bluuebunny/crossref_metadata_2025_split huggingface dataset:
IN VITRO SYNTHESIS AND SECRETION OF LYSOZYME BY MONONUCLEAR PHAGOCYTES
Authors: Gordon Salmon , Todd Jean , Cohn Z. A. 
Published: June 2004

Pure cultures of three types of mononuclear phagocytes—mouse peritoneal macrophages, unstimulated or after thioglycollate stimulation, and human monocytes—synthesize and secrete large amounts of lysozyme in vitro. The macrophage lysozyme is indistinguishable from authentic lysozyme in its ability to lyse M. lysodeikticus, inhibition by specific antisera, a similar size of 14,000 and cationic charge. Lysozyme secretion in culture is characterized by a large net increase in total lysozyme, 4–20-fold in 3 h, 75–95% of which is in the medium, and its continued extracellular accumulation over at least 2 wk in culture. Lysozyme is the major 14C-labeled protein secreted into the medium by both unstimulated and thioglycollate-stimulated macrophages and the 0.75–1 µg produced per 1 x 106 cells/day represents 0.5–2.5% of the total cell protein.
Lysozyme is a cell-specific marker for mononuclear phagocytes and the PMN, which contains preformed enzyme, since it is absent in lymphoid cells and a variety of fibroblast and epithelioid cell lines. Lysozyme production is also a useful measure of mononuclear phagocyte cell number.
The rate of lysozyme production and secretion is remarkably constant for all cell types under a variety of culture conditions. Production by the mouse macrophage increases threefold on the 2nd day in culture and then remains linear with time. Production is optimal at a relatively low serum concentration, but can be maintained, in the absence of serum, in lactalbumin hydrolysate or, at a reduced level in basal media.
The production and secretion of lysozyme are independent of the production of macrophage acid hydrolases. Net increase and secretion of lysozyme occur under conditions where acid hydrolases like N-acetyl ß-glucosaminidase, ß-glucuronidase, ß-galactosidase, and cathepsin D are neither accumulated nor secreted. Massive phagocytosis of latex particles has no effect on lysozyme production and secretion.
Lysozyme production can be rapidly inhibited by treatment with cycloheximide (0.4 µg/ml) whereas inhibition of its production by colchicine (10–6 M) occurs only after a lag period of more than 8 h, and is probably due to a secondary effect.
These results show that mouse macrophages provide a simple in vitro system to measure lysozyme secretion and its control. These studies also indicate the possible importance of mononuclear phagocytes in the secretion of a variety of biologically active products and in the modification of their environment.
INDUCTION OF IMMUNOLOGICAL TOLERANCE TO A THYMUS-DEPENDENT ANTIGEN IN THE ABSENCE OF THYMUS-DERIVED CELLS
Authors: Schrader John W. 
Published: June 2004

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5–10 mg of either FGG or DNP-HGG.
Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive.
Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG.
The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: McGregor D. D. , Logie Pamela S. 
Published: June 2004

Peritoneal exudates induced in rats infected with Listeria monocytogenes contain sensitized lymphocytes which can protect normal recipients against a Listeria challenge. The protective cells arise in lymphoid tissue remote from the peritoneal cavity. Those formed in the caudal lymph nodes of subcutaneously infected rats are delivered to the thoracic duct and hence to the blood from where they are drawn into exudates. Immunoblasts are the most immature members of this protective cell population and they alone among the cells in central lymph localize in exudates induced by killed bacteria. They do so in substantial numbers, but only during the early postinduction period.
The "homing" of immunoblasts to inflammatory foci seems to be determined by a general property of the cells rather than their immunological commitment; however, the intense inflammation induced by organisms to which an animal has been specifically sensitized is accompanied by an exuberant influx of immunoblasts into lesions. Sensitized lymphocytes that extravasate in the inflamed peritoneal may generate more of their own kind, but some give rise to small lymphocytes. The latter also have protective properties and, with time, comprise an increasing portion of the protective cell population.
The results imply that the tissue disposition of sensitized lymphocytes in the body is determined by a complementary relationship between blood-borne immunoblasts and vascular endothelium in inflamed tissue. The results also provide a plausible explanation for the concentration of sensitized lymphocytes at sites of microbial implantation where they alone would be expected to collaborate with monocyte-derived macrophages in the control of infection.
GENETICS OF RESTRICTED ANTIBODIES TO STREPTOCOCCAL GROUP POLYSACCHARIDES IN MICE
Authors: Cramer Matthias , Braun Dietmar G. 
Published: June 2004

The immune response of nine inbred and one outbred strain of mice to the streptococcal group A polysaccharide was investigated with respect to magnitude and restriction. Analytical isoelectric focusing served as a tool to estimate the degree of restriction of Group A polysaccharide-specific antibodies.
It proved feasible to distinguish low and intermediate from high responder strains, and to delineate strain-specificity of isoelectric focusing spectra of the immune sera. For example, immune sera of BALB/c mice, restricted high responders, and of C57BL/6 mice, heterogeneous low responders, had distinct focusing properties.
Responsiveness was a dominant autosomal genetic trait in C57BL/6 x BALB/c F1 hybrid mice, irrespective of the maternal and the paternal genotype; the immune sera of these mice had their own, rather uniform isoelectric focusing spectra whereby structural genes of the low responder strain were expressed to predominant levels in 81% of the hybrids.
Responsiveness in C57BL/6 x BALB/c F2 progeny segregated into 79% high and 21% low responders, and showed no genetic linkage to the following characteristics: hair color, sex, H-2 type, and Ig allotype of the heavy chain. The isoelectric focusing properties of these immune sera indicated segregation into patterns like BALB/c mice (40%), F1 hybrids (48%), and C57BL/6 mice (12%). Since this segregation is independent of any of the above criteria in these F2 mice a regulatory gene(s) is postulated that controls the clonal pattern of the immune response.
CELLULAR INTERACTIONS IN THE PROLIFERATIVE RESPONSE OF HUMAN T AND B LYMPHOCYTES TO PHYTOMITOGENS AND ALLOGENEIC LYMPHOCYTES
Authors: Lohrmann Hans-Peter , Novikovs Ligita , Graw Robert G. 
Published: June 2004

In vitro studies were performed to determine the proliferative responsiveness of human peripheral blood thymus-dependent (T) and thymus-independent (B) lymphocytes to phytomitogens and allogeneic lymphocytes. Recombination of T and B cells, with selective inhibition of proliferation of one of the two populations, was used to identify cellular interactions which may contribute to cell proliferation. The distinctive feature of human T lymphocytes to form rosettes with unsensitized sheep erythrocytes was utilized to separate human peripheral blood lymphocytes into highly purified resetting (T) and non-rosetting (B) cells. The proliferative response of these separated lymphocyte subpopulations to various stimulants was assessed from the uptake of tritiated thymidine into DNA.
Phytohemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic lymphocytes stimulated separated T cells, whereas no proliferation was observed with the T-cell-depleted B-cell population. This suggests that it is the human T cell which is activated directly by these stimulants. In the presence of T cells (proliferating or nonproliferating), B cells were capable of proliferation following stimulation with phytomitogens, but not in response to histocompatibility antigens. Thus, T-cell-mediated B-cell proliferation contributes to the overall lymphocyte response in phytomitogen-stimulated T + B cell mixtures, but not in human mixed leukocyte cultures. T-cell activation by allogeneic cells required the presence of monocytes; in contrast, the three tested phytomitogens stimulated T cells in the absence of monocytes. This indicates that direct interaction of mitogens with lymphocyte membrane receptors is sufficient to trigger T cells into proliferative response. However, monocytes considerably enhanced the proliferative response of T cells in a dose-dependent fashion; this monocyte-dependent mechanism of T-cell activation was predominant at lower concentrations of phytomitogens, and contributed relatively less at higher mitogen doses. Both, the direct, monocyte-independent, and the indirect, monocyte-dependent T-lymphocyte activation contribute to the total in vitro response of lymphocyte preparations to phytomitogens.
ROLE OF MENINGOCOCCAL ENDOTOXIN IN MENINGOCOCCAL PURPURA
Authors: Davis Charles E. , Arnold Karen 
Published: June 2004

Enteric bacilli and meningococci (MGC) both contain potent endotoxins, but purpuric skin lesions indistinguishable from the experimental dermal Shwartzman reaction are much more common during meningococcal bacteremia than during bacteremia with enteric organisms. Highly purified lipopolysaccharides (LPS), virtually free of contamination by protein, RNA, and capsule, were extracted by a modification of the phenol-water technique from MGC (serogroups A, B, and C) and enteric bacilli (Escherichia coli 04 and 0:111, and Salmonella typhimurium). Polysaccharides in these LPS were similar by gas chromatography except for one galactose-deficient strain of MGC (135B).
LPS from MGC and enterics were equally potent for the general Shwartzman reaction and mouse lethality, but LPS from MGC was 5–10 times more potent in inducing the dermal Shwartzman reaction. The greater skin potency of LPS from MGC explains the prominence of purpura in meningococcemia. Comparison of the properties of LPS may explain other differences in clinical syndromes caused by gram-negative bacteria.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Benacerraf Baruj , Kapp Judith A. , Pierce Carl W. , Katz David H. 
Published: June 2004

The conditions for cooperative interactions between nonresponder B10.S B cells and GAT-primed irradiated (C57BL/6 x SJL)F1 T cells in the response by cultures of mouse spleen cells to GAT were investigated. GAT-specific antibody responses could be elicited by soluble GAT in cultures of GAT-primed irradiated (C57BL/6 x SJL)F1 T cells with C57BL/6 B cells but not with B10.S B cells.
In contrast, when GAT was presented to the cultures on F1 macrophages or as aggregates of GAT with MBSA, GAT-specific PFC responses were observed with both B10.S or C57BL/6 B cells. Irradiated GAT-primed T cells were nevertheless essential for the development of these responses. The GAT-specific response of B10.S B cells in these cultures was inhibited by the addition of soluble GAT at culture initiation. These results indicate that genetic disparity at Ir loci is not an absolute barrier to T-B-cell cooperative interactions in the response to antigens under Ir gene control. The significance of these data for the function of Ir gene products in immunocompetent cells is discussed.
TUMOR INDUCTION BY MURINE SARCOMA VIRUS IN AKR AND C58 MICE
Authors: Chieco-Bianchi Luigi , Colombatti Alfonso , Collavo Dino , Sendo Fujiro , Aoki Tadao , Fischinger Peter J. 
Published: June 2004

Adult AKR and C58 mice injected intramuscularly with murine sarcoma virus, Moloney isolate (M-MSV), developed high incidence of nonregressing local tumors. Histologically, these tumors revealed the typical pleomorphism of M-MSV sarcomas; in some cases, however, neoplastic tissue showed a nodular or diffuse growth of monomorphic myoblastlike cells, reminiscent of clonal aggregates. No depression of immune reactivity was found in M-MSV-injected mice as evaluated by direct hemolytic plaque-forming cells against SRBC and by virus-neutralizing antibody production.
The MSV recovered from the induced tumors proved to be, by neutralization assay, a Gross (G)-MSV pseudotype. Moreover, tumor cell suspensions absorbed out cytotoxic antibody directed against G-cell surface antigens. Therefore, the conclusion was drawn that MSV with envelope characteristics of endogenous G leukemia virus had formed in vivo through a phenotypic mixing phenomenon. The failure of tumors to regress has been interpreted as mainly due to the partial unresponsiveness of host immune reactivity towards G-MuLV specified antigens.
Since MSV-tumors arose in AKR mice after a very long latent period, the possibility was considered that this relative resistance might depend on immunologic mechanisms. In fact, M-MSV-injected AKR mice immunodepressed by goat antimouse lymphocyte serum or rendered partially tolerant by neonatal M-MuLV inoculation developed sarcomas with higher incidence and with a shorter latency. Furthermore, the MSV recovered from these early tumors proved to be the original Moloney pseudotype.
HOST-PARASITE INTERACTION IN THE RAT RENAL PELVIS
Authors: Silverblatt Fredric J. 
Published: June 2004

The initial interaction between bacteria and the renal pelvic epithelium may determine whether intrarenal infection occurs. A model of retrograde pyelonephritis was employed to study these events by electron microscopy. Female rats received an intravesicular inoculation of a 0.5-ml suspension of Proteus mirabilis containing 108 organisms. At intervals after inoculation, the kidneys were fixed by intravascular perfusion and the tissues were prepared for electron microscopy.
During the first 24 h, increasing numbers of bacteria were seen to be attached by pili to the renal pelvic epithelial cells. The organism appeared to cross the mucosal barrier by several mechanisms: (a) penetration into the cytoplasm of intact epithelial cells, (b) passage between epithelial cells that were separated by excessive hydrostatic pressure generated during bladder inoculation, (c) passage across necrotic regions of the pelvis, and (d) translocation to the cortex by calicotubular backflow.
Whereas at inoculation bacteria possessed pili 40 Å in diameter (type III pili) 24 h after reflux, the predominant type of pili measured 70 A in thickness (type IV pili). Repetitive subculture induced a similar transition in vitro. To assess the influence of pili type on virulence in this model, 80 rats were challenged with either type III or type IV pilated organisms and the frequency of rats with cortical abscesses were compared at 1 wk. A significantly greater number of rats inoculated with type IV pilated Proteus manifested macroscopic evidence of infection. These results suggest that pili play a role in the pathogenesis of ascending pyelonephritis.
Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor
Authors: Germain RN , Dorf ME , Benacerraf B 
Published: June 2004

After appropriate in vivo or in vitro immunization, cytotoxic T lymphocytes (CTL) are generated which efficiently kill cells bearing particular membrane antigens in common with the immunizing cell (reviewed in reference 1). Such CTL have been most thoroughly studied in mice, employing alloimmunization with cells differing at the major histocompatibility locus, H-2. in such cases, the predominant cell surface antigens recognized by the CTL appear to be the molecules carrying the serologically defined H-2 specificities, coded for by the K and D regions of the H-2 complex (2). In other syngeneic models of cell-mediated specific cytolysis, involving lymphocyte chariomeningitis (LCM) virus- or ectromelia virus-infected cells or TNP-modified lymphoid cells, thymus-derived cells also constitute the main effector cell type. The CTL generated in these latter systems function most efficiently when virus-infected or TNP-modified target cells share identitites at the H-2K or H-2D loci with the effector CTL and stimulator cells (3-5).
Another set of experimental systems in which CTL are generated and play a significant biological role is that of immunity to tumor-associated antigens (TAA) (6). The nature of the TAA which the CTL recognize is only beginning to be understood. Several recent reports indicated the existence of physiochemical and/or antigenic relationships between TAA and H-2 antigens (7,8). These relationships, together with the genetic restrictions cited above in the generation of CTL involving products of the H-2K or H-2D loci suggested the possibility that in certain tumor systems, the TAA which are able to most effectively stimulate CTL responses might be structurally similar to, or linked with, the H-2K or H- 2D molecules on the tumor surface. It has been previously demonstrated in allogenic models that antisera specific for the appropriate H-2K or H-2D products present on a target cell could specifically block CTL-mediated lysis (1,9). This report demonstrates that certain anti-H-2 alloantisera specific for the target tumor cells can block lysis of those target cells mediated by syngeneic tumor-specific CTL effector cells.
Multiple H-2-linked immune response gene control of H-2D- associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region
Authors: Schmitt-Verhulst A , Shearer GM 
Published: June 2004

One of the more recent associations of the murine H-2 major histocompatibility complex (MHC) with immune function has been the finding that cytotoxic T-effector cells generated by sensitization with viral-infected (1-6), chemically modified (7-9), or weak transplantation antigen-associated (10,11) syngeneic cells can efficiently lyse target cells which express the same viral, chemical, or weak antigenic agent, and which share the H-2K and/or H-2D regions of the MHC with the responding and/or stimulating cells. Furthermore, an additional contribution of a gene(s) within the H-2 complex has been demonstrated which controls immune response potential (Ir genes) in the generation of cytotoxic effector cells to trinitrophenyl (TNP)-modified self components (12,13). In such studies it was found that certain B10 congenic strains generated good cytotoxic responses to both TNP- modified H-2K and H-2D region products, whereas other B10 congenic strains exhibited preferential or exclusive reactivity against TNP-modified H-2K region products. Some of these recombinant strains differing in response potential to TNP- modified H-2D products expressed the same haplotype at the D end, but differed at the K end of H-2. The low responsiveness observed in the B10.A strain to TNP-modified H-2D(d) when compared to B10.D2 and (B10.A x B10.D2)F(1) for the same specificity, suggested a role of dominant Ir genes which map in K, I-A, I-B, I-J, and/or I-E (12, 14).
In the present report an attemnpt was made to further map within the MHC the Ir gene(s) controlling cell-mediated lympholysis (CML) to TNP-modified H-2D(d), by using recombinant mouse strains on the A and B10 backgrounds. Irrespective of the genetic background, the s and k haplotypes at the K end generated high and low cytotoxic responses, respectively, to H-2D(d)-TNP. The intermediate responder and low responder status of the A.TL and A.AL strains, respectively, indicated that a gene mapping in the K region of H-2 influences response potential. Furthermore, the differences in the levels of cytotoxicity detected in the A.TH and A.TL strains suggested an additional I region influence. Taken together these findings raise the possibility that multiple genes mapping within different regions of the MHC control the level of T-cell-mediated cytotoxicity to chemically modified autologous cells.
Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes
Authors: Rollinghoff M , Starzinski-Powitz A , Pfizenmaier K , Wagner H 
Published: June 2004

Murine T lymphocytes sensitized in vitro against either allogeneic lymphocytes or syngeneic hapten-conjugated lymphocytes do differentiate into highly effective cytotoxic T lymphocytes (CTL) (1-3). In vivo immunization of T lymphocytes to the same antigens, however, results in the generation of only marginal cytotoxic activity (1,4,5). Recently we found that the weakness of in vivo generated cytotoxicity is not due to a failure of antigen-induced T-cell sensitization but rather due to suppression of the in vivo differentiation of sensitized CTL precursors into effective CTL(6). In keeping with this finding it was postulated that suppressor cells may regulate the in vivo differentiation of CTL.
We now report, that cyclophosphamide-sensitive T cells suppress the in vivo differentiation of antigen-specific CTL. Thus, pretreatment of mice with a single dose of cyclophosphamide (100 mg/kg) converts their state of low responsiveness to a state of high responsiveness.