bluuebunny/crossref_metadata_2025 huggingface dataset:
ELECTRON MICROSCOPIC OBSERVATIONS ON ANTIBODY-PRODUCING CELLS IN LYMPH AND BLOOD
Authors: Hummeler Klaus , Harris T. N. , Tomassini Natale , Hechtel Maureen , Farber Miriam B.
Published: June 2004

Antibody-producing cells have been identified among cells obtained from efferent lymphatic vessels, the thoracic duct, and peripheral blood. These cells, which produced plaques of hemolysis and which were quite rare (20 to 50 per million), due in most instances to 19S antibody, were located and studied by electron microscopy.

Of the antibody-producing cells found in these three sites there were several features common to all: small size (5 to 8 µ), generally spherical shape, approximately central position of the nucleus, and retention in the nucleus of the condensations of chromatin characteristic of the lymphocyte.

The differences among the cells of these sources were largely in the relative amount and state of organization of the organelles of the cytoplasm. In cells of the efferent lymphatic vessel and the thoracic duct, the endoplasmic reticulum showed a range from relative scarcity to considerable numbers of well organized channels. Between these extremes were cells with a considerable amount of endoplasmic reticulum, the channels disorganized and sectioned at various angles. The cytoplasmic matrix of all of these contained a profusion of polyribosomes. Antibody-producing cells obtained from peripheral blood showed, around the roughly spherical nucleus, a ring of cytoplasm which was narrow, but wholly organized into parallel lamellae of endoplasmic reticulum, with many polyribosomes between these, and a large Golgi body.

Some similarities and some differences of these cells, in comparison with antibody-producing cells obtained from lymph nodes, have been indicated.
COMPETITION OF HASTENS
Authors: Amkraut Alfred A. , Garvey Justine S. , Campbell Dan H.
Published: June 2004

Groups of rabbits were injected with either bovine serum albumin, sheep red cell stroma, or keyhole limpet hemocyanin to which 2,4-dinitrophenyl and/or p-azophenyl arsonate groups had been coupled. Groups of animals received either doubly coupled antigen or an equivalent mixture of singly coupled antigens. Materials were injected intravenously as a solution or subcutaneously and intramuscularly in complete Freund's adjuvant.

The presence of dinitrophenyl groups on the immunizing antigen could suppress, partially or completely, the antibody response to p-azophenyl arsonate when this hapten was located on the same molecule. Suppression was dependent on the ratio of haptenic groups on the molecule, appeared to be greatly affected by the method of immunization, and could be demonstrated in all three antigen systems. Partial suppression was manifested in decreased frequency and delayed appearance of the response as well as decreased maximal antibody titers. These findings appear irreconcilable with the possibility of direct clonal selection of antibody-producing cells by unprocessed antigen.
A STUDY OF IMMUNOGLOBULIN STRUCTURE
Authors: Baglioni C. , Cioli D.
Published: June 2004

Urinary proteins of patients with myeloma, prepared by precipitation with ammonium sulphate, have been separated by gel filtration on Sephadex G-100 after reduction and aminoethylation. Many specimens separated into a major peak of Bence Jones protein and into minor peaks of albumin, a protein tentatively identified with heavy chain and a smaller molecular weight protein corresponding to the variable portion of the corresponding Bence Jones protein. The Bence Jones protein purified by gel filtration was analyzed by electrophoresis and by peptide mapping after tryptic digestion. The peptide maps of 24 type K and 20 type L Bence Jones proteins were compared.

A set of common peptides was identified in the peptide maps of the Bence Jones proteins of the same type; the common peptides of type K proteins were completely different from the common peptides of type L proteins. The patterns of distinctive peptides was compared; no similarities were found between distinctive peptides of type K and of type L proteins. Some similarities were observed in the distinctive peptides of proteins of the same type. The similarities involved in many cases peptides containing cysteine, whereas similarities in other peptides were limited. This observation suggested that the amino acid sequence around the cysteines of the variable NH2-terminal half of the Bence Jones proteins may show less variability than other sequences. A few proteins of the same type differed in all their distinctive peptides, an indication that multiple amino acid differences exist between individual Bence Jones proteins.

The genetic mechanisms responsible for the variability in the amino acid sequence of the NH2-terminal half of the light chains of immunoglobulins are discussed in view of the results of the comparison by peptide mapping of the Bence Jones proteins.
MECHANISMS OF IMMUNOLOGIC INJURY OF RAT PERITONEAL MAST CELLS
Authors: Austen K. Frank , Becker Elmer L.
Published: June 2004

There is an absolute requirement for C'1, C'2, C'4, C'3, and C'5 in releasing histamine from rat peritoneal mast cells sensitized with rabbit anti-rat gamma globulin. This conclusion is based upon the restoration of histamine-releasing capacity by adding highly purified complement components to sera deficient in one or more of these components. Of special advantage was the availability of sera from humans with inborn or acquired deficiencies in a single component.

The p-nitrophenyl ethyl phosphonates block this reaction by inhibiting an antigen-antibody-activated esterase which exists in a phosphonate resistant precursor state until activated by the interaction of the sensitized mast cell and serum complement. There is almost complete disparity between the ability of the phosphonates to inhibit complement-dependent histamine release by rabbit anti-RGG and to inactivate C'1a. Even though C'1a is required for complement-dependent histamine release by rabbit anti-RGG, this is not the esterase being blocked by the phosphonates under the experimental conditions used.

The pattern of inhibition by the phosphonates of the antigen-antibody-activated esterase required for complement-dependent, noncytotoxic histamine release is remarkably similar to that of the esterase required for homocytotropic antibody-mediated histamine release. One possible implication is that these two quite different modes of carrying out antigen-antibody-induced histamine release from rat peritoneal mast cells lead to activation of the same esterase and share a common pathway.
INHIBITION OF THE SECONDARY ANTIBODY RESPONSE IN VITRO BY SALICYLATE AND GENTISATE
Authors: Ambrose Charles Tesch
Published: June 2004

Salicylate inhibition of the secondary antibody response initiated in vitro on day 0 has been studied in cultures of rabbit lymph node fragments. Levels of 1.25 to 1.5 mM (0.20 to 0.24 mg/ml) sodium salicylate present in serum-free medium throughout an 18- or 21-day culture period completely inhibit the secondary response. This inhibition is largely accomplished by the drug's action during the first 9 days, which corresponds to the inductive phase for this culture system. Relatively little inhibition is produced by adding the drug only after day 9, although over 90% of the antibody produced during a 21-day experiment is synthesized after day 9. Studies with media of different pH's show that this inhibition is more correctly a function of the nonionized salicylic acid concentration in the medium than of the total salicylate concentration. Arguments are presented against the possibility that salicylate at the levels used here inhibits antibody synthesis by uncoupling oxidative phosphorylation.

Acetylsalicylic acid (aspirin) produces the same degree of inhibition in vitro as do equimolar concentrations of sodium salicylate. Gentisate (5-hydroxysalicylate) is 15-fold more effective in producing 50% inhibition than salicylate; its temporal pattern of inhibition is similar to that of salicylate.
EXPERIMENTAL INDUCTION OF ATHERO-ARTERIOSCLEROSIS BY THE SYNERGY OF ALLERGIC INJURY TO ARTERIES AND LIPID-RICH DIET
Authors: Minick C. Richard , Murphy George E. , Campbell Wallace G.
Published: June 2004

In rabbits that received a dietary supplement of cholesterol, 0.5% by weight, and concommittant injections of horse serum (group III) over a period of 80 days, coronary arterial lesions developed that in the main were different in quality and distribution from those in rabbits that received the cholesterol supplement alone (group I), and of different quality from but in distribution similar to those in rabbits that received horse serum alone (group II).

Fatty lesions developed in small, rarely in medium, but never in large arteries of rabbits in group I, and these changes do not resemble coronary athero-arteriosclerosis in man. Proliferative lesions without fatty change developed in large, medium, and small arteries of rabbits in group II, and some of these closely resemble human coronary arteriosclerosis without fatty change. The changes that developed in large, medium, and small arteries of rabbits in group III were in very large majority fatty-proliferative lesions. Some of these closely resemble the changes that in some cases constitute coronary athero-arteriosclerosis in man.

Nuclei with caterpillarlike chromatin pattern in longitudinal section and owl eye appearance in transverse section were observed to occur in many of the proliferating cells in thickened arterial intima in hearts of rabbits in groups II and III and in some of the lipid rich "foam" cells in arterial intima and subjacent media in hearts of rabbits in group III. Such nuclei have been observed to occur in some reacting smooth muscle cells and normal immature and reacting mature striated muscle cells of the heart. These observations indicate that at least many of the cells, including "foam" cells, in thickened intima in the experimentally induced and in naturally occurring coronary athero-arteriosclerosis are smooth muscle cells that evolved in proliferative reaction to arterial injury.

Fatty change developed in aortas of the rabbits in groups I and III, and was significantly greater in group III.

Results of this investigation support the hypothesis that the synergy of allergic injury to arteries and lipid-rich diet can lead to athero-arteriosclerosis.
THE ROLE OF COMPLEMENT IN RESISTANCE TO ENDOGENOUS AND EXOGENOUS INFECTION WITH A COMMON MOUSE PATHOGEN, CORYNEBACTERIUM KUTSCHERI
Authors: Caren Linda D. , Rosenberg L. T.
Published: June 2004

In mice, the presence or absence of a single complement (C') component, called hc1, is controlled by two alleles at the Hc locus. The sera of mice which lack this C' component do not manifest C'-mediated immune hemolysis. When challenged with the common mouse pathogen, Corynebacterium kutscheri, mice possessing hemolytic C' fare slightly better than C'-deficient mice. When mice harboring latent C. kutscheri are administered hydrocortisone, which depresses mouse serum C' levels, pseudotuberculosis is activated with equal frequency in mice of both C' types. These data suggest that in at least one situation the presence of the complete hemolytic C' system may be advantageous to the mouse. In contrast, evidence is presented which shows that under normal laboratory conditions, C'-deficient B10.D2 "old line" mice (Hc0/Hc0) have a survival advantage over C'-positive B10.D2 "new line" mice (Hc1/Hic1) during the first 3 wk of life. It is therefore concluded that mouse hemolytic C' has a balanced survival value—that is, under one set of conditions it may be advantageous, whereas in another situation, it may be disadvantageous.
POLYMORPHONUCLEAR LEUKOCYTES IN IMMUNOLOGIC REACTIONS
Authors: Cochrane Charles G. , Aikin Barbara S.
Published: June 2004

Vascular basement membrane was disrupted in the presence of polymorphonuclear leukocytes (PMN's) during two immunologic reactions: The Arthus phenomenon and the reaction to locally injected antibody to vascular basement membrane. This disruption was evidenced by (a) the inability of the basement membrane to retain circulating carbon, by (b) loss of antigenic constituents, and by (c) electron microscopic observation showing actual gaps in the structure of the vascular basement membrane.

The factors within PMN's responsible for damage to isolated glomerular basement membrane in vitro were found by isolation procedures to be cathepsins D and E. Cationic proteins of PMN's were separable from the cathepsins. While inducing vascular permeability upon injection, these basic proteins failed to inflict the severe damage to the basement membrane observed in Arthus and antibasement membrane reactions. It is concluded that the full expression of these immunologic lesions requires destruction of the basement membrane possibly brought about by cathepsins D and E.

Some of the physicochemical properties of these pathologically active leukocytic factors are given.
DEFICIENCY OF THE SIXTH COMPONENT OF COMPLEMENT IN RABBITS WITH AN INHERITED COMPLEMENT DEFECT
Authors: Rother Klaus , Rother Ursula , Müller-Eberhard Hans J. , Nilsson Ulf R.
Published: June 2004

A strain of rabbits with an inherited complement deficiency was shown to lack the sixth component of the hemolytic complement system. A method was elaborated for the partial purification of this component from normal rabbit serum. Upon injection of partially purified rabbit C'6 into C'6-deficient animals, an antibody was obtained which specifically inhibited the hemolytic activity of C'6. The data suggest that C'6-deficient serum either lacks the C'6 molecule or contains it in a chemically modified and inactive form.
PRIMARY ANTIBODY RESPONSE IN ORGAN CULTURES
Authors: Globerson Amiela , Auerbach Robert
Published: June 2004

Specific antibody formation has been elicited in vitro following antigenic stimulation by either sheep (in a total of 472 of 875 cultures) or chick erythrocytes (in 65 of 135 cultures tested). The response was manifested by mouse spleen and lymph node explants whereas thymus cultures were inactive. The reaction has been characterized as a primary immune response in view of its kinetics as compared to defined primary and secondary responses, the effect of 2-mercaptoethanol on the antibodies formed, its subject to puromycin inhibition and its sensitivity to X-irradiation. Histological studies revealed preservation of the lymphoid cell populations throughout the entire experimental period.
THE CARRIAGE OF IMMUNOLOGICAL MEMORY BY SMALL LYMPHOCYTES IN THE RAT
Authors: Gowans James L. , Uhr Jonathan W.
Published: June 2004

Lymphocytes were obtained from the thoracic duct of rats 1½ to 15 months after primary immunization with a single dose of bacteriophage ϕX 174. An intravenous injection of these lymphocytes conferred on heavily X-irradiated rats the ability to form antibody in a secondary-type manner after a first injection of ϕX. Negligible responses were obtained after cell transfer if the recipients were not challenged with antigen.

Thoracic duct cells from some immunized donors were incubated in vitro for 24 hr before transfer in order to destroy selectively the large, dividing lymphocytes. The responsiveness conferred on X-irradiated recipients by such "incubated" inocula was then compared with that given by equal numbers of "fresh" thoracic duct cells. In all such comparisons the recipients of the "incubated" cells gave higher and more rapid antibody responses. It was concluded that the cells in thoracic duct lymph which carried immunological memory were small lymphocytes.
STUDIES ON HUMAN PERIPHERAL BLOOD LYMPHOCYTES IN VITRO
Authors: Börjeson Jan , Reisfeld Ralph , Chessin Lawrence N. , Welsh Patricia D. , Douglas Steven D.
Published: June 2004

The saline extract from the roots of Phytolacca americana (pokeweed) possesses three biological properties; hemagglutinin, leukagglutinin, and mitogen. Fractionation and further purification on calcium phosphate column chromatography revealed that the biologically active substance was eluted in the front moving fraction with 0.05 M phosphate buffer pH 7.5. Analytical separation on polyacrylamide gels in disc electrophoresis yielded a single homogeneous band with an Rf value of 0.43 containing all three biological activities. This fraction had an ultraviolet absorption spectrum similar to PHA, was stable to both periodate and mercaptoethanol treatment and gave a single band in double diffusion and immunoelectrophoretic analysis against the antibody prepared to the crude PWM saline extract.

Absorption studies with red cells or stroma revealed that the hemagglutinin could be selectively removed without significantly altering the mitogen, whereas absorption with leukocytes resulted in loss of both the mitogenic and leukagglutinating activities.
STUDIES ON HUMAN PERIPHERAL BLOOD LYMPHOCYTES IN VITRO
Authors: Chessin Lawrence N. , Börjeson Jan , Welsh Patricia D. , Douglas Steven D. , Cooper Herbert L.
Published: June 2004

A study of the kinetics of RNA and DNA synthesis in PWM-stimulated lymphocytes revealed that RNA synthesis preceded the onset of DNA synthesis by approximately 24 hr and that DNA synthesis and transformation was maximal between 66 to 78 hr. Histochemical and radioautographic studies on PWM stimulated cultures indicated that at 72 hr 50 to 60% of the cell population had been transformed by PWM, and that a distinct cell type bearing cytologic resemblance to the early plasma cell had emerged. The RNA sedimentation profile for newly synthesized RNA in PWM-stimulated cells showed that a large peak of 45 to 50 S material was formed after 24 and 40 hr. PWM thus produces a distinctive transformation of human peripheral blood lymphocytes.
IMMUNOPATHOLOGY OF NZB/BL MICE
Authors: Mellors Robert C. , Huang Chen Ya
Published: June 2004

A filtrable agent separable from transplantable malignant lymphomas of NZB/Bl mice was capable, upon inoculation into preweanling NZB/Bl mice, of inducing lymphoid cell hyperplasia, hypergammaglobulinemia, proteinuria, hypoalbuminemia, and pathological changes (focal membranous glomerulonephritis) of kidneys—renal functional and structural changes qualitatively similar to those of spontaneous occurrence in older NZB/Bl mice.

Viruslike particles with close resemblance to the typical "C" type murine oncogenic virus particles were identified by means of electron microscopy in NZB/Bl mouse tissues and cells, including malignant lymphoma cells, benign lymphoid cells of thymus and spleen, epithelial cells of renal tubules, and extracellular sites.

The relevance of these observations, the first of their kind dealing with NZB/Bl mice, is discussed in relation to the several immunopathological disorders which characterize this strain of mice.
HIGH CONCENTRATION OF INJECTED TITANIUM DIOXIDE IN ABDOMINAL LYMPH NODES
Authors: Huggins Charles B. , Froehlich Jeffrey P.
Published: June 2004

In the rat the greatest accumulation, in any anatomical structure, of titanium dioxide following its intravenous injection was found in two small clusters of lymph nodes in upper abdomen behind the peritoneum. These are the lymph nodes of the liver.

This extraordinary quantitative characteristic of the abdominal clusters is attributed to their topography which results in progressive filtration of particulate matter from hepatic lymph.
ANTIGENICITY OF THE M PROTEINS OF GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Fox Eugene N. , Wittner M. K. , Dorfman Albert
Published: June 2004

Highly purified M proteins were used for determining cutaneous hypersensitivity and type-specific circulating antibodies in normal adults and infants. 80% of 91 adults and 8% of 59 infants exhibited a transient delayed cutaneous reaction to at least two of types 12, 14, and 24 M proteins. Antibodies assayed by passive hemagglutination were observed in 90% of the adults and 13% of the infants.

Vaccines of 10 µg of alum-precipitated M protein or 20 µg of the soluble antigen were administered to adults not exhibiting delayed hypersensitivity. Within 2 wk hemagglutination liters increased significantly in 31 of 33 subjects. Preimmunization antibody levels indicated that these responses were probably anamnestic reactions from previous exposures to homologous serotypes of group A streptococci. Sera exhibiting large increments in antibody titers resulting from M protein inoculations also had type-specific bactericidal properties. "Attenuated" M proteins, produced by partial degradation with trypsin induced only minimal cutaneous reactions in hypersensitive adults, but still retained most of the antigenic specificity when assayed in vitro and in vivo.

The utility of M protein vaccines for human use is discussed in reference to the low incidence of cutaneous hypersensitivity in infants, the potentials of polyvalent attenuated M protein vaccines and the apparent absence of immune cross-reactivity between pure M proteins and human heart and kidney tissues.
HURLER'S SYNDROME
Authors: Danes B. Shannon , Bearn Alexander G.
Published: June 2004

Skin fibroblasts from eight families with Hurler's syndrome (X-linked recessive and autosomal recessive) and normal individuals have been studied in cell culture. A good correlation between cellular metachromasia and the quantitative estimation of intracellular mucopolysaccharides was observed provided the culture conditions were standardized.

In both forms of Hurler's syndrome intracellular mucopolysaccharide content could be used to distinguish the affected individual and the carrier from the normal subject, although the total mucopolysaccharide content of fibroblast cultures or the amount in the culture medium did not permit such a distinction.

Retinol, in concentrations similar to those encountered in man in hyper-vitaminosis A, caused a reduction in total mucopolysaccharide content of fibroblast cultures from normal and affected individuals. Cultures from three patients with the X-linked recessive form of Hurler's syndrome showed a gradual but marked decrease in cellular metachromasia and approximately 60% decrease in mucopolysaccharide content. Synthesis of polysaccharides and sulfation appeared to be equally affected. On removal of retinol from the medium the content of intracellular mucopolysaccharides returned to pretreatment levels. The possible relevance of these findings to the treatment of Hurler's syndrome is discussed.
URINARY EXCRETION OF FOREIGN ANTIGENS AND RNA FOLLOWING PRIMARY AND SECONDARY INJECTIONS OF ANTIGENS
Authors: Garvey Justine S. , Campbell Dan H. , Das Manik L.
Published: June 2004

Two soluble antigens, BSA and KLH labeled with sulfanilate-35S, when injected intravenously into normal animals, were excreted in the urine to over 70% in 24 hr. Over the next 6 days, 25% more was excreted after which time only a trace could be detected. Much of the antigen remaining from the primary injection appeared in the urine following a secondary injection of the unlabeled protein carrier at 7 days after primary injection.

The antigen material found in the urine was quite heterogeneous with respect to physical properties and much of it was associated with RNA material as shown by chromatographic analyses. The main difference between the labeled material released following the primary and secondary injection was the higher degree of association of antigen material with nucleotide material after secondary injection as compared with primary injection. Further study is needed to distinguish qualitative from quantitative changes of the components, antigen and nucleic acid, and also the nature of their association. Possible similarities were found for the RNA-antigen material released from tissue after secondary injection of unlabeled antigen, and the material that was isolated previously from liver.
ANTIBODIES INVOLVED IN ANTIGEN-INDUCED RELEASE OF SLOW REACTING SUBSTANCE OF ANAPHYLAXIS (SRS-A) IN THE GUINEA PIG AND RAT
Authors: Stechschulte Daniel J. , Austen K. Frank , Bloch Kurt J.
Published: June 2004

The antigen-induced release of SRS-A and histamine was studied in the guinea pig and rat using whole and fractionated antiserum preparations.

Guinea pig 7Sγ1-antibody sensitized sliced guinea pig lung tissue for antigen-induced release of both SRS-A and histamine; neither substance was released from lung tissue prepared with 7Sγ1-antibody.

Rats injected intraperitoneally with hyperimmune rabbit or rat antiserum released only SRS-A in significant amounts when challenged with antigen by the same route. A definite time interval between the injection of antiserum and challenge with antigen was required for optimal release of SRS-A.

Fractionation of rat antiserum demonstrated that the immunoglobulin responsible for most of the SRS-A release from rat peritoneal tissue was a γG-antibody or fraction thereof. Acting in this capacity, the γG-antibody or its subfraction may be considered a second type of homocytotropic antibody. Fractions of rat antisera containing the first type of homocytotropic antibody, i.e. antibody mediating release of histamine and serotonin, prepared peritoneal tissues for the release of large amounts of these pharmacological agents and only small amounts of SRS-A.

Two different mechanisms for the production of PCA lesions in the rat were considered. One of these involves the antigen-induced release of histamine and serotonin from mast cells sensitized by homocytotropic antibody. This reaction has an optimal latent period of 24–72 hr. The second mechanism involves the local combination of antigen with "hyperimmune" heterologous or homologous antisera. This reaction can be elicited after a latent period of 4 but not 24 hr; host complement and leukocyte lysosomal enzymes, as well as SRS-A, may be involved.
STUDIES OF THE Vi (γ2c) SUBGROUP OF γ-GLOBULIN
Authors: Yount William J. , Kunkel Henry G. , Litwin Stephen D.
Published: June 2004

Further delineation of the antigens characteristic of the Vi or γ2c subgroup of γ-globulin was carried out utilizing a number of rabbit and primate antisera. Two genetic antigens characteristic of this subgroup, Gm(b) and Gm(g), were also detected by precipitation techniques with certain of the antisera. These were clearly differentiated from antigens common to all proteins of this subgroup.

The concentration, of Vi protein in normal and pathological sera from several population groups was measured quantitatively utilizing a variety of immunological procedures. All sera studied showed measurable levels. The mean value for Caucasian sera was 1.06 mg/ml, representing approximately 8% of γG-globulin. This agreed closely with a figure of 8.4% for the incidence of myeloma proteins of the Vi subgroup among all γG-myeloma proteins in Caucasians.

A relationship was found between the Vi subgroup concentration and the specific genetic type of a given individual. Measurements of the Gm(b) genetic determinants, which are found solely in Vi-type proteins, brought forward this relationship. Gm(b+) individuals showed higher concentrations of Vi-type γ-globulin than those who were Gm(b-), and this difference was statistically significant for both the homozygous and heterozygous states. It appeared that the structural genes for Gm(b+) polypeptide chains showed a greater synthetic capacity than those for Gm(b-) types. The possible significance of such effects in governing the relative composition of the antibody population in a given individual is discussed.
RECOVERY OF ANTIBODY ACTIVITY FROM INACTIVE HYBRIDS OF H AND L CHAINS
Authors: Roholt O. A. , Radzimski G. , Pressman D.
Published: June 2004

Hybrid IgG molecules were prepared from the heavy and light chains of specifically purified antibody against two different haptens. One hybrid consisted of the H chains from the anti-p-azobenzoate antibody from one rabbit and L chains from the anti-p-azobenzenearsonate antibody from the second rabbit, and the second hybrid consisted of the opposite combination, light chains from the first rabbit and heavy chains from the second. The two hybrids were mixed at pH 8 and were found to be so stable in the mixture that even after 2 wk at 5°C there was still only low hapten-binding activity toward p-iodobenzoate and p-iodobenzenearsonate. However, exposure of the mixture of hybrids to 1 M propionic acid followed by buffer at pH 8 resulted in recovery of binding activity for p-iodobenzoate and p-iodobenzenearsonate. Thus no exchange occurred between the light and heavy chains of the hybrids in the buffer, but exchange did occur on exposure to propionic acid, and this exchange favored a preferential combination among the chains in such a manner that effective antibody sites resulted.
GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO
Authors: Stecher Vera J. , Thorbecke G. Jeanette
Published: June 2004

The present studies have shown that the influence of X-irradiation on the secondary antibody response in vitro is remarkably similar to its effect on the primary response in vivo.

When sensitized tissue was first irradiated and then reexposed to antigen, the duration of the interval between irradiation and antigen addition determined the degree of inhibition of the secondary response obtained. A delay of 12 hr resulted in stronger inhibition than a delay of 6 hr, and an interval of 24 hr before reexposure to antigen caused complete suppression of antibody production to diphtheria toxoid and almost complete suppression when sheep RBC were used as the antigen.

Induction of the secondary response in rabbit lymph node tissue in vitro followed by exposure to X-irradiation, revealed that immediate exposure to irradiation after antigen produced stronger inhibition of the subsequent response than irradiation on days 2–3. Irradiation on day 6 had no detectable effect. The effectiveness of the early radiation is probably due to prevention of the proliferation of the antibody-forming cells. BUDR was found to be effective at similar time periods as X-irradiation, whereas colchicine could still stop antibody formation when added late during the secondary response in vitro.

It was noted that lymph nodes from some BSA-sensitized rabbits as late as 18 months after sensitization gave a response indistinguishable from a typical secondary response, even when not reexposed to antigen.
STUDIES OF HUMAN ANTI-γ-GLOBULIN FACTORS REACTING WITH PEPSIN-DIGESTED γ-GLOBULINS
Authors: Lawrence Thomas G. , Williams Ralph C.
Published: June 2004

Many sera from normal individuals as well as patients with various disease states contain agglutinating antibodies which show specificity for antigenic determinants of γ-globulin revealed by pepsin digestion at pH 4.1. Sera containing such agglutinating activity as well as sera negative for these agglutinators contain low molecular weight (3S–5S) components of slow γ-mobility which inhibit these agglutination reactions. Low molecular weight inhibitors show both auto- and isospecificity, and are antigenically related to the 5S pepsin fragment of γ-globulin. A common situation is thereby revealed in which human anti-γ-globulin antibodies showing specificity for pepsin-digested γ-globulins are present in serum along with low molecular weight γ-globulin components capable of inhibition. Autoreactivity or autospecificity of such anti-γ-globulin factors is a phenomenon shared by both normal human sera and sera from patients with various disease states.
LARYNGOTRACHEITIS VIRUS IN CHICKENS
Authors: Bang Betsy G. , Bang Frederik B.
Published: June 2004

Infectious laryngotracheitis can be produced in chickens as an experimental model of severe nonfatal rhinitis and sinusitis. Inoculated intranasally into unanesthetized baby chicks it remains limited to the nasal fossa, produces acute desquamation of all nasal epithelia, results in functional recovery of the respiratory epithelium, but leaves important residual abnormalities. From the earliest recognizable lesions through 4½ months' convalescence, the principal changes are as follows:

1. Initial lesions, or small syncytia of intranuclear "inclusions", first identifiable in the mucociliated cells of the shallowest portion of the epithelium at about 21 hr postinoculum (the inner surface of the maxillary conchal scroll).

2. Acute sloughing, (about 3 to 7 days), marked by: (a) spread of lesions from cell to cell via multinucleated "giant cells" which progressively slough and desquamate respiratory, olfactory, and sinus epithelia, epithelial neural elements and blood vessels; (b) appearance of numbers of eosinophilic leukocytes along the basement membrane at the sites of lesions just previous to sloughing; intensive infiltration of the submucosa with small lymphocytes after sloughing begins; (c) histochemical change in the intracellular mucus of the cells which comprise the syncytia: this mucus stains with Alcian blue alone when stained with AB-PAS; and (d) all cartilages of the maxillary conchae become flaccid, and the cell nuclei and matrix lose both basophilic and Alcian blue staining properties, effects which recede by about the 8th day.

3. Repair (about 8 to 21 days), marked by rapid initial spread of a sheet of epithelial cells over the infiltrated subrmucosa, appearance of numbers of plasma cells circulating in the tissues, formation of encapsulated secondary nodules, and mucosal adhesions.

4. Convalescence (about 1 to 4½ months when experiments terminated), marked by functional restoration of the mucociliary lining of the nasal fossa. However, at 4½ months eight specimens all show complete metaplasia of the olfactory organ (end nerves, supporting cells, and glands of Bowman) to mucociliated epithelium, all show abnormal formation and alignment of mucous acini, and about 50% have severe persistent sinusitis.
SPECIFICITY OF THE ANTIBODIES PRODUCED BY SINGLE CELLS FOLLOWING IMMUNIZATION WITH ANTIGENS BEARING TWO TYPES OF ANTIGENIC DETERMINANTS
Authors: Green Ira , Vassalli Pierre , Nussenzweig Victor , Benacerraf Baruj
Published: June 2004

A combination of double immunofluorescent technique and radioautographic localization of radioactive antigens was used to investigate the question whether single antibody-producing cells can make antibodies of more than one specificity after immunization with antigens bearing more than one determinant. When guinea pig γ2-globulins, containing the F(ab')2 and Fc determinants, were used to immunize rabbits, a small percentage of cells (3.7%) were stained with both the anti-F(ab')2 and anti-Fc reagents. These results were shown to be due to the lack of absolute specificity of the detecting antigen and antibody reagents which can be obtained for use in this system.

However, when immunological systems such as hapten-protein conjugates were used, and where completely specific antigen and antibody reagents could be prepared, the results were unequivocal. The individual lymph node cells from rabbits or guinea pigs immunized with hapten-protein conjugates produced antibodies against the hapten or antibodies against the antigenic determinants of the carrier molecule, never antibodies against both specificities.
INTERACTIONS OF THE COMPLEMENT SYSTEM WITH THE SURFACE AND ENDOTOXIC LIPOPOLYSACCHARIDE OF VEILLONELLA ALCALESCENS
Authors: Bladen Howard A. , Gewurz Henry , Mergenhagen Stephan E.
Published: June 2004

Electron microscopic studies demonstrated that lesions were produced on the endotoxic lipopolysaccharide (LPS) as well as on the cell surface of V. alcalescens after reaction with fresh guinea pig serum. These lesions were approximately 90 A in diameter, and were seen on two characteristic structural entities derived from LPS preparations after incubation with serum. The use of numerous inhibitors, inactivators, and reaction conditions affecting hemolytic C' activity revealed that these lesions were mediated by the C' system. Concomitant with lesion formation, C' was fixed; the effect on classical C'3 activity was pronounced. It is concluded that endotoxic LPS, as contained in the outer three-layered membrane of the bacterial cell, is a substrate for the C' enzymes. It is suggested that certain biological activities of endotoxin may derive from its effects on the C' system.
COMPARATIVE EFFECTS OF CORTICOSTEROIDS ON HOST RESISTANCE TO INFECTION IN RELATION TO CHEMICAL STRUCTURE
Authors: Fauve Robert M. , Pierce-Chase Cynthia H.
Published: June 2004

In a comparative study concerning the effect of corticosteroids on host resistance to infections, five compounds were found to decrease host resistance, while three did not have this property, although all eight compounds were highly antiinflammatory.

The compounds capable of decreasing host resistance were (I) hydrocortisone acetate; (III) 9α-fluoro, 16α-methylprednisolone acetate; (IV) 9α-fluoro, 16α-hydroxyprednisolone; (V) 9α-fluoro, 16α-hydroxyprednisolone, 16α–17α-acetonide; and (VII) 9α-fluoro, 16α-hydroxypredmsolone, 16α-, 17α-acetonide, 21 disodium phosphate. Following a single injection of 10 mg of any of these compounds, latent corynebacterial infection was provoked into active pseudotuberculosis. Also, mice injected with these corticosteroids were more susceptible to infection with Corynebacterium kutscheri, Staphylococcus aureus, Klebsiella pneumoniae, or Listeria monocytogenes. These same corticosteroids inhibited the ability of mouse peritoneal macrophages to spread on glass surfaces.

The three compounds incapable of decreasing host resistance, although highly antiinflammatory, were: (II) 6α-methylprednisolone, 21 sodium hemisuccinate: (VI) 9α-fluoro, 16α-hydroxyprednisolone, 16α-, 17α-acetonide, 21 hemisuccinate; and (VIII) 9α-fluoro, 16α-hydroxyprednisolone, 16, 21 dihemisuccinate. These three compounds were also unable to inhibit the spreading of macrophages on glass.

The importance of succinate group bound to the corticosteroid molecule as hemisuccinate is emphasized since it is seen that the infection-provoking property can be dissociated from the antiinflammatory property. This finding may be of practical consequence in selecting a corticosteroid for treatment in disease, and also shows that one cannot use, indifferently, corticosteroids only on the basis of their common antiinflammatory property.
STUDIES ON CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES
Authors: Aisenberg Alan C.
Published: June 2004

Complete immunological tolerance to sheep cells can be induced in mice when cyclophosphamide is injected together with sheep cells or up to 72 hr before or 48 hr after the antigen. As is true for radiation-induced immune suppression, the drug is most effective when given in the 24 hr prior to antigen. Complete cyclophosphamide-induced immunological suppression requires large doses of sheep cells (6.2 x 109 cells), presumably to enable antigen to reach sequestered receptor sites.

The cyclophosphamide tolerance system has been analyzed with the Jerne technique to determine plaque-forming cells and with isotopic methods to measure rates of nucleic acid synthesis. This drug suppression has been found to consist of two components. The first is nonspecific injury to the lymphoid system caused by the cytotoxic drug and is related to the proportion of spleen cells killed. The second is antigen-specific immunological tolerance and appears to correlate with profound depression of deoxyribonucleic acid synthesis in the surviving cells. This tolerance is thought to be most consistent with a mechanism in which antigenic stimulation in the presence of cyclophosphamide-inhibited DNA synthesis and mitosis leads to the elimination or death of the specific immunological clone.

Tolerance induction with cyclophosphamide is associated with loss of the 19S hemolysin plaques which are seen in nonstimulated mouse spleen, implicating these cells in immune responsiveness. The ability to induce tolerance is lost on the 3rd postantigen day at the end of a 24-hr period in which 19S cells have increased 8-fold and 7S cells 200-fold. The data suggest that loss of sensitivity is due to the emergence on day 3 of drug-resistant plaque-forming cells, particularly those of the 19S variety. In the succeeding days after antigen injection there is a progressive increase in the resistance of plaque-forming cells to cyclophosphamide administration.
QUANTITATIVE STUDIES OF PHYTOHEMAGGLUTININ-INDUCED DNA AND RNA SYNTHESIS IN NORMAL AND AGAMMAGLOBULINEMIC LEUKOCYTES
Authors: Tormey Douglass C. , Kamin Roberta , Fudenberg H. Hugh
Published: June 2004

Leukocytes from nine patients with acquired agammaglobulinemia were studied in vitro. Synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) induced by phytohemagglutinin was measured by determination of the degree of incorporation of labeled precursor. Synthesis of both DNA and RNA was decreased in the agammaglobulinemic cells. The presence of an inhibitor in the patients' sera could not be demonstrated. These results suggest that the basic defect in agammaglobulinemia is cellular rather than humoral.
MECHANISMS OF THE INHIBITION OF CHEMOTAXIS BY PHOSPHONATE ESTERS
Authors: Ward Peter A. , Becker Elmer L.
Published: June 2004

Studies in the time course of the response of rabbit polymorphonuclear leukocytes (PMN's) to the complement-associated chemotactic factor have revealed that the response is virtually complete by 60 min with less than 15% additionally responding cells thereafter.

Phosphonate esters with a well defined capacity to inhibit serine esterases have been used to study the cell-associated enzymes of the rabbit PMN required for the chemotactic response. Two types of inhibition of the cell response to the chemotactic factor have been found: (a) cell-dependent inhibition occurring as a result of pretreatment of PMN's with phosphonate esters; and (b) chemotactic factor-dependent inhibition demonstrated only when the phosphonate ester is present during the chemotactic response.

Differences were found in these two modes of inhibition caused by various phosphonates, in terms of their time course of inhibition, in the dose response curves, and in the structure-activity relationships.

It has been conclusively demonstrated that the phosphonate esters have no direct inhibitory effect on the chemotactic factor. This has been shown by retention of activity of the chemotactic factor following incubation with phosphonate esters and subsequent removal by dialysis. In addition, the activity of the chemotactic factor and its physical-chemical characteristics in density gradient ultracentrifugation were unaltered in the continued presence of a potent phosphonate inhibitor of chemotaxis.

The uptake of the dye trypan blue was studied in cells treated with phosphonate in such a manner to induce cell-dependent inhibition of chemotaxis. Even when 84% cell-dependent inhibition of chemotaxis occurred, no uptake of the dye by leukocytes was found. Thus, phosphonate-induced inhibition of cell responsiveness in chemotaxis was not associated with generalized cell damage as defined by exclusion of the dye.

It is concluded that cell-dependent inhibition is due to the presence of a cell-bound esterase which is already activated and thus susceptible to inhibition by phosphonate esters before contact of the cell with the chemotactic factor. The second type of inhibition, chemotactic factor-dependent inhibition, is considered due to a cell-bound esterase which becomes susceptible to inhibition by phosphonate esters only after contact of the PMN with the chemotactic factor. It is postulated that the chemotactic factor activates this phosphonate-resistant precursor making it susceptible to the inhibitory action of the phosphonate ester.
THE EFFECT OF CROSS-REACTING ANTIGENS ON THE TOLERANT STATE
Authors: Cinader B. , St. Rose J. E. M. , Yoshimura M.
Published: June 2004

Rabbits were rendered tolerant to human albumin (HA) and were then injected with azo and oxazolonated derivatives of human albumin. These injections were continued to a time at which all animals would have lost tolerance if they had not been injected. Injection of cross-reacting antigens prolonged the duration of tolerance, as judged by the mode of elimination of lightly iodinated human albumin (HA.131I). Different derivatives of HA differed in their capacity to prolong tolerance.

Those neonatally injected rabbits which were immunized with cross-reacting antigens and lost tolerance, responded much more promptly to HA.131I than animals which were not immunized. Animals immunized with cross-reacting antigen which went on to eliminate HA.131I triphasically, usually had responded earlier by making antibodies. These antibodies contained a fraction which was reactive with HA, and which was usually equally well adapted to determinants on HA and on the cross-reacting antigen.
IMMUNOCHEMICAL STUDIES ON THE GROUP AND TYPE ANTIGENS OF GROUP F STREPTOCOCCI AND THE IDENTIFICATION OF A GROUPLIKE CARBOHYDRATE IN A TYPE II STRAIN WITH AN UNDESIGNATED GROUP ANTIGEN
Authors: Michel Marc F. , Krause Richard M.
Published: June 2004

Two antigens, the group-specific carbohydrate and the Type II carbohydrate, have been isolated by cellulose column chromatography from a formamide extract of a Group F streptococcus. Chemical and immunologic analyses indicate that both antigens are free of other cellular components. Both antigens are components of the cell wall although the Type II antigen is probably more superficial than the group antigen. The Type II antigen is composed of rhamnose, glucose, galactose, and galactosamine. The Group F antigen is composed of rhamnose, glucose, galactosamine and a small percentage of glucosamine.

A grouplike carbohydrate and the Type II carbohydrate have been isolated from a streptotoccal strain which lacks a serologically detectable streptococcal group antigen. This grouplike carbohydrate, which does not cross-react immunologically with Group F serum, is composed of rhamnose, galactose, and glucosamine.

No chemical or immunological differences were observed between the Type II antigen isolated from the Group F strain and the Type II antigen isolated from the nongroupable strain.
THE EFFECT OF PASSIVELY ADMINISTERED ANTIBODY ON ANTIBODY SYNTHESIS
Authors: Dixon Frank J. , Jacot-Guillarmod Hubert , McConahey Patricia J.
Published: June 2004

Suppression of the primary response of rabbits to intravenously administered KLH can be achieved with very small amounts of hyperimmune anti-KLH administered a day later since the rabbit apparently rapidly eliminates most of the KLH by nonimmunologic means. The amount of passive anti-KLH needed to achieve immunosuppression was directly proportional to the dose of injected antigen.

Antibody passively administered as much as 6–8 days after antigen still can be strongly immunosuppressive, which suggests that the antibody must be reacting with immunogen in or on responding cells or perhaps in the process of transfer between cells.

There was no evidence that the presence of passively administered hyperimmune anti-KLH prior to the injection of antigen had any immunosuppressive action beyond the direct neutralization of the injected antigen.

When KLH was injected in Freund adjuvant, anti-KLH incorporated with the KLH in the adjuvant was much more efficient in causing immunosuppression than anti-KLH given intravenously.

The primary responses to 2 mg KLH given intravenously and 2 µg given in adjuvant reached approximately equal peaks and were suppressible by comparable amounts of intravenously administered anti-KLH.

Two observations suggest that passive antibody neutralizes the immunogenic stimulus at the level of individual antigenic determinants and not merely by aggregating or precipitating entire antigenic molecules. First, anti-abalone hemocyanin (AH) which cross-reacts approximately 50% with KLH was only partially immunosuppressive even in extremely large amounts, i.e., amounts which could react with and precipitate much more KLH than could the smaller but more suppressive doses of anti-KLH. Second, when KLH and anti-KLH were given together in adjuvant, effective immunosuppression was achieved only with amounts of anti-KLH sufficient to saturate or cover virtually all available antigenic determinants.

The immunosuppressive quality of passive antibody increases with time after immunization and with repeated immunization of the donor. In view of their relatively weak immunosuppressive properties, antibodies formed in the first weeks of a primary response may not contribute significantly to the turning off of the antibody response. In any event, results obtained by passive transfer of hyperimmune antibody to animals early in a primary response cannot be applied to the natural events in a primary response.