bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Blocking the Active Site of an Antibody on the Expression of Its Idiotypic Determinants during Immunization
Authors: Spring-Stewart Susan , Nisonoff Alfred
Published: December 2022

Antiidiotypic antibodies were elicited in rabbits by immunization with soluble complexes consisting of anti-p-azobenzoate antibody and excess (RGG)-p-azobenzoate. Nearly all of the antiidiotypic antisera, in contrast to such antisera formed in response to free antibenzoate antibody, were not inhibitable by haptens, i.e., by benzoate derivatives of low molecular weight. The results indicate that when the active site is blocked during immunization, antiidiotypic antibodies are directed exclusively to determinants outside the active site. The antigen, RGG-p-azobenzoate, evidently is not removed from the antibenzoate antibody before the recognition process in the recipient animal. The immunogenicity of soluble complexes is lower than that of the free antibody, as indicated by the relatively smaller percentages of donor antibody precipitable by antiidiotypic antisera. This also was attributed to blocking of an important idiotypic determinant.
The Effect of Antibody on Antigen-Induced Lymphocyte Transformation
Authors: Banks Keith L.
Published: December 2022

The influence of antibody on the antigen-induced in vitro uptake of tritiated thymidine by sensitive lymphocytes was determined. The cellular response of ovalbumin (OA)-sensitive lymphocytes was consistently depressed when OA was mixed with anti-OA antisera at concentrations equal to equivalence and 2 times antigen excess with one antiserum and 50 times antibody excess with another antiserum. At five other concentrations of these antisera, involving either antigen excess or antibody excess, the reaction of animals varied between depression and augmentation. Similar increases and decreases in stimulation occurred with cells sensitive to sheep RBC (SRBC) when the antigen was in the presence of anti-SRBC antiserum. Non-sensitive cells were not stimulated by immune complexes formed with OA or SRBC. Depressive complexes did not affect cell viability or response to phytohemagglutinin. Complexes composed of non-sensitizing antigen did not influence stimulation by another antigen to which the cells were sensitive. Depression also occurred when antibody was added to cultures composed of at least 97% lymphocytes. The experiments show that the in vitro response of sensitive lymphocytes may be specifically depressed or augmented by antibody.
A Rabbit Anti-p-Azobenzenearsonate Antibody of Restricted Heterogeneity with Light Chains of b5 Allotype
Authors: Mage Rose G. , Appella Ettore , Young-Cooper Glendowlyn O. , Winfield John B. , Pincus Jack H. , Chersi Alberto
Published: December 2022

A rabbit, partially suppressed for the expression of b5-kappa-type light chains when first immunized, produced anti-p-azobenzenearsonate antibodies at 8, 13, 34 and 41 months of age, after each of four courses of immunization with an edestin-azobenzenearsonate conjugate. The antisera obtained after the second, third and fourth courses of immunization contained antibodies of limited structural heterogeneity. Light chains of b5 allotype were obtained from the purified antibodies. Amino acid sequence analysis of the first 21 residues at the amino terminus of the light chains indicated a single sequence for those from the third course antibody and a major sequence with limited heterogeneity from the second and fourth course antibodies.
The Antibody Response to Polyinosinic · Polycytidylic Acid
Authors: Parker Leroy M. , Steinberg Alfred D.
Published: December 2022

The antibody response to the synthetic double-stranded RNA polyinosinic·polycytidylic acid (rI·rC) was investigated in mice and rabbits. Mice developed an early, largely IgM, antibody response of short duration after a single injection of rI·rC in aqueous solution. The magnitude of this response was unaffected by complexing rI·rC to a protein carrier. Relative tolerance rather than increased amounts of antibody followed subsequent injections of rI·rC. However, there was a shift in antibody class to IgG. When rI·rC was given in Freund's adjuvant prolonged IgG antibody responses occurred with peaks appearing 2 or more weeks after immunization. Administration of rI·rC complexed to an immunogenic protein carrier in adjuvant resulted in highest (IgG) antibody levels. The magnitude of enhancement by carrier was greater in rabbits (10- to 100-fold) than in mice (3- to 10-fold). Inbred strains of mice were separable into “high” and “low” responding strains when rI·rC was given either in aqueous solution or in adjuvant. Low responders could be made high responders by complexing rI·rC to a carrier and immunizing in adjuvant. These studies suggest that the immunogenic properties of rI·rC are similar to other materials, and that differences are also apparent.
Macrophage Migration from an Agarose Droplet: Development of a Micromethod for Assay of Delayed Hypersensitivity
Authors: Harrington John T. , Stastny Peter
Published: December 2022

Inhibition of macrophage migration from a glass capillary is the most widely accepted and best characterized in vitro correlate of delayed hypersensitivity. Significant technical limitations of this method have been eliminated by a modified migration inhibitory factor (MIF) method in which macrophages are stabilized in an agarose droplet instead of a capillary tube. This agarose method is technically simple, permitting the rapid assay of large numbers of samples and requiring relatively small volumes of culture supernatant. Experiments comparing the capillary and agarose methods have established the validity and specificity of the agarose method for assay of MIF.
Effect of Chemical and Enzymatic Radioiodination on in Vitro Human Clq Activities
Authors: Heusser Christoph , Boesman Mary , Nordin John H. , Isliker Henri
Published: December 2022

Conditions are described whereby human Clq may be enzymatically radioiodinated with full retention of hemolytic activity. A comparison is made between the chloramine T (CT) and lactoperoxidase (LP) methods of iodination which indicates the following: 1) Clq may be iodinated to a level of 0.2 atoms iodine/molecule by using LP with no detectable loss in hemolytic activity, whereas, at a level of 0.02 atoms incorporated/molecule with CT, Clq is only 50% active. Thus the hemolytic activity of Clq is quite labile to either low levels of iodide incorporation or the oxidizing conditions of the labeling procedure. 2) Its ability to bind immune complexes, conversely, is virtually resistant to the levels and conditions of iodination reported here. 3) With either labeling method, iodide is incorporated exclusively into only the smallest of the three covalently bonded subunits.
Purification, Molecular Properties, and Activation of C1 Proesterase, Cls
Authors: Sakai Kouko , Stroud Robert M.
Published: December 2022

A method to obtain a highly purified Cls in the proesterase form is described for the first time. Neutral euglobulins were precipitated from fresh heparinized plasma in the presence of 0.06 M l-lysine, followed by extraction of Cls after suspending the euglobulin in 0.02 M EDTA, 0.005 M l-lysine (pH 7.5, relative salt concentration 0.04), and then DEAE cellulose column chromatography. The Cls preparation was shown to be homogeneous on immunoelectrophoresis developed against a potent anti-whole human serum and on analytical acrylamide gel electrophoresis. The yield of Cls was 10 to 20%. The Cls preparations have a specific hemolytic activity which is 20 to 30 times lower than C1s̅ and have a slower electrophoretic mobility on agar at pH 8.6.

After incubating purified Cls with fractions containing Clr, Cls was activated as shown by an increase in its specific hemolytic activity and its faster migration to the anode on immunoelectrophoresis. The activating fractions were obtained from the DEAE column used to purify Cls and, although primarily Clr, they contain a few other proteins which do not bind at a relative salt concentration of 0.140. In addition to the different hemolytic activity and electrophoretic mobility, structural differences between Cls and C1s̅ were demonstrated by reduction and alkylation. Reduction of C1s̅ resulted in two major subunits with estimated molecular weights of 36,000 and 77,000. On the other hand, after reduction of Cls only one chain was found. Moreover, reduction of Cls which had been activated after purification resulted in the formation of two subunits similar to the subunits from C1s̅. The data indicate that activation is due to the cleavage of a peptide bond which converts a single polypeptide chain into two polypeptide chains linked by disulfide bonds. Experiments using insoluble C1s̅ (C1s̅ coupled to Sephadex G-25) showed that the destruction of C2 by C1s̅ occurred both in the presence of metals and in EDTA.
Intestinal Sphingoglycolipids with A and Lea Activity from Humans and A, H-Like and Leb-Like Activity from Dogs
Authors: Hiramoto Raymond N. , Smith Edwin L. , Ghanta Vithal K. , Shaw June F. , McKibben John M.
Published: December 2022

Glycolipids containing fucose (fuco-lipids) have been shown to constitute an individual specific class of compounds both in humans and dogs. Since only trace amounts of some fuco-lipids can be isolated, immunologic techniques are invaluable in identifying these compounds and giving some insight into their structure. By using human and rabbit antisera and ulex lectin with precipitation and agglutination techniques, fuco-lipids isolated from human small intestine were shown to have human A and Lea blood group activity. Fuco-lipids isolated from dog small intestine had human A, H-like and Leb-like blood group activity. With fluorescein-labeled rabbit antisera it was demonstrated that Forssman activity was associated with the lamina propria whereas Leb-like activity was in the glandular epithelium of the small intestine.
Rabbit Antiserum to Brain-Associated Thymus Antigens of Mouse and Rat
Authors: Clagett James , Peter Hans-Hartmut , Feldman Joseph D. , Weigle William O.
Published: December 2022

Rabbit anti-mouse brain and anti-rat brain sera detect thymic antigens unique to mice and rats, respectively, and detect antigens shared by these two species. Specifically, θC3H and θAKR murine phenotype cells share with rats an heteroantigenic determinant not revealed by alloanti-θ serum because of an unresponsive state among mice to this determinant. AKR thymocytes share with rat thymocytes an additional antigen, most likely associated with the θAKR alloantigen. Tissue distribution of the species-specific and shared markers was compatible with that of the classical θ alloantigens.
Genetics of Stimulation of in Vitro Hemolytic Plaque-Forming Cell Responses by Irradiated Allogeneic Spleen Cells
Authors: Kennedy James C. , Ekpaha-Mensah J. Ampoe
Published: December 2022

The addition of heavily irradiated spleen cells to cultures containing syngeneic spleen cells and foreign erythrocytes may stimulate to some extent the hemolytic plaque-forming cell responses of those cultures, but the addition of allogeneic irradiated spleen cells may cause much greater stimulation. Irradiated spleen cells from mice of various inbred strains were tested for their ability to produce such stimulation in cultures containing spleen cells from an allogeneic or congenic resistant partner. It was found that a genetic difference in the region of the K end of the H-2 locus was sufficient to cause strong reciprocal stimulation, while a difference in the region of the D end was not. Multiple non-H-2 histocompatibility differences were ineffective, with two interesting exceptions. It is suggested that reciprocal allogeneic stimulation of in vitro hemolytic plaque-forming cell responses may be a useful means of detecting major histocompatibility differences. A model for allogeneic stimulation is proposed.
Human Blood T Cells: Response to Phytohemagglutinin
Authors: Wybran Joseph , Chantler Shireen , Hugh Fudenberg H.
Published: December 2022

Evidence has accumulated to indicate that two different populations of lymphocytes are responsible for immunologic responsiveness. The functional characteristics of these cells appear to differ; thymic-derived or T lymphocytes3 are associated with cellular immune responses whereas B lymphocytes (probably bone marrow-derived or bursa-dependent) have been implicated in humoral aspects of the immune response (1). The isolation and characterization of T and B lymphocytes are essential for a full assessment of their functions.

Recently surface markers on lymphocytes have provided a tool for identifying their origin. With direct immunofluorescent technique, lymphocytes with surface immunoglobulins have been shown in animals to be bone marrow- or bursa-derived, whereas lymphocytes of thymic origins are not stained by this technique (2–4). On the basis of this distinction it has been suggested that human peripheral blood lymphocytes bearing immunoglobulins are also B cells (5).
Arylhydroxytriazenes: A New Class of Immunosuppressants
Authors: Brian Stewart P. , Possanza G. J. , Hess F. K.
Published: December 2022

In a search for new immunosuppressants, it was found that some members of the arylhydroxytriazenes were active in suppressing the immune response in experimental animals. One member of this group, 3-methyl-3-hydroxy-1-(p-isopropyl-carbomoylphenyl)triazene and designated PR-H-286 BS,1 has been studied more closely and has the following structural formula.

This compound was readily prepared by the general method of Bamberger (1); diazotization of 4-amino-N-isopropylbenzamide and subsequent coupling with N-methylhydroxylamine gave reasonable yield. Its structure was confirmed by elemental analysis as well as by infrared and nuclear magnetic resonance spectroscopy.

The immunosuppressant activity of PR-H-286 BS was first demonstrated in the Jerne plaque-forming cell (PFC) test (2). It was equally effective when given either by the intraperitoneal or oral route, suppressing the number of PFC by 96.6% and 96.4%, respectively (Table I). With this experience all further tests were done by the oral route.
Absence of Cell-Mediated Immunologic Tolerance to Leukemia Virus in Carrier Mice
Authors: Proffitt Max Rowland , Hirsch Martin S. , Black Paul H.
Published: December 2022

Several viruses have been reported to induce immunologic tolerance in mice when infection occurs in the prenatal or immediate postnatal period. Among these are lymphocytic choriomeningitis (LCM)3 virus (1–3) and murine leukemia viruses (MuLV) (4–6). Although Moloney murine leukemia virus (MuLV-M) can induce leukemia in both newborn and adult mice (7), there is a marked difference in host response in these two age groups. Inoculation into adults results in development of both humoral and cell-mediated immune responses to the virus, whereas in neonatally infected mice these responses appear to be either greatly reduced or undetectable (5, 8).

Recent results have cast doubt on the validity of the concept of immunologic tolerance to viruses. It now is generally accepted that humoral antibodies can be formed after neonatal infection with LCM virus (9), MuLV-M (10), Harvey murine sarcoma virus (MuSV-H) (10), and Gross murine leukemia virus (MuLV-G) (11, 12).
A Quantitative Assay for the Mixed Leukocyte Reaction by Mouse Spleen Cells
Authors: El-Arini M. O. , Osoba David
Published: December 2022

A method for culturing mixtures of allogeneic mouse spleen cells which gives quantitative results is described. The kinetics of the response is reproducible from experiment to experiment and the dose-response curve is linear. Radiation survival studies indicate that the responding cells require the capacity to proliferate during the mixed-leukocyte reaction (D37 = 95 rads). From experiments with the spleen cells of congenic resistant strains it is evident that the response is controlled by minor histocompatibility loci as well as by the H-2 locus.
Modulation of Immunoglobulin Ontogeny in the Chicken: Effect of Purified Antibody Specific for µ Chain on IgM, IgY, and IgA Production
Authors: Leslie Gerrie A. , Martin Louis N.
Published: December 2022

The administration of anti-µ antibody to chick embryos in conjunction with bursectomy at hatch resulted in long-term suppression of IgM, IgY, and IgA synthesis. Anti-µ-suppressed chickens had less ability to produce antibody than bursectomized controls. Graft-vs-host responsiveness was normal or enhanced, indicative of the specific effect of anti-µ on bursa-dependent lymphocytes. Suppression of IgM, IgY, and IgA production could be achieved by anti-µ injection of 18-day-old embryos, providing evidence that IgY- and IgA-forming cells develop subsequent to that time. Repeated injection of anti-µ in early life was capable of producing abnormalities in immunoglobulin synthesis, including long-term IgY and IgA deficiency. These results were discussed in terms of the concept that IgY- and IgA-forming cells are derived from IgM-forming precursors.
Reconstitution of T Cell-Depleted Spleen Cell Populations by Factors Derived from T Cells
Authors: Gorczynski R. M. , Miller R. G. , Phillips R. A.
Published: December 2022

At least part of the interaction between bone marrow-derived (B) and thymus-derived (T) lymphocytes during the initiation of an in vitro immune response to sheep erythrocytes (SRBC) is mediated by a nonspecific activity released from antigen-stimulated T cells. The release of the activity requires stimulation with specific antigen, but the activity produced by different antigens can reconstitute an in vitro response to SRBC. The assay used to investigate the activity has been the reconstitution of spleen cell populations treated with anti-θ antibody. Preparations active in this assay can also initiate immune responses in B cells obtained from thymectomized, irradiated, bone marrow-reconstituted mice and in B cells separated from normal bone marrow.

Three pieces of evidence suggest that cells liberating the active factors are T cells. First, pretreatment of such a population of cells with anti-θ antibody abolishes its capacity to produce the activity. Second, the sedimentation profile of SRBC-stimulated factor-producing cells is identical to the sedimentation profile of T cells required to initiate anti-SRBC antibody production in vitro. Third, the sedimentation profile of factor-producing cells in a population of alloantigen-stimulated cells is identical to the sedimentation profile of cells involved in cell-mediated immunity in the same population.
Decline in Mixed Lymphocyte Reactivity of Spleen Cells from Aged Mice of a Long-Lived Strain
Authors: Konen T. G. , Smith G. S. , Walford R. L.
Published: December 2022

The mixed lymphocyte reaction was measured in male C57BL/6J mice 21 to 25 weeks, 90 to 94 weeks, and 150 weeks of age. A statistically significant decline in reactivity was noted for the oldest group of mice, compared to both younger groups. These results are interpreted in relation to survival patterns and age-specific incidences of spontaneous neoplasia in this long-lived strain.
Lymphocyte Activation
Authors: Jones G.
Published: December 2022

Mouse lymphocytes were cultured with phytohemagglutinin or concanavalin A and at various times antiserum to each mitogen was added. Incorporation of thymidine was partially inhibited even when antisera were added after 48 hr. Quantitative analysis of the inhibition produced in normal cultures or cultures containing colchicine suggested that the inhibition observed could not be explained simply by prevention of activation in the first division cycle. This was confirmed in other experiments where tritium-labeled cells were prevented from entering a second division cycle by specific antiserum. It is concluded that the continued presence of these mitogens is required to initiate division cycles beyond the first activation and that lymphocyte transformation is thus not an irreversible derepression leading to repetitive cell divisions.
Modulation of Membrane Associated Immunoglobulins of Cultured Human Lymphoid Cells by Specific Antibody
Authors: Hütteroth T. H. , Cleve H. , Litwin S. D.
Published: December 2022

Modulation of membrane associated immunoglobulins by specific antibodies was studied on lymphoid cells of established suspension cultures derived from four normal individuals. Changes in κ and µ surface immunoglobulins were monitored by the mixed antiglobulin reaction. Exposure to anti-κ antiserum led to rapid disappearance of both κ and µ antigen; exposure to anti-µ antiserum resulted in complete loss of µ antigen, while κ antigens were unaffected or only partially affected. Restoration of κ and µ antigens occurred from 3 to 12 hr. Monovalent antibody was unable to modulate surface κ immunoglobulins. Modulation would not occur at low temperature or in the presence of sodium azide.
Eosinophils and Immune Mechanisms
Authors: Colley Daniel G.
Published: December 2022

Exposure of eosinophil-rich peritoneal cell populations obtained from Schistosoma mansoni-infected mice to a soluble schistosomal egg antigen stimulates eosinophil migration. Supernatant fluids from serum-free lymph node cell cultures stimulated with antigens to which the donor mice had been specifically sensitized, or stimulated with phytohemagglutinin, also stimulate eosinophil migration. The active principle in such culture supernatant fluids is soluble, nondialyzable and heat-stable (56°C/30 min). It is tentatively classed as a lymphokine and designated eosinophil stimulation promoter.
The Kinetics of the Serum Immunoglobulin Response of Rabbits to the Capsular Polysaccharide Antigen of Gaffkya Tetragena
Authors: Eisenberg George H. G. , Roberson Bob S.
Published: December 2022

Passive hemagglutination using the purified capsular polysaccharide antigen of Gaffkya tetragena, strain GT8, was employed to study the primary, secondary and hyperimmune responses of rabbits after sequential single intravenous injections of a formalinized whole cell vaccine. Radioimmunodiffusion and radioimmunoelectrophoresis with 14C-labeled capsule were used to identify the antibodies produced. Systems for long-lasting synthesis of 19S IgM and 7S IgG anticapsule hemagglutinins were found to coexist in primary and anamnestic responses. Evidence for the presence of 19S IgG was also found. At no time in any of the responses studied was there any indication of a major shift from production of one antibody type to production of the other. These findings show that there is no feedback inhibition of 19S synthesis by 7S IgG. Indications of the presence of a true 19S IgM memory were found. Typical 7S immunologic memory was also observed. Autoradiography revealed the presence of two additional antibody activities in the hyperimmune response. These activities were tentatively identified as IgA and α2 macroglobulin. These observations, considered with the unrelated changes in the levels of the two antibody species produced during the responses and differences in rates of synthesis of the two antibodies during the maintenance phases of the response lead to the conclusion that at least two, and possibly four, separate components of the rabbit's immune mechanism were stimulated by administration of the capsular polysaccharide antigen of G. tetragena, strain GT8.
Corneal Immune Response to Herpes Simplex Virus Antigens
Authors: Meyers Roberta L. , Pettit Thomas H.
Published: December 2022

The immune response to herpes simplex virus (HSV) antigens was studied in sensitized guinea pigs. The animals were sensitized by footpad injections with viable HSV in complete Freund's adjuvant and challenged intracorneally with purified viral antigens at 3, 7, and 21 days later. Corneal opacities occurred only in the eyes of the sensitized animals receiving the viral antigens, not in the contralateral control eye receiving uninfected tissue culture cell antigens.

The corneal opacities occurring in the sensitized animals correlated with the appearance of edema and a cellular infiltrate. The corneal infiltrate was primarily polymorphonuclear in cell type and occurred in animals with delayed type hypersensitivity before circulating antibody was detectable and was not altered by the later appearance of circulating antibody. The reaction at the corneal limbus was also characterized by polymorphonuclear leukocytes, but lymphocytes and monocytes were also present. The appearance of plasma cells at the limbus correlated with the appearance of circulating antibodies which were first detectable 10 days after sensitization.

The ability of HSV antigens to inhibit migration of peritoneal exudate cells from the sensitized animals paralleled the onset of the cutaneous delayed hypersensitivity response at 7 days after sensitization. The in vitro inhibition of proliferation of HSV-sensitized corneal explants exposed to HSV antigens also correlated well with the onset of the delayed dermal hypersensitivity.
The Effect of Gm (23) on the Concentration of IgG2 and IgG4 in Normal Human Serum
Authors: Steinberg Arthur G. , Morell Andreas , Skvaril Frantisek , van Loghem Erna
Published: December 2022

The IgG2 and IgG4 levels in 55 serum samples from family members with known Gm (23) genotype were studied. No correlation between IgG2 or IgG4 concentration and age or between these subclasses and sex was observed. Gm (23) shows no marked effect on the concentration of IgG2, but the concentration of IgG4 in serum is in the sequence Gm (23) homozygotes τ; Gm (23) heterozygotes τ; Gm (-23), and the differences are significant.

Since the IgG4 allotype 4b appears, on the basis of limited data, to be transmitted with Gm (23), the observed relation between the Gm (23) genotype and IgG4 concentration may be due to an effect of 4b and not to Gm (23). More data are needed.
Cytotoxicity Mediated by Human Lymphocyte-Dependent Antibody in a Rapid Assay with Adherent Target Cells
Authors: Yust Israel , Wunderlich John R. , Mann Dean L. , Buell Donald N.
Published: December 2022

A rapid in vitro assay for lymphocyte-dependent antibody (LDA)-mediated cytotoxicity against adherent target cells has been characterized. Adherent HeLa and human melanoma cell lines were labeled with 51Cr, coated with sera from patients who had received multiple whole blood transfusions, and incubated for 4 hr with human peripheral blood lymphocytes from normal donors. Significant lysis was detected as early as 20 min after incubation with rapid progression in the reaction during the next several hours. Morphologically, the early phase of the reaction was characterized by adherence of lymphocytes to LDA-coated cells. Cytotoxic activity was proportional to LDA concentration, attacking cell concentration, and incubation time. LDA-mediated cytotoxicity was blocked by anti-IgG, supporting the concept that this factor is an antibody. LDA-coated target cells were killed by lymphocytes but not by adherent peripheral blood cells or tissue culture lymphoid cells. Conventional complement did not play a role in target cell destruction because carrageenan, a C1 inhibitor, was included in the reactions and serum samples were heat-inactivated before use. This rapid in vitro assay will prove useful in distinguishing between cytotoxicity resulting from lymphocyte-dependent antibody and other types of cell-mediated cytotoxicity.
Binding and Vesiculation of Rabbit IgG by Rabbit Yolk Sac Membrane
Authors: Sonoda S. , Shigematsu T. , Schlamowitz M.
Published: December 2022

Studies are described which establish the glycocalyx as the morphologic site for the binding of IgG to the membrane of the rabbit yolk sac and which indicate that micropinocytotic vesiculation is the mechanism for its cellular uptake.

Yolk sac membranes were exposed in vivo and in vitro to rabbit antihorse ferritin antibody. The membranes were then treated with ferritin and examined by electron microscopy for deposition of ferritin. Deposits of IgG-bound ferritin were found localized at the glycocalyx coat of the microvilli, intermicrovillar pits, and incipient micropinocytotic vesicles.

Stages in the micropinocytotic process are shown, depicting internalization of microvillial membrane surfaces, indicating that this is the mechanism by which IgG is taken up by the fetal yolk sac from the maternal uterine lumen for transfer to the fetus.

These findings are discussed in the context of the specificity and kinetic characteristics of the transfer process.
Encephalitogenic Activity of Peptides from the Smaller Basic Protein of Rat Myelin
Authors: Dunkley P. R. , Coates A. S. , Carnegie P. R.
Published: December 2022

Experimental autoimmune encephalomyelitis (EAE) can be induced in laboratory animals by injection of the basic protein of myelin in Freund's complete adjuvant. Certain peptides derived from this protein are also encephalitogenic and the potency of these peptides varies depending on the species selected for injection. The tryptophan region of the human and bovine basic proteins is highly encephalitogenic in guinea pigs (1, 2), while for rabbits a potent encephalitogenic determinant is located in the center of the protein (3).

Recently the smaller of the two basic proteins from rat myelin (rat S protein) was found to have little encephalitogenic activity in guinea pigs yet was fully active in rats (4). Since the amino acid sequence of the tryptophan region of the rat S protein is altered when compared with the human and bovine proteins (5, 6), Martenson et al. (4) concluded that this region was unlikely to be the determinant responsible for the induction of EAE in rats.
Evidence for the Domain Hypothesis: Location of the Site of Cytophilic Activity toward Guinea Pig Macrophages in the CH3 Homology Region of Human Immunoglobulin G
Authors: Yasmeen D. , Ellerson J. R. , Dorrington K. J. , Painter R. H.
Published: December 2022

Most of the effector functions of human immunoglobulin G (IgG), such as complement fixation, transplacental transfer, cytophilic activity toward macrophages and control of catabolic rate are mediated through the Fc region of the molecule. Some of these functions have been shown more recently to be associated with particular subfragments of the Fc region corresponding to either the CH2 or CH3 homology regions of the IgG1 heavy chain. Minta and Painter (1) showed that the pFc' fragment which comprises the CH3 homology region was able to interfere with the passive cutaneous anaphylactic reaction in guinea pigs, presumably by competing with antibody for sites on the cutaneous mast cells. Kehoe and Fougereau (2) showed that fragments from the CH2 region of a mouse immunoglobulin were able to activate the complement system when suitably aggregated. More recently Ellerson et al. (3) showed that a fragment comprising the whole CH2 homology region of human IgG was able to activate the complement system when aggregated on polystyrene latex.
Thymus Dependency of Antibody-Mediated Helper Effect
Authors: McBride Raymond A. , Schierman Louis W.
Published: December 2022

In chickens the immune response to haptenic A alloantigens is markedly enhanced if the inoculated erythrocytes also possess foreign B alloantigens which are coated with specific antibody. In the present study the ability of anti-B alloantibody to augment the anti-A immune response is shown to be thymus-dependent.
On the Nature of the Presumed Receptor for IgE on Mast Cells
Authors: Bach Michael K. , Brashler John R.
Published: December 2022

The preparation of mixed rat peritoneal cells for antigen-induced release of histamine by IgE-rich antibody preparations is accompanied by the removal of passive cutaneous anaphylaxis-reactive antibodies from the antibody solution. This removal of antibody from the solutions is directly related to the mast cell content of the mixed cell suspension: little antibody is removed when cells from distilled water-treated rats are used, and the amount of antibody removed by isolated mast cells accounts for the antibody-binding activity of mixed cell preparations. Lysis of isolated mast cells in distilled water or their disruption by mild sonication does not destroy their apparent IgE antibody-binding capacity. Frozen, washed particulate preparations from isolated mast cells retain their ability to bind IgE. Binding of IgE is time dependent. The binding is inhibited by IgGa antibody preparations in a manner which is consistent with competitive inhibition.
Mitogenicity of Bacterial Endotoxins: Characterization of the Mitogenic Principle
Authors: Peavy Duane L. , Shands Joseph W. , Adler William H. , Smith Richard T.
Published: December 2022

Endotoxins from smooth strains of Salmonella typhimurium and from rough variants of Ra, Rc and Re chemotype were mitogenic for mouse spleen cells. Haptenic polysaccharides and native protoplasmic polysaccharides possessed very little mitogenicity. Lipid A was strongly mitogenic. Mild alkaline hydrolysis of complete endotoxin or lipid A, a procedure which cleaves off ester-linked fatty acids, caused a substantial loss of mitogenic activity. These data indicate that endotoxin acts as a nonspecific or general mitogen and that the mitogenic response is not mediated by immunologic mechanisms.
Pulmonary Host Defenses
Authors: Reynolds Herbert Y. , Thompson Russell E.
Published: December 2022

The opsonic properties of immune bronchial secretions and IgA and IgG antibodies separated from them were assessed in an in vitro alveolar macrophage system for their effect on phagocytosis and intracellular killing of Pseudomonas aeruginosa. Although IgA and IgG antibodies had specific agglutinative activity, IgG had superior opsonizing properties when compared with IgA. Also, it seemed to be the principal opsonin in normal respiratory secretions. Immune IgG whether isolated from bronchial fluid or serum was indistinguishable in its opsonic activity; however, the intact IgG molecule was required for optimal function. Opsonins specifically facilitated the phagocytosis of bacteria by macrophages; once ingestion had occurred, intracellular killing of Pseudomonas organisms was rapid and seemingly unrelated to the immune status of the opsonins.
The Spontaneous Induction of Anamnestic Antibody Synthesis in Lymph Node Cell Cultures Many Months after Primary Immunization
Authors: Tew John G. , Self Colin H. , Harold Weldon W. , Stavitsky Abram B.
Published: December 2022

An in vitro model system was developed in which interactions between persisting antigen, humoral antibody, and the various lymphoid cells involved in the immune response may be analyzed. In this system IgG antibody synthesis was spontaneously induced—no extrinsic antigen required—simply by transferring lymphoid cells from a human serum albumin (HSA) immunized rabbit into cell culture. Vigorous spontaneous antibody responses were obtained in cell cultures from 1 month up to a year after immunizing with 1 mg of polymerized-HSA. Induction of the spontaneous antibody response requires a 2- to 3-day period in vitro. The quantity of antibody synthesized per day, for a 3-day period after induction, was as high as 1000 times the amount obtained on the 1st day of culture. Addition of specific antibody to cultures inhibited the inductive but not the synthetic phase of the response. Addition of microgram quantities of antigen inhibited spontaneous induction, whereas nanogram quantities inhibited in some experiments and induced additional antibody synthesis in others. Initiation of the spontaneous in vitro response was attributed to cell-associated persisting antigen, whose activity is subject to an antibody feedback mechanism.
Treatment of E. Coli and Klebsiella Bacteremia in Agranulocytic Animals with Antiserum to a UDP-GAL Epimerase-Deficient Mutant
Authors: Ziegler Elizabeth J. , Douglas Herndon , Sherman James E. , Davis Charles E. , Braude Abraham I.
Published: December 2022

In order to produce antiserum with broad protection against different Gramnegative bacteria we immunized rabbits with a UDP-galactose-deficient mutant (J5) of Escherichia coli O111 that is unencumbered by O antigen since it cannot incorporate galactose into core LPS. Without O side chains, core is accessible for producing antiserum to a wide range of bacteria with similar cores. Such antiserum has previously been shown to prevent unrelated endotoxins from producing dermal and generalized Shwartzman reactions, and death. The current study reports the results of treating bacteremia with this antiserum.

Bacteremia was produced in rabbits made granulocytopenic with nitrogen mustard and fed either Klebsiella pneumoniae, E. coli O17 (multiply antibiotic-resistant), or E. coli O4. Since most rabbits are coliform-free, the organisms colonized the gut and overwhelming bacteremia occurred as granulocytes disappeared. When nonimmune serum was given intravenously (i.v.) at the onset of bacteremia with any of these three organisms, only 3.1% to 5.7% survived. In contrast, survival rates in animals given antiserum to the J5 mutant were 33.3% from E. coli O4, 40% from Klebsiella, and 69.2% from the multiply antibiotic-resistant E. coli O17 (combined p < 0.0005). Antiserum to the parent E. coli O111, (with O antigen intact) provided no significant protection. The protection against death from E. coli O17 by J5 antiserum was greater than that obtained from gentamicin (50%), the only antibiotic to which this strain was sensitive. Rabbits given J5 antiserum cleared labeled bacteria more rapidly than those given nonimmune sera. Antiserum to the J5 mutant is thought to prevent lethal bacteremia from unrelated Gram-negative bacteria by acting as both antitoxin and opsonin.
Use of an Aqueous Polymer Phase System as an Assay for Antibodies to Escherichia Coli Alkaline Phosphatase
Authors: Reese R. T. , Treffers H. P.
Published: December 2022

Escherichia coli alkaline phosphatase in both crude and purified forms was used to produce antibody in rabbits. With this antigen-antibody system it was demonstrated that a polyethyleneglycol-dextran aqueous polymer phase system could be used as a rapid, sensitive and precise means of measuring quantitatively the interaction of antibodies and biologically active macromolecules. Similar results were obtained whether crude or highly pure forms of the enzyme were used. In experiments using nanogram quantities of both antigen (190 ng) and antibody (27 to 32 ng), it was possible to demonstrate differences between the three electrophoretic forms of this enzyme which are thought to be coded for by a single structural gene. Serologic phase system analysis was shown to be versatile enough to compare the native enzyme with forms of the enzyme which were virtually inactive (CRM) as well as with the Zn(II) and Co(II) reconstituted apoenzyme.
Effects of Bursectomy and Thymectomy on Ontogeny of Fowl IgA, IgG, and IgM
Authors: Perey Daniel Y. E. , Bienenstock John
Published: December 2022

The role of the thymus and bursa in the ontogeny of IgA, IgG, and IgM was studied in fowl by using isolated or combined bursectomy (Bx) and thymectomy (Tx) at hatching. Bx birds had markedly elevated serum IgM levels together with moderately decreased IgG and IgA. Tx birds had normal IgM levels but moderately decreased IgG and IgA. BxTx birds had normal IgM levels but markedly depressed IgG and lacked IgA totally even when followed to 5 months of age. The predominant IgA-containing cells in the duodenal lamina propria of normal birds were completely replaced by IgM-containing cells in BxTx birds. These experimental models document the requirement for normal thymus-derived and bursa-derived cell interactions in the ontogeny of both IgG and the IgA system and should provide useful approaches to studies of the post bursal differentiation of the plasma cell lines.
Competitive Effect of Homologous IgG or Fc in Sensitization of Rabbits for PCA Mediated by Reaginic Antibody
Authors: Revoltella Roberto , Ovary Zoltan
Published: December 2022

Rabbit IgG or their Fc fragment inhibit sensitization for homologous passive cutaneous anaphylaxis by rabbit IgE. Fab fragment from rabbit IgG had no inhibitory effect.
RNA-Mediated Immunologic Depression
Authors: Colmerauer M. E. M. , Rumi Lia , Saal Fortuna , Pasqualini Christiane Dosne , Rabasa S. L.
Published: December 2022

RNA extracted from normal liver had a specific immunodepressive effect in syngeneic BALB mice when administered 1 or 5 days before the antigen, as demonstrated in three different systems: 1) syngeneic leukemic colonization was accelerated and death anticipated; 2) spleen lymphocytes cultured in vivo within Millipore chambers showed a lower rate of spontaneous blastogenesis and lack of response to phytohemagglutinin; 3) after immunization with sheep red blood cells, spleen lymphocytes had a decreased rosette-forming capacity and the titer of hemagglutinins in serum was lower. It can be concluded that RNA pretreatment affects both cellular and humoral components of the immunologic system; the effect would be exerted on macrophages and/or lymphocytes.
Expression of the a, x, and y Variable Region Genes of Heavy Chains among IgG, IgM, and IgA Molecules of Normal and a Locus Allotype-Suppressed Rabbits
Authors: Kim Byung S. , Dray Sheldon
Published: December 2022

The contribution of the VH subgroup genes, a, x and y, to the formation of individual IgG molecules has been studied in normal and a locus allotype-suppressed rabbits. Using anti-x32, anti-y33 and antisera to the a locus allotypes (anti-a1, anti-a2 and anti-a3), we used indirect precipitation of 125I-labeled IgG or Fab of specific allotype or inhibition of precipitation for the quantitative analyses. In normal rabbits homozygous with respect to the a locus, about 70 to 90% of the total IgG molecules possess the a locus allotypic specificities and most or all of the remaining molecules, depending on the genotype, could be accounted for as x32 or y33 molecules. Additional IgG molecules with unknown allotypic specificities for the VH region were found in two normal a3 rabbits and in an a1 allotype-suppressed rabbit; these molecules are probably the products of allelic alternatives to x32 and/or y33. Allotype-suppression of a locus molecules was compensated for by an increase in the number of molecules synthesized by closely linked VH subgroup genes, x and y. A similar ratio of the a2, x32, and y33 molecules was observed among Ig fractions with different net electrical charges. In a partially a2-suppressed rabbit, the results of indirect precipitation and sequential precipitation indicated that no two of the allotypic specificities, a2, x32, or y33, are located on the same IgG molecule or on the same Fab fragment. In homozygotes, a locus suppression was found for IgM and IgA as well as for IgG. The expression of a selected VH gene in a cell synthesizing Ig molecules results from linked gene exclusion apparently independent of CH gene selection.
Immunoglobulin Production in Synchronized Cultures of Human Hematopoietic Cell Lines
Authors: Watanabe Shinichiro , Yagi Yasuo , Pressman David
Published: December 2022

Human lymphoid cells in established culture have been shown to synthesize immunoglobulins (Ig). Utilizing a lymphoid cell line (RPMI 1788) from a normal individual, we have now examined the synthesis and secretion of λ-IgM during various phases of the cell cycle. The cells were synchronized by double treatment with excess thymidine, or by a combination of treatments with thymidine and colcemid. After synchronization, the cells were collected at 1- or 2-hr intervals and pulse-labeled with 14C-leucine for 1 hr. The rate of IgM secretion was determined by assaying total IgM secreted during the pulse period. The rate of IgM synthesis was determined by specific precipitation of the labeled IgM which accumulated in the medium after culturing the pulse-labeled cells for an additional 24 hr in the regular medium. The results showed that there are two peaks of the synthetic activity during the cell cycle, one in the late G1 or early S and the other in the G2 phase. Thus, the expression of Ig genes appears to be limited to certain portions of the cell cycle as has been found for enzymes and other cell products. On the other hand, the rate of secretion does not vary as much during the cell cycle, although both the rate of synthesis and of secretion are at the lowest level in the mitotic phase.
Antigen-Macrophage Interaction
Authors: Cohen Benjamin E. , Rosenthal Alan S. , Paul William E.
Published: December 2022

The macrophage appears to bind and present antigen to the lymphocyte in the induction and elicitation of the immune response. We have studied the nature of the interaction between dinitrophenyl-guinea pig albumin (DNA-GPA) and macrophage-rich peritoneal exudate cells (PEC) in vitro. PEC from non-immune guinea pigs are not capable of binding sufficient DNP-GPA to induce DNA synthesis in vitro by immune lymphocytes when low (10-2 µg/ml) concentrations of DNP-GPA are employed although PEC from immune animals function quite well under these conditions. At high antigen concentrations (10+2 µg/ml) PEC from both immune and non-immune animals function equally well. Incubation of non-immune macrophages in serum from immune animals causes a marked increase in the sensitivity to low antigen concentrations on the part of non-immune PEC. There is a parallel increase in the amount of DNP-GPA bound to the PEC and the degree to which these cells can stimulate immune lymphocytes to divide. This enhanced capacity of PEC to stimulate lymphocytes can be inhibited by DNP-ovalbumin (OVA), a hapten on a heterologous carrier. Also, the binding of DNP-GPA, at low concentrations, to immune PEC can be blocked by anti-immunoglobulin sera. Neither of these agents has a significant effect on the binding of DNP-GPA at high concentrations to immune macrophages or on the binding of DNP-GPA, at either low or high concentrations, to non-immune macrophages. We conclude that there are at least two mechanisms of antigen binding to the macrophage surface. One involves sites of low avidity which are effective only at relatively high antigen concentrations and which appear not to be immunoglobulin. These sites dominate at high DNP-GPA concentration for both the immune and the non-immune PEC populations. In addition, cytophilic antibody, which in hapten-carrier systems is hapten-specific and of high avidity, is present on PEC from immune animals and is the primary means by which small amounts of antigen are concentrated by immune macrophages in quantities sufficient to stimulate lymphocytes.
The Homing Pattern of Thymus-Derived Lymphocytes in Calf and Neonatal Mouse Peyer's Patches
Authors: Waksman Byron H.
Published: December 2022

Differential morphologic criteria are summarized which permit distinction of three basic elements of the gut-associated lymphoid tissues (GALT): the dome, follicle, and “thymus-dependent” area (TDA). These criteria were applied to a reexamination of Peyer's patches from calves and newborn mice, in which 3H-thymidine had been administered by perfusion via the thymic artery or by a single intrathymic injection at birth, respectively. In calves, heavily labeled cells were found exclusively in regions morphologically identified as TDA and, in mice, there was a great preponderance of labeled cells in the TDA and the adjacent lateral dome epithelium. These observations confirm the description of the TDA as containing T cells and suggest that the migration of these cells, first to the TDA and then to the lumen via the lateral dome epithelium, may provide a major pathway of T cell migration in both newborn and older animals.