bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON TUBERCULIN FEVER
Authors: Hall William J. , Francis Lorraine , Atkins Elisha
Published: June 2004

Utilizing techniques of passive transfer, we have investigated the factors responsible for production of fever when tuberculin is given intravenously to specifically sensitized rabbits.

The ability to develop a febrile response to tuberculin could be passively transferred to normal recipients with viable mononuclear cells from peritoneal exudates, spleen, or lymph nodes of donor rabbits sensitized with BCG. Sensitivity was usually apparent 48 hr after transfer, maximal at 7 to 14 days, and rapidly declined thereafter. Granulocytes and nonviable, sonicated, mononuclear cells from similarly sensitized donors were unable to transfer this form of reactivity.

Passive transfer of reactivity was also effected with plasma and serum, suggesting that the reaction of antibody with antigen contained in tuberculin is one of the initial steps by which the host cells are activated to release the endogenous pyrogen (EP) that mediates this form of hypersensitivity fever.

An intravenous infusion of granulocytes, as well as of several types of mononuclear cells from sensitized donors, made most recipients responsive to the pyrogenic effect of old tuberculin (OT) given 2 hr later. Some of these passively transferred cells, such as the granulocyte and alveolar macrophage, may be activated in vivo by OT, as they are in vitro. However, in the case of splenic and lymph node cells that cannot be activated by OT to produce EP in vitro, it seems likely that an intravenous injection of OT causes these transferred, sensitized cells to liberate an intermediate substance that either directly, or in association with antigen, activates the host's normal cells to produce EP.

In support of previous suggestions that leukocytes of several types, as well as phagocytic cells of the reticuloendothelial system, serve as potential sources of EP in tuberculin-induced fever, evidence was presented that OT also activates both granulocytes and mononuclear cells from sterile exudates of BCG-sensitized donors to produce EP in vitro.
SYNTHESIS, ASSEMBLY, AND SECRETION OF GAMMA GLOBULIN BY MOUSE MYELOMA CELLS
Authors: Laskov Reuven , Scharff Matthew D.
Published: June 2004

MPC-11 myeloma tumor cells were adapted to growth in continuous culture. The cultured cells resembled the parent tumor in that they produced the fully assembled gamma globulin molecules as well as six unassembled molecules. Although cultured and tumor cells synthesized excess light chains, the molar ratio of light (L) to heavy (H) chains was approximately 1.7:1 in the culture, and 3.5:1 in the tumor. The cultured cells also produced fewer half molecules and free light chains than the parent tumor. Peptide column analysis did not reveal differences in the primary structure of the H chains derived from the parent tumor and the culture. The L chains may have differed by a minor peptide.

As much as 20% of the newly labeled cytoplasmic proteins and almost 100% of the proteins secreted by the cultured myeloma cells could be precipitated by specific antiserum. The immune precipitates contained seven different gamma globulin molecules, six of which were characterized according to their molecular size and H and L chain content as fully assembled molecules (H2L2), heavy chain dimers (H2), half molecules (HL), H, light chain dimers (L2), and L chains.

All gamma globulin subunits as well as the complete H2L2 molecule were produced and secreted by splenic clones of the parent MPC-11 tumor, and agar clones of the cultured cells. This indicates that the various gamma globulin subunits were produced by the same cell and did not reflect cellular heterogeneity with respect to gamma globulin synthesis.
ASSOCIATION OF LACTOFERRIN WITH SPECIFIC GRANULES IN RABBIT HETEROPHIL LEUKOCYTES
Authors: Baggiolini M. , de Duve C. , Masson P. L. , Heremans J. F.
Published: June 2004

Lactoferrin has been identified in rabbit heterophil leukocytes on the basis of its immunological reactivity, electrophoretic mobility, acid-resistant iron-binding properties, and spectral characteristics.

Leukocyte lactoferrin was found to be exclusively localized in the specific (secondary) granules, which have been resolved from other subcellular components by zonal differential centrifugation and by isopycnic equilibration.
THE ROLE OF IMMUNOGENICITY IN THE INDUCTION OF TOLERANCE WITH CONJUGATES OF ARSANILIC ACID
Authors: Collotti Clelia , Leskowitz Sidney
Published: June 2004

A number of azobenzenearsonate (ABA) conjugates have been prepared and tested for ability to react with antibody, to sensitize for hapten-specific delayed hypersensitivity and to induce hapten-specific unresponsiveness. All conjugates tested by in vitro or in vivo methods show a capacity to react with preformed antibody. Conjugates of L-amino acid polymers are immunogenic and induce tolerance. Conjugates of D-amino acid polymers or conjugates with high density of ABA groups are nonimmunogenic and fail to induce tolerance.

Since paired D- and L-polymer conjugates react comparably with preformed antibody but differ markedly in tolerance induction, it is argued that combination with an antibody-like receptor molecule on the surface of an immune-competent cell is not a sufficient condition for tolerance. The lack of effectiveness of sterically crowded conjugates as well as D-polymer conjugates argues for a preliminary biologic "processing" of antigen necessary for induction of immunity or tolerance. Such a processing event might well involve enzymatic attack on the antigen.
THE IMMUNOGENICITY OF ANTIGEN BOUND TO THE PLASMA MEMBRANE OF MACROPHAGES
Authors: Unanue Emil R. , Cerottini Jean-Charles
Published: June 2004

Macrophages were cultured for several hours after a brief exposure to radio-iodinated keyhole limpet hemocyanin. Most of the hemocyanin taken up by the macrophages was rapidly catabolized and eliminated from the cell. A few molecules were retained on the plasma membrane of the cells for prolonged periods and were not subject to endocytosis and catabolism. These few molecules of hemocyanin bound to the plasma membrane were identified by observing the fixation of antibody fragments to macrophages at low temperature. The membrane-bound antigen, which could be removed by trypsin or EDTA, was of large molecular size, though heterogeneous. A great part of the immune responses of mice to hemocyanin bound to live macrophages could be abrogated by treatment of the macrophages in vitro with antibody or trypsin. Hence, most of the immunogenicity of hemocyanin bound to macrophages was attributed to the few molecules of antigen bound to the plasma membrane.
IN VITRO INTERACTION OF MOUSE HEPATITIS VIRUS AND MACROPHAGES FROM GENETICALLY RESISTANT MICE
Authors: Shif Ilan , Bang Frederik B.
Published: June 2004

A variant mouse hepatitis virus MHV(C3H) to which cultured peritoneal macrophages from both PRI and C3H mice were susceptible was isolated from stocks of the MHV(PRI) strain of mouse hepatitis virus. It was cloned on C3H macrophage monolayers and killed both adult PRI and C3H mice when injected intraperitoneally. This new variant was antigenically indistinguishable from the wild type virus. While the emergence of the variant virus was delayed in the course of infecting C3H macrophages with large inocula of MHV(PRI), the second passage grew to a high titer in both cell types without delay. Thus, adaptation to the new host was immediate. Interference, apparently not interferon-mediated, between the two variant viruses may have been the cause for the delay in the emergence of the variant virus. The delayed destruction of C3H-cultured macrophages by large inocula of MHV(PRI) uniformly resulted in the emergence of MHV(C3H). Whether the new variant emerged as a result of a selection of a pre-existing stable mutant or was conditioned by "growth" in the resistant host was not determined.
BACTERICIDAL SUBSTANCE FROM STAPHYLOCOCCUS AUREUS
Authors: Dajani Adnan S. , Gray Ernest D. , Wannamaker Lewis W.
Published: June 2004

A bactericidal substance previously isolated from phage type 71 Slaphylococcus aureus has been further identified and characterized. Staphylococci belonging to phage type 71 produce the substance in higher titers than staphylococci lysed by other phages in group II in addition to phage 71. Other staphylococci do not produce the bactericidal substance. The bactericidal substance shares several of the properties of bacteriocins but differs from this group of antibiotic substances in some respects. A combination of ammonium sulfate fractionation and gel filtration on a Sephadex G-100 column resulted in considerable degree of purification of the bactericidal substance. The substance is a previously unrecognized product of S. aureus and is distinct from other extracellular products of this organism.
THE NATURE OF COLICIN K FROM PROTEUS MIRABILIS
Authors: Jesaitis Margeris A.
Published: June 2004

The colicinogenic factor K has been transferred from E. coli K 235 to Proteus mirabilis. The DNA of the colicinogenic Proteus has been shown to contain a small amount of a satellite DNA which presumably harbors the Col K factor.

In the presence of mitomycin C the colicinogenic Proteus secretes colicin K into the growth medium. The bacteriocin has been purified by chromatography and obtained as an immunologically homogeneous substance unconjugated with other antigens of the Proteus bacillus.

Proteus colicin K is a protein of relatively low molecular weight. It contains all of the usual amino acids except cysteine and is free of lipids and polysaccharides. The bacteriocin can be separated by electrofocusing into two major components. The latter have the same biological properties but differ in their specific electrical charges.
THE ROLE OF THE LYMPHATIC SYSTEM IN THE REJECTION OF HOMOGRAFTS: A STUDY OF LYMPH FROM RENAL TRANSPLANTS
Authors: Pedersen Niels C. , Morris Bede
Published: June 2004

The rejection of renal homografts has been studied in sheep by transplanting kidneys into the neck and preserving the renal lymphatic drainage intact. Chronic fistulae were established in the transplanted renal lymphatics and lymph collected throughout the life of the graft.

The changes that occurred in homografts during the process of rejection were reflected in changes in the lymph. Large numbers of basophilic, blast, lymphoid cells appeared in the lymph, and lymph production in the grafted kidney increased 20–50 fold. Over a period of about 10 days, up to 60 g wet weight of lymphoid cells and up to 10 liters of lymph were collected from the graft.

Within 24 hr of grafting, the host cells present in the renal lymph had become sensitized to the graft and transformed into blast cells when cultivated in Millipore chambers in vitro. When the cells leaving the graft during the first 18–48 hr were injected into distant nonstimulated lymph nodes of the host sheep, they evoked significant cellular and antibody responses in the nodes.

Within the graft, the main pathological changes were found in the vascular endothelium and many of the peritubular capillaries become plugged with emboli comprised of blast cells. There was extensive infiltration of the renal parenchyma with lymphoid cells and evidence of their transformation and proliferation within the renal blood capillaries.

When all the lymph and cells leaving the homograft were diverted from the body, there was a greatly decreased reaction in the regional prescapular lymph node, and no reaction in lymph nodes distant from the graft. In these circumstances, the survival of the graft was not prolonged, and it was rejected without involvement of the lymph nodes of the host.

Humoral antibody was produced in the lymph node regional to the homograft within 48–60 hr of grafting. Antibody was not detected in the blood or in the renal lymph until near to the time the graft was rejected. It was thought that this was due to the binding of antibody by the kidney graft tissue.

We conclude that all the events which lead to the recognition and rejection of renal homografts can occur centrally within the graft itself.
AUGMENTATION OF THE VIRULENCE OF MURINE COXSACKIE-VIRUS B-3 MYOCARDIOPATHY BY EXERCISE
Authors: Gatmaitan Bienvenido G. , Chason Jacob L. , Lerner A. Martin
Published: June 2004

Coxsackievirus B-3 myocardiopathy was induced in weanling mice by intraperitoneal and intracerebral inoculations of the Nancy strain. Acute mortality was 5.5%. The cardiomyopathy is characterized by an early phase lasting about 9 days with myocardial necrosis, associated inflammation, and healing by fibrosis and calcification involving 25 to 50% of the contractile fibers in each affected mouse. Infectious coxsackievirus may be recovered from the heart during this phase. Continuing myocardial inflammatory lesions follow during the later phase, but infectious virus is no longer present.

When mice were forced to swim in a preheated pool (33°C) during both phases of their myocardiopathy, virulence was strikingly augmented. Fully half of the mice died of congestive failure, the majority while swimming. Hearts were dilated, hypertrophied, and grossly necrotic. The myocardium was transformed to a completely necrotic, inflammatory, calcifying mass.

At the peak of the infectious phase, myocardial replication of coxsackievirus was increased 530 times in nurslings which had been forced to swim. Myositis in hind limbs was more frequent, and inflammatory lesions in perirenal and pericardial fat were more severe in the mice which were forced to swim.

When swimming was begun on the 9th day after infection, the virulence and lethality (13.8%) of infection were moderately increased.
DETECTION OF SIMULTANEOUS ANTIBODY SYNTHESIS IN PLASMA CELLS AND SPECIALIZED LYMPHOCYTES IN RABBIT LYMPH NODES
Authors: Avrameas Stratis , Leduc Elizabeth H.
Published: June 2004

Antibody to horseradish peroxidase was localized by electron microscopic immunocytochemistry in cells of the popliteal lymph nodes of the rabbit after a single injection of antigen with complete Freund's adjuvant and after a second antigen administration. Synthesis of antibody, chiefly of 7S type, occurred simultaneously in two types of cells: large, clear, fixed, typical plasma cells, and small, dense, circulating cells which exhibit morphological characteristics of both small lymphocytes and plasma cells. We call the latter "lymphoplasmacytes" and propose that they arise from small lymphocytes. They secrete antibody by clasmatosis and continue to develop an elaborate endoplasmic reticulum after specific antibody synthesis ceases. In the presence of an additional antigenic stimulation, a second cycle of antibody synthesis may begin around the nucleus in the same cell, with antibody accumulating in the perinuclear space sometimes even before the previously synthesized antibody has been entirely secreted at the cell periphery. On this basis, we propose that the lymphoplasmacyte is a memory cell and that memory and antibody synthesis are two different activities of the same cell. The appearance of a small amount of 19S antibody may be correlated with the presence of a small number of antibody-containing, large lymphocytes.
AUSTRALIA ANTIGEN (A HEPATITIS-ASSOCIATED ANTIGEN)
Authors: Millman Irving , Loeb Lawrence A. , Bayer Manfred E. , Blumberg Baruch S.
Published: June 2004

Australia antigen [Au(1)], a particle associated with viral hepatitis, was isolated from the plasma of a patient with chronic anicteric hepatitis and leukemia who had received radioactive phosphorus.

We have found that the immunoreactivity and appearance of Au(1) in the electron microscope were not altered by treatment with enzymes including trypsin, pronase, lipase, phospholipase C, ribonuclease, deoxyribonuclease, amylase, and neuraminidase. In contrast, other serum constituents were degraded by these enzymes. Therefore, treatment of the patient's plasma with many enzymes was exploited as an initial step for the isolation of Au(1). Subsequently, Au(1) was purified from the enzyme-treated 32P-labeled plasma by gel filtration through Sephadex G-200 and centrifugation through sucrose and in cesium chloride gradients. There were no detectable human serum components in the purest fractions, as tested by immunoelectrophoresis and immunodiffusion. The density of the purified Au(1) was 1.21 in CsCl. The particle measured about 200 A in diameter, was predominantly spherical in shape and appeared to be composed of subunits. Nucleic acids were not detected by spectrophotometric, radiochemical, and chemical analyses. Immunoreactivity of purified Au(1) was destroyed by heating for 1 hr at 85°C but was stable at 56°C. Treatment with Carnoy's solution (3 parts ethanol:1 part glacial acetic acid) followed by pronase disrupted the particles as seen with the electron microscope. These findings, combined with other published information on Australia antigen and viral hepatitis, suggest that the bulk of Australia antigen in the blood of this patient is an incomplete virus or virus capsid.
PEYER'S PATCHES: IMMUNOLOGIC STUDIES
Authors: Henry Claudia , Faulk W. Page , Kuhn Lotte , Yoffey J. M. , Fudenberg H. Hugh
Published: June 2004

The immune capabilities of the Peyer's patches have been investigated by the use of an in vitro system.

Despite our failure to stimulate Peyer's patch lymphocytes in vivo it appears that Peyer's patches behave immunologically as peripheral lymphoid tissues.

Cultures prepared from the dissociated Peyer's patches of normal rabbits respond to sheep erythrocytes. The response is comparable to that obtained with spleen cultures from the same animals and is not dependent on the presence of the epithelial cells which line the lumen. Similar thymic cultures do not respond.

Our experiments with cultures prepared from rabbits which have received one or two injections of SRC show that the Peyer's patches contain both IgM and IgG "memory" cells which have migrated from the spleen. The concentration of these cells in the spleen remains several hundredfold higher.
MORPHOLOGIC CHANGES ACCOMPANYING SENESCENCE OF CULTURED HUMAN DIPLOID CELLS
Authors: Robbins E. , Levine E. M. , Eagle H.
Published: June 2004

The lysosomes of serially propagated human fibroblasts gradually transform to residual bodies which increase in number and size, and show progressive degenerative changes. There is an accompanying, and less regular, decrease in the number of cytoplasmic polyribosomes and an increased number of glycogen particles. The onset of these morphologic alterations occurs shortly after culture initiation and precedes any marked decrease in the rate of cellular growth; however, in their extreme form these changes may be related to the ultimate cessation of cellular multiplication ("senescence"). The lysosomal changes were seen only in those cell strains which eventually showed senescence, and were absent or minimal either in cell lines which can be propagated indefinitely ("spontaneous" and viral transformants, cancer cells), or in skin sections from aging subjects.
MECHANISM OF EOSINOPHILIA
Authors: Basten Antony , Beeson Paul B.
Published: June 2004

A possible role for the lymphocyte in the mechanism of eosinopoiesis has been examined.

Procedures known to deplete or inactivate the pool of recirculating lymphocytes such as neonatal thymectomy, administration of antilymphocyte serum, and prolonged thoracic duct drainage, either singly or in combination, resulted in a highly significant reduction in the eosinophil response to trichinosis.

Irradiated animals exposed to parasitic challenge did not develop eosinophilia unless reconstituted with lymphocytes as well as bone marrow cells. When "memory" cells were used instead of normal lymphocytes, a "secondary" type of eosinophil response was observed.

Transfer of a primary eosinophilia was achieved adoptively with a population of living large lymphocytes from thoracic duct lymph and peripheral blood, but not with blood plasma or cell-free lymph. The potency of the active lymphocytes was not impaired by enclosing them in cell-tight diffusion chambers, indicating that they exerted an effect on bone marrow by agency of a diffusible factor.

The demonstration of a role for lymphocytes in induction of the eosinophil response to this kind of stimulus supports the conclusion that eosinophilia belongs in the category of immunologic phenomena.
STUDIES ON THE ULTRASTRUCTURE OF BORDETELLA PERTUSSIS
Authors: Morse Jane H. , Morse Stephen I.
Published: June 2004

Two distinct particles have been recognized in the extracellular fluid of B. pertussis cultures. Both appeared to arise from the surface (cell wall) of the organism.

One of these, a membranous particle, seemed to derive from long projections on the organism composed of the outer membrane of the cell wall.

The second particle, a fine filament, was not readily comparable with any previously described bacterial structure.

The two particles could be separated from each other by gradient centrifugation in CsCl.

Lymphocytosis-promoting factor and histamine-sensitizing activity were only associated with fractions containing the fine filaments.
AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS
Authors: Streilein J. Wayne , Billingham R. E.
Published: June 2004

F1 hybrid hamsters derived from genetically disparate strains develop a severe and often lethal cutaneous disorder when inoculated intracutaneously with immunologically competent lymphoid cells from either parental strain, The disease is characterized clinically by extensive epidermal necrolysis, and histologically by a complete dissolution of the dermal-epidermal junction. The requisites for elicitation of this syndrome were determined to be: (a) the parental strains must differ from each other at a major histocompatibility locus, and (b) the donor inoculum must contain immunologically competent parental strain cells. In addition it was found that specifically sensitized cells surpassed normal unsensitized ones in their ability to elicit the disease, and that the disease can be transferred adoptively from affected to normal F1 hosts by means of lymphoid cells. On the basis of these observations, it was concluded that the disease was immunologic in nature, and graft-versus-host in type. However, a series of critical studies failed to demonstrate that the epidermolysis had an immunogenetically specific basis, thus invalidating the provisional assumption that this lesion resulted from a direct immunologic attack upon parenchymal cells of the epidermis and dermis. With the aid of radiation chimeras, it was clearly established that typical epidermolysis could be induced in skin of the same genetic constitution as the attacking donor lymphoid cells. This paradox was taken into account by the possibility that, amid the intense local cutaneous graft-versus-host reactions, "skin-specific" antigenic determinants are bared which incite a quasi autoimmune response that in turn is responsible for the epidermolytic lesions.
AN ANALYSIS OF GRAFT-VERSUS-HOST DISEASE IN SYRIAN HAMSTERS
Authors: Streilein J. Wayne , Billingham R. E.
Published: June 2004

The epidermolytic syndrome that can be obtained at will in F1 hybrid hamsters by the cutaneous inoculation of adequate doses of parental strain lymphoid cells has been investigated to determine whether the cutaneous lesions are due to an autoimmune process arising from the severe, initial GVH reactions in the skin. It was amply demonstrated that inoculation of donor cells into the skin was of crucial importance to the development of epidermolysis. Parental strain lymphoid cells in similar doses delivered by any other route into normal F1 hybrids failed absolutely to incite the acute syndrome. If "immune lymphocyte transfer" reactions incited by donor cells in the host's skin were surgically removed at timed intervals after inoculation, only complete excision within 24 hr prevented the appearance of epidermolysis in F1 hybrid hosts, indicating that inoculated donor cells must remain within the confines of the skin for approximately 24 hr in order to evoke the disease, persistence for longer periods of time being unnecessary for the subsequent course of the disease. However, reconstitution experiments involving the intramuscular inoculation of suspensions containing mixtures of donor cells and host lymphoid cells, in the presence or absence of epidermal cells, unequivocally indicated that no intimate exposure of lymphoid cells to putative skin-specific antigens was essential. Similarly, the elicitation of generalized epidermolysis in F1 hybrids irradiated with 300 r and then inoculated intravenously with donor cells casts further doubt on the pathogenic importance of the skin as a source of tissue-specific antigen.

The results of subsequent experiments indicated that host leukocytes, rather than parenchymal cells of the dermis or the epidermis, were important contributors of the transplantation antigenic stimulus. Moreover, a series of experiments, using (CB x MHA)F1 hybrid hosts that had been lethally irradiated and reconstituted with bone marrow cells from ALS-treated MHA donors, indicated that from 6 to 10 wk after reconstitution—when direct and immune lymphocyte transfer reactions showed a virtual absence of native F1 leukocytes from the circulation—donor cells obtained from specifically sensitized MHA donors were completely ineffective in inducing epidermolysis, while equivalent lymphoid cell inocula derived from CB donors evoked the cutaneous disease irrespective of the time elapsed since reconstitution.

To explain these findings it is postulated that in hamsters, the primary targets in graft-versus-host disease incited by the intracutaneous inoculation of donor cells are leukocytes originating in bone marrow or lymph node, or both.
AN ANALYSIS OF THE SEQUENCES OF THE VARIABLE REGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIR IMPLICATIONS FOR ANTIBODY COMPLEMENTARITY
Authors: Wu Tai Te , Kabat Elvin A.
Published: June 2004

In an attempt to account for antibody specificity and complementarity in terms of structure, human κ-, human λ-, and mouse κ-Bence Jones proteins and light chains are considered as a single population and the variable and constant regions are compared using the sequence data available. Statistical criteria are used in evaluating each position in the sequence as to whether it is essentially invariant or group-specific, subgroup-specific, species-specific, etc.

Examination of the invariant residues of the variable and constant regions confirms the existence of a large number of invariant glycines, no invariant valine, lysine, and histidine, and only one invariant leucine and alanine in the variable region, as compared with the absence of invariant glycines and presence of three each of invariant alanine, leucine, and valine and two each of invariant lysine and histidine in the constant region. The unique role of glycine in the variable region is emphasized. Hydrophobicity of the invariant residues of the two regions is also evaluated. A parameter termed variability is defined and plotted against the position for the 107 residues of the variable region. Three stretches of unusually high variability are noted at residues 24–34, 50–56, and 89–97; variations in length have been found in the first and third of these. It is hypothesized that positions 24–34 and 89–97 contain the complementarity-determining residues of the light chain—those which make contact with the antigenic determinant. The heavy chain also has been reported to have a similar region of very high variability which would also participate in forming the antibody-combining site. It is postulated that the information for site complementarity is contained in some extrachromosomal DNA such as an episome and is incorporated by insertion into the DNA of the structural genes for the variable region of short linear sequences of nucleotides. The advantages and disadvantages of this hypothesis are discussed.
CARRIER FUNCTION IN ANTI-HAPTEN IMMUNE RESPONSES
Authors: Katz David H. , Paul William E. , Goidl Edmond A. , Benacerraf Baruj
Published: June 2004

Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 µg of BGG is more effective than a dose of 50 µg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for ϵ-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization.

These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.
SOME BIOLOGICAL PROPERTIES OF PNEUMOCOCCUS TYPE 37 AND THE CHEMISTRY OF ITS CAPSULAR POLYSACCHARIDE
Authors: Knecht Judith C. , Schiffman Gerald , Austrian Robert
Published: June 2004

Pneumococcus Type 37, like pneumococcus Type 3, is characterized by the production of large mucoid colonies on the surface of solid media and by its very large capsule. It differs from the highly virulent pneumococcus Type 3 in that it is only slightly virulent for mice and rats and is isolated infrequently from man. A study of the behavior of pneumococcus Type 37 in systems comparable to those used in the study of pneumococcus Type 3 and an examination of the chemical structure of the capsule of pneumococcus Type 37 are described. The capsular polysaccharide of pneumococcus Type 37 is a viscous, optically inactive polymer composed of 95% hexose. Glucose is obtained in 88% yield upon acid hydrolysis. Periodate oxidation studies and the behavior of the polysaccharide on acid hydrolysis suggest that the molecule consists of a core of repeating units of 1,3 glucosyl-glucose to which short chains of glucose are attached at frequent intervals. Isolation of a disaccharide, the properties of which are identical with those of sophorose (ß1 → 2 glucosyl-glucose), and of a trisaccharide are described. A tentative structure for the capsular polysaccharide of pneumococcus Type 37 is proposed.
DELAYED HYPERSENSITIVITY-TYPE GRANULOMA FORMATION AND DERMAL REACTION INDUCED AND ELICITED BY A SOLUBLE FACTOR ISOLATED FROM SCHISTOSOMA MANSONI EGGS
Authors: Boros Dov L. , Warren Kenneth S.
Published: June 2004

A soluble material has been isolated from schistosome eggs which in minute quantities without the addition of adjuvant induces sensitization to a delayed hypersensitivity type of granuloma forming around intact schistosome eggs. This material is secreted by intact eggs and is found in high concentration in the fluid released during the hatching process. When adsorbed to bentonite particles this substance elicits hypersensitivity type granuloma formation in specifically sensitized animals. The granuloma sensitizing factor also both induces and elicits delayed footpad swelling in mice. Quantities which sensitize with respect to these delayed type reactions do not induce antibody formation detectable by a sensitive hemagglutination. technique within the duration of the above experiments.
THE RELATIVE IMPORTANCE OF BLOOD MONOCYTES AND FIXED MACROPHAGES TO THE EXPRESSION OF CELL-MEDIATED IMMUNITY TO INFECTION
Authors: North R. J.
Published: June 2004

Infection in mice with Listeria monocytogenes results in a substantial accumulation of migrant macrophages in the liver. The immigrant cells populate both the infective foci and intervening sinusoids. They have the labeling characteristics of blood monocytes, and their appearance in infective foci in the liver corresponds to the expression of a high level of antimicrobial immunity in this organ. The infected liver acquires additional new macrophages by Kupffer-cell division. The proliferation of these cells, however, is not essential for the expression of immunity in the liver. The results indicate that the macrophages which express immunity to a primary infection with L. monocytogenes are those derived from circulating monocytes. Most of these cells are quickly lost once the parasite is eliminated from the tissues.
CUTANEOUS BASOPHIL HYPERSENSITIVITY
Authors: Dvorak Harold F. , Dvorak Ann M. , Simpson Blanche A. , Richerson Hal B. , Leskowitz Sidney , Karnovsky Morris J.
Published: June 2004

Delayed onset erythematous skin reactions elicited in guinea pigs early in the course of sensitization with azobenzenearsonate-protein conjugates or with protein antigens in incomplete Freund's adjuvant or in saline were found to have a characteristic morphology which sets them apart from delayed hypersensitivity and the classic antibody mediated reactions. The principle feature was massive dermal infiltration with basophilic leukocytes. Mononuclear cells of several types including activated and small lymphocytes, monocytes, macrophages, and blast cells were also present. Such reactions have in the past been designated Jones-Mote hypersensitivity, but we prefer the descriptive term cutaneous basophil hypersensitivity (CBH) for the reasons given.

Occasional basophils extruded their granules, and individual granules, retaining their characteristic ultrastructure, were commonly seen in the interstitium. However, intercellular junctions between endothelial cells were closed except during cell emigration and there was no morphologic evidence of an histamine-like effect. The majority of basophils, moreover, did not degranulate but underwent nuclear pyknosis and cytoplasmic degeneration and were phagocytosed by macrophages. Phagocytosed basophil granules retained their ultrastructure.

Skin tests performed at late intervals after sensitization had a different time course and morphology. Animals sensitized with protein antigens in complete Freund's adjuvant developed delayed hypersensitivity; however, reactions elicited in such animals at early (but not late) intervals after sensitization contained a prominent basophil component. We interpret such reactions to be a mixture of delayed hypersensitivity and cutaneous basophil hypersensitivity. The function of the basophil in CBH and its relation to the mononuclear cells which accompany it are unknown, and various possibilities are discussed.

We conclude that cutaneous basophil hypersensitivity is a distinct immunologic and morphologic entity, occurring early in the course of sensitization with protein antigens incorporated in any of several vehicles. The mechanism of the reaction is presently unknown, and a general hypothesis to explain its pathogenesis has been proposed.
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE
Authors: Cudkowicz G. , Shearer G. M. , Ito T.
Published: June 2004

Marrow cells and 5 x 107 thymocytes of unprimed (C57BL/6 x DBA/2)F1, (C57BL/10 x WB)F1 and (C3H x C57BL)F1 donor mice were mixed in vitro and transplanted into X-irradiated syngeneic hosts. Upon injection of sheep erythrocytes, splenic plaque-forming cells (PFC) secreting IgM (direct PFC or IgG (indirect PFC) hemolytic antibody were enumerated at the time of peak responses.

By grading the numbers of marrow cells, inocula were found that contained few immunocompetent cells reaching the recipient spleens, interacting with thymocytes or other accessory cells (or both), and generating PFC. The frequency of responses in BDF1 mice conformed to Poisson statistics, indicating that immunocompetent marrow cells participated in a single-hit interaction limiting PFC responses. The marrow cells assayed were not restricted for the antibody class (IgM versus IgG) to be secreted by mature PFC. Unrestricted marrow cells could have been either the precursors of PFC or accessory cells. Different results were obtained in BWF1 and C3BF1 mice. The frequency of responses in relation to the number of marrow cells grafted did not follow Poisson statistics, and the limiting cells were restricted for antibody class. Presumably, immunocompetent cells of these strains were more heterogeneous than those of BDF1 mice and participated in a multiplicity of cell-to-cell interactions. The strain differences reflected inherent properties of marrow cells and not influences of the environment in which PFC were produced. The results confirmed for bone marrow the heterogeneity of immunocompetent cells reported by others for spleen, and suggested that genetic factors such as "immune response" genes regulate cellular differentiation also for functions other than those related to antibody specificity.
IMPLANTATION, TRANSPLANTATION, AND EPITHELIAL-MESENCHYMAL RELATIONSHIPS IN THE RAT UTERUS
Authors: Beer Alan E. , Billingham R. E.
Published: June 2004

Free tail skin grafts or suspensions of viable epidermal cells have been placed in the atraumatized uterus of isologous rat hosts and allowed to "implant" of their own accord to study the possible uniqueness of this site for other than nature's transplants, i.e. conceptuses, and its response to unnatural grafts.

Despite the presence of an intact endometrial epithelium, free skin grafts heal-in rapidly, provided that a state of estrogen excess is established at the time of transplantation. In the absence of estrogen most of the grafts failed to implant. Once established, the grafts survive indefinitely without further estrogen. However, if at any stage a state of continual estrus is established, skin epidermis migrates centrifugally from the graft perimeter invasively replacing the native uterine epithelium.

The results of an analysis of the modus operandi of this estrogen-facilitated epidermal migration in utero sustain the view that the hormone acts upon the uterine stroma rather than upon the epidermal cells.

When grafts of lingual mucosa or vaginal "skin" were placed in the uteri of rats maintained in chronic estrus, migration of epidermis took place even more vigorously than from tail skin. These epithelia conserved their distinctive histologic specificities indefinitely when growing as heterotypic recombinants on the alien mesenchymal stroma of the uterus.

Monodisperse suspensions of epidermal cells appear to "implant" and establish small epidermal plaques in the uterus only at sites predestined to accept conceptuses.

That the endocrinologic parameters for the establishment of skin grafts in the uterus are similar to those for blastocysts is suggested by the finding that both kinds of graft can become established in the same uterine horn in the absence of exogenous hormones.
FURTHER STUDIES ON METACHROMASIA IN CULTURED HUMAN FIBROBLASTS
Authors: Danes B. Shannon , Scott J. E. , Bearn Alexander G.
Published: June 2004

Staining with Alcian blue in various concentrations of magnesium chloride (alcianophilia) has been found to be a useful supplement to metachromatic staining to detect increased cellular concentrations of glycosaminoglycans (mucopolysaccharides). In many instances alcianophilia at 0.3 M MgCl2 is more specific than metachromasia and does not give "false positives" sometimes found in normal individuals and in those with cystic fibrosis, Gaucher’s disease, familial amaurotic idiocy, and pseudoxanthoma elasticum. On the other hand, it gives a "false negative" reaction in the Sanfilippo syndrome (perhaps because the characteristically elevated glycosaminoglycan in this disease, heparan sulfate, is not synthesized by cultured skin fibroblasts), and in the Marfan syndrome. It detects the Maroteaux-Lamy syndrome, which metachromasia does not.

The "false positives" given by metachromasia in all six families studied thus far are genuine, reproducible reactions that can be traced through at least three generations of normal individuals within a family. There is therefore, in these families, a genetic factor that causes such metachromasia, but it is not increased glycosaminoglycan concentration.
THE KINETICS OF PROMONOCYTES AND MONOCYTES IN THE BONE MARROW
Authors: van Furth Ralph , Diesselhoff-den Dulk Martina M. C.
Published: June 2004

The mononuclear phagocytes of the bone marrow can be classified into two cell types, promonocytes and monocytes. The present study was performed to establish whether the promonocytes are the progenitors of the monocytes and to determine the kinetic characteristics of the promonocytes and monocytes in the bone marrow compartment.

Both in vitro labeling studies with thymidine-3H and determination of the relative amount of DNA in the nuclei of individual cells showed that under normal steady-state conditions the promonocytes are proliferating cells and the monocytes, nondividing cells.

In vivo labeling studies provided further evidence that the promonocytes are the progenitor cells of the monocytes. During the first 24 hr after labeling, the promonocytes showed a constant high level of labeling (about 70%). The mean grain count of these cells decreased with time.

The labeling index of the monocytes of the bone marrow increased during the first 24 hr after in vivo labeling, but during the same period the mean grain counts remained almost constant, with values amounting to about half those of the promonocytes during the first 6 hr of the experiment.

The data concerning the labeling indices and the percentage distribution ratio of the promonocytes and monocytes in the bone marrow, and the labeling indices of the peripheral blood monocytes are used to construct a model population. The results lead to the conclusions that the promonocytes are multiplicative cells and that both daughter cells arising from the division of a promonocyte are monocytes.

The DNA-synthesis time found for the promonocytes is 13.6 hr. From this value, the average generation time was computed to be 19.5 hr.
STUDIES ON SOME PHYSICOCHEMICAL PROPERTIES OF A THYMUS HUMORAL FACTOR CONFERRING IMMUNOCOMPETENCE ON LYMPHOID CELLS
Authors: Trainin Nathan , Small Myra
Published: June 2004

By means of an assay of graft-versus-host activity some properties of the thymic humoral factor which confers immunocompetence upon lymphoid cells in vitro have been studied. Allogeneic and xenogeneic thymic preparations were found to activate lymphoid cells from neonatally thymectomized mice, enabling initiation of a graft-versus-host response. Thus, this thymus factor is apparently neither strain nor species specific.

The active principle of calf thymus extracts was found to be in the supernatant after prolonged ultracentrifugation. When exhaustive dialysis and ultrafiltration through Diaflo membranes were performed, the active thymus agent was found to pass through both the dialysis sac and Diaflo UM-2 membranes. The molecule which confers immunocompetence upon lymphoid cells thus seems to be of molecular weight of an order of magnitude of 1000 or less. Dialyzed thymus preparations injected into neonatally thymectomized mice also restored the capacity of spleen cells of these mice to induce graft-versus-host activity. When injected into intact mice, thymus extract also increased the proportion of competent cells in the spleens of these animals, probably by activation of target cells originating outside the spleen.
LYSIS OF ERYTHROCYTES BY COMPLEMENT IN THE ABSENCE OF ANTIBODY
Authors: Götze Otto , Müller-Eberhard Hans J.
Published: June 2004

A new pathway of complement-mediated hemolysis has been described. It is independent of antibody and does not require binding of the first four complement components to the target-cell surface. The actual attack of the target cell begins with the attachment of C5, C6, and C7. The binding reaction is catalyzed by C4, 2, 3, an enzyme which may be formed in cell-free solution. C4, 2, 3 may effect binding of C5, 6, 7 by acting from the fluid phase or from the surface of another cell to which it is specifically bound (EAC 4, 2, 3). In either case, the resulting product is EC5, 6, 7 which is susceptible to lysis by C8 and C9.

Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) were particularly susceptible to lysis by the above described mechanism. PNH cells, but not normal human erythrocytes, could also be lysed through activation of complement by cobra factor. These observations allow the operational distinction of an activation and an attack mechanism of complement.
IN VITRO-INITIATED SECONDARY ANTI-HAPTEN RESPONSE
Authors: Bullock Wesley W. , Rittenberg Marvin B.
Published: June 2004

Decreasing antigen in vivo may preferentially stimulate cells with the potential for synthesis of high-affinity antibody through activation of surface receptors with similarly high affinity. This selection should result in cells with increased sensitivity to lower antigen concentrations, cells with greater avidity for antigen. We have followed the in vivo changes in anti-TNP memory-cell sensitivity by initiating the secondary anti-hapten response in vitro. This response was determined by anti-TNP plaque assay. The results indicate that cell populations with increased sensitivity for antigen continue to emerge with time after priming and that this sensitivity may increase 1000-fold in a 4 month period. Increased sensitivity to stimulation by antigen is concomitant with suppression by higher, previously stimulatory doses as in high zone immune tolerance. The data support the hypothesis that memory cells of high avidity result from the selective pressure of diminishing in vivo antigen concentration.
QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES
Authors: Brient Bruce W. , Nisonoff Alfred
Published: June 2004

Rabbit anti-idiotypic antibodies were prepared by injection of specifically purified anti-p-azobenzoate antibodies (D) from individual donor rabbits. Benzoate derivatives were found to be strong inhibitors of the reactions of D with anti-D antisera. There was a close correlation between the combining affinities of the benzoate derivatives used and their effectiveness as inhibitors. Compounds tested that are chemically unrelated to benzoate were ineffective. The results indicate either that the combining site of anti-benzoate antibody is part of an important idiotypic determinant, which is sterically blocked by hapten, or that the hapten induces a conformational change which alters idiotypic determinants not involving the active site. Such conformational changes, if they occur, must be restricted since hapten has little effect on the reactions of F(ab')2 fragments of anti-benzoate antibodies with antisera directed to rabbit fragment Fab and no detectable effect on reactions with antibodies directed to allotypic determinants.