bluuebunny/crossref_metadata_2025 huggingface dataset:
Hapten-Specific IgE Antibody Responses in Mice
Authors: Katz David H. , Hamaoka Toshiyuki , Newburger Peter E. , Benacerraf Baruj
Published: December 2022

The studies presented in this paper were performed to compare the responses of B lymphocytes of the IgG and IgE classes, respectively, to relatively constant conditions of activated T cell participation in antibody production by these cells. Two systems were employed: a) regulation of antibody responses by a potent nonantigen-specific T cell influence provided by the reaction of allogeneic T cells with alloantigens on the surface of antigen-specific B cells (“allogeneic effect”); and b) induction of adoptive secondary cooperative anti-hapten antibody responses by administering hapten and carrier determinants on separate molecules. The data presented here demonstrate that the allogeneic effect, although providing a potent mechanism for stimulating IgG B lymphocytes, either fails to stimulate or suppresses IgE B cells under the same conditions. Furthermore, under circumstances where antibody responses are elicited by administering nonlinked hapten and carrier determinants, the evidence implies that IgE B cells can be stimulated to a greater extent than IgG B cells in conditions of limited T cell participation. Taken collectively, these data support the concept that differences observed in the degree of helper function for one or the other antibody class may reflect differences in sensitivities of IgE vs IgG B cells to the complex enhancing and suppressive regulatory influences of the same T cell populations rather than to the existence of different T cells for different immunoglobulin classes.
Host Responses to Infectious Bovine Rhinotracheitis Virus
Authors: Rouse Barry T. , Babiuk Lorne A.
Published: December 2022

An investigation was made to determine if the nylon wool column technique of Julius et al., (9), could be used to fractionate bovine peripheral blood lymphocytes into T enriched (effluent) and B enriched (adherent) cells. After column filtration, the subpopulations were checked for surface-labeling characteristics with fluorescein-labeled anti-Ig serum (membrane fluorescence), phagocytic activity, response to mitogens, and their reactivity in two in vitro assays that quantitate cell-mediated immunity (CMI) against a bovine herpes virus-infectious bovine rhinotracheitis (IBR) virus. The effluent cells appeared enriched in T cells since few cells showed membrane fluorescence and these cells responded well to the T cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A). The adherent cells appeared enriched in B cells since many cells showed membrane fluorescence and the cells responded well to lipopolysaccharide (a B cell mitogen) but poorly to PHA and Con A. In the in vitro CMI assays against IBR virus, the effluent cells were far more reactive than the adherent cells implying that these assays are essentially measures of T cell activity.

The implications of the results for the understanding of the mechanism of resistance to herpes virus infections is discussed.
Expression of New Antigens by HL-A Variants of Cultured Lymphoid Cells
Authors: Pious Donald , Soderland Carl
Published: December 2022

Antisera were raised in rabbits to a number of spontaneously occurring and mutagen-induced HL-A2 loss variants of the cultured lymphoid line 8866. The antisera to the variant sublines were absorbed with 8866 and with one or both of the spontaneously occurring variant sublines, and the absorbed antisera were tested to determine whether they retained reactivity for the variant against which the antiserum was raised. A positive result was taken as evidence that the variant expressed a new antigen. By this criterion, neither spontaneously occurring variant appeared to express a new antigen. However, at least two of four mutagen-induced variants appeared to do so. Antiserum against 8866 absorbed with either of the spontaneously occurring HL-A2 loss variants appeared to be a specific HL-A2 reagent, supporting the idea that antigen loss in these variants is limited to the HL-A2 allele.
Specificity of in Vitro Murine B Cell Activation by Protein and Polysaccharide Polymers
Authors: Strong Douglas M. , Ahmed Aftab A. , Scher Irwin , Knudsen Richard C. , Sell Kenneth W.
Published: December 2022

The ability of various polynucleotide and carbohydrate polymers to induce B cell mitogenesis as measured by the uptake of 3H-thymidine was studied. Cell suspensions depleted of T cells were obtained from spleens of Nu/Nu, TxBm mice, or by treatment of normal spleens with anti-θ serum and complement. Specific B cell activation was demonstrated by the use of the following single and double stranded ribopolynucleotides, poly A, U, A·U, G, and X. In addition, carbohydrate polymers, such as dextran sulfate and methylcellulose, as well as the thymic-independent antigens, pneumococcal polysaccharide (SSSIII) and polymerized flagellin (POL), produced B cell activation. Two other B cell antigens, polyvinylpyrrolidone and Ficoll, did not appear to act as mitogens. A highly charged polymer, CM-Ficoll, also failed to stimulate. Although dextran sulfate (m.w. 500,000) produced activation, the lower molecular weight dextran sulfate (m.w. 75,000) did not. LPS contamination of all mitogenic materials was ruled out by the use of an antisera directed against the active portions of LPS, lipid-A. Confirmation of specific B cell activation was obtained by the eliminations of responses by anti-MBLA treatment of cell suspensions and the failure of activated suspensions to produce lymphotoxin, a T cell lymphokine which can be induced with PHA or Con A. These studies indicate that B cell activation requires a unique molecular structure not limited singly by polymeric repeating determinants or a polyanionic nature but also a minimum molecular weight as well as secondary and tertiary characteristics of the mitogenic compound. The characteristics associated with the ability of a molecule to activate specifically B cells is discussed.
Role of T Lymphocytes in the Humoral Immune Response
Authors: Davie Joseph M. , Paul William E.
Published: December 2022

The humoral response to dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) was measured in thymectomized, irradiated, bone marrow-reconstituted, and rabbit antimouse thymocyte antiserum-(ALS)treated (Tx-BM) mice. The total anti-DNP antibody response, as measured by plaque-forming cells, was not severely decreased, but was changed in character from the normal predominantly IgG secondary response to a persistently IgM response. The IgG secondary response was partially restored to Tx-BM mice by injecting syngeneic thymocytes i.v. as late as 1 week before or activated thymus-derived (T) lymphocytes on the day of secondary antigen administration, implying that significant changes occur in the precursor population in the absence of T cells. This was supported by the finding that antigen-binding cells (ABC), the presumed precursors of antibody-secreting cells, proliferated normally in Tx-BM mice. However, instead of the replacement of µ-bearing ABC by significant numbers of ABC bearing other classes of immunoglobulin, as seen in the normal response to antigen, the ABC in Tx-BM animals possessed µ-receptors throughout the immune response. It is suggested that the generation or activation of non-µ-bearing ABC is strikingly impaired in the absence of a normal complement of T cells and may be responsible for the decreased IgG antibody production.
Antibody-Dependent Cell-Mediated Cytotoxicity
Authors: Scornik Juan Carlos
Published: December 2022

The early interactions between effector and target cells in antibody-dependent cell-mediated cytotoxicity were analyzed in a system with hapten-coated target cells and anti-hapten antibodies. Direct contact between effector and target cells through the antibody molecule is required for lysis of target cells. Establishment of contact can be prevented by free hapten, but once contact has occurred, free hapten is ineffective in preventing lysis of target cells. After effector cell-target cell interactions, target cell damage is first manifested by increased osmotic fragility and later by a progressive, temperature dependent, increased permeability for intracellular components. Effector cells and target cells remain in contact during the lytic process, which is completed in several hours.
Generation of C5-Derived Lysosomal Enzyme-Releasing Activity (C5a) by Lysates of Leukocyte Lysosomes
Authors: Goldstein Ira M. , Weissmann Gerald
Published: December 2022

Leukocyte lysosomes contain materials which interact with the complement system in at least two ways to generate C5-derived lysosomal enzyme-releasing activity (C5a). Firstly, a lysosomal protease is capable of cleaving purified C5 at neutral pH to yield a low molecular weight product which selectively releases lysosomal, but not cytoplasmic, enzymes from isologous, cytochalasin B-treated, human polymorphonuclear leukocytes. The activity of this enzyme is inhibited by EACA and by normal human serum. Secondly, in fresh serum, lysosomal lysates generate the active form of the C3 proactivator and produce nonimmune hemolysis of dithiothreitol-treated erythrocytes, presumably by activation of the alternate pathway. Therefore, C5a activity is generated in human serum treated with lysates of leukocyte lysosomes as a consequence of complement activation: lysosomal constituents further their own release in a positive feed-back loop.
Immune Responses Against Native and Chemically Modified Albumins in Mice
Authors: Schirrmacher Volker , Wigzell Hans
Published: December 2022

Albumin antigens were chemically modified at their charged residues by various means (i.e., methylation, acetylation, succinylation) and the effect of the modification reactions on humoral and cellular immune responses was compared. The modifications resulted in profound changes of the molecules' physicochemical properties (charge, conformation, state of aggregation) and in a destruction of the majority of serologically detectable native albumin determinants. On the level of the humoral antibody response the effects of the modifications were i) pronounced reduction of the response against native determinants and ii) induction of an antibody response against new antigenic determinants (NAD) on the modified proteins.

Helper (T) lymphocyte responses as a test for cellular immunity were investigated in cell transfer experiments. When using limiting doses of immunogen for primary immunization, it could be shown that none of the modification reactions had any negative impact on the capacity of the albumin to induce helper cells reacting with the native albumin. In the same experiments, however, a marked reduction on the level of albumin-specific antibody-forming cell precursors (B cells) was observed. These results suggest that there are different structural requirements for the induction of B and T cell responses against native protein antigens.

Compared to antibodies, helper cells induced by differently modified albumins seemed to have a higher degree of cross-reactivity. However, they also revealed a notable discriminating capacity, suggesting that both antibodies and helper cells were able to distinguish on the modified proteins NAD from native determinants. Possible interpretations of the results are discussed.
Identification by Peroxidase Staining of Monocytes in Surface Immunofluorescence Tests
Authors: Preud'Homme Jean-Louis , Flandrin Georges
Published: December 2022

Surface immunoglobulins (S.Ig)2 on human lymphocytes have been widely studied in the last few years, mainly with surface immunofluorescence (IF) tests. These studies have led to somewhat contradictory results (reviewed in 1) and most discrepancies are likely explained by methodological reasons since S.Ig detection is exposed to a number of pitfalls (2). Monocytes represent an important source of potential errors. They bind serum IgG by their Fc receptor and therefore stain with conjugated antisera to γ-, κ- and λ-immunoglobulin chains. In addition some monocytes are able to bind rabbit IgG used as reagents and show positivity in IF tests whatever the specificity of the conjugate is. Two approaches may be used in order to avoid erroneous interpretation due to monocytes, either the use of cell suspensions free of monocytes or the identification of monocytic cells.
Involvement of T Lymphocytes in the Pathogenesis of Coxsackie Virus B3 Heart Disease
Authors: Woodruff Jack F. , Woodruff Judith J.
Published: December 2022

Coxsackie virus B3, inoculated i.p., replicated to high titer in the hearts of adult CD-1 and BALB/c mice but virus growth was completely suppressed 6 to 8 days after infection. On day 6 histologic examination showed that the hearts were infiltrated with mononuclear inflammatory cells which surrounded foci of necrotic myofibers. CD-1 animals survived the infection but most BALB/c mice died 8 to 14 days after virus challenge. CD-1 mice pretreated with rabbit anti-thymocyte serum (ATS) and T lymphocyte-deprived BALB/c mice (thymectomized, lethally irradiated, and bone marrow reconstituted) exhibited no reduction in their capacity to terminate viral replication suggesting that the development of effective anti-Coxsackie viral resistance occurred independently of T cell function. In addition, evidence was obtained implying that antiviral antibody synthesis during the 1st week of infection was not T cell dependent. However, observations in ATS-treated mice suggested that at later intervals T cells were required for optimal serum antibody production.

T cell dependent reactions were also found to play an important role in the pathogenesis of the heart disease induced by the virus. Thus administration of ATS greatly suppressed the production of inflammation and tissue injury in infected hearts of CD-1 mice. Similarly, T cell deprivation protected BALB/c mice against lethal infection. Moreover, the degree of cardiac inflammation and necrosis in virus-infected T cell-deprived BALB/c mice was significantly less than that found after infection of both intact mice and thymectomized irradiated mice which had been reconstituted with both bone marrow and thymus cells.
Influence of Cyclophosphamide on the Delayed Hypersensitivity in the Mouse After Immunization with Histocompatibility Antigen
Authors: Kerckhaert Joseph A. , van den Berg Gert J. , Hofhuis Frans M. A.
Published: December 2022

The use of delayed hypersensitivity (DH) reactions as a measure of the immunity against histocompatibility antigens in mice has been described. The DH was only provoked to a measurable level if the sensitization was preceded by cyclophosphamide (CY) treatment. CY treatment before i.p. immunization caused an initial suppression of the DH. This was followed by an enhancement when the interval between immunization and challenge was 10 days. Immunization i.p. with allogeneic or F1 spleen cells only resulted in a sensitization for DH if preceded by CY treatment. Differences in dose response curves between i.p. administered allogeneic and semi-allogeneic cells after CY treatment suggested that the graft-vs-host reaction (GvH) interfered with the DH. Comparison of 1) DH reaction after i.p. immunization and CY treatment and 2) GvH activity of cells from different lymphoid organs gave further indications of this interference.
The Presence of Arginyl Residues and Carboxylate Groups in the Phosphorylcholine-Binding Site of Mouse Myeloma Protein, HOPC 8
Authors: Grossberg Allan L. , Krausz Leon M. , Rendina Leonard , Pressman David
Published: December 2022

The participation of certain amino acid residues in the phosphorylcholine-binding sites of the mouse myeloma protein, HOPC 8, has been investigated by chemical modification procedures. Glyoxalation of two-thirds of the arginyl residues of HOPC 8, in the absence of protecting ligand, resulted in the complete loss of binding activity; glyoxalation in the presence of phosphorylcholine resulted in retention of about 50% of the sites. Maleylation of all free amino groups of HOPC 8 caused a minor loss (∼20%) of binding activity whether or not ligand was present during the modification. Esterification of approximately one-quarter of the carboxylate groups of HOPC 8 resulted in a significant loss of binding sites and this loss could be partially prevented by the presence of ligand.

These results are interpreted as indicating the presence of arginyl and glutamyl or aspartyl residues as contact amino acids in the binding site of HOPC 8, providing complementary positive and negative charges for binding, respectively, the negatively charged phosphoryl moiety and the positively charged choline moiety of the ligand. Lysyl residues are probably not involved directly in the specific site-ligand interaction.
Effect of Preinfection and Preimmunization on the Serum Antibody Response to Subsequent Immunization with Heterotypic Influenza Vaccines
Authors: Jennings Roy , Potter Christopher W. , McLaren Colin
Published: December 2022

The serum hemagglutination-inhibiting and neuraminidase-inhibiting antibody response of hamsters, ferrets, and mice to inactivated influenza virus vaccination was enhanced by the prior infection of these animals with live, heterotypic influenza viruses. This priming effect was also elicited by prior immunization with inactivated, heterotypic influenza virus vaccines in adjuvant. Enhancement of the serum antibody response to inactivated influenza vaccines was not observed if the priming infection was given 20 weeks before immunization. No priming effect was demonstrated for type B influenza viruses.
Comparison of T Lymphocyte-Dependent and B Lymphocyte-Dependent Mitogen-Stimulated DNA Synthesis in Serum-Free Medium with Spleen Cells from Animals Chosen for Broad Variation in Genetically Determined Differences in T Lymphocyte Mitogen Responsiveness
Authors: Williams R. Michael , Benacerraf Baruj
Published: December 2022

To determine whether or not the T lymphocyte-dependent mitogens Concanavalin A (Con A) and Phytohemagglutinin (PHA) and the B lymphocyte-dependent mitogens pokeweed mitogen (PWM) and Escherichia coli lipopolysaccharide (LPS) elicit fundamentally different patterns of responsiveness by mixed cell populations, we studied unmanipulated murine spleen cell populations in cultures free of exogenous serum. Advantage was taken of genetically determined differences in Con A- and PHA-stimulated responses of spleen cells from mice in F2 populations with (BALB/c × B10.D2)F2 animals (all H-2d homozygotes) being used in order to control for possible ongoing H-linked Ir gene-dependent immune responses. That is, broad genetically determined variability in T-dependent mitogen response was utilized in order to evaluate the correlations among spontaneous DNA synthesis and that stimulated by the four mitogens, Con A, PHA, PWM, and LPS. Spontaneous DNA synthesis when no mitogen was added to the cultures was significantly correlated with the LPS-stimulated response (r = 0.659, p < 0.005). The PWM response also showed a slight positive correlation with the no mitogen response (r = 0.444, p < 0.05), but Con A and PHA responses were not correlated with the level of spontaneous DNA synthesis. Con A and PHA responses were highly correlated with each other (r = 0.812, p < 0.001) as were LPS and PWM responses (r = 0.806, p < 0.001). There was some positive correlation between Con A and LPS responses (r = 0.603, p < 0.005), whereas the PHA response was not correlated with any response other than that to Con A. These data support the concept that there is an exogenous serum independent, fundamental difference in the response to the T lymphocyte-dependent mitogens Con A and PHA compared to the response to the B lymphocyte-dependent mitogens PWM and LPS.
The PHA Dose-Response Curve: Validation of the Use of Logarithmic Graph Paper by Computer Analysis Results
Authors: Ziegler John B. , Hansen Prudence J. , Davies Wayne A. , Penny Ronald
Published: December 2022

Phytohemagglutinin in concentrations of 0 to 800 µg/ml was used to stimulate peripheral blood lymphocytes of normal donors and responses were determined using tritiated thymidine incorporation into DNA after 68 hr incubation. A computer program was used to rank responses at each dose of phytohemagglutinin and to test for a normal distribution by the technique of probit transformation of cumulative frequencies. The procedure was repeated using logarithms, square roots, and cube roots of ranked values. Results indicated that the logarithmic function provided the closest approximation to a normal distribution over the range of the dose-response curve. These results validate the practice of plotting lymphocyte culture data on logarithmic graph paper and indicate that geometric statistics should be used to compare sets of data by methods which assume a normal distribution.
Subepidermal Deposition of Immunoglobulin in NZB/NZW F1 Hybrid Mice
Authors: Gilliam James N. , Hurd Eric R. , Ziff Morris
Published: December 2022

The dermal-epidermal junction of NZB/NZW F1 hybrid mice is a site of immunoglobulin (Ig) deposition. This produces a fluorescent band which is very similar to that seen in the skin of patients with systemic lupus erythematosus. The deposition of Ig in the mouse skin is first observed at six months of age and increases in frequency thereafter. After an initial lag of 1 to 2 months, it parallels the age-related deposition of Ig in the kidney. The observed temporal relationship between glomerular and cutaneous Ig deposition supports the concept that the presence of immunoglobulin in the skin is highly indicative of the presence of immune complexes in the kidney.
Intracellular Events Involved in the Induction of Immune Competence in Lymphoid Cells by a Thymus Humoral Factor
Authors: Kook Abraham I. , Trainin Nathan
Published: December 2022

A humoral factor extracted from calf thymus (THF) restores the immunocompetence of spleen cells from neonatally thymectomized (NTx) mice to induce an in vitro graft-vs-host (GVH) response. This acquisition of immunocompetence consists of a series of biochemical events, the first of which involves an obligatory rapid increase in adenyl cyclase activity and in intracellular levels of cyclic AMP. Protein synthesis occurs as a further step in the events leading to induction of immunocompetence by THF and could be blocked by cycloheximide with the consequent abolishment of the immunocompetence of the lymphoid cells tested. The induction of competence by THF is accompanied by a simultaneous reduction in DNA synthesis resulting from the increase in intracellular cyclic AMP levels. These steps have been studied in the absence of antigenic stimulation which is not required for the induction of competence by THF. Spleen extracts prepared by a similar procedure as THF were found to be devoid of the properties described above.
Antigenic Relationship between the Fourth Component of Human and Guinea Pig Complement
Authors: Ohanian Sarkis H. , Borsos Tibor
Published: December 2022

Antigenic similarity between cell-bound human and guinea pig C4 was detected with antisera specific for each of these molecules. No cross-reaction could be detected between C4 of normal guinea pig or human sera or after treatment of the sera with antigen-antibody C1 complexes. The cross-reactivity between cell-bound human and guinea pig C4 may reflect conformational changes in the C4 molecule as a result of binding to the cell surface.
Restriction of Heterogeneity of Goat Antibodies Specific for Human Hemoglobin S
Authors: Schreiber Robert D. , Noble Robert W. , Reichlin Morris
Published: December 2022

Previously, we had reported the isolation of an antibody population (termed antiVal antibody) specific for the site of difference between human hemoglobin S (HbS) (β6Val) and hemoglobin A1 (HbA) (β6 glu). This population has a stoichiometry of reaction of unity in combining with HbS (αβ dimer) and shows no reaction with HbA. The combination of antiVal Fab fragments with HbS was found to be kinetically homogeneous and had a second order rate constant of 0.58 × 106M-1 sec-1 at 20°C. In this report we have studied other properties of the antiVal population. These antibodies are restricted to only one of the two heavy chain subclasses of goat IgG. Electrophoresis experiments indicated that the antiVal population is much less polydisperse than the total antiHbS response. A method was developed to measure the dissociation kinetics of antiVal-HbS complexes. This dissociation was also found to be kinetically homogeneous and could be described by a single first order rate constant of 2.67 × 10 5sec 1at 20°C. With homogeneous association and dissociation rate constants, an affinity constant of 2.1 × 1010M-1 at 20°C was calculated. It appears, then, that this population of antibodies, which are directed toward a single antigenic determinant on a globular protein, exhibit limited structural heterogeneity associated with great functional homogeneity.
The Characterization of Human Anti-IgG Autoantibodies by Liquid Isoelectric Focussing
Authors: Trieshmann Helmuth W. , Abraham George N. , Santucci Edward A.
Published: December 2022

A series of human anti-IgG autoantibodies (AGA) have been analyzed by liquid isoelectric focusing in order to a) determine their isoelectric points (pI) and b) assess their heterogeneity. The 13 AGA examined include five IgM, five IgA, and three IgG AGA. All demonstrate a single major peak indicative of restricted heterogeneity and each is characterized by an acidic pI. This anodal pI is distinct from other immunoglobulins isolated from the same serum that do not exhibit anti-IgG activity. It is speculated that the acidic pI is the result of acidic amino acid substitutions in the variable regions of immunoglobulin chains. The restricted heterogeneity and distinctive pI of the AGA suggest the selection of structurally similar antibody molecules from the large repertoire available in the human genome.
Antigen-Induced Inhibition of Experimental Allergic Encephalomyelitis
Authors: Swanborg Robert H.
Published: December 2022

Defined peptide fragments were isolated from the N-terminal half of the myelin basic protein (BP) molecule and employed for antigen-induced inhibition of experimental allergic encephalomyelitis (EAE). Guinea pigs pretreated with peptide 44–89, obtained by limited pepsin digestion and purified by column chromatography, were significantly protected against EAE subsequently induced by sensitization with BP in complete Freund's adjuvant. Peptide 1–20, derived by cyanogen bromide cleavage, did not inhibit EAE, nor did the synthetic EAE peptide (residues 114–122), although this peptide was only weakly encephalitogenic for guinea pigs. These findings directly support our previous conclusion that different sites on the BP molecule are responsible for induction and inhibition of EAE, and suggest that disease inhibition can be attributed, at least in part, to a site within peptide 44–89.
Macrophage Cytotoxicity in the Mouse Immune Response Against a Skin Allograft
Authors: Dimitriu Alexandra , Dy Michel , Thomson Napier , Hamburger Jean
Published: December 2022

Macrophage-rich peritoneal cell populations from C57BL/6 mice grafted with DBA/2 skin were found to be cytotoxic against 51Cr-labeled target cells from the donor strain. Normal peritoneal macrophages were also rendered cytotoxic by incubation with acellular supernatants of mixed lymphocyte cultures (MLC) between an allograft recipient and a donor mouse. Supernatants alone were not cytotoxic. The macrophage arming factor(s) was found in supernatants when the MLC was performed after more than 6 to 9 days following grafting. In order to produce MAF, sensitized lymphocytes must usually be stimulated in a specific way by donor type cells. The armed macrophage cytotoxicity was, however, not found to be specific in these experiments.
Relation of DNA Synthesis and Suppression to Development of Memory by T Cells
Authors: Mills Vern A. , Orbach-Arbouys Simone , Gershon Richard K.
Published: December 2022

Parental thymocytes, inoculated into lethally irradiated F1 mice, synthesize DNA in response to the histocompatibility antigens of the reciprocal parent in the F1 cross. The DNA synthetic response is characterized by a 1 to 3 day latent period and a 1- to 2-day period of peak activity which is followed by a sharp decline. Cells transferred to secondary recipients at the time of peak activity in the primary hosts respond only minimally in the spleens of the secondary hosts. Cells transferred 1 day later, when DNA synthetic activity in the primary hosts is sharply curtailed, exhibit striking secondary responsiveness. Thus, the decline in activity in the primary host is not due to the loss of potentially reactive cells from the spleens. It seems more likely that the preceding response creates a suppressive milieu in the primary host. The inability to transfer significant secondary responsiveness with cells harvested at the time of peak activity in primary hosts suggests that the acquisition of memory by these cells requires more than their clonal expansion. The occurrence of an additional differentiational event is suggested by the correlation of a marked increase in memory with the sharp cessation of the primary DNA synthetic response.
Immunopathology of Mouse Hepatitis Virus Type 3 Infection
Authors: Prevost C. Le , Levy-Leblond E. , Virelizier J. L. , Dupuy J. M.
Published: December 2022

Humoral and cell-mediated immune responses were studied in resistant and susceptible strains of mice infected with mouse hepatitis virus type III (MHV3). Virus was maintained by regular passages in susceptible DBA/2 mice and assayed in DBA/2 mice by LD50 determination. Normal resistant A strain mice were able to clear the virus from liver, brain, and serum within 7 days after infection. No neutralizing antibody was found. Transfer of serum from immunized A strain mice was not effective in protecting susceptible DBA/2 mice against challenge with virus. In A strain animals resistance to MHV3 developed rapidly during the 3rd week of life. During the period of susceptibility, newborns were protected neither by transplacental passages of anti-MHV3 antibodies nor by injection of “educated” thymus cells.

These results suggest that the development of resistance to MHV3 infection in mice cannot be explained solely on the basis of humoral or cell-mediated immunity.
In Vitro Studies on the Cellular Immune Response of Tumor-Bearing Mice to SV40-Transformed Cells
Authors: Blasecki John W. , Tevethia Satvir S.
Published: December 2022

Specific cell-mediated immunity to SV40 tumor-specific transplantation antigen (TSTA) in mice undergoing tumorigenesis by syngeneic SV40-transformed BALB/c cells was investigated by the macrophage migration inhibition (MMI) and transplantation rejection tests. Specific cellular reactivity to SV40 TSTA could be demonstrated in BALB/c mice early after tumor cell inoculation. This activity was no longer detectable during the later stages of tumor growth but was again demonstrable 2 weeks after tumor excision. Addition of an equal number of non-reactive peritoneal exudate (PE) cells from tumor-bearing mice to PE cells from mice immune to SV40 TSTA specifically abrogated the reactivity of the latter cells to soluble SV40 TSTA. When lymphoid cells with blocking activity were cultured in vitro they not only lost their blocking capacity but also regained their reactivity to SV40 TSTA in the MMI test. These findings indicate that tumor-bearing hosts possess lymphocytes specifically sensitized to the TSTA of the tumor and that the specific reactivity of these cells can be regained after culture in vitro.
Capacity of Sensitized Thymus-Derived Lymphocytes to Induce Fatal Lymphocytic Choriomeningitis Is Restricted by the H-2 Gene Complex
Authors: Doherty Peter C. , Zinkernagel Rolf M.
Published: December 2022

Adoptive immunization of syngeneic, immunosuppressed recipients infected with lymphocytic choriomeningitis (LCM) virus causes fatal neurologic disease within 2 to 4 days of cell transfer, providing that donors are sampled when the in vitro 51Cr release assay shows maximal specific activity of sensitized thymus-derived lymphocytes (T cells). Prior treatment of immune spleen cells with AKR anti-θ ascitic fluid and complement causes total abrogation of this in vivo activity. Fatal neurologic disease is induced only when donor and recipient share at least one set of H-2 antigenic specificities. Parent → F1 and F1 → parent combinations are as effective as syngeneic systems, but mice given allogeneic immune cells survive as long as controls. Differences at the M-locus in H-2 compatible mice do not inhibit effector activity. Homing of transferred lymphocytes to spleen is similar in syngeneic or allogeneic recipients, but only syngeneic immune cells cross the blood-cerebrospinal fluid (CSF) barrier and cause choriomeningitis. Fatal LCM, is, therefore, apparently induced by a specifically sensitized θ-bearing cell population, activity of which is restricted by the H-2 gene complex.
The Selective Action of Poly A:U on the Electrophoretic Mobility and Surface Charge of a Subpopulation of B Cells
Authors: Hanjan S. N. S. , Talwar G. P.
Published: December 2022

Electrophoretic mobility (E.P.M.) of lymphoid cells has been determined in three species. In chicks, the E.P.M. of bursa cells was 0.47 ± 0.07 and of thymocytes 0.64 ± 0.10 µm/sec/volt/cm. On the basis of the E.P.M. profile of the Ficoll gradient purified lymphocytes from the rat spleen, two populations of cells present in the proportion of 65 and 35% were identifiable. The former had a mobility of 1.06 ± 0.08 and the latter 1.24 ± 0.09. The E.P.M. of lymphocytes prepared from athymic nude mice was 0.86 ± 0.06 with a Gaussian distribution profile.

On incubation of these cells with poly adenylate-poly uridylate (poly A:U) for 30 min at 37°C followed by extensive washings, the E.P.M. of thymocytes from the chick and rat as well as the thymus-derived cells in rat spleen remained essentially unchanged. On the other hand, poly A:U increased the E.P.M. of avian bursa cells and of a subpopulation of B cells in rat spleen and of splenocytes from nude mice. The proportion of cells markedly affected by poly A:U was 70 to 83% of the total B cells in these species.
Relationship of Cloning Inhibition Factor, “Lymphotoxin” Factor, and Proliferation Inhibition Factor Release in Vitro by Mitogen-Activated Human Lymphocytes
Authors: Jeffes Edward W. B. , Granger G. A.
Published: December 2022

Human lymphocytes were stimulated in vitro with mitogens, phytohemagglutinin and concanavalin A to secrete proliferation inhibitory factor (PIF), cloning inhibitory factor (CIF), and lymphotoxin (LT). These three activities were demonstrable in the same supernatant, moreover, the particular effect observed was shown to depend on the concentration of the medium and the type of target cell employed. In general, the medium effects on target cells were: a) cytotoxic at high concentrations, b) growth inhibitory at intermediate concentrations, and c) only temporarily growth inhibitory at low concentrations. The absolute concentration producing a certain effect varied, depending on the target cell type employed. In addition, the sensitivity of the target cells to LT parallels the sensitivity of the cell to each of the other activities, PIF and CIF, and no species specificity was observed.
Studies on the Composition of Adjuvants Which Selectively Enhance Delayed-Type Hypersensitivity to Lipid Conjugated Protein Antigens
Authors: Champlin Richard , Hunter Robert L.
Published: December 2022

Hen egg albumin (HEA), heavily conjugated with dodecanoic acid (D-HEA), stimulated sustained delayed type hypersensitivity (DTH) specific for HEA without detectable antibody formation in guinea pigs. An oil-in-water emulsion containing purified BCG cell walls attached to the oil drops was found to be a very effective adjuvant for enhancing DTH to D-HEA, but not to HEA. Animals immunized with D-HEA in the BCG cell wall emulsion produced skin test reactions 2.4 cm in diameter when challenged with HEA 21 days after a single immunization. Control animals immunized with D-HEA in saline produced skin reactions 1 cm in diameter to similar challenge. Neither group of animals produced detectable antibody to HEA or D-HEA. The emulsion had no adjuvant effect if the BCG cell walls were suspended in the aqueous phase and not attached to the oil droplets. Dodecanoic acid conjugated Salmonella typhi organisms could be used in place of the BCG cell walls to produce effective adjuvant preparations. Freund's complete adjuvant and other water-in-oil emulsions, however, were found to be ineffective adjuvants for enhancing the degree of DTH produced by D-HEA. Experiments with autoradiography demonstrated that effective adjuvant preparations promote the localization and retention of both 125I-labeled D-HEA and 125I-labeled BCG cell walls in the paracortical area of lymph nodes where they are in close proximity to many T-type lymphocytes which proliferate in the induction of DTH.
Differential Susceptibility of Strain 2 and Strain 13 Guinea Pigs to Induction of Experimental Autoimmune Thyroiditis
Authors: Braley-Mullen Helen , Sharp Gordon C. , Kyriakos Michael
Published: December 2022

Twenty-seven of 30 Strain 2 guinea pigs immunized with 100 µg guinea pig thyroglobulin (GPTG) prepared either from Hartley (H) or Strain 13 (13) thyroids developed experimental autoimmune thyroiditis (EAT) whereas only 1 of 39 similarly immunized Strain 13 guinea pigs developed EAT. F1 hybrids behaved like the Strain 2 parent in that 16 of 20 developed EAT. The susceptible Strain 2 and F1 guinea pigs had higher hemagglutinating antibody titers to GPTG than the Strain 13 guinea pigs whereas all three strains had similar delayed skin reactivity to GPTG. The results suggest that susceptibility of guinea pigs to thyroiditis is genetically controlled and that production of anti-thyroglobulin antibody may be important in determining disease susceptibility.
Effects of Bacterial Lipopolysaccharide on the Induction and Expression of Cell-Mediated Immunity
Authors: Lagrange Philippe H. , Mackaness George B. , Miller Thomas E. , Pardon Pierre
Published: December 2022

Bacterial lipopolysaccharide (LPS), being a B cell mitogen, enhances antibody production. When given prior to an injection of sheep red blood cells (SRBC) it caused a premature but not significantly increased production of antibody forming cells in regionally stimulated lymph nodes. There was a corresponding depression of T cell activity, as measured by the relative levels of delayed-type hypersensitivity (DTH) in normal and LPS-treated mice. Although LPS also induced hyperplasia of the reticuloendothelial system, and a consequent reduction in the effective antigenic dose of SRBC, this was not the reason for the reduced level of T cell activity. The opposing effects of LPS on T and B cell responses was due to premature inhibition of the T cell response by an accelerated production of antibody. This caused an earlier onset of the inhibitory mechanism which regulates the T cell response and is specific for the inducing antigen.
Effects of Bacterial Lipopolysaccharide on the Induction and Expression of Cell-Mediated Immunity
Authors: Lagrange Philippe H. , Mackaness George B.
Published: December 2022

The delayed-type hypersensitivity (DTH) produced by subcutaneous or intravenous immunization of mice with sheep red blood cells (SRBC) is mediated by T cells in cooperation with accessory cells (monocytes). Different effects of bacterial lipopolysaccharide (LPS) on this T cell activity were found at different stages of the immune response. a) T cell activity was enhanced by LPS given 1 to 3 days after sensitization. Enhancement, which was most marked when treatment was given on the 2nd day of the immune response, did not occur unless LPS was introduced into a site that drains to the responding lymph node. This stimulatory effect was dose dependent. b) A similar effect on the response to intravenous immunization caused DTH to appear transiently in mice given a T cell-blocking dose (109) of SRBC. c) DTH was suppressed by LPS given at the height of the T cell response (day 4). This effect, which was short lived and reversible, was due to the action of LPS on the accessor cells needed for the expression of DTH.

Treatment of recipients with LPS completely blocked the adoptive transfer of DTH to both normal and spenectomized mice. The ability to react was regained slowly, but it returned promptly to splenectomized recipients. LPS has clearly more than one effect on the expression of cell-mediated immunity because it affects specific and non-specific mediator cells in different ways.
Thymic Regeneration after Lethal Irradiation: Evidence for an Intra-Thymic Radioresistant T Cell Precursor
Authors: Kadish Julian L. , Basch Ross S.
Published: December 2022

The data presented indicate the existence of a significant pool of radioresistant stem cells which are capable of partially restoring the thymus of heavily irradiated mice. 3H-TdR incorporation by the thymus of lethally irradiated mice begins 48 to 72 hr after irradiation and increases throughout the next 8 days. By the 9th day after 760 rads, typical corticomedullary architecture has been restored. 890 rads markedly suppressed, but did not totally eliminate this regeneration. Injection of large numbers of syngeneic bone marrow cells immediately after irradiation was without effect on the rate or extent of regeneration. Mice whose bone marrow and spleen were shielded from irradiation showed an identical amount of thymic regeneration as those receiving total body irradiation indicating that the precursor cell pool responsible for the early post irradiation phase of thymic regeneration is most likely an intrathymic population.

The cells repopulating the thymus were morphologically indistinguishable from normal thymocytes and were susceptible to cytotoxic antisera against the thymic differentiation antigens Thy-1, TL, LyA2 and LyC2.
Inhibition of Mitogen Stimulation of Human Peripheral Blood Leukocytes by Vibrio Cholerae Enterotoxin
Authors: Hart David A. , Finkelstein Richard A.
Published: December 2022

It has been found that the enterotoxin (choleragen) of Vibrio cholerae, strain 569B, can interfere with Phytohemagglutinin-P, pokeweed mitogen and concanavalin A stimulation of human peripheral blood leukocytes. The viability of cultured cells was not affected by the toxin. The toxin does not interfere with stimulation by direct competition for mitogen receptor sites. The ability of choleragen to inhibit stimulation by mitogens declines with time after initiation of stimulation. The biologically inactive, spontaneously formed, derivative of choleragen, choleragenoid, did not inhibit mitogen stimulation. However, choleragenoid did block the inhibition of stimulation caused by choleragen. Choleragenoid did not block inhibition of mitogen stimulation by a lymphocyte chalone preparation indicating that a different mechanism may be involved with the chalone. Since the diverse biological effects of choleragen are all believed to result from its interaction with cell membrane receptors followed by activation of adenyl cyclase, the results add to evidence which suggests that increases in the intracellular concentrations of 3′,5′-adenosine cyclic monophosphate diminishes the mitotic activitity of cells.
β-Adrenergic Inhibition of Human T Lymphocyte Rosettes
Authors: Galant Stanley P. , Remo Robert A.
Published: December 2022

The cyclic nucleotides adenosine and guanosine monophosphate (CAMP and CGMP)1 have been reported to affect significantly the magnitude of cellular and humoral in vitro immune responses. Mitogenic lymphocyte stimulation (1, 2), lymphocyte-mediated cytotoxicity (LMC) (3, 4) and the effect of migration inhibitory factor on target cells (5) are inhibited by β adrenergic stimulants of intracellular CAMP, and dibutyryl CAMP. CGMP has been shown to enhance LMC (4). In vitro antibody synthesis has recently been shown to be inhibited by CAMP and enhanced by CGMP (6). Furthermore, CAMP has been reported to alter significantly mammalian cell morphology in vitro (7). Since the cyclic nucleotides have profound effects on the morphology and function of cells, we chose to study the effects of dibutyryl CAMP and the β adrenergic stimulant isoproterenol on the human T lymphocyte's binding affinity to sheep red cells (E rosettes).
Enhancement of Nitroblue Tetrazolium Dye Reduction by Leukocytes Exposed to a Component of Complement in the Absence of Phagocytosis
Authors: Goldstein Ira M. , Feit Fred , Weissmann Gerald
Published: December 2022

Enhancement of in vitro nitroblue tetrazolium dye reduction by human polymorphonuclear leukocytes may be mediated by a low molecular weight fluid phase component of the complement system. This occurs in the absence of phagocytosis and is associated with an increase in leukocyte hexose monophosphate shunt activity. The stimulatory component may be generated by activating the alternate complement pathway in serum, and shares many of the properties of human C5a. Thus, the enhanced spontaneous reduction of nitroblue tetrazolium by leukocytes from patients with bacterial sepsis may not necessarily be due to the phagocytic activity of these cells, but rather may occur as a consequence of in vivo complement activation by either intact microorganisms or their products.
Experimental Allergic Encephalomyelitis in Resistant and Susceptible Guinea Pigs: In Vivo and in Vitro Correlates
Authors: Lisak Robert P. , Zweiman Burton , Kies Marian W. , Driscoll Bernard
Published: December 2022

Strain 2 guinea pigs develop less severe experimental allergic encephalomyelitis than do strain 13 and Hartley guinea pigs when sensitized with equivalent amounts of homologous myelin basic protein (BP) in complete Freund's adjuvant. In vivo and in vitro correlates of delayed hypersensitivity to myelin basic protein are depressed in the strain 2 guinea pigs relative to the two susceptible strains. The incidence of circulating anti-BP antibodies is also lower in sera from strain 2 guinea pigs than in sera from strain 13 or Hartley guinea pigs. There was no difference among the three strains in their ability to mount delayed hypersensitivity to tuberculin, nor in the response of their cells to PHA in vitro.
Induction of Acquired Cellular Resistance Following Transfer of Thymus-Dependent Lymphocytes from Syphilitic Rabbits
Authors: Schell R. , Musher D. , Jacobson K. , Schwethelm P.
Published: December 2022

Syphilitic rabbits have previously been shown to resist challenge with Listeria monocytogenes. Thirty days after rabbits were infected with Treponema pallidum, transfer of 4 to 6 × 108 viable spleen cells along with T. pallidum conferred resistance to Listeria on normal recipients. Treatment of the spleen cells with anti-thymus serum and complement inhibited or abolished their ability to transfer resistance to Listeria. These results support the hypothesis that the ability of syphilitic rabbits to suppress the growth of Listeria reflects stimulation of cell-mediated immunity during active infection with T. pallidum.
Allotypic Suppression in Rabbits: Competition for Target Cell Receptors between Isologous and Heterologous Antibody and between Native Antibody and Antibody Fragments
Authors: Shek Pang-Nin , Dubiski Stanislaw
Published: December 2022

Neonatal injection with various foreign proteins (normal goat serum, human Cohn fraction II, human albumin) caused a stimulation of immunoglobulin synthesis. This effect was not antigen-specific and did not constitute a conventional antibody response directed against the injected substance. When this stimulatory effect of foreign protein was minimized, the heterologous (goat) anti-rabbit allotype antibody and rabbit antibody F(ab′)2 fragments not only failed to induce suppression but also competed with the suppression-inducing native rabbit antibody. Allotypic suppression in a rabbit can thus only be induced by an antibody molecule possessing an intact Fc portion of isologous, rabbit origin.

Antibody to Ae14, an allotypic specificity located on the Fc portion, failed to induce suppression or stimulation of immunoglobulin synthesis. This was attributed to the position of Ae14 in the cell membrane which reduced its accessibility to antibody.