bluuebunny/crossref_metadata_2025 huggingface dataset:
A NEUTROPHIL-DEPENDENT PATHWAY FOR THE GENERATION OF A NEUTRAL PEPTIDE MEDIATOR
Authors: Wintroub Bruce U. , Goetzl Edward J. , Austen K. Frank
Published: June 2004

A biologically active neutral peptide mediator is cleaved from a plasma protein substrate by an α-1-antitrypsin-inhibitable serine protease apparently residing on the membrane of the human neutrophil. The peptide mediator has an approximate mol wt of 1,000, and is distinguished from the kinin peptides by a neutral isoelectric point, susceptibility to inactivation by trypsin as well as chymotrypsin and activity on the isolated, atropinized, and antihistamine-treated guinea pig ileum with relatively little action on the estrous rat uterus. The neutrophil protease is fully inhibitable by DFP, trypsin inhibitors from lima or soy bean, and α-1-antitrypsin and is associated with the high mol wt fragments of the neutrophil and not the nuclear, lysosomal, or cytoplasmic subcellular fraction. The substrate has an approximate mol wt of 90,000 and is chromatographically separable from kininogen. The exquisite sensitivity of the neutrophil protease to α-1-antitrypsin was established both by inhibition with highly purified α-1-antitrypsin and by the inability of the protease to generate detectable neutral peptide in a homozygous (ZZ) α-1-antitrypsin-deficient patient without heat inactivation of the residual inhibitor. On the other hand, plasma from a (null) α-1-antitrypsin-deficient patient supported neutral peptide generation and revealed an additional factor which inactivated neutral peptide.
CHARACTERIZATION OF A NEW INTRA-H-2 RECOMBINANT
Authors: Dorf Martin E. , Lilly Frank , Benacerraf Baruj
Published: June 2004

This report characterizes the intra-H-2 crossover in the D2.GD mouse strain. Recombination occurred within the I region between the immune response (Ir) gene controlling immune responsiveness to ragweed extract (RE). Ir-RE, and the Ir gene governing responsiveness to the random linear terpolymers of glutamic acid and lysine with either tyrosine or pheylalanine (Ir-GLT and Ir-GLϕ). The Ir-RE gene was tentatively located in the Ir-1A subregion and the Ir-GLT and Ir-GLϕ gene(s) tentatively placed in the Ir-1B subregion. The importance of this recombinant strain to further studies on the fine structure of the I region is discussed.
THE VIRAL ENVELOPE GLYCOPROTEIN OF MURINE LEUKEMIA VIRUS AND THE PATHOGENESIS OF IMMUNE COMPLEX GLOMERULONEPHRITIS OF NEW ZEALAND MICE
Authors: Yoshiki Takashi , Mellors Robert C. , Strand Mette , August J. T.
Published: June 2004

The use of monospecific antisera for the analysis by radioimmunoassay and immunofluorescence study of two major viral proteins, gp69/71 and p30 of murine leukemia virus, that could be of significance in the pathogenesis of immune complex glomerulonephritis of mice, particularly NZB and B/WF1 hybrid mice, yielded the following conclusions. A remarkably high concentration of viral envelope glycoprotein, gp69/71, was detected in the spleen and serum of New Zealand mice (NZB, NZW, B/WF1, and W/BF1); the concentration in the spleen was 10-fold greater than that found in AKR mice and 30-fold greater than that present in C57BL/6 mice. The gp69/71 was deposited along with bound immunoglobulins, apparently as an immune complex, in the diseased kidneys of mice, and the glomerular site and extent of deposition of gp69/71 was related to the severity of the glomerulonephritis. This study suggests that the pathogenesis of immune complex glomerulonephritis (and vasculitis) in mice is related to the expression of this specific viral envelope glycoprotein and to the host immune response to this protein.
IMMUNOPATHOGENICITY AND ONCOGENICITY OF MURINE LEUKEMIA VIRUSES
Authors: Croker Byron P. , del Villano Bert C. , Jensen Fred C. , Lerner Richard A. , Dixon Frank J.
Published: June 2004

This report clearly demonstrates that a systemic lupus erythematosus (SLE)-like syndrome and lymphoma can be induced in immunologically normal (BALB/c x NZB)F1 mice by infection of neonates with a murine leukemia virus (MuLV) (Scripps leukemia virus [SLV] 60A) isolated from NZB lymphoblasts. SLV 60A was titered in vitro (XC test) and administered to newborn and adult (BALB/c x NZB)F1 mice over six log10 dilutions. Propagation of MuLV in the newborn recipients was indicated by greatly elevated serum Mu gs-1 levels which were proportional to the dose of virus given.

The SLE-like syndrome was characterized by antinuclear antibodies (ANA) and immune complex-type glomerulonephritis. ANA production was related to the dose of virus and reached the highest levels at 8–16 wk. The incidence of glomerulonephritis was also correlated with the dose of virus and reached nearly 50% in the animals given the highest virus dose. Both titers of ANA and incidence of glomerulonephritis were greater in females than in males, although the amounts of Mu gs-1 in sera of both sexes were equal. The incidence of direct Coombs' positivity was not significantly affected by inoculation of this virus.

The incidence and time of onset of thymocytic lymphoma were linearly related to the amount of virus inoculated. High serum Mu gs-1 levels predicted lymphoma development and reflected increases in the amount of infectious virus in the spleen. No induction of tumors, autoimmunity, or high serum Mu gs-1 levels followed administration of SLV 60A to 6-wk old (BALB/c x NZB)F1 mice or inactivated 60A or active AKR virus to newborns.
THE INVOLVEMENT OF LACTOFERRIN IN THE HYPOSIDEREMIA OF ACUTE INFLAMMATION
Authors: van Snick Jacques L. , Masson Pierre L. , Heremans Joseph F.
Published: June 2004

The hyposideremia of inflammation was found to be based on a three-step mechanism involving lactoferrin, the iron-binding protein from the specific granules of neutrophilic leukocytes.

(a) Lactoferrin is Released from Neutrophils in an Iron-Free Form. When phagocytosis was induced in neutrophils by zymosan or bacteria, lactoferrin was recovered in the incubation medium together with other constituents of the specific granules, such as alkaline phosphatase and lysozyme. Lactoferrin extracted from leukocytes was able to bind the amount of iron corresponding to its theoretical iron-binding capacity. After injection of endotoxin into rats, lactoferrin was detected in various tissues where it was normally absent, or in the plasma when the reticuloendothelial system (RES) had previously been blocked by injections of India ink or aggregated albumin.

(b) Lactoferrin is Able to Remove the Iron from Transferrin. Significant exchange of iron from transferrin to lactoferrin was observed in vitro only at a pH below 7.0 or in the presence of a high concentration of citrate. However, the fast elimination of lactoferrin in vivo, when saturated with iron, might account for the observed transfer of iron to endogenous or administered apolactoferrin. Intravenous injection of human apolactoferrin into rats caused a marked decrease of the plasma iron level. The kinetics of this process, as well as controls with other proteins, ruled out the possibility of a secondary inflammatory effect due to phlogogenic contaminants.

(c) Fe-Lactoferrin is Taken-up by the RES. By immunofluorescence, lactoferrin was shown to be bound and ingested by monocytes. The rate of elimination of human Fe-lactoferrin injected into rats was particularly fast when compared to that of human apolactoferrin, succinylated Fe-lactoferrin, or other human proteins. Blockade of the RES slowed down the rate of clearance of Fe-lactoferrin and was also found to retard the elimination of endogenous rat lactoferrin released by endotoxin. These experiments suggest the existence of specific receptors for Fe-lactoferrin on the membrane of macrophages.
BINDING OF SOLUBLE IMMUNE COMPLEXES TO HUMAN LYMPHOBLASTOID CELLS
Authors: Theofilopoulos Argyrios N. , Dixon Frank J. , Bokisch Viktor A.
Published: June 2004

In the present work we studied the expression of membrane-bound Ig (MBIg) as well as receptors for IgG Fc and complement on nine human lymphoblastoid cell lines. When MBIg and receptors for IgG Fc were compared, four categories of cell lines could be distinguished: (a) cell lines having both MBIg and receptors for IgG Fc, (b) cell lines having MBIg but lacking receptors for IgG Fc, (c) cell lines lacking MBIg but having receptors for IgG Fc, and (d) cell lines lacking both MBIg and receptors for IgG Fc. Two types of receptors for complement could be detected on the cell lines studied, one for C3-C3b and one for C3d. When sensitized red cells carrying C3b or C3d were used for rosette tests, three categories of cell lines could be distinguished: (a) cell lines having receptors for C3b and C3d, (b) cell lines having receptors only for C3d and (c) cell lines lacking both receptors. However, when a more sensitive immunofluorescent method was used instead of the rosette technique, it was found that cell lines unable to form rosettes with EAC1423bhu were able to bind soluble C3 or C3b which indicated the presence of these receptors on the cell surface. Inhibition experiments showed that receptors for C3-C3b and receptors for C3d are distinct and that receptors for C3-C3b and C3d are different from receptors for IgG Fc.

A cell line (Raji) without MBIg but with receptors for IgG Fc, C3-C3b, and C3d was selected for use in studying the binding mechanism of soluble immune complexes to cell surface membrane. Aggregated human gamma globulin was used in place of immune complexes. Immune complexes containing complement bind to Raji cells only via receptors for complement, namely receptors for C3-C3b and C3d. Binding of immune complexes containing complement to cells is much greater than that of complexes without complement. Immune complexes bound to cells via receptors for complement can be partially released from the cell surface by addition of normal human serum as well as isolated human C3 or C3b. We postulate that such release is due to competition of immune complex bound C3b and free C3 or C3b for the receptors on Raji cells.
RESTRICTION OF GENE EXPRESSION IN B LYMPHOCYTES AND THEIR PROGENY
Authors: Jones Patricia P. , Cebra John J.
Published: June 2004

Fluorescent antibody staining with antibodies to the f and g locus allotype markers present on rabbit α-chains revealed that the α-chain is the heavy chain on the Peyer's patch lymphocytes which previously had been shown to be the precursors of IgA-producing plasma cells. In addition, lymphocytes which had been stripped of membrane Ig with pronase and then cultured overnight to allow the sole expression of endogenous membrane Ig were found to have either the µ-chain or the α-chain on their membranes, but not both. These results suggest that most lymphocytes are restricted to the synthesis of one class of heavy chains at a time and that the commitment to synthesizing that particular heavy chain is maintained during the differentiation of lymphocytes into plasma cells.

The proportion of lymphocytes with membrane α-chains is higher in the Peyer's patch and appendix, two gut-associated lymphoid tissues (GALT), than in other lymphoid tissues. Since the GALT are enriched sources of precursors for IgA-producing plasma cells compared to nongut-associated tissues, the presence of cells bearing membrane α-chains correlates well with the relative abilities of these tissues to generate IgA plasma cells.
GENETIC CONTROL OF THE IMMUNE RESPONSE
Authors: Lonai Peter , McDevitt Hugh O.
Published: June 2004

In vitro antigen-induced tritiated thymidine uptake has been used to study the response of sensitized lymphocytes to (T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L in responder and nonresponder strains of mice. The reaction is T-cell and macrophage dependent. Highly purified T cells (91% Thy 1.2 positive) are also responsive, suggesting that this in vitro lymphocyte transformation system is not B-cell dependent. Lymphocytes from high and low responder mice stimulated in vitro react as responders and nonresponders in a pattern identical to that seen with in vivo immunization. Stimulation occurs only if soluble antigen is added at physiological temperatures; antigen exposure at 4°C followed by washing and incubation at 37°C fails to induce lymphocyte transformation. Stimulation is specific for the immunizing antigen and does not exhibit the serologic cross-reactivity which is characteristic of these three antigens and their respective antisera. The reaction can be inhibited by anti-H-2 sera but not by anti-immunoglobulin sera. The anti-immunoglobulin sera did, however, inhibit lipopolysaccharide or pokeweed mitogen stimulation. These results suggest that the Ir-1A gene(s) are expressed in T cells, and that there are fundamental physiologic differences between T- and B-cell antigen recognition.
GENETIC CONTROL OF RESPONSES TO BACTERIAL LIPOPOLYSACCHARIDES IN MICE
Authors: Watson James , Riblet Roy
Published: June 2004

In vivo immune responses and in vitro mitogenic responses to bacterial lipopolysaccharides (LPS) have been compared in strains of C3H mice. C3H/HeJ spleen cultures did not support mitogenic responses to LPS and in vivo these mice produce low IgM responses to LPS. On the basis of these two responses, C3H/HeJ mice have been termed low LPS responders. All other strains of C3H mice tested (C3HeB/FeJ, C3H/DiSn, C3H/Str, CWB, CSW, and C3H/Sf and its H-2 congenics) are high LPS responders supporting large in vitro mitogenic and in vivo immune responses to LPS. The immune response difference between low and high LPS responders is a quantitative one. IgM responses are observed in C3H/HeJ mice in the range of 1.0–10 µg LPS. At lower and higher LPS concentrations, immune responses are not observed. In contrast, high LPS responders elicit LPS immune responses over a much wider dose range (0.1–200 µg). The ability to respond well to LPS is dominant as shown by the response of F1 hybrid mice of low responder and high responder strains. The linkage relationships of mitogenic and immune responsiveness to LPS have been investigated in backcross (C3H/HeJ x CWB)F1 x CWB mice. All mice that gave in vivo immune responses to LPS also supported mitogenic responses to LPS. The defect in C3H/HeJ mice that limits mitogenic and immune responsiveness to be due to a single autosomal gene which is not linked to the H-2 histocompatibility or heavy-chain allotype loci.
MACROPHAGE-LYMPHOCYTE CLUSTERS IN THE IMMUNE RESPONSE TO SOLUBLE PROTEIN ANTIGEN IN VITRO
Authors: Nielsen Morten H. , Jensen Henning , Brændstrup Otto , Werdelin Ole
Published: June 2004

Macrophage-lymphocyte clusters are formed when lymph node cells and autologous peritoneal exudate cells from guinea pigs immunized with tubercle bacilli are cultured in the presence of purified protein derivative of tuberculin (PPD) for 20 h. We have studied the ultrastructure of these clusters employing transmission and scanning electron microscopy. The most simple macrophage-lymphocyte cluster consisted of one macrophage, one large central lymphocyte with a blastoid appearance attached to the macrophage with a broad area of contact, and from a few to more than 20 small peripheral lymphocytes attached to the central lymphocyte by their uropods. Some clusters were of more complex type, containing two or three macrophages or one macrophage with more than one central lymphocyte attached to the surface, but even in these clusters each peripheral lymphocyte was attached only to one central lymphocyte. By morphological criteria the peripheral lymphocytes were T lymphocytes.
GENETIC CONTROL OF CELL-MEDIATED LYMPHOLYSIS IN MOUSE
Authors: Schendel Dolores J. , Bach Fritz H.
Published: June 2004

H-2 congenic mouse strains were tested in vitro to investigate the genetic control of cell-mediated lympholysis (CML). Combinations were selected such that differences in various segments of H-2 could be examined for their ability to stimulate production of effector cells and to serve as targets for lysis. Particular emphasis was directed towards understanding the roles of LD and SD.

SD-region differences are important in the sensitization of effector cells and they also function as strong targets for lysis, or as markers for the CML targets. LD differences are also important for sensitization of cytotoxic effector cells, but they serve only as very weak targets for lysis.

Collaboration occurs between LD and SD in generation of CML. The nature of this interaction can be of two types: together LD and SD can produce CML which neither difference alone can stimulate; LD can enhance a CML response stimulated by SD-region differences alone.
REGULATORY MECHANISMS IN CELL-MEDIATED IMMUNE RESPONSES
Authors: Rich Susan Solliday , Rich Robert R.
Published: June 2004

Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.
Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T cells.
Authors: Shiku H , Kisielow P , Bean M A , Takahashi T , Boyse E A , Oettgen H F , Old L J
Published: June 2004

The cell-mediated cytotoxicity (CMC) of nonadherent cells from the peritoneal cavity (NAPC) of alloimmunized mice can be measured by the [3H]proline microassay. The exhibition of thymus-derived (T) cell antigens on these killer cells was studied by incubating them with the relevant T-cell antisera and complement (C), under optimal conditions for lysis, before performance of the CMC assay. Under these conditions, the following T-cell antigens were demonstrable on the killer population in terms of percent reduction in CMC by the respective antisera: (a) Thy-1.1 (83%) and Thy-1.2 (100%), (b) MSLA (86%), (c) NTA-RA (a T-cell antigen recognized by naturally occurring autoantibody of NZB mice) (62%), (d) Ly1.1 )58%, (e) Ly-2.1 (11%; considered a marginal result) and Ly-2.2 (63%), and (f) Ly-3.2 (77%). The following were not demonstrable: (g) TL, and (h) Ly-1.2. (i) The antigen Ly-3.1 was not studied. Omission of C deprived all T-cell antisera tested of their capacity to suppress CMC, indicating that the cell components recognized by such antisera may perform no direct function in CMC. On the assumption that all Ly+ cells are Thy-1+, it is clear that the T-cell members of the immune NAPC population must be heterogenous. This follows from the fact that the proportions of T cells lysed by different Ly antisera did not correspond with ensuing degree of loss of CMC capacity. The extremes were represented by anti-Ly-1.2 (74% Thy-1+ cells lysed, but no reduction in CMC) and Ly-3.2 (54% Thy-1+ cells lysed, with 77% reduction in CMC). From this initial survey it appears that the C57BL/6 mice killer T-cell population active in CMC in vitro is relatively rich in surface antigens of the Ly-2/Ly-3 category and relatively poor in representation of the Ly-1 surface antigens. It remains to be seen whether this killer cell phenotype, poor in Ly-1 and rich in Ly-2/Ly-3, is characteristic of the mouse generally. From these results it appears that subsets of T cells with different immunological functions may exhibit qualitative or quantitative differences in surface antigens specified by different Ly loci; this will be easier to assess in the future when the results of experiments with the same Ly antisera but dealing with T-cell functions other than CMC become available.
Guinea pig immune response-related histocompatibility antigens. Partial characterization and distribution.
Authors: Findelman F D , Shevach E M , Vitetta E S , Green I , Paul W E
Published: June 2004

We have previously demonstrated that guinea pig alloantisera directed at strain 2 and strain 13 membrane antigens block specific lymphocyte activation in immune response gene-controlled systems. In this communication we describe the partial characterization of the antigens against which these antisera are directed (the 2 and 13 antigens) and, in addition, that of the B antigen which by distribution resembles the human HL-A and mouse H-2 major histocompatibility antigens. Lymphoid cells from strain 2 and strain 13 guinea pigs were surface labeled with 125I by the lactoperoxidase technique. Nonidet P-40 extracts of these labeled cells were precipitated by sandwiches of strain 2 antistrain 13, strain 13 antistrain 2, or outbred anti-B antisera, followed by rabbit antiguinea pig immunoglobulin antisera. Precipitates were dissolved in sodium dodecyl sulfate (SDS) and electrophoresed on SDS polyacrylamide gels. Radioactive peaks representing the 2 and B-cell membrane antigens were obtained from strain 2 lymph node cells, as well as from a B-lymphoid cell population (L2C leukemia cells) and a T-lymphocyte population (STRAIN 2 PERITONEAL EXUDATE LYMPHOCYTES [PELs]). Radioactive peaks representing the 13 and B-cell membrane antigens were obtained from strain 13 lymph node cells and strain 13 PELs. All anti-B precipitates produced two peaks when electrophoresed on SDS polyacrylamide gels; one representing an antigen with a mol wt of approximately 45,000, and one representing an antigen with a mol wt of about 12,000. Both may be components of a single protein. All anti-2 and anti-13 precipitates produced a single peak when electrophoresed on SDS polyacrylamide gels. Both the 2 and 13 antigens were found by this technique to have mol wt of approximately 25,000. By molecular weight criteria, as well as by previously investigated distributional criteria, the B antigen is similar to the human LA and Four antigens, and to the mouse D and K antigens, and the 2 and 13 antigens are similar to the mouse Ia antigens.
Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response.
Authors: Murgita R A , Tomasi T B
Published: June 2004

Mouse amniotic fluid was shown to contain a noncytotoxic inhibitor of primary gammaM and secondary gammaM, gammaG subclass splenic plaque forming cells in vitro to SRBC. The suppressive effect was not abolished by exhaustive dialysis or by absorption of mouse amniotic fluid (MAF) with SRBC. Polyacrylamide gel analysis showed that dialyzed MAF was composed of three major protein components, transferrin, albumin, and alpha-fetoprotein (AFP). The selective removal of each of these patients from MAF by affinity chromatography suggested that AFP was the immunosuppressive substance in MAF. This conclusion was verified by the demonstration that pure AFP suppressed in vitro antibody synthesis in microgram quantities whereas equivalent amounts of normal mouse serum, transferrin, or albumin did not. Dose-response studies showed that the effect of AFP in the isolated form was equivalent to the suppressive effect of comparable amounts of AFP in MAF. gammaA and gammaG plaque-forming cell (PFC) responses were suppressed by a significantly lower concentration of AFP than was the gammaM PFC response. The degree of suppression watration of AFP than was the gammaM PFC response. The degree of suppression was dependent on the time at which AFP was added to the cultures; MAF added to antigen-stimulated cultures up to 24 h after initiation of cultures was immunosuppressive whereas similar additions of MAF at 48 h after initiation or later did not suppress. The duration of exposure of spleen cells to MAF in cultures without antigen necessary to achieve suppression of a subsequent primary immune response was determine-d to be approximately 8 h. The results suggest that AFP may have an immunoregulatry function. This has potentially important implications in the maternal-fetal relationship, the immune capabilities of the fetus and newborn, and in certain malignant and nonmalignant diseases in which AFP is elevated.
Inhibition of multiplication of Toxoplasma gondii by human monocytes exposed to T-lymphocyte products.
Authors: Borges J S , Johnson W D
Published: June 2004

The multiplication of Toxoplasma gondii was quantitated in human monocytes in vitro by phase-contrast microscopy. Toxoplasma multiplication was identical in monocytes from subjects byt was significantly inhibited in cells from both sources if the monocytes were preincubated with immune lymphocytes and toxoplasma monocytes were preincubated with immune lymphocytes and toxoplasma antigen. Supernates prepared from toxoplasma-immune lymphocytes incubated with toxoplasma antigen were also effective in inducing in monocytes the capacity to inhibit toxoplasma multiplication. Supernative acitivty was evident after lymphocytes and antigen were incubated for as little as 15 min. The instruction of monocytes was also repid and reversible. Monocytes were fully induced to inhibit toxoplasma multiplication after a 2 h exposure to an active supernate, but they lost their inhibitory capacity on culture in vitro for 48 h in the absece of immune cells or their products. The lymphocytes particupating in the monocyte induction were identified as t cells. The in vitro stimulation of monocytes appeared to exhibit some specificity, since no inhibition of toxopreotein derivative and lymphocytes from tuberculin-positive subjects, concanavalin a-stimulated lymphocytes, or their supermates. Supernates which induced monocytes to inhibit toxoplasma multiplication did not influence parasite growth in HeLa cells.
Interaction of soluble fibroblast surface antigen with fribrinogen and fibrin.
Authors: Ruoslahti E , Vaheri A
Published: June 2004

A cell-type specific glycoprotein antigen (SFA) from fibroblast surface appears in human plasma and serum. The amount of SFA in serum was reduced if the blood coagulation clot was removed at a low temperature. SFA could be bound to Sepharose-conjugated fibrinogen and to fibrin powder at 0 degrees C and was subsequently released when the temperature was elevated to plus 37 degrees C. This procedure resulted in a 10-fold enrichment of SFA relative to other serum proteins. SFA was found to be concentrated in the cryoprecipitate fraction of human plasma and was copurified with the cold insoluble globulin (CIG) with procedures published for the purification of the latter component. SFA/CIG is not soluble at low temperatures as such and its appearance in the cryoprecipitate fraction of plasma is likely to be due to its affinity to cryofibrinogen evident from these experiments. The biological significance of the interaction of fibroblast surface SFA moleculres with fibrin(ogen) is not known.
H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus.
Authors: Doherty P C , Zinkernagel R M
Published: June 2004

Maximal cell-mediated lysis of targets infected with lymphocytic choriomeningitis virus occurs only within a H-2 compatible system. Syngeneic immune spleen cells are at least 100 times as effective as are allogeneic lymphocytes. Reciprocal restriction of cytotoxic T-cell activity has been shown to operative between H-2k, H-2d, and H-2b. Experiments with cogenic mice have localized the effect to the H-2 gene complex. Furthermore, the observation that lymphocytes from H-2a mice cause high specific 51Cr release from either H-2d virus-infected cells, indicates that identity at either the K or the D end of the H-2 gene complex is sufficient for this lytic interaction.
Competition between concanavalin A-induced stimulatory and inhibitory effects in the in vitro immune response to antigen.
Authors: Scavulli J , Dutton R W
Published: June 2004

The humoral response of nude spleen cells (b cells) to sheep erythrocytes was measured in the presence of varying numbers of concanavalin A (ConA)-acvated stimulatory spleen T cells (helper) and Con A-activated inhibitory spleen T cells (suppressor) from BDF1 mice. It was found that suppressive effects could be reversed by the presence of additional numbers of stimulatory cells. These results seem incompatible with the hypothesis that suppression is mediated by supraoptimal numbers of stimulatory cells and provides additional evidence that separate populations of T cells mediate stimulation and suppression.
Role of C'3 and Fc receptors in B-lymphocyte activation.
Authors: Möller G , Coutinho A
Published: June 2004

Attempts were made to identify the non-Ig lymphocyte receptor responsible for B-cell induction by antigen and polyclonal B-cell activators (PBA). As a first step, the role of C'3 and Fc receptors was analyzed. It was shown that complement could be fixed onto B cells to such an extent that the lymphocytes could not bind complement-coated red cells, but this did not result in induction of polyclonal antibody synthesis, nor did it inhibit the lymphocytes response to PBA. However, the C'3 receptros possessed a passive focussing role in the induction of polyclonal antibody responses. Thus, PBA that had fixed complement activated polyclonal responses at lower concentrations than the same substances that had not fixed complement. Most likely the dual binding of PBA molecules to B cells by the PBA and the C'3 receptors caused more PBA molecules to be bound to each cell. However, the focussing function of the C'3 receptors was several orders of magnitude smaller than that of the Ig receptors. Analogous studies were carried out with Fc receptors. Binding of different types of antigen-antibody complexes did not cause activation of polyclonal or specific antibody synthesis, nor did it significantly interfere with induction of antibody synthesis by PBA substances.
Colchicine effects on lysosomal enzyme induction and intracellular degradation in the cultivated macrophage.
Authors: Pesanti E L , Axline S G
Published: June 2004

The effects of colchicine on lysosomal fusion and lysosomal enzyme induction in the cultivated mouse peritoneal macrophage have been examined. Colchicine (10- minus 6 M), but not lumicolchicine, inhibited lysosomal enzyme induction by both phagocytic and pinocytic stimuli. In addition, the drug significantly retarded pinocytic uptake of [3-H] sucrose and transport of the amino acids [3-H] alpha aminoisobutyric acid and L-[3-H] leucine. In contrast, lumicolchicine had no effect on pinocytosis or amino acid transport. Thus, a role for intact microtubules in lysosomal enzyme induction, pinocytosis, and amino acid uptake in these cells is suggested. That colchicine inhibited lysosomal enzyme induction by phagocytic stimuli under conditions in which pinocytosis contributed little to the enzyme rise indicated that inhibition of pinocytosis was unlikely to account for colchicine effects on lysosomal enzyme induction. Effects of colchicine on degradation of phagocytized and pinocytized substrates were examined to determine if intact microtubules are required for fusion among lysosomes, pinosomes, and phagosomes. Colchicine did not alter the rate of intracellular digestion of radiolabeled bacteria by the cultivated macrophage. Similarly, it had no effect on enzymatic hydrolysis of intracellular [3-H] sucrose resulting from uptake of exogenous invertase. The finding that colchicine had no effect on the functional consequences of fusion of lysosomes with endosomes suggests that intact microtubules are not required for fusion among these constituents of the vacuolar apparatus.
Lymphocyte-induced angiogenesis: a quantitative and sensitive assay of the graft-vs.-host reaction.
Authors: Sidky Y A , Auerbach R
Published: June 2004

A new and sensitive assay for the effect of intracutanous administration of immunocompentent lymphocytes into the skin of irradiated unimmunized mice is described. The assay, which we have termed lymphocyte-induced angiogenesis (LIA) involves enumeration of new vascular branches induced by the action of these competent cells. As is the case for the previously described normal lymphocyte transfer reaction, LIA is a manifestation of the graft-vs.-host reaction, as shown by experiments utilizing appropaiate genetic combinations. The reaction is dose-dependent, and within the dose range of 2 times 10 minus 5 -4 times 10-6 cells the mumber of vessels induced correlates with the mumber of immunocompetent cells injected. At these dose levels spleen, lumph node, and hydrocortisone-resistant thymocytes are effective; bone marrow and thymus cells are not. Spleen cells from nude mice are incapable of inducing LIA, while mitomycin-C and irradiated lymphocytes can initiate but not maintain the reaction. The relationship between lymphocyte-induced angiogenesis has been discussed as have the implications of these findings to delayed hypersensitivity, inflammation, and vascular pathology.
Tumor-secific immunity to chemically induced tumors. Evidence for immunologic specificity and shared antigenicity in lymphocyte responses to soluble tumor antigens.
Authors: Frbes J T , Nakaw Y , Smith R T
Published: June 2004

Experiments were designed to explore the apparent paradox that methylcholanthrene-induced tumors of mice evoke tumor-unique transplantation immunity but reveal almost complete cross-reacting antigenicity in tests of lymphocyte behavior in vitro. The approach involved use of tumor membranes solubilized in 3 M KCl, employed both as the stimulating antigen source in a new in vitro proliferation assay of lymphocyte recognition, and as immunogens in vivo. The kinetics of the assay resembled those of in vitro tests of mitogen or specific antigen stimulation in other systems. Lymphoid cell proliferation was assessed in peripheral blood leukocytes, lymph nodes (LN), and spleen over the course of tumor bearing, and in animals immunized by tumor amputation or with the solubilized antigens. The pattern of spread of reactivity was from regional LN to spleen, peripheral blood, and nonregional nodes in each circumstance. An unexplained low antigen dose inhibitory phenomenon was encountered in spontaneously proliferating cell subpopulations taken from some tumor-bearing animals. In vitro responses to some but not all solubilized antigens made from multiple syngeneic tumors were detected in each circumstance. The soluble antigens also induced shared resistance to some tumors. The patterns of spread of responsiveness to syngeneic tumor antigens, the time-course, and relative intensity were most compatible with independent clonal responses to multiple tumor-borne antigens, some but not all of which are shared in any family of syngeneic tumors.
Interactions of Fc receptors with antibodies against Ia antigens and other cell surface components.
Authors: Schirrmacher V , Halloran P , David C S
Published: June 2004

Two Fc receptor-dependent tests were investigated to study the question of a relationship between Fc receptors and known cell surface antigens, in particular I region-associated (Ia) antigens: (a) a rosette assay with antibody-coated erythrocytes (EA) as indicator cells and normal mouse lymphoid cells as source of rosette-forming cells, and (b) a cytotoxicity test with antibody-coated erythrocytes as target cells and normal mouse spleen cells as a source of cytotoxic cells (K cells). EA rosettes were specifically inhibited by antibodies reacting with Ia antigens. Various other antisera reacting with antigens on B lymphocytes, like anti-Ly 4.2 (raised in H-2 identical mice), rabbit antimouse B-cell serum, or rabbit antimouse immunoglobulin, also specifically inhibited the rosettes. No inhibition occurred in the presence of allogeneic or xenogeneic antisera reacting with T lymphocytes. K-cell cytotoxicity was specifically inhibited by each of the antisera (reacting with either B cells or T cells). F(ab')2 fragments of anti-Ia antibodies could still specifically inhibit EA rosettes but they could not inhibit K-cell cytotoxicity. Similar results were obtained with F(ab')2 fragments of anti-immunoglobulin antibodies. These results indicate that the mechanism of inhibition of Fc receptors in the two tests was different. In neither of the tests could we find any evidence for a unique association between the Fc receptors and Ia antigens. The Fc receptors on K cells did not seem to be associated at all with Ia antigens.
The mechanism of action of the C3b inactivator (conglutinogen- activating factor) on its naturally occurring substrate, the major fragment of the third component of complement (C3b)
Authors: Gitlin JD , Rosen FS , Lachmann PJ
Published: June 2004

The fixation of the third component of complement (C3) results in many important biological phenomenon, among which are (a) immune adherence (1), (b) enhancement of phagocytosis (2,3), (c) the release of an anaphylatoxin which is a potent releaser of histamine (4), and (d) the feedback activation of the alternative pathway (5,6). The physiological mechanisms involving C3 fixation require the generation of a C3 convertase which may occur by two separate pathways. C3 convertase can be generated, in the form of C42, by the so-called classical pathway of activation or in the form C3b,B by the alternative or properdin pathway (7). In both cases, C3 is converted to C3b by cleavage of a small peptide, C3a. Normal human serum contains an inactivator of activated C3b. This C2b inactivator or conglutinogen-activating factor (KAF) has been shown to inhibit both immune hemolysis and the immune adherence properties of C3b and to cause cleavage of C3b in the fixed and fluid- phase stages (8-11).

Although it is known that the C3b inactivator is not depleted during its reaction with C3b and that C3b treated with the C3b inactivator becomes extremely sensitive to proteolytic digestion by trypsin and trypsin-like enzymes (9), the exact molecular nature of the action of the C3b inactivator on C3b has not been studied. In an effort to delineate the products of this interaction, purified C3b and C3b inactivator were allowed to react for various specific lengths of time and the products of these reactions were then analyzed.
Enhancement of blood coagulation by soluble fibrin complexes.
Authors: Hansen M S , Bang N U , Barton R D , Mattler L E
Published: June 2004

We have detected a species of soluble fibrin complexes with significant biological properties. Agarose gel chromatography of normal plasma or purified fibrinogen previously incubated with small amounts of thrombin revealed the presence of a species of high molecular weight soluble fibrin complexes, which contained only small quantities of fibrinogen by immunological assays but which exhibited enhanced sensitivity to thrombin. In addition, these complexes substantially shortened the thrombin-clotting time of normal plasma and enhanced the resistance of normal plasma to heparin action. Similar thrombin-sensitive soluble fibrin complexes were demonstrated in vivo in rabbits for up to 10 min after the infusion of 50 U of thrombin. Thrombin-sensitive soluble fibrin complexes were also demonstrated in 3 of 12 patients with documented thromboembolic disease and in 2 of 20 patients after major surgery. High molecular weight soluble fibrin complexes, which exhibit enhanced thrombin sensitivity and which are capable of increasing the rate of normal fibrinogen-to-fibrin conversion by thrombin, may appear consequent to clinical thrombosis and situations involving trauma (e.g., major surgery). Such soluble complexes, although they have no proven role in the primary pathogenesis of intravascular thrombosis, may contribute to a temporary "hypercoagulable state" and may accelerate the build-up and extension of already existing thrombotic deposits.
Rubella cataract in vitro: Sensitive period of the developing human lens.
Authors: Karkinen-Jääskeläinen M , Saxén L , Vaheri A , Leinikki P
Published: June 2004

The clinically known sensitive period of rubella cataract was studied in vitro by infecting 79 human eye rudiments from embryos aged 4-10 wk with rubella virus. The course of the infection was followed by histological and indirect immunofluorescence methods. Of the rudiments, 12 pairs were in the lens placode or open-lens-vesicle stage, 40 already had closed lens vesicles and in another 27 closed-stage pairs an incision was made in the lens capsule before infection to allow the virus to enter the lens. Uninfected controls differentiated well in vitro for 4-6 wk. The eye rudiments infected in the open-lens-vesicle stage showed lens fiber destruction and viral antigens within the lens. No damage or viral antigens were detected in rudiments infected in the closed stage unless the lens capsule was incisedmwhen this was done, however, fiber damage ensued and viral antigens appeared. The lens capsule was concluded to form a protective barrier around the sensirive fibers at the time of closure of the lens vesicle, confirming the earlier hypothesis and clinical findings.
Characterization of the macrophage receptro for complement and demonstration of its functional independence from the receptor for the Fc portion of immunoglobulin G.
Authors: Griffin F M , Bianco C , Silverstein S C
Published: June 2004

The complement receptor of the macrophage membrane recognizes particle-bound C3b but does not recognize particle-bound C3d. C3-b-coated sheep erythrocytes were bound to macrophages via their C3b receptors, and the preparations were then incubated with either latex particles or opsonized pneumococci (test particles). Macrophages ingested the test particles, but erythrocytes were not ingested; they remained bound to C3b receptors of the macrophage plasma membrane. Thus, a signal initiating ingestion via one type of receptor is not transmitted to all receptors which have the potential to mediate phagocytosis.
Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation.
Authors: Bianco C , Griffin F M , Silverstein S C
Published: June 2004

We have examined the roles of Fc receptors and complement receptors in mediating the interaction of sensitized sheep erythrocytes (E) with activated and with nonactivated mouse peritoneal macrophages. Both activated and nonactivated macrophages ingest IgG-coated erythrocytes [E(IgG)]; activated cells intest 1.5-2 times as man E(IgG) as do nonactivated macrophages. Thus, there is a quantitative difference in Fc receptor-mediated ingestion between activated and nonactivated macrophages. There is, however, a qualitative difference in function of complement receptors of activated and nonactivated macrophages. Nonactivated macrophages avidly bind complement-coated E [E(IgM)Ia1, but do not ingest them to a significant degree. Activated macrophages, on the other hand, bind and ingest E(IgM)C. The possibility of Fc receptor participation in mediating ingestion of E(IgM)C by activated macrophages was eliminated by blocking Fc receptors with an antimacrophage IgG fraction. Activated macrophages treated with antimacrophage IgG did not ingest E(igG) but did ingest both E(IgM)C AND E(IgM)C. Nonactivated macrophages treated with antimacrophage IgG did not interact at all with E(IgG). These cells bound, but did not ingest, E(IgM)C and E(IgM)C. Complement receptor-mediated ingestion is a marker for macrophage activation and may be physiologically important in the elimination of complement-coated particles.
The mechanism of tolerance induction in thymus-derived lymphocytes; I. intracellular inactivation of hapten-reactive helper T lymphocytes by hapten-nonimmunogenic copolymer of D-amino acids.
Authors: Hamaoka T , Yamaskita U , Takami T , Kitagawa M
Published: June 2004

Treatment of a p-azobenzoate (PAB) derivative of a copolymer of D-glutamic acid and D-lysine (D-GL) induced a profound state of unresponsiveness to PAB-reactive helper T lymphocytes generated in PAB-mouse gamma globulin (MGG)-primed mice. This unresponsiveness in T lymphocytes was specific for PAB-reactive cells, since the bacterial alpha-amylase-, keyhole limpet hemocyanin-, or ovalbumin-primed helper T lymphocytes were not suppressed by PAB-D-GL treatment. Taking advantage of the relative ease with which PAB-D-GL can induce specific unresponsiveness to helper T lymphocytes in an animal previously primed with PAB-MGG, it was possible to approach certain questions concerning the mechanisms of tolerance-induction and the fate of tolerant helper T lymphocytes in the PAB-D-GL model by utilizing a classical adoptive cell transfer systemmelimination of the possibility of carry-over of the tolerogen with cells or of the generation of suppressor cells as the result of PAB-D-GL treatment as an explanation of the suppression of helper T-cell activity strongly inplicates the existence of a central intracellular mechanism of specific tolerance on the helper T-cell level. The possibility that suppression of the activity of PAB-reactive helper T lymphocytes by PAB-D-GL reflects simple blocking of surface receptor molecules on T lymphocytes was ruled out as it was found that the helper activity of PAB-reactive cells was minimally suppressed even when PAB-D-GL was directly exposed in vitro to helper T lymphocytesmmoreover, the most conclusive evidence on te the tolerant state induced by in vivo exposure of primed T cells to PAB-D-GL. It appears, therefore, that specific tolerance induced by PAB-D-GL' TO PAB-reactive helper T lymphocytes is an example of irreversible inhibition of T-cell reactivity to antigen, reflecting yet to be determined events at the intra- and subcellular levels.
Experimental autoimmune myasthenia: A model of myasthenia gravis in rats and guinea pigs.
Authors: Lennon V A , Lindstrom J M , Seybold M E
Published: June 2004

Immunization of animals with acetylcholine receptor (AChR) protein from the electric organs of Electrophorus electricus and Torpedo californica induces an autoimmune response to the AChR of mammalian skeletal muscle. Rats and guinea pigs develop experimental autoimmune myasthenia gravis (EAMG) after a single inoculation with small quantities of AChR and adjuvant. The indicence and severity of disease appears to depend on the dose of AChR and stability of the emulsion. EAMG is strikingly similar to myasthenia gravis (MG) of man in its clinical picture and its electrophysiological abnormalities. The presence of antibodies to syngeneic rat muscle AChR in the serum of rats with EAMG documents the existence of autoimmunity in the experimental disease. A common immunopathogenesis is suggested for both EAMG and mg.
Polymorphonulcear leukocyte chemotaxis toward oxidized lipid components of cell membranes.
Authors: Turner S R , Campbell J A , Lynn W S
Published: June 2004

Polymorphonuclear leukocyte chemotaxis has been elicited by oxidized arachidonic acid and other oxidized polyenoic lipids in the Boyden micropore filter assay system. This chemotactic activity was observed in the absence of serum and chemotactic proteins. The esterfied arachidonic acid present in plasma membranes may be a precursor of chemotactic messages as well as prostaglandins in vivo.
Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system.
Authors: Clark R A , Klebanoff S J
Published: June 2004

A cytotoxic effect of human neutrophils on mammalian tumor cells is demonstrated. Cytotoxicity depends on the presence of intact neutrophils, phagocytosable particles, and a halide cofactor and is inhibited by azide, cyanide, and catalase. Neutrophils from patients with myeloperoxidase (MPO) deficiency or defective H1O2 production are not cytotoxic, but activity is resotred by addition of purified MPO or H2O2 respectively. The findings support a mechanism involving the phagocytosis-induced extracellular release of MPO and H2O2 and their reation with a halide cofactor to damage the target cells.