E. , Krause Richard M.
Published: December 2022

The antibody response to the group A carbohydrate antigen was measured in SWR/J and A/J mice after intravenous (i.v.) immunization with whole heat-killed streptococcal vaccines. Microzone electrophoresis revealed antibodies with limited heterogeneity in both mouse strains. The light chains exhibited a restricted banding pattern by polyacrylamide disc electrophoresis. With the immunization procedure employed here, most SWR/J mice produced less than 1 mg of antibody per ml. The occasional mouse, however, produced 2 to 4 mg of antibody with restricted heterogeneity; such mice were used as donors for spleen cell transfers (107 spleen cells per recipient) to irradiated (500 R) recipient SWR/J mice. Antisera of recipient mice had antibody components identical to that of the donor as detected by microzone electrophoresis. Isolated antibody from one such SWR/J spleen cell recipient was used to prepare anti-idiotypic sera in rabbits. Idiotypy was detected by a hemagglutination inhibition assay. Antibody with the same idiotype was detected in the original donor mouse of the cell transfer experiments and in the majority of the mice of the first and second passage. This idiotypic specificity was not apparent in the antisera of SWR/J mice which received immune cells from a different donor.

By use of the hemagglutination inhibition test, at least 5 out of 14 immunized SWR/J mice had a minor antibody component with the same idiotypy as that of the proband. This idiotype was not detected in the group A antibodies of 16 A/J mice immunized with the same antigen. This SWR/J idiotypic marker may be useful for genetic studies, because an antibody component with this idiotype occurred in the hybrid SWR/J × A/J.
Dissociation of MIF Production and Cell Proliferation
Authors: Bloom Barry R. , Gaffney Judith , Jimenez Luis
Published: December 2022

The principal methods currently employed to explore the mechanism of cell-mediated immunity are blast cell transformation, production of soluble mediators and direct lymphocyte-target cell cytotoxicity. It is important to understand the nature of the cell detected in each of these assays in vitro, and to establish its relationship to the cell-mediated response in vivo.

While it appears clear that the induction phase in sensitization requires the proliferation of stem cells to fully competent lymphocytes, there is considerable evidence in vivo to suggest that the effector arm of the response does not require cell proliferation. The most obvious example in vivo of this is the well known radiation resistance of the cell-mediated immune response in comparison to the humoral responses (1, 2). Additionally, cells treated with mitomycin C, under conditions in which they can synthesize some RNA and protein but cannot divide, are capable of effecting passive transfer (3).
Specific Resistance As Influenced by Nonspecific Agents
Authors: Schatz William J.
Published: December 2022

Summary and Results

Distilled water employed intravenously failed to initiate antisheep hemolytic sensitizer production. Without exception, a dose was found for each agency with which it was attempted to call forth increased sensitizer production that brought the desired result The same was also true as regards the elicitation of depression. Both protein and nonprotein agencies were used. Hypotonic, isotonic and hypertonic agencies were included. Weekly bleeding apparently exerted no appreciable influence on sensitizer production. Among the doses calling forth increased sensitizer production, it was always the larger dose that called forth the greater production. The production of sensitizer following the use of the same dosage amount when employed subsequent to two sheep cell injections exceeded strikingly that following its use subsequent to only a single dose. The dose used to elicit depression exceeded considerably that employed in eliciting increased production. The amount of sensitizer produced when water and water containing increasing amounts of salts were injected subsequent to sheep cell injection, was inversely proportional to the amount of salt contained. There was no appreciable difference in the production between water injection on the one hand and Ringer's solution and normal saline on the other. Nor was there any appreciable difference in the results obtained with saline on the one hand and saline containing the microörganisms in quantity to make the typhoid-paratyphoid agency on the other.
The Optimal Dosage in the Treatment of Hay Fever
Authors: Rackemann Francis M. , Graham Lillian B. , Scully Margaret A.
Published: December 2022

The method of plotting the several doses to make a curve for the course of treatment in hay fever is new. By this method several observations can be made.

In the majority of cases, the routine treatment in one season has but little effect upon the degree of hypersensitiveness at the outset of the next season, or upon the rate at which the tolerance to ragweed can be raised during the next season. Similar courses of treatment in different years are followed by similar end results. In those cases in which the courses of treatment have varied, it has been observed in about 20 per cent that a larger dosage was followed by a better end result. In at least 14 per cent of the cases, it has been possible to show that excessive dosage was responsible for the poor end results and that in many instances the result was much better when a smaller dose and a less vigorous course of treatment was employed. From this it is evident that success in the treatment demands a course of doses of a size and extent which is optimal for the particular patient. What this means so far as the underlying mechanism of hay fever is concerned, is a problem, the solving of which must wait upon the collection of data of another kind.
Studies in Anaphylaxis
Authors: Goodner Kenneth
Published: December 2022

Frogs do not seem to show acute allergic manifestations as do mammals and it is suggested that this is due to certain pecularities of physiology and innervation of the smooth muscle fibers. The excised sensitized frog heart is markedly affected on contact with the specific sensitizing substance and this reaction seems to resemble light peripheral parasympathetic stimulation. It was shown that the muscle cells still respond to direct cellular stimulation. Excised smooth muscle from the alimentary tract of the frog did not exhibit the Schultz-Dale phenomenon and it is suggested that this may be explained by the fact that peripheral parasympathetic stimulation in this case does not produce contraction. These results would seem to offer further evidence that the precise site of the reaction is some portion of the neuro-muscular complex. It would seem that the characteristic features of anaphylactic intoxication in different animals depends not alone on the distribution of non-striated muscle but also on the character of the innervation of this muscle.
The Effect of Heat and Hydrogen Ion Concentrations on the Extract of Short Ragweed
Authors: Gay Leslie N.
Published: December 2022

An extract of short ragweed pollen was subjected to heat—100°C. for periods of time ranging from one to twenty minutes. The extract was heated in concentrated solution and then diluted; it was also diluted and than heated. These dilutions were than titrated intradermally in patients suffering from ragweed hay-fever, and the reactions were studied by comparison. Variation of the reactions in a mild sufferer and in a severe sufferer of hay-fever was observed. An extract of short ragweed pollen was subjected to varying degrees of heat: 60°C., one hour; 100°C., one hour; and autoclaved 15 pounds pressure, twenty minutes. This abtract was diluted: one part to 1000, one part to 10,000 and one part to 100,000; the intradermal reactions were studied and compared. An adjustment of the neutral ragweed extracts to pH 8.4 and 4.0 was made; these solutions were diluted, heated as described above and then titrated in ten patients.
An Immunological Study of an Atypical Meningococcus Strain
Authors: Kirkbride Mary B. , Hutton Alice I.
Published: December 2022

When isolated, the meningococcus strain under study was not agglutinated in the standard monovalent rabbit serums of groups I, II and III; nor in polyvalent serums obtained by immunization of horses with 4, 6, 20 and 60 strains. After prolonged cultivations, however, it acquired a certain degree of agglutinability in polyvalent serum and a slight tendency to react in low dilutions of monovalent serums of group II and finally of group III. It was found to be highly agglutinable in the homologous monovalent serums obtained by immunization of rabbits, a horse and a mule after it had been grown on media for about a year.

Although the organism should be classified in the indeterminate group “X” of the international classification, its remote relationship to groups I, II and III is shown by the definite agglutinative action of its homologous monovalent serums with representative cultures of these groups. It absorbed the group agglutinins from these serums as well as its own specific agglutinins. No specific agglutinins for strains of the classified groups I, II and III were, however, absorbed by it from the corresponding monovalent serums.

The observations recorded in this study, as far as they relate to the classification of the meningococcus, are in accord with the results published in a previous paper as to the existence of three distinct groups. The remaining atypical strains should be placed in group “X” of the international classification.

Finally, this strain is a striking example of a meningococcus giving rise to a serious infection that apparently yielded to treatment with polyvalent serum in which, when first isolated and for some time afterward, it failed to agglutinate. Moreover, it is interesting to note that as the culture became more agglutinable it reacted at least as well with the polyvalent serums produced by immunization with six selected strains belonging to the three main groups of meningococci, in which groups the “Rna” strain could not be classified, as with the polyvalent serum produced against sixty strains among which were included many atypical strains.
Studies in Hypersensitiveness
Authors: Fineman A. H.
Published: December 2022

Neither the localization of the clinical manifestations of atopic hypersensitiveness nor their severity is dependent upon the degree of sensitiveness as determined by any method of clinical testing. Individuals sensitive to pollen (early and late hay fever) can be classified by the intradermal method into A, B and C groups, depending upon the degree of skin sensitivity. This classification serves as a guide in the treatment of cases (R. A. Cooke). Hay fever patients can also be classified, with the scratch method, into groups corresponding to the A, B and C classes of the intradermal method, but solutions 500, 100 and 30 times as strong must be employed in the respective groups. The eye (conjunctival) test is less sensitive than the intradermal, and more sensitive than the scratch method, but cannot be used with any degree of accuracy to classify pollen cases into A, B and C groups. It is an excellent test to determine the presence, but not the degree, of pollen sensitivity.
Studies on the Secretory Immunologic System of Fowl
Authors: Leslie Gerrie A. , Martin Louis N.
Published: December 2022

A new immunoglobulin (IgA) was purified from chicken serum and secretions by using immunoabsorbent columns, Sephadex G-200 gel filtration and DEAE-cellulose chromatography. The immunoglobulin nature of IgA was confirmed by the presence of heavy (H) and light (L) chains, and antibody activity of serum IgA obtained from immunized chickens.

In chicken serum, IgA exhibited size heterogeneity, the major portion eluting from Sephadex G-200 in a volume corresponding to τ; 200,000 with a minor peak of approximately 170,000 to 180,000. In secretions IgA was mainly of high molecular weight (350,000 to 360,000). The IgA/IgY ratio in all secretions examined was greater than that in serum. Secretory IgA found in the bile contains an additional antigenic determinant not found in serum IgA, perhaps indicating the presence of secretory piece and/or J chain.

Serum IgA was dissociated by partial reduction to a size comparable to that of IgMs (∼175,000). Gel filtration in 8 M urea—0.05 M propionic acid separated H and L chains. The α H chains were approximately the size of µ chains (∼70,000). These results indicate that IgA is composed of H and L polypeptide chains and suggest the polymeric nature of most serum and secretory IgA.

The demonstration of an immunoglobulin in the chicken similar to mammalian IgA reconfirms the presence of a secretory immunologic system in the fowl.
Surface Immunoglobulins of Bovine Lymphosarcoma Cells
Authors: Tsuyuguchi Izuo , Ku Ming-Ming , Karush Fred
Published: December 2022

Bovine lymphosarcoma cells grown in tissue culture were examined for the presence of surface immunoglobulins. The experimental criterion employed was the specific binding of 125I-labeled antibody directed to bovine immunoglobulin determinants. It was noted that lymph node cell suspensions and peripheral blood leucocytes from a lymphosarcomatous animal exhibit specific binding of rabbit antibody directed to such determinants. However, thymocytes from such an animal fail to bind antibody. Normal peripheral blood leucocytes also show specific binding of rabbit anti-BγG and anti-µ chain antibody. It is also apparent that tissue culture cells adsorb exogenous immunoglobulin by exposure to equine serum and bovine serum. Tissue culture cells grown in medium containing 10% rabbit serum, however, exhibit BγG-like determinants. They clearly bind anti-BγG antibody but this binding does not seem to involve Fc determinants of the γ chain. Anti-µ chain antibody is not specifically bound and the binding of anti-γ chain antibody is ambiguous. It appears, however, that there are at least L chain determinants on the cell surface.
Chicken Antibodies to Group a Streptococcal Carbohydrate
Authors: Leslie Gerrie A. , Clem L. W.
Published: December 2022

Adult chickens were hyperimmunized with group A streptococcal vaccine in an attempt to elicit the formation of high levels of antibody of restricted heterogeneity. All birds produced precipitating antibody after 3 weeks of immunization. The highest concentration was ∼8.6 mg/ml. After 6 weeks of immunization the highest level was ∼13 mg/ml and even after 6 weeks most birds had both IgM and IgY. Approximately 10% of specifically purified antibody preparations contained some IgA. In each case this was associated with the macroglobulin fraction of Sephadex G-200. Of the 37 different antibody preparations examined only ∼5% (two IgM preparations) showed a clear restriction in L chain heterogeneity. These data indicate that like rabbits and sharks, chickens can produce high levels of antibody to a group A streptococcal carbohydrate with some antibody preparations showing restricted heterogeneity.
Antigenic Properties of Rabies Virus Components
Authors: Wiktor Tadeusz J. , György Emese , Schlumberger H. Dieter , Sokol Frantisek , Koprowski Hilary
Published: December 2022

The envelope glycoprotein of rabies virus was shown to be the antigen responsible for the induction of virus neutralizing (VN) antibody formation and for the protection of animals against subsequent challenge with rabies virus. Preparation of two other envelope proteins and of the nucleocapsid protein, derived from disrupted virions, induced the formation of only low levels of VN antibody and protection of animals against rabies, which could be explained by the amount of residual glycoprotein present in these preparations. Purified preparations of free viral nucleocapsid, isolated from infected cells, did not induce VN antibody formation, but elicited, in immunized animals, the formation of antibodies demonstrable by complement fixation or fluorescent antibody tests.
Some Rabbit Allotypic Determinants Are Isotypes in Hare
Authors: Tosi Simonetta Landucci , Tosi Roberto , Perramon Arturo
Published: December 2022

Both a and b group rabbit allotypes, which are localized respectively on the variable region of the heavy chains and on the κ type light chains of Ig molecules, are known to be associated with multiple amino acid interchanges (1, 2). How multiple differences between alleles can accumulate during evolution is not clear. It cannot even be excluded that the structural genes for the polypeptide chains characteristic of each allotype are not truly allelic but coexist on the same chromosome. Allelism would be present at a different (regulatory) locus which would allow the expression of only one of the structural genes (3). Another hypothesis, put forward by Smith et al. (4) especially with reference to the a group allotypes, is that the sequences specifying the different allotypes may have evolved not as alleles but as gene duplications. Linked genes which diverged long before the rabbits became a species, and thus accumulated a large number of differences, might have become alleles (or pseudoalleles) in contemporary rabbits.
Neutrophilic Leukocytes in Immunologic Reactions in Vitro: Effect of Cytochalasin B
Authors: Hawkins David
Published: December 2022

Neutrophilic leukocytes (neutrophils) participate in immunologic tissue injury through the extracellular release of pro-inflammatory lysosomal bioactive factors (1). The translocation of lysosomes and the selective extrusion of their contents occur in response to phagocytizable (2, 3) and non-phagocytizable immune complexes (4, 5). It has been observed recently that cytochalasin B inhibits phagocytosis in neutrophils (6) as well as a number of other cellular functions apparently dependent on the microfilament system (7, 8). Since phagocytosis and lysosomal release have been clearly linked in the neutrophil the possibility that cytochalasin B might modulate this release reaction was investigated. The effect of cytochalasin B on the closely related if not identical process of non-phagocytic immune complex induced lysosomal release was examined concurrently.

Neutrophilic leukocytes were isolated from rabbit peripheral blood as described previously (2). Polystyrene latex particles (Dow Chemical Co., Don Mills, Ontario), 1.10 nm in diameter, were coated with rabbit γ globulin (RGG)2 and employed as the phagocytizable particles.
Genetic Control of the Immune Response in Mice. IV. Relationship Between Graft vs Host Reactivity and Possession of the High Tumor Genotypes Aya and Avya
Authors: Gasser David L. , Fischgrund Terry
Published: December 2022

The graft vs host (GVH) reactivity of spleen cells from mice possessing the high tumor genotypes Aya and Avya was compared with the reactivity of spleen cells from histocompatible nonagouti animals. Spleen cells from YBR aa mice caused significantly greater GVH reactions than YBR Aya cells, and spleen cells from C57BL/6J aa donors were more reactive in GVH assays than cells from C57BL/6J Avya mice. These results suggest that reduced immune responsiveness may be involved in the tumor susceptibility of Aya and Avya mice.
The Role of Humoral Factors in the Initiation of in Vitro Primary Immune Responses
Authors: Watson James , Epstein Ruth
Published: December 2022

Mouse spleen cells cultured in medium containing deficient fetal bovine serum (deficient medium) do not support primary immune responses to heterologous erythrocyte antigens. A factor, here termed deficient serum restoring factor (DSRF), has been isolated which stimulates primary immune responses in spleen cells cultured in deficient medium. DSRF alone does not stimulate DNA synthesis in mouse spleen cultures. It is required along with the immunogen in the period before the onset of DNA synthesis in the activation of precursors of antibody-forming cells. Deficient medium supports the induction of secondary immune responses by spleen cells which have been primed with antigen in vivo. DSRF does not substitute for thymus-derived cells, adherent cells or allogeneic lymphocytes in the initiation of in vitro immune responses. Unless precursor antibody-forming cells are exposed to DSRF they are not susceptible to the inductive stimulus in deficient medium. The in vitro system utilizing deficient medium appears to distinguish between virgin and experienced precursor antibody-forming cells, and offers a new way of identifying the role of humoral factors in the differentiation of antibody-forming cells.
Binding of 125I-Labeled Anti-IgG, Rheumatoid Factor and Anti-C3 to Immune Complexes on the Surface of Virus-Infected Cells
Authors: Hayashi Kozaburo , Lodmell Donald , Rosenthal Joel , Notkins Abner Louis
Published: December 2022

Recently, we reported that 125I-labeled antiviral antibody could be used to detect newly synthesized viral antigens on the surface of infected cells (1). The present report describes an indirect radioimmunoassay for detecting viral antigens and antiviral antibody and demonstrates that rheumatoid factor and complement can bind to immune complexes on the surface of infected cells.

Primary rabbit kidney cells (PRK)1 were prepared and maintained as described previously (2) in tissue culture trays containing 24 wells, each 16 mm in diameter (Bellco Glass, Inc., Vineland, N. J.). Herpes simplex virus (HSV), type 1, and vaccinia virus (CVI-79) were grown and assayed in PRK cells (2, 3). Antiserums to HSV and vaccinia were prepared in rabbits and the 50% neutralization titers were approximately 1:2000 (4). Normal rabbit serum was obtained from unimmunized rabbits. Pooled human serum, used as a source of anti-vaccinia antibody, had a 50% neutralization titer of 1:80.
Studies on the Mechanism of Lymphocyte-Mediated Cytolysis
Authors: Henney Christopher S.
Published: December 2022

The lysis of DBA/2 mastocytoma cells by splenic lymphocytes from C57BL mice obtained 10 days after alloantigenic stimulation has been investigated by following the release of various target cell markers. Although the events initiating the cytolytic pathway occurred very rapidly, the rupture of the cell membranes took place some considerable time later, following a period of gradual, progressive increases in permeability. Thus, when the efflux of low molecular weight indicators (e.g., ATP, 86Rb) from target cells was measured, increases in membrane permeability could be demonstrated within 20 min of the addition of sensitized lymphocytes. Target cell indicators which became associated with intracellular components, however, (51Cr, 3H-thymidine-DNA) could not be demonstrated extracellularly unless considerably longer periods of incubation were used. The rate of appearance of these indicators was inversely related to their effective molecular size.

Although the rate of efflux of different indicators varied considerably, the number of effector lymphocytes necessary to initiate specific release was comparable, and events leading to release of label were in all cases similar. Thus, all indicators were released in a linear manner both as a function of time and as a function of the number of effector cells present. Similarly, in the absence of divalent cations, none of the indicators were specifically released.

Measurement of the ATP released after incubation of cytolytically active lymphocytes with target cells indicated that both interacting cell types undergo membrane permeability changes as the result of their interactions, although in the case of the lymphocyte this increase was apparently of a nonprogressive nature.
A Human IgG Myeloma Protein with Anti-α2 Macroglobulin Antibody Activity
Authors: Seligmann Maxime , Sassy Catherine , Chevalier Annette
Published: December 2022

A human IgG 1 κ myeloma protein which specifically precipitates with α2 macroglobulin (α2 M) from horse, rabbit and pig is described. This protein did not combine with human α2 M nor with α2 M from various other species. The binding activity was exclusively located in the Fab regions of the molecule. Quantitative studies showed that this protein gave a flocculation type of precipitin curve with horse α2 M and that rabbit α2 M behaved as a cross-reacting antigen. This patient had received two injections of horse antitetanus serum in 1930 and 1936. That the antibody specificity of this myeloma protein was related to an extrinsic source of antigenic stimulation is emphasized.
Induction of Reagin Synthesis in the Rat with Associated and Dissociated Hemocyanin: Effect of Antilymphocyte Serum
Authors: White G. J. , Holm M. S.
Published: December 2022

Dissimilar reagin synthesis patterns were observed in Bordetella pertussis-treated rats which were immunized with equivalent amounts of associated or dissociated keyhole limpet hemocyanin (KLH). The associated form induced low titers of reagin in about 50% of the animals which peaked 30 days post-immunization. The dissociated form induced higher titers in 75% of the animals which peaked 10 days post-immunization. In contrast, the associated form of KLH was a more potent antigen than the dissociated form in the production of KLH agglutinins. Administration of equine antilymphocyte serum (ALS) to rats before or after immunization produced an alteration in the reagin synthesis pattern which was dependent on the time of ALS treatment. If given before immunization, early synthesis was enhanced. If given after immunization, late synthesis was enhanced. ALS treatment was suppressive for KLH agglutinin production, particularly with dissociated KLH immunized animals. The dissimilar antibody response to different forms of the same antigen, coupled with the exquisite dependence of early reagin synthesis on time of administration of ALS, leads to the speculation that macrophages may control an early event which determines reagin response.
Functional Heterogeneity of Murine Lymphoid Cells
Authors: Stobo John D. , Paul William E.
Published: December 2022

The mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) stimulate only those mouse lymphocytes which have undergone differentiation within the thymus and thus bear the differentiation antigen θ. However, not all thymus-derived lymphocytes (T cells) react equally to both mitogens, and the differential responsiveness of T cells to PHA and Con A may be used to indicate the existence of T cell subsets. One subpopulation of T cells exists which demonstrates approximately equal reactivity to both mitogens and bears a relatively high density of θ determinants. Another subpopulation exists which responds mainly to Con A, and bears a relatively reduced density of θ determinants. T cell subsets so delineated also differ in their recirculation patterns, radiation sensitivities, location in peripheral lymphoid tissue, and most importantly, in their function. These differential characteristics may represent the capabilities of T cells in various stages of differentiation within one T cell line. On the other hand, these cells may be representative of two distinct T cell lines and preliminary evidence consistent with this possibility is presented.
Studies in Myasthenia Gravis: Active Antigenic Sites Related to Humoral Antibody Induction
Authors: Rule Allyn H. , Bartlett Patricia , Osserman Kermit E.
Published: December 2022

Purification of human muscle proteins by 0.5 M KCl extraction, differential solubility and centrifugation produced fractions which reacted with human myasthenic sera. Absorption with either actomyosin or myosin removed all activity shown by the indirect immunofluorescent assay. Quantitative complement fixation showed that active fractions included the initial crude preparations, highly purified actomyosin and myosin. Actin preparations had no antigenic activity. Myosin contained at least 50 times more activity than actomyosin in both the complement fixation and the absorption studies. These data suggest that myosin contains the antigenic sites related to humoral antibody induction in myasthenia gravis.
A Solid Phase Radioimmunoassay for the Quantitation of Human Reaginic Antibody against Ragweed Antigen E
Authors: Zeiss C. Raymond , Pruzansky J. J. , Patterson Roy , Roberts Mary
Published: December 2022

IgE antibody directed against antigen E (AgE) of ragweed extract was measured quantitatively in the sera of 15 ragweed sensitive patients before initiation of immunotherapy. The assay employed polystyrene tubes which were successively coated with myeloma IgE and excess rabbit anti-IgE. This matrix which was specific for IgE bound IgE from the patients' serum in a reproducible and measurable manner. Radiolabeled AgE then reacted quantitatively with IgE antibody from the patients' serum which was attached to the solid phase. A double antibody method was developed simultaneously and gave comparable results for sera assayed by both procedures. Total serum IgE and the dose response of histamine release by AgE from washed leukocytes of the patients were also determined.

The concentration of IgE anti-AgE in the 15 sera ranged from 3.2 to 400 ng/ml by polystyrene tube assay. Serum IgE ranged from 82 ng to 6 µg/ml and the percentage of the serum IgE specific for AgE varied from 0.3 to 41. Leukocyte sensitivity measured by the reciprocal of the minimum concentration of AgE resulting in release of 50% of the total histamine encompassed a 300-fold range.

The level of IgE antibody to AgE was not correlated significantly with total serum IgE. Cell sensitivity varied independently of total serum IgE or nonspecific IgE. A highly significant correlation was found between IgE anti-AgE and cell sensitivity. Leukocyte sensitivity was found to be an exponential function of the serum antibody concentration.
Suppression of the in Vitro Anamnestic Response of Rabbit Lymph Node Cells by Anti-IgG Serum
Authors: Herscowitz Herbert B.
Published: December 2022

Treatment of previously primed rabbit popliteal lymph node cell suspensions with specific, absorbed anti-IgG serum resulted in significant suppression of the in vitro anamnestic response to keyhole limpet hemocyanin (KLH). Anti-IgM treatment did not interfere with antibody formation. The degree of suppression observed was dependent on the amount of anti-IgG added to the cultures. High dilutions of anti-IgG consistently enhanced antibody synthesis. Maximum suppression was achieved when the anti-IgG was added within the first 12 hr after culture initiation. For effective suppression, the anti-IgG had to be in the cultures for up to 48 hr. Suppression could be reversed by the addition of purified rabbit IgG to the cultures, but not by an excess of KLH. Although anti-IgG was cytotoxic in the presence of complement, this does not appear to be the mechanism of action. The results suggest that cells involved in the anamnestic response to KLH bear a surface receptor which is a reflection of the immunoglobulin product ultimately synthesized.
The Fate of Anti-Ig-Surface Ig Complexes on B Lymphocytes
Authors: Engers Howard D. , Unanue Emil R.
Published: December 2022

The fate of 125I-rabbit IgG anti-mouse immunoglobulin complexed to the surface-bound immunoglobulin of B lymphocytes was investigated. Each immunoglobulin-bearing B lymphocyte bound an average of 160,000 molecules of antibody to immunoglobulin under saturating conditions. These preparations of B lymphocytes had been previously depleted in their content of non-lymphoid cells. The B lymphocytes were placed in culture and the fate of the 125I-anti-Ig was determined. Early during culture a small amount of anti-Ig sedimenting heavier than IgG was released into the culture supernatants. Most of the remaining Ig was catabolized. Examinations of culture and cell supernatants identified the 125I bound to amino acids or to smaller protein fragments. This metabolism of the anti-immunoglobulin molecules was temperature-dependent and also specific for that fraction of the rabbit IgG capable of interacting with the surface immunoglobulin present on B lymphocytes. We conclude that the B lymphocyte sheds a small percentage of the immune complex and internalizes and effectively degrades the remainder.
Migration Inhibitory Effect of Cell-Free Supernatants from Tuberculin-Stimulated Cultures of Human Mononuclear Leukocytes Demonstrated by Two-Step Mif Agarose Assay
Authors: Clausen Jens Erik
Published: December 2022

Agarose gel technique with human peripheral blood leukocytes as migrating indicator cells was used to demonstrate migration inhibition factor (MIF) in cell-free supernatants from cultures of tuberculin-stimulated human peripheral blood mononuclear leukocytes. In this two-step MIF agarose assay only a few hundred microliters of supernatant were used. MIF was produced if cells from Mantoux-positive persons were cultured with purified protein derivative of tuberculin (PPD), but also if the sensitive cells after preincubation with PPD were washed and cultured in medium without PPD. There was a good correlation between the migration inhibitory effect of supernatants from PPD-stimulated cultures and the Mantoux reaction. The two-step MIF agarose assay was more sensitive than the direct leukocyte migration agarose test and makes possible the testing of several pairs of supernatants and a standard of MIF activity on the same migrating indicator cell population.
Immunologic Tolerance in C4 Deficient Guinea Pigs
Authors: Cohen Benjamin E. , Green Ira , Davie Joseph M.
Published: December 2022

The precise mechanisms by which immunologic tolerance is induced have not as yet been elucidated. There are a variety of different types of tolerance (1–3) and tolerance in both thymus-derived lymphocytes (T lymphocytes)2 and bone marrow-derived lymphocytes (B lymphocytes) has been described (4).

Tolerance induction may involve the destruction of specific immuno-competent cells upon contact with antigen. Support for this concept comes from the finding by some investigators that the number of antigen-binding cells, which appear to be precursors of antibody-secreting cells, are reduced in tolerant animals (5, 6). One possible mechanism for tolerance induction is that antigen, upon reacting with cell surface-bound immunoglobulin receptors, may under certain conditions activate complement at the surface of the cell and thus cause destruction of these cells. Azar et al., following this line of reasoning, have produced a transient complement deficiency in mice with a variety of agents and have reported that in such temporarily complement deficient animals tolerance is more difficult to achieve than in normal animals (7–9).
Effect of Specific Antibody on the Antigen-Induced Proliferative Response of Rabbit Lymph Node Cells
Authors: Thorbecke G. J. , Siskind G. W.
Published: December 2022

High concentrations of antibody specifically inhibited the proliferative response of sensitized rabbit lymph node cells to antigen. In contrast, low concentrations of antibody, in the presence of a heat labile component of fresh serum, markedly augmented the antigen-stimulated uptake of thymidine by sensitized lymph node cells.