bluuebunny/crossref_metadata_2025 huggingface dataset:
THE REQUIREMENT OF SERINE ESTERASE FUNCTION IN COMPLEMENT-DEPENDENT ERYTHROPHAGOCYTOSIS
Authors: Pearlman David S. , Ward Peter A. , Becker Elmer L.
Published: June 2004

The p-nitrophenyl ethyl phosphonate esters have been shown to inhibit complement-dependent erythrophagocytosis when exposed to guinea pig polymorphonuclear leukocytes prior to the initiation of phagocytosis. Inhibition of phagocytosis occurred in a manner characteristic of the well-defined capacity of phosphonate esters to inactivate serine esterases: inhibition was irreversible, dependent upon the temperature of reaction and pH of the reaction medium, and proportional to the concentration of inhibitor used and the duration of exposure between leukocytes and inhibitor. Phosphonate inhibition was further shown to be independent of any general cell damaging effects of the compounds used. The phagocytic enzyme inhibited by phosphonate esters apparently exists in or on leukocytes in an already activated state prior to the initiation of the phagocytic process.

The inhibitory profile of the activated phagocytic esterase was found to be essentially identical to the profile of inhibition previously obtained for the activated chemotactic esterase of rabbit polymorphonuclear leukocytes, suggesting that the same enzyme may function in both chemotaxis and phagocytosis. Various substrates including acetate esters reported to protect the activated chemotactic esterase from inhibition by phosphonate esters did not exhibit a clear protective effect in the phagocytic system and attempts to define the relationship between the two enzymes were unsuccessful.

Suggestive evidence was also obtained for the requirement of the function of a second, activatable esterase in the phagocytic process.
IMMUNOCOMPETENCE OF SPLEEN CELLS FROM NEONATALLY THYMECTOMIZED MICE CONFERRED IN VITRO BY A SYNGENEIC THYMUS EXTRACT
Authors: Trainin Nathan , Small Myra , Globerson Amiela
Published: June 2004

Impaired immunological competence of spleen cells from neonatally thymectomized C57B1/6 young adult mice was apparent when these cells were tested in an in vitro graft-versus-host assay. Spleen cell inocula prepared from thymectomized mice did not induce enlargement of (C3H/eb x C57BI/6)F1 newborn spleen explants, whereas the same number of cells from intact donors consistently initiated splenomegaly. Spleen enlargement was observed, however, when the explants were challenged by cells from thymectomized donors in the presence of syngeneic thymus extract, indicating that the spleen cells in suspension attained immunological competence under the influence of a non-cellular component of the thymus. Immunocompetence was also evident when the cells from thymectomized donors were first incubated with thymus extract for 1 hr and subsequently tested for reactivity. Cells from the same thymectomized donor mice exposed in parallel to extracts from syngeneic spleen or mesenteric lymph node at an equivalent protein concentration did not initiate a graft-versus-host response.

These experiments demonstrate that immune reactivity in the graft-versus-host response involves activation of lymphoid cells by a humoral factor of the thymus acting directly upon these cells.
IMMUNOLOGIC STUDIES OF WATER-SOLUBLE HUMAN AMYLOID FIBRILS
Authors: Franklin Edward C. , Pras Mordechai
Published: June 2004

Eight preparations of soluble amyloid and degraded amyloid (DAM) were compared immunologically. Unlike amyloid fibrils, six of eight preparations of DAM proved to be relatively strong immunogens. Antisera to DAM reacted weakly or not at all with normal human serum or extracts of normal tissues, but were specifically reactive with amyloid fibrils or DAM.

Comparative studies of DAM'S from eight different subjects showed some degree of cross-reactivity among them, yet demonstrated that they were not identical. Similar conclusions were obtained by quantitative precipitin and complement fixation analyses.

Comparison of the amyloid fibrils with the homologous DAM by complement fixation and absorption studies demonstrated the existence in DAM of antigenic determinants that were lacking or inaccessible in the native fibrils.

A search for amyloid precursors and antibodies to amyloid in the sera of 12 patients proved unsuccessful.
CARCINOGEN-INDUCED TUMORS OF THE THYMUS
Authors: Stutman Osias , Yunis Edmond J. , Good Robert A.
Published: June 2004

A progressive decrease of the restoring effectivity of syngeneic or allogeneic thymus and functional thymoma grafts was observed when the treatment of neonatally thymectomized mice was delayed. Early treatment (5–20 days postthymectomy) was effective, while the number of restored animals was markedly decreased after late treatment (30–50 days postthymectomy). Similar results were obtained with subcutaneous or intraperitoneal thymus grafts and with thymus grafts within cell-impenetrable diffusion chambers. After the onset of the postthymectomy-wasting syndrome the only successful treatment was the implantation of multiple thymus grafts. On the other hand, single thymus grafts, thymoma grafts, or thymus or thymoma within diffusion chambers were ineffective. When spleen cells from 5-day old or 45-day old neonatally thymectomized animals were given in association with thymoma grafts, only the cells derived from the 5-day old thymectomized mice proved effective in restoring wasted thymectomized hosts. These results suggest that a population of cells sensitive to the action of the thymus decreases progressively with time in the absence of thymic function.
RABBIT HOMOCYTOTROPIC ANTIBODY
Authors: Zvaifler Nathan J. , Robinson Jennifer O.
Published: June 2004

Rabbits immunized with egg albumin produce a homocytotropic antibody. The antibody is identified by its ability to produce passive anaphylaxis in rabbit skin. The time of appearance of this antibody, its persistence and recall after booster injections depends, in part, on the route of immunization and the adjuvant employed. The physicochemical characteristics of the homocytotropic antibody obtained was similar regardless of the immunization schedule used. The anaphylactic activity of these antisera showed some heterogeneity when chromatographed on diethylaminoethyl (DEAE)-cellulose, but all fractions were inactivated by heating and absorption with a specific antisera. The anaphylactic activity could be separated from rabbit IgG and IgA, and was not blocked by absorption with antisera specific for these classes of immunoglobulins. Anaphylactic activity was completely removed by absorption with a specific antiserum which did not react with any of the known rabbit immunoglobulins. The passive cutaneous anaphylaxis titer of a rabbit serum containing homocytotropic antibody was reduced by 50% after absorption with an antisera (anti-FcND) specific for human IgE. On the basis of these distinctive physicochemical characteristics, it is concluded that rabbit homocytotropic antibody represents a unique class of rabbit immunoglobulin, analogous to human IgE.
COLICIN K
Authors: Tsao Shuang-Shine , Goebel Walther F.
Published: June 2004

Partially purified colicin K (mCol K) has been obtained from cultures of Escherichia coli K235 induced with mitomycin C. Unlike colicin K (Col K) derived from noninduced cultures of E. coli K235, mitomycin-induced colicin K (mCol K) is not associated with the type O-specific antigen of the colicinogenic bacillus.

mCol K elicits in rabbits specific antibodies which precipitate and neutralize the homologous bacteriocin. These colicin-specific antibodies are not precipitated by the colicin-O antigen complex derived from noninduced bacteria.

Colicin-neutralizing antibodies can be separated by zone electrophoresis into fractions having different electrophoretic mobilities. The antibodies with lower mobility strongly precipitate the homologous antigen mCol K; those with higher mobility neutralize the bacteriocin and form soluble antigen-antibody complexes.
PHYLOGENY OF IMMUNOGLOBULIN STRUCTURE AND FUNCTION
Authors: Leslie Gerrie A. , Clem L. W.
Published: June 2004

Chicken 7.1S immunoglobulin was purified from whole chicken serum by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. The macroglobulin was purified by a combination of salt precipitation and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded 75% heavy (H) chains and 25% light (L) chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. The 7.1S and 16.7S immunoglobulin H chains were antigenically unrelated to each other, whereas the L chains were antigenically indistinguishable from one another. The 16.7S H chains were found to have a mass of ∼70,000, and the 7.1S H chains had a mass of 67,500. The mass of the L chains was ∼22,000.

Sedimentation equilibrium studies of the 7.1S immunoglobulin molecule gave a mol wt of ∼170,000 which is in good agreement with the 179,000 predicted on the basis of 2 H and 2 L polypeptide chains. The 16.7S molecule was shown to have a mol wt of ∼890,000. A reductive subunit that has a mol wt of ∼174,000 has been isolated from the 16.7S molecule. These values are consistent with the chicken macroglobulin having five subunits, each of which has 2 H and 2 L chains. The hexose contents of the chicken 7.1S and 16.7S immunoglobulins are 2.2% and 2.6%, respectively. The extinction coefficients of the 7.1S and 16.7S immunoglobulins were 13.18 ± 0.04 and 12.72 ± 0.77, respectively, when measured in 0.3 M KCl.

Based upon physical-chemical and antigenic characteristics, the 16.7S immunoglobulin most closely resembles IgM of mammals. The 7.1S immunoglobulin definitely belongs to a different class than the 16,7S immunoglobulin, but it does not align itself very well with any of the mammalian immunoglobulins. We propose that this molecule be designated as IgY. Furthermore, this designation would be useful for the immunoglobulins of other species for which there is insufficient correlation with any of the known human immunoglobulins.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Moore Douglas M. , Cheuk S. Fai , Morton J. Dennis , Berlin Richard D. , Wood W. Barry
Published: June 2004

Blood leukocytes, in contrast to exudate leukocytes, release little or no pyrogen when incubated in 0.15 M NaCl unless previously activated by exposure to endotoxin or to a protein activator that is present in acute exudate fluid. The activation process, which also occurs during phagocytosis, involves the synthesis of cellular protein, presumably related to the pyrogen molecule. Evidence is presented that generation of pyrogen in sterile inflammatory lesions depends on both the activator and the anaerobic conditions in the exudate fluid.
QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES
Authors: Hopper John E. , MacDonald A. Bruce , Nisonoff Alfred
Published: June 2004

Idiotypic antibodies were investigated quantitatively by a method of indirect precipitation, which utilizes labeled F(ab')2 fragments of specifically purified antibenzoate antibody from the donor, anti-antibody, and an antiglobulin reagent. The contribution of allotypic and hidden determinants to these reactions was excluded.

Greater fractions of an idiotypic antibody population are precipitated by this method, as compared to direct precipitation, and in two instances large proportions of idiotypic antibodies were detected in populations which failed to form precipitates by double diffusion in agar gel. The greater sensitivity of the indirect method was attributed to its capacity to detect molecules bearing a small number of antigenic determinants.

Extensive studies of cross-reactions, carried out by an inhibition technique, failed to reveal any strong reactions of anti-idiotypic antibodies with heterologous antibenzoate antibody preparations, heterologous sera, or IgG, although a few weak cross-reactions were noted. One definite cross-reaction was observed by a direct binding measurement with heterologous antiserum.

Antisera prepared in more than one recipient against a single donor preparation reacted with identical or overlapping subpopulations of the donor molecules. Instances in which two recipient antisera reacted with different proportions of the molecules of a single donor provided evidence for the existence of more than one idiotypic antibody population in the antibenzoate antibody of an individual rabbit.
THE LOCALIZATION OF AUSTRALIA ANTIGEN BY IMMUNOFLUORESCENCE
Authors: Coyne(Zavatone) Veronica E. , Millman Irving , Cerda James , Gerstley B. J. S. , London Thomas , Sutnick Alton , Blumberg Baruch S.
Published: June 2004

We have studied the localization of Australia antigen, a particulate substance associated with hepatitis, by means of the fluorescent antibody technique. Preparations were made from 61 liver biopsy specimens taken from patients with infectious hepatitis, serum hepatitis, and a variety of other diseases. When tested with fluorescein-conjugated rabbit anti-Au(1) antisera all 26 patients who had Au(1) in their serum had specific fluorescence in their liver cells. The fluorescence appeared in three forms: as discrete particles within the nucleus, diffuse fluorescence of the entire nucleus, and fluorescence of the nuclear rim. Occasionally there were also fluorescent particles in the cytoplasm. Other specimens were tested with the fluorescent antibody including a variety of human tissues, buffy coat smears, peripheral lymphocyte cultures, and cells obtained from bile and duodenal drainage. Among these specimens, fluorescence was found in the cytoplasm of a few cells in the bone marrow of two patients with hepatitis and Au(1) in their serum, and in the liver, spleen, mesentery, and testis of one patient with leukemia, chronic hepatitis, and Au(1) in his serum. We have shown that the presence of fluorescent particles in the liver cells is strongly associated with the presence of Au(1) in the serum and the diagnosis of viral hepatitis. We believe that this study adds support to the hypothesis that Australia antigen is an antigenic determinant of a virus capable of causing hepatitis.
AN ANALYSIS OF THE GENETIC REQUIREMENTS FOR DELAYED CUTANEOUS HYPERSENSITIVITY REACTIONS TO TRANSPLANTATION ANTIGENS IN MICE
Authors: Streilein J. Wayne , Billingham R. E.
Published: June 2004

The experiments reported herein provide ample evidence that mice, like most other mammalian species, are capable of displaying readily observable and reproducible delayed cutaneous hypersensitivity reactions indicative of transplantation immunity. By employing a variety of genetically defined strains, it has been shown that a genetic requirement for the development of a positive normal lymphocyte transfer reaction in mice is a difference between host and cell donor at the H-2 locus. By contrast, the immune lymphocyte transfer reaction consistently reflected the full range of histoincompatibility, both inclusive and exclusive of the H-2. It was incidentally discovered that erythema regularly accompanied delayed cutaneous reactions in the skins of female mice, whereas no local redness accompanied their counterparts in male skins. The influence of cutaneous erythema on the scoring of delayed skin reactions is discussed.
THE EFFECT OF GLUCOCORTICOSTEROIDS ON THE KINETICS OF MONONUCLEAR PHAGOCYTES
Authors: Thompson Jan , van Furth Ralph
Published: June 2004

The effect of glucocorticosteroids on the kinetics of mononuclear phagocytes, i.e., peripheral blood monocytes and peritoneal macrophages, was studied in normal mice, as well as in mice in which an inflammatory reaction was evoked in the peritoneal cavity.

The administration of glucocorticosteroids resulted in a rapid decrease (within 3–6 hr) in the number of circulating monocytes, the duration being dependent on the nature and dose of the compound. The water-soluble dexamethasone sodium phosphate is only briefly active (less than 12 hr), but hydrocortisone acetate, which forms a subcutaneous depot, reduced the number of monocytes for more than 2 wk.

In normal mice, hydrocortisone did not affect the number of macrophages already present in the peritoneal cavity, but the transit of mononuclear phagocytes from the circulation into the peritoneal cavity was arrested.

During an inflammatory response in the peritoneal cavity, hydrocortisone suppresses both the increase in the number of monocytes in the peripheral blood and the increase in the number of peritoneal macrophages. This reduction of the inflammatory exudate appeared to be due to a diminished influx of mononuclear phagocytes from the peripheral blood. No lytic action of glucocorticosteroids on the mononuclear phagocytes could be demonstrated.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Hahn Helmut H. , Cheuk S. Fai , Elfenbein C. Dianne S. , Wood W. Barry
Published: June 2004

Only intact exudate granulocytes from rabbits generated large amounts of endogenous pyrogen when incubated in 0.15 M NaCl. No matter how whole-cell lysates or combinations of subcellular fractions were incubated, their yields of pyrogen never approached those of whole cells; at most, only minimal amounts of pyrogen were formed, once the integrity of the cells had been destroyed.

Some pyrogen could be extracted from disrupted cells, but never more than a fraction (<25%) of that released from incubated whole cells. The yield could be slightly improved by lowering the pH (to 3.5) and by increasing the volume of extraction fluid.

Virtually all of the preformed pyrogen that could be extracted from sucroselysed cells was found in their cytoplasmic fraction. Contrary to the results of Herion et al. (3), none could be detected in the granular (or lysosomal) fraction. Likewise, all efforts to recover pyrogen from the membrane-nuclear fraction were unsuccessful.

In keeping with the finding that preformed pyrogen is contained in the cytoplasmic fraction were the observations that practically all of the aldolase, a cytoplasmic enzyme, and very little of the acid phosphatase, a granular enzyme, were lost from the cells during the release of pyrogen. Lysozyme, an enzyme stored in both the granules and the cytoplasm, was partially released from the cells under the same circumstances.

Neither the release of pyrogen nor its slight intracellular buildup that precedes release (4) were affected by concentrations of puromycin that block protein synthesis in the cells and prevent their activation. Hence, it is concluded that the release process, which also involves the formation of active pyrogen (4), does not require protein synthesis, whereas activation of the cells, which may involve the synthesis of an inactive precursor (2), does.
STUDIES ON THE ORIGIN OF HUMAN LEUKOCYTIC PYROGEN
Authors: Nordlund James J. , Root Richard K. , Wolff Sheldon M.
Published: June 2004

Release of the protein molecule, leukocytic pyrogen, is one of the many reactions exhibited by leukocytes after phagocytosis. After the ingestion of heat-killed S. albus, a 3–4 hr latent period exists, during which human peripheral leukocytes release no pyrogen, yet cellular metabolism is altered in such a way that pyrogen output may subsequently occur in the absence of further phagocytosis. Transcription of messenger RNA and translation of new protein are initial events in the. activation process, since addition of the inhibitors, actinomycin D, and cycloheximide or puromycin, during this period markedly depressed or abolished subsequent pyrogen release. These effects were noted to be dependent upon the time of addition of the inhibitors. None of the inhibitor drugs interfered with cell viability as measured by phagocytosis and hexose monophosphate shunt activity, nor did they alter the pyrogenicity of preformed leukocytic pyrogen. Vincristine did not inhibit pyrogen formation, consistent with its reported failure to alter RNA synthesis in mature human granulocytes. The glycolytic inhibitor, sodium fluoride, blocked pyrogen release both when added prior to particle ingestion or 1 hr after the initiation of phagocytosis. Whereas inhibition of phagocytosis would explain the sodium fluoride effect prior to 1 hr, this was not observed in leukocyte preparations incubated for 1 hr with S. albus before adding sodium fluoride. When sodium fluoride was added to preparations 2 hr after the start of incubation, the LP production was unimpaired. Potassium cyanide had no effect on cell activation or pyrogen release. These findings suggest that the primary energy supply for the activation process is derived from high energy phosphate bonds provided by anaerobic glycolysis. Since the major amount of cell activation appears to occur in the 1st hr after phagocytosis, this energy might be involved in the induction of a genome leading to the transcription of m-RNA and its translation into new protein or is required for polysome integrity during protein synthesis. It is suggested that this new protein may be leukocytic pyrogen itself, or an enzyme responsible for cleaving it from an inactive precursor.
THE TOXICITY OF STREPTOLYSIN O FOR BEATING MAMMALIAN HEART CELLS IN TISSUE CULTURE
Authors: Thompson A. , Halbert S. P. , Smith U.
Published: June 2004

Pulsating mammalian myocardial cells were found to be highly susceptible in tissue culture to rapid destruction by streptolysin O. Cessation of beating occurred almost immediately, followed within minutes by multiple cell membrane bleb formation. Parallel with these changes, the cytoplasm became intensely granular and the nuclear membrane apparently thickened when viewed by phase microscopy. At the ultrastructural level, the cell membrane blebs were found to contain relatively small numbers of granular fragments. The endoplasmic reticulum of damaged heart cells was quite swollen, and its contents were considerably condensed. The myofibers were not strikingly altered, but cytoplasmic and mitochondria vacuoles were rather abundant.

Cardiac endothelial, kidney epithelial, and fibroblast cells were also susceptible to lysis by this toxin, but the reactions occurred more slowly or bleb formation was less evident. An antiserotonin drug known to be protective against streptolysin-O in vivo (UML-491), did not protect against killing of cardiac cells at the tissue culture level. Serotonin could not be detected in the culture fluid after lysis of cardiac cells by streptolysin O.
DEFICIENCY OF C1r IN HUMAN SERUM
Authors: Pickering R. J. , Naff G. B. , Stroud R. M. , Good R. A. , Gewurz H.
Published: June 2004

The experiments presented here utilize a human serum markedly deficient in hemolytic complement activity to show that: (a) The hemolytic deficiency is the result of a selective deficiency in hemolytic C1. (b) The relative absence of hemolytic C1 is due to a profound deficit in C1r function associated with less than normal C1s protein and hemolytic function and normal C1q protein concentration and function. This deficit in C1r in the face of normal C1q suggests that different cell types are responsible for the synthesis of each of these components. (c) Whatever the basis for the deficiency of C1r function, this defect results in an inadequate association of the remaining C1 subcomponents, C1q and C1s, even in the presence of calcium ions, thus suggesting that C1r has an important role in the assembly and/or maintenance of macromolecular C1.
INDIRECT VISUALIZATION OF STAPHYLOCOCCUS AUREUS PROTEIN A
Authors: Nickerson D. Scott , White James G. , Kronvall Göran , Williams Ralph C. , Quie Paul G.
Published: June 2004

Specific but nonimmunologic reaction between staphylococcal protein A and the Fc portion of gamma globulin provided the basis for ultrastructural studies to determine the localization of protein A, using intact staphylococci and labeled myeloma gamma G-globulin.

Protein A appeared to be part of the outermost layer of the staphylococcal cell wall. Strains with protein A demonstrated a coating of myeloma globulin over the entire bacterial surface. There was no coating of strains without protein A.

Identification of protein A on the surface of the staphylococcal cell wall provides evidence that this may be the first material in contact with host environment. It probably accounts for apparent cross-reactions of staphylococci with antibodies to many antigens. More importantly, even in the nonimmune host protein A immunoglobulin reactivity may initiate complement activation and inflammatory reactions including chemotaxis and pus formation.
IN VITRO STIMULATION OF ANTIBODY FORMATION BY PERITONEAL CELLS
Authors: Nossal G. J. V. , Bussard A. E. , Lewis H. , Mazie J. C.
Published: June 2004

An improved method for the short-term culture of mouse peritoneal cells in a medium containing carboxymethylcellulose (CMC), sheep erythrocytes (SRBC), and guinea pig complement is described. It involves preparation of microcultures, of thickness 12–15 µ and volume 3.6 µl, under paraffin oil. With such cultures, peritoneal cells from normal, unimmunized young male CBA mice give about 3000 hemolytic plaques per million cells cultured, this figure being attained within 24 hr. The plaque detection method is about four times as sensitive as the Jerne technique.

A method is described whereby such plaque-forming cells (PFC) can be transferred, by micromanipulation, to fresh monolayer cultures containing SRBC, CMC, and complement. In this fashion, the secretory capacity and susceptibility to inhibitors of peritoneal PFC can be tested in detail. Using this technique, evidence is presented that the hemolytic substance responsible for plaque formation is actually secreted by the cell at the center of the plaque, and is not a complement component but probably an antibody. Studies on the time of plaque appearance after cell transfer, and the subsequent growth rate of the zone of hemolysis, have been performed. They speak against the idea that the PFC is either a reservoir of cytophilic antibody or a "background" PFC. Rather they suggest that active antibody secretion is induced in the cell at some defined time point in culture.

Detailed kinetics of the rate of appearance of plaques in peritoneal cell cultures revealed an exponential phase lasting from about 3 to about 13 hr with a doubling time of 2 hr. The reasons for this are not known.

A greatly heightened reactivity was shown in peritoneal cells of mice that had been pregnant several times. Cultures of such cells showed more rapid plaque appearance and a peak activity about 20 times higher than with cells from young male mice. Cultures in which 1 cell in 10 formed a plaque were not infrequent. A series of experiments on germ-free mice showed reactivity similar to that of conventional mice from the same strain and source.

The significance of the findings for cellular immunology are discussed.
CELLULAR RECOGNITION BY MOUSE LYMPHOCYTES IN VITRO
Authors: Adler W. H. , Takiguchi T. , Marsh B. , Smith R. T.
Published: June 2004

The media and culture conditions required for in vitro stimulation of mouse lymphoid cells are described. The medium was arginine-rich and contained heat-inactivated human serum. A component of the human sera necessary for stimulation of the cells was a natural mouse cell agglutinin, which affected both background stimulation and the degree of induced stimulation with phytohemagglutinin (PHA). Absorption of the agglutinin from the human serum rendered the medium incapable of sustaining DNA synthesis in the presence of PHA.

The response to PHA of mouse spleen and thymus cells was age-dependent and, although this response was not present at birth, it rapidly rose to adult levels. Spleen cells from mice immunized with bacillus Calmette-Guérin (BCG) or sheep erythrocytes (SRBC) showed increased in vitro reactivity to added purified protein derivative (PPD) or SRBC stroma, dependent on the time of immunization.

The dose response curve for the SRBC stroma stimulated, immune spleen cells is compatible with a theory of cell to cell interaction being necessary for an in vitro reaction to antigen.

The possible role of the mouse cell agglutinin (AMLG) is discussed.
GELS OF NORMAL AND SICKLED HEMOGLOBIN
Authors: White James G. , Heagan Beatrice
Published: June 2004

Electron microscopic studies of the sickling phenomenon have described at least three different structural arrangements of sickled hemoglobin, including empty hexagonal crystals, microtubules, and solid rods. It is unlikely that sickling results in several different polymers, and it is essential to determine the true structure of sickled hemoglobin in order to define the mechanism of molecular assembly. The present study has explored the fine structure of gels formed in cell-free solutions of normal and sickle reduced and oxyhemoglobin. Gels of reduced sickled hemoglobin consisted entirely of solid rods. The gels formed from sickle oxyhemoglobin, normal oxyhemoglobin, and normal reduced hemoglobin contained masses of hollow polymers essentially identical in appearance with microtubules. These findings indicate that solid rods are the characteristic polymers of sickled hemoglobin and tubular polymers represent aberrant structures which are not related to erythrocyte sickling.
MATURATION OF HEMOLYSIN-PRODUCING CELL CLONES
Authors: Saunders George C. , Swartzendruber Douglas
Published: June 2004

Cells capable of reacting with sheep erythrocyte (SRBC) antigen to maturate and produce hemolysin appear simultaneously in the bone marrow and spleen of 1-day old Swiss-Webster mice. However, hemolysin-producing cell clones (HPCC) do not result.

Complete functional precursor units generally appear in the spleens of mice older than 3 days. In vivo and in vitro data correlate well in this regard. Complete precursor units are not seen in the bone marrow and only very rarely in the thymus.

The efficiency of precursor units of neonatal mice when they become functional approximates that of the mature animal when based on the doubling time of plaque-forming cells (PFC).

Possible explanations of the initial appearance of incomplete precursor units have been discussed.
SURFACE ALLOANTIGENS OF PLASMA CELLS
Authors: Takahashi Toshitada , Old Lloyd J. , Boyse Edward A.
Published: June 2004

A serological study of immunoglobulin-forming cells of the mouse, normal and malignant, shows that they lack all known surface differentiation antigens of the thymocyte-lymphocyte axis: TL, θ, Ly-A, Ly-B, and MSLA. Two systems of normal alloantigens are expressed on these cells, H-2 and a new system named PC.

The gene Pca (Plasma cell antigen) which specifies PC.1 alloantigen segregates as a mendelian dominant not closely linked with H-2. This cell surface antigen is absent from thymocytes, leukemias, and very probably from thymus-derived lymphocytes also; it is present on cells of the liver, kidney, brain, and lymph nodes as well as on hemolytic plaque-forming cells of the spleen, and on myelomas. So PC.1 is properly classified as a differentiation alloantigen. The strain distribution of PC.1 does not conform to that of any known immunoglobulin allotype or cell surface alloantigen previously described.

Thus the cell surface antigens of immunoglobulin-producing cells are clearly different from those of cells belonging to the thymocyte-lymphocyte axis. Each family of cells has distinctive alloantigens, and the two families share alloantigens of only one known system, H-2. This implies that either immunoglobulin-producing cells are not derived from thymic lymphocytes, or if they are, the program responsible for the transition must include extensive revision of cell surface structure.
SEPARATION OF NORMAL AND IMMUNE LYMPHOID CELLS BY ANTIGEN-COATED COLUMNS
Authors: Wigzell H. , Mäkelä O.
Published: June 2004

Specific fractionation of immunologically competent cells derived from normal or immune animals was achieved by filtration through antigen-coated bead columns. This selective retention of the relevant reactive cells could be shown to produce a cell population, which after passage through the column would behave like a suspension rendered immunologically tolerant by "classical" means. The immunologically specific elimination of potential antibody-forming capacity of the filtered cells could be shown to affect the IgM and the IgG system to a similar extent. Analysis of the binding characteristics of the membrane antibodies responsible for this selective retention indicate striking similarities to those of the humoral antibodies produced against the antigen. Thus, the surface receptor could distinguish isolated haptenic groups on a "foreign" carrier background and the receptor of the hapten-reactive cells in the present system (high-rate antibody-forming cells against NIP) failed to combine with carrier specific determinants in analogy with the binding behavior of the serum anti-hapten antibodies. The binding of anti-hapten reactive cells to bead-attached haptens could be specifically inhibited by the presence of free hapten in the columnar fluid during cellular filtration. The results strongly suggest that the potential humoral antibody-forming cell has preformed receptors on its outer surface with binding characteristics, indicating similarity, if not identity, to those of the eventual product of the cell, the humoral antibody.
TRANSFER OF ANTIBODY PRODUCTION WITH CELLS FROM BURSA OF FABRICIUS
Authors: Gilmour D. G. , Theis G. A. , Thorbecke G. J.
Published: June 2004

F1 hybrid chicks isogenic for the strong B histocompatibility locus and for most weak H-loci were X-irradiated on day 1 after hatching, injected intraperitoneally on day 2 with dispersed cells of bursa, spleen, or thymus from 4- or 10-wk-old F1 hybrid donors, and immediately challenged by the same route with either Brucella abortus, sheep erythrocytes, or a mixture of both together. The agglutinin titers were measured in sera obtained 1 wk later. With 4-wk-old donors, a greater primary response to Brucella abortus was obtained after transfers of cells from bursa than from spleen, while thymus was much less effective. With 10-wk-old donors, the decreasing order of response was spleen, bursa, thymus.

Only splenic cells were effective in transferring a response to sheep erythrocytes, at either donor age. In tests of synergism by cell mixtures from pairs of organs, the only positive finding was a modest augmentation of titer against sheep erythrocytes by bursa + spleen as compared with spleen alone. Bursal cells from 6- or 10-wk-old donors were effective in transferring a response to sheep erythrocytes when antigen injection was delayed until 5 days after cell transfer.

Splenic cells from hormonally bursectomized donors were ineffective in transferring a primary response, even when the donors had been injected with antigen 1 wk before transfer. Preimmunization of normal donors led to marked increases in the responses to Brucella abortus produced by transferred splenic or thymic cells. With bursal cells, an increased response was obtained only if the interval between preimmunization and transfer was 17 rather than 7 days. With the 17-day interval, both bursal and thymic cells could also transfer a response to sheep erythrocytes.

The primary sera to Brucella abortus produced after transfers of bursal or splenic cells contained almost entirely 19S antibodies. A 7S component was found in all the secondary sera tested.
SYNTHESIS AND ASSEMBLY OF IMMUNOGLOBULINS BY MALIGNANT HUMAN PLASMACYTES
Authors: Zolla Susan , Buxbaum Joel , Franklin E. C. , Scharff M. D.
Published: June 2004

Three basic patterns of γ-globulin synthesis are described in malignant human plasmacytes: extreme unbalanced synthesis where only L chains are synthesized; unbalanced synthesis in which intact γG globulin and an excess of free L chains are synthesized and secreted; and balanced synthesis where H and L chains appear to be synthesized in equimolar amounts. Studies of the cellular products appear to reflect the biosynthetic processes of the cells in a more reliable fashion than does analysis of serum or urinary proteins.

The absence of Bence Jones proteins from the urine does not necessarily indicate that free L chains are not being synthesized and secreted at the cellular level. Similarly, the completed globulin molecule secreted by malignant plasma cells may not be demonstrable by examination of serum.

Patterns of globulin synthesis in human myelomatous tissues vary as do patterns of globulin synthesis in mouse plasmacytomas.

Pulse-chase studies of the cells from one patient showed that a γG myeloma protein was assembled via an HL (half molecule) intermediate.
THE TERMINATION OF IMMUNOLOGICAL UNRESPONSIVENESS TO BOVINE SERUM ALBUMIN IN RABBITS
Authors: Benjamin D. C. , Weigle W. O.
Published: June 2004

Rabbits made unresponsive to BSA at birth were given two courses of immunization with various cross-reacting albumins at 3 months of age. Normal control rabbits, of equivalent age and weight, were similarly immunized. Sera obtained 7 days after the last injection were assayed for binding and precipitating antibody to six albumins and for their avidity for BSA. No significant differences were found between unresponsive and normal rabbits in the amount of antibody reacting with any of the six albumins used. This was the case regardless which albumin was used to terminate the unresponsive state. Avidity differences were seen and seemed to depend on the antigen used and not on the immunological status of the animal. The simultaneous injection of small amounts of BSA inhibited the termination of unresponsiveness. These results were discussed in the light of the more recent theories of the termination of unresponsiveness and of antibody formation.
THE EFFECT OF INDUCED CHRONIC VIRAL INFECTIONS ON THE IMMUNOLOGIC DISEASES OF NEW ZEALAND MICE
Authors: Tonietti Giorgio , Oldstone Michael B. A. , Dixon Frank J.
Published: June 2004

Chronic infections induced at birth with either LCM, an RNA virus, or polyoma, a DNA virus, in NZB, NZW, and NZB x W mice enhance ANA formation, aggravate the immune complex glomerulonephritis, and increase the associated mortality. The ANA titer was increased without apparent change in specificity of the antibodies involved in all three types of mice. Glomerulonephritis, while more severe in infected mice, was of the same type as occurred spontaneously and was characterized by a granular to lumpy accumulation of host IgG and C3 in the mesangia and along the capillary walls of the glomeruli. Of the LCM infected mice of all three types over 50% had died of glomerulonephritis by 6 months and over 85% by 9 months. Of the polyoma infected mice of all three types approximately 20% had died of glomerulonephritis by 6 months and over 40% by 9 months. Of the uninfected controls of all three types less than 10% had died by 6 months and less than 20% at 9 months except for the NZB x W females which had a 67% mortality at 9 months as a result of their spontaneous glomerulonephritis.

The two viral infections had significant effect on the incidence of anti-red cell antibodies or the severity of autoimmune hemolytic anemia in any of the three NZ mice.
THE ANAEROBIC BACTERIAL FLORA OF THE MOUSE CECUM
Authors: Gordon James H. , Dubos René
Published: June 2004

Refinements of the anaerobic technique such as the utilization of prereduced media and the removal of traces of oxygen from the gases used by passage through a hot copper oven resulted in quantitative and qualitative improvements in the recovery of anaerobic bacteria from the cecum of SPF mice.

The commonest morphologic types of bacteria in the mouse cecum were tapered rods. These characteristically gave "speckled" colonies on agar plates. Those identified were species of the genera Fusobacterium, Eubacterium, and Clostridium. Several of the morphologic types seen with phase microscopy still could not be cultivated.

The implications of these findings for the study of the intestinal flora are discussed.
CARRIER FUNCTION IN ANTI-HAPTEN IMMUNE RESPONSES
Authors: Paul William E. , Katz David H. , Goidl Edmond A. , Benacerraf Baruj
Published: June 2004

Transfer of live lymphoid cells from BGG-immunized strain 2 guinea pigs into syngeneic animals primed with DNP-OVA prepares the recipients for a markedly enhanced secondary anti-DNP antibody response upon challenge with DNP-BGG. This phenomenon has been demonstrated when the recipients were challenged 1 day after cell transfer, but it was considerably more striking when an interval of 6 days was allowed between transfer of cells and challenge with antigen.

As demonstrated in the preceding paper (6), BGG preimmunization enhanced anti-DNP antibody responses to challenge with DNP-BGG. An analysis of the characteristics of substances to which preimmunization was effective in enhancing subsequent anti-hapten responses was made. It was shown that preimmunization of strain 13 guinea pigs with a copolymer of glutamic acid and lysine (GL), to which these animals are genetically unable to accord an immune response, failed to prepare them for an enhanced anti-DNP response to DNP-GL. Tolerance to BGG specifically abrogated the capacity of subsequent BGG immunization to prepare DNP-OVA primed rabbits for an enhanced anti-DNP response to DNP-BGG.

Sensitization of animals to haptens by preimmunization with hapten-protein conjugates failed to prepare them for enhanced primary or secondary antibody responses to other determinants associated with that hapten on a different carrier.

These studies indicate that the enhancing effect of carrier preimmunization reflects a cooperative interaction between lymphoid cells specific for carrier and cells specialized for haptenic determinants. Furthermore, the capacity of a substance to behave as a carrier requires more than its possession of a variety of antigenic determinants.
HOST DEFENSE AGAINST BACTERIAL ENDOTOXEMIA: MECHANISM IN NORMAL ANIMALS
Authors: Skarnes Robert C.
Published: June 2004

The present study defines the early response of normal rabbits to the intravenous injection of a single, sublethal dose of endotoxin. Within the first few hours following endotoxin there occurs in the circulating plasma of recipients a decrease in ionized calcium, a threefold increase in the heat-stable, organo-phosphate-resistant esterase level, and a striking increase in the endotoxin-detoxifying capacity. These results are fully consistent with the thesis that circulating plasma represents a principal site of detoxification and that plasma esterases of the nonspecific, carboxylic type are of major concern in defense against circulating endotoxins.
ANTIGEN-SPECIFIC SYNERGISM IN THE IMMUNE RESPONSE OF IRRADIATED MICE GIVEN MARROW CELLS AND PERITONEAL CAVITY CELLS OR EXTRACTS
Authors: Kennedy James C. , Treadwell Perry E. , Lennox Edwin S.
Published: June 2004

A synergistic immune response to foreign erythrocytes may be induced in heavily irradiated mice injected with a mixture of isologous cells obtained from marrow and from the peritoneal cavity. Under appropriate conditions, homologous or heterologous peritoneal cavity cells, heat-killed cells, or cellfree extracts made from such cells are also effective. The activity of the peritoneal cavity cells or extracts is antigen-specific, in the sense that cells or extracts obtained from animals previously immunized with the test antigen produce much stronger synergistic effects than do cells from animals immunized with some other antigen; however, the peritoneal cavity cells or extracts are not immunogenic when tested in primed animals. The marrow cells, demonstrated to contain precursors of the antibody-forming cells produced during this synergistic immune response, also show a form of antigen-specificity.
GENETIC VARIANTS OF γG4 GLOBULIN
Authors: Kunkel H. G. , Joslin F. G. , Penn G. M. , Natvig J. B.
Published: June 2004

Two types of γG4 proteins, termed 4a and 4b, were characterized through antigenic studies of myeloma proteins. Both were recognized by specific antigens on the Fc fragment which were shared with other γG classes. The distinctive antigen of the common 4a type was shared with all γG1 and γG3 proteins but missing in those of the γG2 class; that for the rarer 4b type was selectively found in proteins of the γG2 class.

Analyses on γG4 fractions isolated from normal sera showed that either the 4a or the 4b or a mixture of the two types was present in each serum. Evidence was obtained that these differences were on a genetic basis and that allelic genes linked to those of the Gm system were involved.

Such a reciprocal occurrence in other classes of γG globulin of the antigenic markers distinguishing genetic variants has not been observed previously. A number of questions regarding the evolutionary development of the genes responsible are discussed. The possibility is raised that those for the γG4 class arose relatively early and preceded the development of those for the other γG classes.
CUTANEOUS BASOPHIL HYPERSENSITIVITY
Authors: Richerson Hal B. , Dvorak Harold F. , Leskowitz Sidney
Published: June 2004

Jones-Mote reactivity, defined as a delayed-type skin reaction, occurs transiently early in the course of immunization with protein antigens or hapten conjugates with or without the adjuvant effect of tubercle bacilli. The skin reaction is typically a flat, well-circumscribed erythema with little induration beginning at about 6 hr, reaching a peak at 18–24 hr, and fading or gone at 48 hr.

Immunogenic carrier requirements for hapten-specific Jones-Mote hypersitivity resemble those of antibody production rather than of classic delayed hypersensitivity. Skin test antigen requirements indicate that the Jones-Mote reaction involves an active stimulatory response rather than combination with preformed antibody, since ABA conjugates of nonimmunogenic D-polymers do not work. Studies with ALS and carrageenan suggest that the lymphocyte is an important contributor to the reaction, but the macrophage is not.

Because the reactions studied here are operationally different from those described by Jones and Mote and because they have a characteristic histology, the term "cutaneous basophil hypersensitivity" is proposed.
STUDIES ON THYMUS FUNCTION
Authors: Stutman Osias , Yunis Edmond J. , Good Robert A.
Published: June 2004

Immunological restoration of 45-day old, neonatally thymectomized C3Hf mice by treatment with humoral thymic function (thymoma grafts, thymus or thymoma in diffusion chambers) ranges from 0 to 12% and is difficult to acheive. When small numbers (5–20 x 106) of young adult lymphohemopoietic cells, ineffective by themselves, are given in association with humoral thymic function, a cooperative effect is observed and restoration ranges from 30 to 60%. With a particular cell dosage (20 x 106), effectivity for cooperation with thymic function was the following in decreasing order: spleen, lymph nodes, thoracic duct cells, bone marrow, blood leukocytes, thymus, and Peyer's patch cells. Comparable results were obtained using spleen, thymus, and hemopoietic liver from newborn donors in association with thymic function. For similar cell dosages, newborn thymus cells were more effective than adult thymus in their cooperative effect with thymic function. Dispersed thymus cells in association with young adult bone marrow or newborn hemopoietic liver cells showed no synergism for the cooperative effect with thymic function in the present model.

Using hemiallogeneic cells (F1 hybrid into parent) it was possible to show that restoration was mediated by proliferative expansion of the injected cells. This was indicated by specific tolerance to tissues of the other parental strain and by cellular chimerism, especially of lymphoid tissues, as indicated by chromosome markers and absence of significant numbers of immunocompetent cells of host origin.

A population of paritally differentiated cells of hemopoietic origin, termed postthymic, sensitive to humoral activity of the thymus and present in the lymphohemopoietic tissues of adult and newborn mice is postulated to explain our results. These cells are postthymic and thymus dependent in the sense that they already received thymic influence, probably through traffic, and are incapable of self-renewal in absence of the thymus. Sensitivity to humoral activity of the thymus is characterized by proliferative expansion and/or a differentiative process eventually leading to larger numbers of competent cells.