bluuebunny/crossref_metadata_2025 huggingface dataset:
The Specificity and Cross-Reactivity of Antimyelin Antibodies as Determined by Sequential Adsorption Analysis
Authors: McMillan Paul N. , Mickey Don D. , Kaufman Bernard , Day Eugene D.
Published: December 2022

Through the process of sequential adsorption analysis of antimyelin I antibodies, raised in rabbits, rat myelin I was shown to possess a class of determinants distinct from synaptosomes and brain mitochondria, a class shared with synaptosomes but not brain mitochondria, and a class shared with synaptosomes and brain mitochondria as well as with liver mitochondria. Myelin and synaptosomes were thus distinguished immunologically from mitochondria and from each other. Although most of the antimyelin I antibodies also cross-reacted with myelin II some remained distinctive for myelin I, thus revealing a class of determinants in I not prominent in II. Crossreactions of the rabbit antirat-myelin antibodies with myelin I from different species in increasing order were bullfrog, 23%; chicken, 37%; rabbit, 50%; guinea pig, 50%; dog, 53%; human, 59%; neonatal rat, 61%; mouse, 72%; and hamster, 73%. The last three values were felt to be underestimated.
The Effect of Excision of the Site of Application on the Induction of Delayed Contact Sensitivity
Authors: Godfrey H. P. , Baer Harold
Published: December 2022

The effect of excision of the site of topical application of 3 µmols of PDC on the development of contact sensitivity in guinea pigs has been studied. The mean sensitivity induced was decreased by excision within the first 24 hr but more than half of the animals developed some degree of sensitivity even when excision took place at 1 hr. Animals with reduced geometric mean sensitivity were similar to control guinea pigs sensitized with 1 µmol of PDC; they were not tolerant to PDC when resensitized with 3 µmols. If two processes are associated with contact sensitization—1) passive drainage of sensitizer into the regional lymph node, and 2) assisted drainage into the node in association with lymphocytes (“peripheral sensitization”), then sensitization to the substituted dinitrobenzenes may be associated to a greater degree with assisted drainage of sensitzer into the regional node than is sensitization to PDC.
Antigen Binding Cells
Authors: Unanue E. R.
Published: December 2022

Bone marrow cells of non-immune mice are rendered immunologically incompetent by incubation with highly radioactive hemocyanin. Lethally irradiated mice that are reconstituted with such bone marrow cells respond poorly to KLH but well to sheep erythrocytes and exhibit a lower number of lymphocytes binding KLH in spleen. These results suggest that some bone marrow cells are already differentiated to respond immunologically to a given antigen.
Murine Amyloidosis: Immunologic Characterization of Amyloid Fibril Protein
Authors: Isersky Chaviva , Page David L. , Cuatrecasas Pedro , DeLellis Ronald A. , Glenner George G.
Published: December 2022

Immunization of rabbits with amyloid-laden murine tissue denatured with 6 M guanidine-HC1 produced antibodies to denatured purified murine amyloid fibril protein. Attempted immunization with native amyloid-laden murine tissues, however, failed to produce antibodies to any component unique to amyloid tissues, indicating that native murine amyloid was not immunogenic. Radioimmunoassay and immunofluorescence studies, nonetheless, demonstrated that native amyloid possessed antigenic determinants in common with denatured amyloid. A high degree of immunologic cross-reactivity was detected between extracts of amyloidotic tissues from different strains of mice regardless of the method of amyloid induction. Sera from amyloidotic mice were shown to contain a component capable of inhibiting the reaction between specific antibodies and purified amyloid protein.
Bence Jones Proteins and Light Chains of Immunoglobulins
Authors: McLaughlin Carla L. , Solomon Alan
Published: December 2022

Extensive immunochemical comparisons among κI, κII and κIII Bence Jones proteins belonging to different κ-chain groups can have identical antigenic sites in the amino terminal (variant) half of the light polypeptide chain. Certain antisera prepared against κ-chains belonging to one group have the capacity to detect antigenic differences among proteins of another group, i.e., an anti-κI antiserum can differentiate among κIII proteins. Immunochemical studies on Bence Jones proteins and light chains of known sequence and the subsequent integration of immunochemical and sequence data have permitted the localization of certain regions in the light polypeptide chain for which our antisera have specificity and which are responsible for the intragroup differences and intergroup similarities among κ-chains.
Lymphoproliferative Cycles in the Thymus Cortex
Authors: Bryant B. J.
Published: December 2022

The belief held for many years that small lymphocytes are terminal cells of lymphocytopoietic differentiation has recently been challenged by observations that antigens and nonspecific lymphomitogens can stimulate peripheral small lymphocytes to enlarge and proliferate. The resulting blastoid cells may form descendant clones of antibody-forming cells or small lymphocytes (1). These complex, perhaps cyclical, differentiative actions of small lymphocytes outside the thymus prompted efforts to reexamine lymphocyte differentiation within the thymus.

Animals used in this study comprised 6-week-old male mice of Swiss-Webster (SW) and C3H strains and 1-month-old guinea pigs of the Hartley strain. Animals of adolescent age were used because a steadier state of thymocytokinetics obtains during this period of interphase between organ growth and involution than at other ages (2).

Counts of lymphocyte mitoses in thymus sections of SW mice killed at 2-hr intervals during a 24-hr period were used to estimate mean mitotic indices of 1.88 ± 0.30% in cortex and 0.38 ± 0.08% in medulla.
Hepatitis-Associated Antigen: Detection by Antibody-Sensitized Latex Particles
Authors: Fritz Robert B. , Rivers Shirley L.
Published: December 2022

Latex particles sensitized with anti-hepatitis-associated antigen were found to agglutinate specifically when mixed with hepatitis-associated antigen-containing human serum. An assay for the agent based on this reaction was found to be slightly more sensitive than complement fixation. Comparison of this method with other assays done independently in different laboratories on the same coded samples showed excellent correlation. Results obtained by testing 4255 normal random blood donors by latex particle agglutination and counterimmunoelectrophoresis are included. The rapidity and simplicity of the latex particle agglutination assay suggest that it may be adaptable to large scale blood donor screening.
Carboxy-Terminal Amino Acid Sequences of Canine Immunoglobulin G Subclasses
Authors: Grant J. Andrew , Harrington John T. , Johnson John S.
Published: December 2022

The carboxy-terminal octadecapeptides from canine heavy chains of 1) IgGa, b (from normal serum) and 2) IgGd (from a paraprotein) were isolated. The amino acid sequences of both octadecapeptides were determined. Both peptides are clearly homologous to the same heavy chain region of IgG's from other mammals. Previously it has been shown that canine IgGd and equine IgG (T) share certain biologic properties; however, comparison of the sequences of their C-terminal octadecapeptides reveals no uniquely shared residues which would support a close phylogenetic relationship.
In Vitro Immunity to TNP and Penicillin: Specific Inhibition with Hapten-Conjugated Isologous Red Cells
Authors: Naor David , Mishell Robert
Published: December 2022

Syngeneic mouse red cells conjugated with trinitrophenyl (TNP) or penicillin inhibit immune responses to these haptens in vitro, The inhibition is specific and requires a significant excess of inhibiting red cells over immunogenic red cells. Inhibition is probably due to competition for specific binding sites during the initiation of the response, since the inhibitor must be present at the time of immunization. Specific inhibition with free haptens was not observed.
Electrokinetic Behavior of Intermediate Cells in Immune Hemolysis
Authors: Okada H. , Kojima K. , Yoshida T. O. , Nishioka K.
Published: December 2022

Electrophoretic mobility of intermediate cells was increased with the reaction of C2 and further increased with the addition of C3. Less than 18 molecules of C2 per cell produced detectable change in electrophoretic mobility. The increase in mobility by the formation of C2 sites diminished with the decay of C2 sites. C1 is required to maintain the high mobility of EAC142, EAC1423 or EAC143. No change in the mobility of intermediate cells was observed by the reaction of C5, C6, C7 or C8. After the reaction of C9, the electrophoretic mobility of E* decreased significantly before rupture of the cell.
In Vitro Cooperation of Cells of Bone Marrow and Thymus Origins in the Generation of Antibody-Forming Cells
Authors: Vann Douglas C. , Kettman John R.
Published: December 2022

B cells and T cells cooperate in the in vitro generation of hemolytic plaque-forming cells to sheep, horse and burro erythrocytes. The B cells are obtained from the spleens of lethally irradiated mice injected with bone marrow cells. The T cells are obtained from the spleens of lethally irradiated mice injected with thymus cells and heterologous erythrocytes. Both cell populations are obtained after 7 days residence in the irradiated hosts. Neither cell population can respond when cultured alone. The in vitro function of B cells, but not T cells, is inactivated by exposure to 2000 R γ irradiation. The T cells function best in in vitro response to the erythrocyte antigens with which they were injected into the irradiated hosts. Responses were also generated to other foreign erythrocytes and to the trinitrophenyl hapten coupled to erythrocyte carriers.
Precipitin Reactions between Polyribonucleotides and Heat Labile Serum Factors
Authors: Natali Pier Giorgio , Tan Eng M.
Published: December 2022

Immunodiffusion in agarose was used to study precipitin reactions between synthetic polyribonucleotides and human sera. A high incidence of precipitin lines was observed between certain polyribonucleotides and normal human sera. These were due to heat labile serum factors, one of which was related to C1q component of complement. In addition, heat stable serum factors were present in a few systemic lupus erythematosus sera which precipitated with polyribonucleotides. The latter precipitin reactions could be abolished by absorption of sera with heat-denatured single-stranded DNA.
Immunologic Deficiencies in Senescence
Authors: Price G. B. , Makinodan T.
Published: December 2022

The purpose of this investigation was to characterize immunologic deficiencies which occur in senescent mice. Extrinsic deficiencies, i.e., environmental deficiencies, were studied by transfer of immunocompetent cells into either young or old mice and assessment of the capacity of the cells to generate IgM antibody-forming cells. Non-cellular (environmental) factor(s) in the old mice were observed to be detrimental to the rate of growth of the antibody-forming cell population and to the full expression of the immune potential of normal young immunocompetent cells.
Expression of HL-A Antigens in Synchronized Cultures of Human Lymphocytes
Authors: Pellegrino M. A. , Ferrone S. , Natali P. G. , Pellegrino A. , Reisfeld R. A.
Published: December 2022

Human histocompatibility loci control the expression of antigenic factors which elicit an immune response resulting in the destruction of allografts. These HL-A alloantigens located on the surface of all nucleated cells thus play an important role in the graft rejection phenomenon. Recently there have also been reports linking the occurrence of certain HL-A determinants with the susceptibility to several diseases (1). In order to investigate these phenomena at the molecular level, there have been several efforts to isolate HL-A antigens in soluble form to facilitate their thorough biologic and chemical characterization. Since it is practically impossible to isolate sufficient amounts of antigens for this purpose from genetically uniform tissue sources, there has been an increased utilization of cultured human lymphocytes (2).

To gain an understanding of the expression of HL-A antigenic determinants on the surface of both synchronized and non-synchronized cultured cells during the cell cycle, we applied a quantitative microabsorption technique and an indirect immunofluorescence test.
Suppressor T Cells
Authors: Gershon Richard K. , Cohen Philip , Hencin Ronald , Liebhaber Stephen A.
Published: December 2022

The antigen-induced DNA synthetic response of a number of different thymocyte populations was studied in the spleens of lethally irradiated recipients by incorporation of 125I 5-iodo-2-deoxyuridine. The response of certain cell combinations was not only less than the sum of the two responding alone but less than one of the individual cell populations in the combination. The following combinations had this effect: 1) “Educated” and normal thymocytes < “educated” alone in the response to sheep red cells (SRBC); 2) parental and F1 thymocytes < parental alone in F1 hosts; 3) cortisone resistant (in a low dose) and normal thymocytes < normal alone in the response to SRBC. Thus, thymocytes are capable of suppressing the antigen-induced response of other thymocytes without the mediation of B cells or their product (i.e., antibody).
Friend Leukemia Virus Infection in Germfree Mice Following Antigen Stimulation
Authors: Kouttab N. M. , Jutila J. W.
Published: December 2022

The course of leukemia produced by Friend leukemia virus (FLV) in male and female BALB/c mice was compared in conventionally-reared (CR) and germfree (GF) mice. Hematologic and pathologic studies showed that whereas the disease process in CR mice was severe and resulted in death of the mice within a period of 2 to 3 months, few or mild symptoms appeared in GF mice. However, when GF mice were stimulated with sheep erythrocytes (SRBC), mortality from FLV challenge was markedly increased but without typical symptoms of a leukemic process. Immunologic assays showed that FLV completely inhibited the spleen plaque-forming cell response to SRBC in CR mice. This indicates that GF mice may not possess the “target cell” for FLV, and that this “target cell” is probably a precursor to antibody-producing cells.
The Requirement for Serum Complement in the Detoxification of Bacterial Endotoxin
Authors: Johnson Kent J. , Ward Peter A.
Published: December 2022

The in vitro detoxification of bacterial endotoxin requires both the fifth (C5) and and sixth (C6) components of complement and proceeds in the presence of 0.01 M EDTA. Addition of purified C5 or C6 to the genetically deficient serum corrects the defect in detoxification of endotoxin. Mice lacking C5 show a greatly increased susceptibility to the lethal effects of endotoxin and C6 deficient rabbits, in contrast to normal rabbits, fail to develop an increased detoxifying capacity in serum as a result of recent exposure to endotoxin. While human plasma is more effective than serum in detoxifying endotoxin, this cannot be completely ascribed to the reduction in levels of cations. The mechanism by which the complement system participates in the detoxification of endotoxin is peculiarly different from the usual sequential pathways of the complement system. In broad biologic terms, these findings suggest a previously unrecognized, protective function of the complement system.
Sensitization and Neutralization of Adenovirus by Specific Sera Against Capsid Subunits
Authors: Wadell Göran
Published: December 2022

The relative importance of the two different type-specific determinants (one on the hexons, the other on the distal part of the vertex projections) on the adenovirus capsid for the induction of antibodies capable of neutralizing virus infectivity in vitro was studied. Rabbit antisera against fibers or pentons displayed no demonstrable or low neutralizing activity when assayed by end point titration in tubes. Antisera against hexons of members of subgroup I and II and of serotype 4 consistently displayed high ratios of neutralizing capacity over type-specific complement fixation (CF) activity. However, sera against hexons of adenovirus types belonging to subgroup III showed a lower neutralizing capacity relative to type-specific CF activity. Two different populations of hexons of serotype 2 (subgroup III) could be separated by anion exchange chromatography and iso-electric focusing. Sera against certain preparations of hexons obtained by these techniques displayed very low neutralizing activity in spite of the presence of large amounts of type-specific CF antibodies.

Neutralization by sera against hexons of members of subgroup III (except type 4) was enhanced after addition of sheep anti-rabbit sera, whereas the high titers of the corresponding sera of the remaining serotypes remained unaffected. By employing the same technique, dramatic enhancement of the neutralizing capacity of sera against fibers or pentons of members of all subgroups was demonstrated. Fab and F(ab′)2 fragments of hexon or fiber specific antibodies were totally devoid of virus-neutralizing activity but retained the capacity to interact with antigenic determinants on fibers and hexons as demonstrated by hemagglutination enhancement, hemagglutination inhibition and an antibody blocking test based on CF. Combined with sheep anti-rabbit antibodies, these virus-specific antibody fragments were capable of neutralizing adenovirus infectivity indicating that Fc fragments of virus-specific antibodies were not required.
The Purification of Adenovirus Neutralizing Antibody: Adenovirus Type 5 Hexon Immunoadsorbent
Authors: Haase A. T. , Pereira H. G.
Published: December 2022

Preparation of an immunoadsorbent of crystalline hexon of adenovirus type 5 bound to Sepharose is described. The immunoadsorbent was employed to purify antibody to adenovirus type 5 hexon from antiserum prepared against a mixture of the three capsid antigens. In addition, separation of antibody with type-specific neutralizing activity from group-specific non-neutralizing hexon antibody has been achieved.
Age Dependent Resistance to Polyoma and Murine Sarcoma Viruses in Mice
Authors: Hirsch Martin S. , Proffitt Max R. , Tracy Gay S. , Black Paul H.
Published: December 2022

The mechanisms of age-dependent resistance to polyoma virus and murine sarcoma virus-Harvey (MSV-H) were evaluated in inbred mice. Transfer of unsensitized, adult CBA lymphocytes to syngeneic neonatal mice protected them against tumor development following subsequent inoculation of polyoma virus. The protective effect was proportional to the number of lymphocytes transferred, and was related both to enhanced rejection of polyoma virus transformed cells, and to more effective elimination of virus. Equal numbers of adult macrophages or mixtures of lymphocytes and macrophages were less effective in transferring protection against polyoma-oncogenesis. In contrast to the effects of cell transfer on polyoma virus infection, transfer of unsensitized adult C3H lymphocytes or macrophages to syngeneic neonatal mice had no effect on subsequent infection with MSV-H.
Activation of the First Component of Complement
Authors: Loos M. , Borsos T. , Rapp H. J.
Published: December 2022

We present evidence for an activation step in the C1 molecule that occurs after the binding of C1 and before the appearance of C1̄ activity. Evidence for this internal activation step was obtained by the use of two different inhibitors of C1̄: C1̄-inactivator (I1) and a pentosan-poly-sulfo-ester (Sp54). Sp54 and I1 do not inhibit the uptake of C1. Sp54 inhibits a population of bound C1 not inhibitable by I1. C1 taken up in the presence of Sp54 are not inhibitable either by I1 or by Sp54. C1 taken up in the presence of I1 are inhibitable by Sp54 but not by I1. Sp54 is capable of inhibiting the hemolytic action of EAC1q4 while I1 is not.

The data suggests that the internal activation step involves the subcomponent C1q.
Pharmacologic Control of Allergic Histamine Release in Vitro: Evidence for an Inhibitory Role of 3′,5′-Adenosine Monophosphate in Human Leukocytes
Authors: Bourne Henry R. , Lichtenstein Lawrence M. , Melmon Kenneth L.
Published: December 2022

The ability of catecholamines, prostaglandins and histamine to stimulate accumulation of 3′,5′-adenosine monophosphate (cyclic AMP) in human leukocytes correlated well with their ability to inhibit antigen-induced release of histamine from cells of allergic donors in vitro. In both systems the order of potency of adrenergic agents was characteristic of the beta-receptor (isoproterenol τ epinephrine τ norepinephrine τ phenylephrine), and prostaglandins E1 and E2 were equally active, while PGF1α produced no effect. A beta-adrenergic blocking agent, propranolol, specifically antagonized the effect of catecholamines on both cyclic AMP and histamine release, but had no effect against either the prostaglandins or histamine.

These results strongly support the hypothesis that cyclic AMP acts as a “second messenger” in leukocytes to inhibit allergic release of histamine. Like dibutyryl cyclic AMP and the methylxanthines, all agents which increase synthesis of leukocyte cyclic AMP act to block antigenic histamine release at an early stage of the release process, although the precise mechanism has not yet been defined.
Immunologic Alterations in Bovine Serum Albumin Resulting from Partial or Complete Reduction and Alkylation
Authors: Goetzl Edward J. , Peters John H.
Published: December 2022

Purified monomer (4S) and dimer (7S) bovine serum albumin (BSA) were isolated from solutions of crystalline BSA by gel filtration. Mercaptoethanol reduction of BSA in buffered saline resulted in the appearance of only three sulfhydryl groups per molecule (3-SH BSA). Complete reduction in 8 M urea produced 34 free sulfhydryl groups per molecule (34-SH BSA). These BSA preparations were studied by optical rotatory dispersion, ultracentrifugation, quantitative precipitation and hemagglutination with homologous and heterologous antisera, and immunologic cutaneous reactions.

Significant distortion of the native BSA conformation by complete reduction and carboxymethylation (34-SH BSA) resulted in loss of precipitation with anti-native BSA. Partial unfolding of the native conformation of BSA resulted in greater precipitation with anti-native BSA and greater reactivity with anti-3-SH BSA hemagglutinins. This increase in antigenic reactivity was directly proportional to the loss of native α-helix content and accordingly was greater for 3-SH BSA than dimer native BSA. The augmented antigenic binding is felt to be due to an exposure of hidden antigenic determinants or the creation of new determinants associated with these conformational alterations.

Completely reduced carboxymethylated 34-SH BSA is a potent immunogen inducing high titers of non-IgG antibodies with passive hemagglutination and cutaneous anaphylactic activities, but no precipitating ability. Monomer 34-SH BSA does not precipitate or fix complement with any anti-BSA antisera, and therefore may be a univalent antigen. The strong Arthus reaction produced by the 34-SH BSA immunologic system despite a lack of precipitation and complement fixation in vitro suggests the possibility of antigenic aggregation in vivo.
Synergism Between Peyer's Patch Cells and Spleen Cells in Humora Antibody Production
Authors: Coppola Edward D. , Aboul-Enein Adel , Kopycinski Clark F. , DeLuca Frank
Published: December 2022

Good and his colleagues have suggested that vertebrate immunity may have evolved into a two-component system: a thymus-dependent component primarily regulating cellular immunity, and a bursal-dependent system primarily regulating humoral immunity. These workers proposed that such structures as the tonsils, appendix and Peyer's patches may be the primary or central mammalian analogue of the avian bursa of Fabricius, whose removal causes ablation of humoral antibody responses in birds. They found that extirpation of gut-associated lymphoepithelial tissue in rabbits, followed by irradiation, produced deficiencies of specific antibody and immunoglobulin formation (1–3).

We have been interested in defining a possible role for Peyer's patches in humoral immunity. We studied first the immune response of spleen and Peyer's patch cells in 1-month-old C57BL/6 mice stimulated with intraperitoneal (i.p.) injections of 2.5 × 108 sheep red blood cells (SRBC).
Synthesis of Rat IgE by Aerosol Immunization
Authors: Van Hout Christine A. , Johnson Herbert G.
Published: December 2022

After a single 5-min exposure to an aerosol containing ovalbumin, rats produced a heat labile, skin sensitizing antibody by 14 days. By radioiodination of the protein the amount of antigen deposited in the respiratory tract during this immunization was calculated to be 12.8 µg. The amount of protein swallowed by the animals (80 µg) was incapable of elaborating an IgE response. The synthesis of IgE under these conditions was absolutely dependent on heat-killed Bordetella pertussis vaccine given i.p. before exposure. Second exposures to antigen resulted in renewed and accelerated IgE production. Repeated aerosolization with a low dose of antigen (0.1%) caused no detectable antibody synthesis.
Human Mononuclear Leukocyte Chemotaxis: A Quantitative Assay for Humoral and Cellular Chemotactic Factors
Authors: Snyderman Ralph , Altman Leonard C. , Hausman Marvin S. , Mergenhagen Stephan E.
Published: December 2022

The participation of the mononuclear leukocyte (MNL) in wound healing and in host immunity is well documented (1, 2). Despite this, the mechanism by which these cells accumulate in local tissue sites is poorly defined. Recent studies have shown that MNLs derived from rabbit or guinea pig inflammatory exudates can respond chemotactically to various stimuli in vitro (3–6; M. S. Hausman, R. Snyderman and S. E. Mergenhagen, submitted for publication). However, quantitative methods for the study of human MNL chemotactic activity have not been previously reported. An assay of human MNL chemotaxis would allow a clearer definition of human MNL chemotactic factors and also the assessment of MNL function in various human disease states. The present report describes a reproducible, quantitative assay for humoral and cellular factors of human origin which are chemotactic for human MNLs.

Materials and Methods. Source of MNLs.
A New Serum Factor in Normal Rabbits
Authors: Woolsey M. E. , Mandy W. J.
Published: December 2022

Newborn rabbits were given various doses of immunosuppressive drugs (6-mercaptopurine, cortisone or cytosine arabinoside) shortly after birth and at various intervals thereafter. The effect of these drugs on the production of homoreactant (HR) was demonstrated by a decrease in the levels of HR significantly below the levels found in control rabbits of the same litter at the same age. The reduction in HR activity was not attributed to an overall decrease in the immunoglobulin synthesis.

Since immunosuppressive drugs presumably alter the immune response at the level of antigen recognition, these findings provide indirect but supportive evidence that HR production is mediated by antigenic stimulation.
Differentiation of Binding from Complete Activation by Use of Heterologous Components of Complement
Authors: Koethe Susan M. , Austen K. Frank , Gigli Irma
Published: December 2022

C2hu can bind to cellular intermediates of the complement system in three forms. Native C2 fixes to the EAC4̄ intermediates presumably without alteration such that it can transfer quantitatively to a compatible EAC1̄hu4̄hu recipient cell, or can be activated on the cell by the introduction of C1̄. C2hu interaction with a homologous EAC cell forms a convertase capable of continuing the hemolytic sequence upon the addition of the terminal components. Finally C2hu can be bound by EAC1̄gp4̄gp to achieve an intermediate designated EAC1̄gp4̄gp2hhu; C2hhu differs from native C2hu by its failure to transfer and from fully activated C2hu by its failure to decay or efficiently mediate the hemolytic sequence. An EAC1̄gp4̄gp2hhu intermediate will, however, bind C3hu in a hemolytically inactive state designated C3hhu. C3hhu differs from native C3hu in that it is inactivated by the C3b inactivator and from C3b in that it fails to participate in immune adherence. Addition of C2gp to EAC1̄gp4̄gp2hhu3hhu intermediate imparts hemolytic activity and the ability to react in immune adherence. The C2gp presumably forms a homologous convertase on vacant SAC1̄gp4̄gp and in this way activates a neighboring C3hhu. C2hhu will fulfill the C2 requirements for C5 activation in the presence of C3b even though C2hhu does not fully activate C3hu and cells containing both C2hhu and C3hhu apparently do not activate C5.
Recombination of Genes Coding for Constant and Variable Regions of Immunoglobulin Heavy Chains
Authors: Kindt T. J. , Mandy W. J.
Published: December 2022

In one member of a rabbit family evidence has been obtained for a cross-over for genes coding from group a and group d rabbit heavy chain allotypic markers. Subsequent breeding of the animal in which the recombination occurred showed persistence of this new linkage. This observation is most readily interpreted in terms of a multi-gene system coding for the immunoglobulin heavy chain.
In Vitro Responses of Peripheral Blood Lymphocytes in Experimental Allergic Encephalomyelitis
Authors: Fowler Ira
Published: December 2022

Tritiated thymidine incorporation was determined in cultures of peripheral leucocytes taken from rabbits in which experimental allergic encephalomyelitis (EAE) was produced by immunization against either whole brain (WB) or myelin basic protein (BP). There was a significant increase in 3H-thymidine uptake in cultures of lymphocytes of animals with EAE induced with WB when stimulated with WB, but there was no increase with BP added to these cultures. When the lymphocyte donors were rabbits in which EAE was produced by BP, 3H-thymidine incorporation was increased significantly by the addition of either WB or BP to the cultures. Lymphocytes of all donors responded to stimulation in vitro before the onset of symptoms of EAE and failed to respond after the disease progressed. Lymphocytes taken from animals given protective injections of either WB or BP failed to respond to stimulation by these antigens.
The Early Immune Response and Immunoglobulins of Opossum Embryos
Authors: Rowlands David T. , Blakeslee Dennis , Lin Hshu-Hshing
Published: December 2022

The immune responses of developing opossoms were studied after one or two injections of bacteriophage f2. Antibodies could be detected in serum of developing opossums as early as 7 days after immunization and peak antibody responses were reached 14 or more days after immunization. A second injection of antigen usually increased the level of serum antibodies only slightly. The antibodies of these embryos were further studied by sucrose density gradient centrifugation. The earliest antibodies appeared as 13S “embryonic” antibodies localized between 19 and 7S positions in the sucrose density gradients. IgM antibodies appeared later as the embryonic antibodies decreased. IgG antibodies were never prominent and were the last to appear in measurable amounts during development.
The Influence of Calcium, Magnesium and Cyclic Adenosine 3′,5′-Monophosphate on the Mixed Lymphocyte Reaction
Authors: Whitney Richard B. , Sutherland Robert M.
Published: December 2022

EDTA inhibits lymphocyte transformation in the mixed lymphocyte culture reaction as it does in PHA containing cultures. The effect is most likely due to binding of Ca++ and Mg++ required for the initiation and completion of the response since transformation does not occur in cultures deficient in these ions. Exogenous cyclic adenosine 3′,5′-monophosphate (cAMP) can potentiate or inhibit the mixed lymphocyte reaction depending on concentration and duration of exposure. The possible interaction of divalent cations and cAMP in lymphocyte transformation is discussed.
γM Alloantibody Elicited by First-Set Renal Allografts: in Vivo and in Vitro Studies
Authors: van Breda Vriesman Peter J. C. , Feldman Joseph D.
Published: December 2022

γM alloantibody (allo γM) was produced in Lewis (Le) rats after a 5- to 7-day residence of Brown Norway (BN) renal grafts. The isolated, purified and isotopically labeled allo γM fixed to spleen, lung, liver and erythrocytes after intravenous injection into BN target rats, but did not fix to kidney unless the renal vein was clamped for 3 min. Allo γM fixed promptly in BN kidneys grafted into Le recipients. In such kidneys allo γM specifically bound to endothelia of glomerular and intertubular capillaries and of medium-sized arteries. It did not bind in vivo to renal tubular cells but did so in vitro. At least two γM antibodies were detected. One reacted with kidney, spleen cells and erythrocytes, the second only with spleen cells. Intravenous infusion of allo γM into target BN rats produced extensive pulmonary hemorrhages but the production of these lesions lacked specificity. Allo γM elicited by renal graft was strain but not organ specific, i.e., it reacted with transplantation antigens shared by kidney and by other organs and tissues of the immunizing strain. Its role in the rejection process could not be established.
Induction of Antiidiotypic Antibodies Directed to Antibenzoate Antibody in Rabbits Actively Synthesizing High Titers of Antibenzoate Antibody
Authors: Spring-Stewart Susan , Brient Bruce W. , Nisonoff Alfred
Published: December 2022

In efforts to elicit antiidiotypic antibodies, each of 16 rabbits was immunized with purified antibenzoate antibodies prepared in an individual donor rabbit of allotype matched to the recipient. Two types of recipients were used: 1) rabbits hyperimmune to the benzoate hapten; 2) rabbits hyperimmune to the noncross-reacting hapten, DNP. Nearly all recipient rabbits responded by producing anti-idiotypic antibodies, and no significant quantitative differences were detected in the two groups. This result implies that the rabbits producing antibenzoate antibodies at the time of immunization were not tolerant to the antibenzoate antibodies injected.

Efforts were also made to elicit antiidiotypic antibodies by self-immunization of donor rabbits with their own antibenzoate antibodies after rest periods totaling 23 to 36 weeks. Such experiments were unsuccessful, indicating that a state of tolerance to the rabbit's own antibodies had persisted.

Thus rabbits remained tolerant to their own idiotypic determinants, whereas the capacity to respond of other rabbits, actively synthesizing high titers of antibenzoate antibody, was not impaired. The results emphasize the broad spectrum of idiotypic specificities in different rabbits on molecules specific for a single hapten group.
Promethazine-HCl as an Immunosuppressant
Authors: Gusdon John P. , Moore Vernon L. , Myrvik Quentin N. , Holyfield Paul A.
Published: December 2022

The effects of promethazine-HCl on humoral antibody synthesis and on delayed hypersensitivity have been evaluated. The primary and secondary immune responses to bovine serum albumin (BSA) and bovine γ globulin (BGG) were significantly reduced. There was a highly significant reduction in tuberculin hypersensitivity when the drug was administered before and during the development of the hypersensitive state.
Enhancing Effect of Bacterial Endotoxins on Bone Marrow Cells in the Immune Response to SRBC
Authors: Jones J. Miriam , Kind Phyllis D.
Published: December 2022

The synergistic involvement of bone marrow (B) cells and thymus (T) cells in the immune response to sheep erythrocytes (SRBC) has been well established. Injection of both cell types into irradiated mice challenged with SRBC results in far greater than additive numbers of antibody-producing cells (1–3). An interpretation of these findings is that following the interaction of the T cell, the B cell and antigen, the B cell proliferates and differentiates into the antibody-forming cell (4).

When the antibody response is augmented by bacterial endotoxins, the number of antibody-forming cells in the spleen is increased (5, 6). Thus the enhanced antibody response could be a result of increased proliferation of T cells, B cells or both.

Recipient BDF1 mice were irradiated by whole body exposure to 1000 R from a 60CO source. B cells from donor BDF1 mice were flushed from femurs and tibias by using Hank's balanced salt solution (BSS). T cells were teased in BSS.
Changes of γ Globulin Carrying Cells in NZB Mice before Autoimmune Disease
Authors: Weinerman B. , Paraskevas F.
Published: December 2022

New Zealand black (NZB) mice have an impressive array of immunologic aberrations, and the female of the species seems to bear the heavier burden of autoimmune phenomena (1). These mice appear to be hyperresponsive to certain antigenic stimuli, but not to others (2–5). Both sexes display defective thymus function, and recently they have been shown to have a circulating thymocytotoxic autoantibody which is a macroglobulin (6).

These abnormalities prompted us to look systematically at the γ globulin-carrying cells of both male and virgin female mice from an early age onward by using the reverse immune cytoadherence technique (RICA) (7). This technique uses a 5S hybrid antibody carrying one anti-γ-globulin site and one anti-ferritin site so that γ globulin-carrying cells form rosettes (rosette-forming cells, RFC) with ferritin-coated sheep red blood cells. While this work was in progress there was a report of a decrease in the percentage of cells carrying membrane immunoglobulins in the peripheral blood of NZB mice with advancing age.
Masking of Human Transplantation Antigens by Diverse Substances
Authors: Hirata Arthur A. , Terasaki Paul I.
Published: December 2022

The reaction of HL-A antibodies with the HL-A determinants on the surface of lymphocytes can be blocked by preincubation of lymphocytes with diverse substances such as normal human serum, autologous plasma, fetal calf serum, newborn serum, heat-inactivated rabbit serum and guinea pig serum, serum albumins from various species, lactalbumin, dextrans, synthetic polyglucose, and polyvinylpyrrolidone. The inhibitors can be washed off readily from lymphocytes. The inhibition procedure described here differs from the conventional inhibition tests in that the inhibitor is added first to the target cells. This “masking inhibition” procedure produces substantially greater inhibition than the standard inhibition methods in which the inhibitor is added first to antiserum before the addition of the target cells. The nonspecific nature of masking inhibition indicates that numerous substances adhere to the lymphocyte surface at HL-A sites or closely adjacent sites.
An Escherichia Coli Antigen Cross-Reactive with the Capsular Polysaccharide of Haemophilus Influenzae Type b: Occurrence Among Known Serotypes, and Immunochemical and Biologic Properties of E. Coli Antisera Toward H. Influenzae Type b
Authors: Schneerson Rachel , Bradshaw Major , Whisnant John K. , Myerowitz Richard L. , Parke J. C. , Robbins John B.
Published: December 2022

An Escherichia coli antigen was shown to be cross-reactive with the capsular polysaccharide of Hemophilus influenzae type b. The cross-reactive antigen was identified as a thermostable, acidic, capsular polysaccharide consistent with its designation as E. coli “K” antigen (type A). Antibodies raised by intravenous injection of formaldehyde-treated E. coli possessing the cross-reactive antigen precipitated with the H. influenzae type b capsular polysaccharide and had “protective” activity against H. influenzae type b in biologic assays. The cross-reactive antigen was identified in E. coli with various O and H serotypes and did not appear to be associated with pathogenicity.
Opsonic Activity in Human Serum Deficient in C2
Authors: Johnson Frank R. , Agnello Vincent , Williams Ralph C.
Published: December 2022

Human serum deficient in C2 was studied for opsonic activity by using test strains of Escherichia coli, Proteus mirabilis, Staphylococcus aureus and Diplococcus pneumoniae in an in vitro system of phagocytosis and bacterial killing. Heat labile opsonic activity was apparently effected through the alternate C3–C9 pathway since absorption of fresh serum with inulin at 37°C abolished opsonic activity concurrent with β1c to β1a conversion. The same treatment was shown to activate the C3 activator system. In addition, activation of C3 with isolated 140,000 m.w. cobra venom factor resulted in loss of opsonic activity for test organisms. The alternate complement activation pathway may be important in the opsonic functions necessary for in vivo phagocytosis of organisms.
The Distribution of Brain-Associated ϑ Antigen Cross-Reactive with Mouse in the Brain of Other Species
Authors: Golub Edward S.
Published: December 2022

θ is a mouse alloantigen which serves as a marker for thymus-derived (T) cells (1). Anti-θ antisera have proven to be powerful tools in elucidating the roles of bone marrow-derived (B) and T lymphocytes (2). θ is shared by T lymphocytes and brain tissue in the mouse (1). We had previously shown (3) that immunization of rabbits and goats with mouse brain results in the production of potent anti-θ-like antisera. We have termed these anti-brain-associated θ antisera (BAθ). It would be a great advantage in studying immune systems other than the mouse if antigen comparable to θ were available. We have taken a variety of approaches in an attempt to develop anti-θ-like antisera to other species. One of these is to investigate brain tissue of other species to determine if it contains cross-reacting antigens with mouse BAθ.
Simplified in Vitro Method for Measuring Delayed Hypersensitivity to Latent Intracellular Infection in Man (Toxoplasmosis)
Authors: Gaines J. David , Araujo Fausto G. , Krahenbuhl James L. , Remington Jack S.
Published: December 2022

There are relatively few organisms which are known to cause persistent latent infection in man, and which for years produce an antigenic stimulus. Toxoplasma gondii is one such organism, and serologic evidence of infection with this protozoan is present in 20 to 50% of normal adults in the United States. In recent years serious infection with this intracellular parasite has been recognized with increased frequency in patients receiving immunosuppressive therapy (1, 2). The underlying host factors which control this infection, despite persistent activity in its latent form, are not completely understood, but resistance appears to be mainly cell mediated (3).

A skin test elicits delayed hypersensitivity but does not become positive for months or years after the acute infection (4, 5). Lack of standardization and the possibility of adventitious agents in the antigen have prevented the widespread use of this skin test in this country (6).
Structure and Biologic Functions of Human IgD
Authors: Leslie Gerrie A. , Swate Tommy E.
Published: December 2022

Analysis of human cord sera showed that approximately 4.5% contained IgD. Comparisons of the concentration of maternal and cord IgD, IgA, IgM and haptoglobin suggest that the IgD present in at least half of these cord sera was of fetal origin.
Macrophage Accumulation, Division, Maturation and Digestive and Microbicidal Capacities in Tuberculous Lesions
Authors: Ando Masayuki , Dannenberg Arthur M. , Shima Kiyoshi
Published: December 2022

During the first 2 weeks the rate of entry of mononuclear cells (MN) into rabbit dermal BCG lesions was roughly proportional to the increase in size of the lesions. Lesions of reinfection increased in size much faster than primary lesions.

After caseous necrosis was prominent, changes in lesion size no longer reflected the entry of new MN because many were dying. Tritiated thymidine (H3T) was therefore used to label MN (mostly in the bone marrow), and their rate of entry into dermal BCG lesions was determined by autoradiographic techniques. Multiple lesions were produced and biopsied, each at a different time after a single intravenous (i.v.) pulse of H3T. This pulse was given when the BCG lesions were -1, +6, +14 or +27 days of age. Five days afterward 20 to 30% of the MN present were labeled, regardless of whether the lesion was beginning (-1 and +6 days), at its height (+14 days) or regressing (+27 days). Thus there was a continuous entry of new MN into the lesions throughout their life. Many more H3T-labeled MN entered the BCG lesions after hypersensitivity to tuberculin developed.

The rate of local MN division in dermal BCG lesions was determined by H3T grain count analyses. A single i.v. pulse of H3T was given to rabbits when their lesions were -1, +6, +14 or +27 days of age, and biopsies were made 1, 2, 5 and 8 days after the pulse. The reduction in H3T grain counts caused by previous MN division in the bone marrow was compared with the grain count reduction caused by MN division in the BCG lesions. The rate of MN division in these lesions was highest when delayed hypersensitivity was strong, namely in lesions of reinfection and in 14-day primary lesions.

Similar H3T grain count analyses indicated that the MN which divided in the BCG lesions did so only once (or twice) during their first week of residence. After such division, they still functioned awhile before they died and were replaced by new MN from the bloodstream. Thus most of the MN in tuberculous lesions were relatively recent immigrants, and their local division did not contribute substantially to the total number present.
Activation of Complement by Endotoxin: A Role for γ2 Globulin, C1, C4 and C2 in the Consumption of Terminal Complement Components by Endotoxin-Coated Erythrocytes
Authors: Phillips Jean K. , Snyderman Ralph , Mergenhagen Stephan E.
Published: December 2022

Sheep erythrocytes (E) coated with endotoxin (LPS) from Salmonella typhosa or Veillonella alcalescens (E-LPS) have been employed to define more precisely the nature of a pathway by which LPS activates the terminal components of complement (C). E-LPS consumed C in normal guinea pig serum in a manner identical to free LPS, that is, with marked consumption of C3 through C9 and little utilization of C1, C4 and C2. A γ2-migrating globulin, isolated from normal guinea pig serum by DEAE-cellulose chromatography, was required for C-mediated lysis of E-LPS in diluted guinea pig serum. Absorption experiments with E-LPS indicated that the heat stable γ2 globulin showed specificity for the LPS employed. Cobra venom factor, known to activate C by the alternate pathway (C3 proactivator system), was equally able to deplete C activity in normal serum or serum absorbed with E-LPS. E-LPS reacted with γ2 globulin, C1, C4, C2, followed by C-EDTA resulted in lysis of E-LPS. Deletion of γ2 globulin or any of the earlier acting C components from the reaction prevented lysis. The small amounts of the early acting C components employed, particularly C4 and C2, indicated that it would be difficult to measure their loss in whole serum after activation with LPS by conventional hemolytic assay. This could explain the finding of a relative sparing of C1, C4 and C2 during consumption of C3 through C9 by LPS in normal guinea pig serum. Thus, a classical C pathway involving a “natural” γ2 globulin and early components of C has been defined as a mechanism by which endotoxin can efficiently activate the terminal components of C.
Interspecies Occurrence of Immunoglobulin Antigens Reactive with Anti-Allotype Antisera
Authors: Rodkey L. Scott , Conrad A. H.
Published: December 2022

Studies were done to ascertain whether antigenic similarities of serum proteins in New Zealand White and cottontail rabbits included similarities in the immunoglobulin allotype markers. Indirect precipitation techniques were used to identify markers coded at both the a and the b locus on cottontail IgG F(ab′)2 molecules. Inhibition tests suggested that cottontail IgG F(ab′)2 fragments carry only a portion of the full complement of allotype determinants coded for in the New Zealand White rabbit. These determinants were shown to be related to surface determinants on New Zealand White IgG F(ab′)2 molecules. The results suggested that immunoglobulin antigens reacting with specific anti-allotype antisera are not restricted to a single genus and species.