bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANTIGEN-SPECIFIC CELLS IN MOUSE BONE MARROW
Authors: Miller Harold C. , Cudkowicz Gustavo 
Published: June 2004

Quantitative and qualitative changes of mouse bone marrow cells were studied by limiting dilution assays 2–3.5 months after immunization of donors with sheep erythrocytes or unrelated antigens (Salmonella typhimurium, horse and chicken erythrocytes). Irradiated (C3H x C57BL/10)F1 mice were reconstituted with an excess of nonprimed thymocytes and small graded numbers of primed bone marrow cells. Direct and indirect plaque-forming cells (PFC) were induced by secondary stimulation with SRBC and enumerated on the 9th day after cell transplantation.
Marrow precursors of PFC (P-PFC) cooperated with thymocytes in the production of direct and indirect PFC after SRBC priming. The limiting dilution plots, which were not compatible with predictions of the Poisson model before immunization, changed and conformed to this model afterwards, as if the population of P-PFC had become functionally more homogeneous. The concentration of marrow P-PFC increased up to the 3rd month after priming, and decreased during the 4th, varying over two logarithms of nucleated marrow cells. The fluctuation was simultaneous and of the same order of magnitude for precursors of direct and indirect PFC, which were class restricted. A third effect of immunization was detected at 3.5 months: individual precursor units generated 3–4 times more direct and indirect PFC than at earlier intervals. Qualitative and quantitative changes of marrow P-PFC participating in anti-sheep responses were specific, since antigens unrelated to SRBC failed to induce them. The data suggested that marrow-derived cells were the major carriers of immunologic memory, but that they functioned in cooperation with thymus-derived inducer cells during secondary anti-sheep responses.
REGULATION OF THE IMMUNE RESPONSE: SUPPRESSIVE AND ENHANCING EFFECTS OF PASSIVELY ADMINISTERED ANTIBODY
Authors: Pincus Carolyn S. , Lamm Michael E. , Nussenzweig Victor 
Published: June 2004

The ability of passively administered antibody to suppress the immune response against homologous antigenic determinants while concomitantly enhancing the response against other unrelated determinants of the same antigen molecule has been established in two distinct antigen-antibody systems: (a) guinea pig γ2-immunoglobulin + passive anti-F(ab')2 antibody, where suppression of anti-F(ab')2 antibody synthesis is accompanied by enhancement of the anti-Fc response; and (b) human secretory IgA + passive anti-serum IgA antibody, where suppression of antibody production against the α and L chains accompanies augmentation of the response to the secretory component.
The mechanisms of the suppressive and enhancing effects are probably unrelated for the following reasons: (a) Enhancement of the response to certain determinants may be obtained without discernible suppression of the response to the homologous determinants; and (b) the F(ab')2 fragments of passive antibody can mediate immune suppression but were not observed to enhance the response against the unrelated determinants of the same antigen molecule. Also, the timing for achieving maximum suppression or enhancement of antibody formation is not the same; enhancement was obtained only at a later time.
Both the enhancement and suppressive effects were obtained with the purified γG fraction of antisera. This finding rules out an exclusive role of γM antibody in the enhancement phenomenon.
A MAJOR GENETIC LOCUS AFFECTING RESISTANCE TO INFECTION WITH MURINE LEUKEMIA VIRUSES
Authors: Pincus Theodore , Hartley Janet W. , Rowe Wallace P. 
Published: June 2004

Previous studies have indicated that all naturally occurring murine leukemia viruses propagate significantly more efficiently on embryo cells of either NIH Swiss or BALB/c mice.
Studies of the plaquing efficiency of representative viruses on embryo cells of various inbred and hybrid mice indicate that the pattern of sensitivity of the cells is genetically determined. All of 23 strains tested were found to resemble either NIH Swiss (N-type) or BALB/c (B-type) with respect to plaquing efficiency of these viruses. Virus growth on embryo cells derived from (N-type x B-type)F1 hybrids indicated dominance of resistance to both types of viruses. Backcross hybrid studies indicated that a single locus is the primary determinant of the host-range patterns observed. This locus has no effect on growth of certain laboratory-passaged leukemia viruses which propagate equally well on embryo cells of all mouse strains, F1, and backcross hybrids. Though other genetic and nongenetic factors influence viral growth or expression in vitro and in vivo, the genetic locus described appears of major significance in the biology of murine leukemia.
THE FUNCTIONAL DISSECTION OF AN ANTIGEN MOLECULE: SPECIFICITY OF HUMORAL AND CELLULAR IMMUNE RESPONSES TO GLUCAGON
Authors: Senyk George , Williams E. Brady , Nitecki Danute E. , Goodman Joel W. 
Published: June 2004

Bovine glucagon, a polypeptide of 29 amino acids, was immunogenic in guinea pigs. The immunologic determinants of glucagon were investigated using isolated tryptic peptides of the hormone. Antibodies from virtually all of more than two dozen animals had specificity primarily for the amino-terminal heptadecapeptide (NM) and showed little or no binding with the carboxy-terminal undeca- and dodecapeptides (C). The smallest synthetic peptide of a series initiated at residue 16 which measurably bound antibody comprised residues 5–16 of glucagon.
In cellular immune assays, both NM and C elicited delayed cutaneous reactions and inhibited the migration of peritoneal cells from immune animals. However, only intact glucagon and its C fragment stimulated lymphoid cells to synthesize DNA. While glucagon was somewhat more active than C, the addition of NM to C did not enhance its transforming activity. The smallest synthetic carboxy-terminal peptide with discernible transforming activity comprised residues 19–29 of glucagon. In both native and synthetic C peptide preparations, the undecapeptide was generally more active than the dodecapeptide, although cells from different animals gave different response patterns. The difference between the two is the presence of arginine at the amino-terminus of the peptide chain. Thus, the recognition specificity of populations of antigen-reactive cells from different animals displays a variation which is at least superficially analogous to that of populations of antibody molecules.
In limited experiments using NM and C peptides as immunogens, neither gave rise to delayed hypersensitivity or to glucagon-binding circulating antibody, following a regimen which invariably provoked these responses when glucagon itself served as the immunogen.
These results indicate that glucagon was cleaved by trypsin along functional lines into two parts, one of which housed the major antigenic determinant and the other of which carried the major immunogenic determinant, and they are highly compatible with a two-cell mechanism of immune induction. An apparent dissociation between the capacity to provoke delayed hypersensitivity reactions and to transform antigen-reactive cells in culture was observed.
THE DISTRIBUTION OF ANTIGENIC DETERMINANTS IN RAT SKIN COLLAGEN
Authors: Lindsley Herbert , Mannik Mart , Bornstein Paul 
Published: June 2004

Immunological studies of rat skin collagen were carried out with a sensitive and quantitative radioimmunoassay. Hyperimmune rabbit antisera to rat skin collagen and isolated α2 chains were used. Iodine-labeled α chains and CNBr-produced peptides served as test antigens, and native collagen, α chains, and CNBr peptides were employed as inhibitors in the assay.
The α1 and α2 chains were immunologically distinct. Although the α1 chain was not immunogenic, antibodies to α1 were detected in antisera to the intact collagen molecule. The major antigenic determinant of the α1 chain was located in α1-CB6 which constitutes the carboxy-terminal region of the chain. The α2 chain contained two non-cross-reacting antigenic determinants, one in the amino-terminal region (α2-CB1) and the other in the carboxy-terminal region (α2-CB5) of the chain. The native collagen molecule was less effective than isolated α chains in inhibiting binding of labeled peptides to antisera, indicating that antigenic determinants were less accessible in the triple helical molecule.
These immunologic studies are consistent with preliminary comparative biochemical data which indicate that interspecies structural differences in collagen predominate at both the amino- and carboxy-terminal ends of the chains.
CELLULAR IMMUNITY IN VITRO
Authors: Simon Harvey B. , Sheagren John N. 
Published: June 2004

An in vitro model of cellular immunity in the guinea pig was established. Animals were immunized with tubercle bacilli, bovine gamma globulin, or picrylated human serum albumin in complete Freund's adjuvant. Oil-induced peritoneal exudates from immune and control animals were cultured overnight with and without specific antigen. The cultures were washed and the macrophage monolayers were infected with Listeria monocytogenes. At intervals the monolayers were lysed and the numbers of viable intracellular bacteria were quantitated by pour plate cultures. Random monolayers were also evaluated in sequence by visually counting the intracellular bacteria on Gram-stained plates. Both methods demonstrated that the macrophages from immune animals had markedly enhanced listericidal activity when the peritoneal exudates were cultured with antigen before infection. Macrophage migration inhibition was also demonstrated under these conditions.
The experiments reported here describe an in vitro model of cellular immunity which will allow separation and recombination of cell types and direct assay of cell products in efforts to elucidate further the mechanisms of the immunologically mediated enhancement of macrophage bactericidal capacity.
ANTIBODIES TO POLYNUCLEOTIDES IN HUMAN SERA: ANTIGENIC SPECIFICITY AND RELATION TO DISEASE
Authors: Koffler D. , Carr R. , Agnello V. , Thoburn R. , Kunkel H. G. 
Published: June 2004

The specificities of anti-polynucleotide antibodies found in human sera were studied using several immunological procedures. Anti-native DNA (NDNA) antibodies and certain anti-double-stranded RNA (DSRNA) antibodies were found to react with single-stranded DNA (SDNA), and anti-NDNA antibodies were observed to react more avidly with SDNA than with NDNA in most sera tested. Antibodies to NDNA showed no preferential reactivity with NDNA or SDNA derived from mammalian tissue, bacterial, or viral sources. Precipitating antibodies reactive with individual bases, with common determinants of bases, and with common determinants of SDNA and NDNA were detected utilizing synthetic polydeoxyribonucleotides. Antibodies to DSRNA were also heterogeneous and reactive with both Poly A · Poly U and Poly I · Poly C in addition to reactivity with Poly A and SDNA. In contrast, antibodies to a ribonucleo-protein determined by hemagglutination and by precipitation showed no reaction with NDNA, SDNA, or DSRNA.
Serial studies of serum specimens from patients with systemic lupus erythematosus (SLE) indicated that anti-NDNA antibodies were closely associated with disease activity. Titers of antibodies to SDNA or DSRNA were also frequently increased during these periods but in addition showed peaks during quiescent periods. Anti-NDNA antibodies were detected in most patients' sera at sometime during the course of the disease. Three patients were observed with active SLE, who did not develop anti-NDNA antibodies, even in the presence of severe renal disease. Evidence that other antigen-antibody systems may also play a role in the pathogenesis of the renal disease was particularly apparent in these patients. Anti-ribonucleoprotein antibodies were not well correlated with the peaks of antibody activity of other polynucleotide antibodies, suggesting that an independent immunogen was responsible for induction of these antibodies.
The close association of certain populations of anti-polynucleotide antibodies during the course of active SLE, the presence of cross-reacting antigenic determinants of SDNA, NDNA, and DSRNA, the preferential avidity of anti-NDNA antibodies for SDNA, and the frequent increase of anti-SDNA antibodies in SLE and other diseases associated with active tissue destruction suggest that SDNA is a ubiquitous antigen that may stimulate the formation of antibodies reactive with a variety of polynucleotides.
PECULIAR IMMUNOBIOLOGY OF BONE MARROW ALLOGRAFTS
Authors: Cudkowicz Gustavo , Bennett Michael 
Published: June 2004

Mice are capable of rejecting H-2-incompatible bone marrow grafts after a single lethal exposure to X-rays. The onset of rejection begins 18–24 hr after transplantation and is completed by 96 hr. Maturation of this type of allograft reactivity does not occur until the 22nd day of life. In adult mice, the resistance to marrow allografts can be weakened by administration of cyclophosphamide or dead cultures of Corynebacterium parvum, but not heterologous anti-thymocyte serum. Sublethal exposures to X-rays 7 or 14 days before transplantation also weaken resistance. There is considerable interstrain variation in the ability of mice to resist allografts, even when H-2 differences between hosts and donor are kept identical. Although H-2 incompatibility is a necessary prerequisite for resistance, additional genetic factors influence the outcome of marrow allografts, presumably by controlling recognition. The regulator genes are determinant specific and the alleles for resistance or responder status appear to be dominant. The responder phenotype is expressed by hemopoietic cells and not by the environment. Accordingly, resistance is conferred to otherwise susceptible mice upon transfer of bone marrow cells but not of serum. The production and differentiation of effector cells for marrow graft rejection are thymus independent.
In conclusion, bone marrow allografts elicit a particular transplantation reaction, previously unknown, in irradiated mice. Peculiar features of this reaction are the lack of proliferation of host lymphoid cells, tissue specificity, thymus independence, and regulation by genetic factors which apparently do not affect the fate of other grafts.
TOXIC EFFECTS OF STREPTOCOCCAL M PROTEIN ON PLATELETS AND POLYMORPHONUCLEAR LEUKOCYTES IN HUMAN BLOOD
Authors: Beachey Edwin H. , Stollerman Gene H. 
Published: June 2004

Purified M protein isolated from Group A streptococci produced cytotoxic reactions in normal human blood in vitro. In the presence of M antigen, platelets aggregated, fused, and lysed. Polymorphonuclear leukocytes (PMN) surrounded the platelet aggregates, then became highly vacuolated and lysed. In addition, PMN progressively lost their capacity to phagocytose unrelated bacteria and to migrate in glass capillary pipettes.
Platelet-PMN reactions were directly proportional to the type-specific precipitin reactivity of each M preparation and could be removed with homologous M antibody, only. Moreover, the reactivity of M protein was abolished by enzymatic digestion with trypsin, but not with lysozyme, strongly suggesting that cell-wall mucopeptide was not involved.
Preliminary studies showed that platelet-PMN reactions require heat-stable and heat-labile serum factors, presumably antibody and complement. It is suggested that cytotoxic determinants are uncovered by the extraction and purification process and are intimately associated with the type-specific M determinant, possibly in a molecular complex.
BEHAVIOR OF ATTENUATED MYCOBACTERIA IN ORGANS OF NEONATAL AND ADULT MICE
Authors: Costello Richard , Izumi Takateru , Sakurami Takehiko 
Published: June 2004

The consequences of Calmette-Guérin bacillus (BCG) vaccination were followed in newborn and adult mice.
BCG failed to multiply in the organs of adult mice when administered peritoneally. In contrast, extensive multiplication of the vaccine occurred in both splenic and pulmonary tissue after its peritoneal administration to newborn mice. This absence of tuberculostasis occurred during the period when the animal's spleen, lung, and thymus were rapidly growing.
Animals achieved similar levels of resistance to virulent respiratory challenge 10 wk after vaccination irrespective of whether the vaccine had been administered when the mice were newly born and BCG had multiplied in vivo or administered when the animals were fully grown and the BCG had remained in the dormant state.
Although neonatal infection with BCG was severe, as shown by the large numbers of organisms recovered from the animals' tissues, the animals suffered no mortality or overt signs of disease. Neonatal vaccination did not significantly affect either the animal's growth rate or the gross development of its organs.
CELLULAR AND HUMORAL RESPONSE TO TRANSPLANTATION ANTIGENS
Authors: Cerottini J.-C. , Nordin A. A. , Brunner K. T. 
Published: June 2004

After transfer into heavily-irradiated allogeneic mice, spleen cells were found to produce two types of effector cells directed against the recipient alloantigens, namely alloantibody plaque-forming cells (PFC) and cytotoxic lymphocytes (CL). Both types of effector cells were detectable in vitro by virtue of their lytic effect on target cells carrying the recipient alloantigens.
Alloantibody PFC activity was dependent on the presence of an exogenous source of complement and could be inhibited by the addition of heterologous antisera to mouse µ-chain or Fab fragment in the assay system. CL activity was independent of added complement, was not affected by anti-immunoglobulin antisera, but was inhibited by the addition of antibody against target cell alloantigens. Treatment of the transferred spleen cells with anti-θ-serum and complement before in vitro assays for PFC and CL completely abolished the CL activity but had no effect on alloantibody-plaque formation. These results indicate that the two types of effector cells can be differentiated in vitro by virtue of their susceptibility to anti-θ-serum and the mechanisms by which they cause cell lysis.
EXPERIMENTAL INFECTION OF THE SKIN IN THE HAMSTER SIMULATING HUMAN IMPETIGO
Authors: Dajani Adnan S. , Wannamaker Lewis W. 
Published: June 2004

The interaction between staphylococci and Group A beta hemolytic streptococci in mixed lesions was investigated in an experimental impetigo model. A strain of staphylococcus of phage Type 71, which has been shown in vitro to produce a bacteriocin for streptococci and other Gram-positive organisms, eliminates or reduces Group A streptococci in mixed lesions. In contrast, staphylococcal strains of phage Types 75 and 81, which do not produce a demonstrable bacteriocin in vitro, exhibit no such effect.
Some variation was noted in the in vivo response of two different streptococcal M Types to the bactericidal effect of phage Type 71 staphylococci. Bacterial antagonism is more pronounced when staphylococci and streptococci are injected simultaneously into animals than when staphylococci are superimposed on preexisting streptococcal lesions.
Marked variations were found in the numbers of viable streptococci (colony-forming units) recovered from individual lesions containing identical mixtures of streptococci and phage Type 71 staphylococci. The frequency of a demonstrable bactericidal effect was related to the number of streptococci injected. With small inocula of streptococci, the tendency towards an all-or-none effect was particularly striking. No evidence of selection of streptococcal or staphylococcal mutants which might explain this phenomenon was obtained.
These observations suggest that the bactericidal effect of phage Type 71 staphylococci on other Gram-positive organisms, previously demonstrated in vitro, appears to operate also in vivo.
CUTANEOUS BASOPHIL (JONES-MOTE) HYPERSENSITIVITY AFTER "TOLEROGENIC" DOSES OF INTRAVENOUS OVALBUMIN IN THE GUINEA PIG
Authors: Richerson Hal B. 
Published: June 2004

Cutaneous basophil hypersensitivity (CBH) was studied for tolerogenic requirements. Graded doses of intravenous ovalbumin (OA) were given to guinea pigs which were subsequently immunized appropriately to produce CBH, classic delayed hypersensitivity (classic DH), and/or antibodies of both passive cutaneous anaphylaxis (PCA) and hemolytic types.
Results showed that doses of intravenous antigen sufficient to induce subsequent tolerance for classic DH and hemolytic antibody actually stimulate CBH reactivity and PCA antibody production.
Other studies of dose-route relationships for CBH production demonstrated that optimal immunogenic dosage requirements for CBH varied widely with route of antigen employed. OA in incomplete Freund's adjuvant (IFA) injected into footpads had low dosage requirements, intravenous OA had high dose requirements, and intradermal soluble OA dosage requirements were intermediate.
The observation that blatant immunogenic responses occur during the early period of tolerance induction amplifies the significant heterogeneity of the cellular immune response and may be of importance in understanding tolerogenesis.
Similar immunogenic-tolerogenic requirements and the prime role played by the basophil suggest a developmental or functional relationship between CBH and PCA antibody response.
LYMPHOID CELL DEPENDENCE OF EOSINOPHIL RESPONSE TO ANTIGEN
Authors: McGarry M. P. , Speirs R. S. , Jenkins V. K. , Trentin J. J. 
Published: June 2004

Quantitative determinations were made of the capacity of isogenic bone marrow, spleen, and thymic cells from primed and/or nonprimed mice to repopulate the hemopoietic tissues and to mount an inflammatory and antibody response to specific antigen (tetanus toxoid) in heavily irradiated and reconstituted recipients.
Spleen cells from primed mice but not from normal mice had the capacity to adoptively transfer an anamnestic antitoxin titer in irradiated animals in the absence of transplanted bone marrow cells, and during retarded myeloid regeneration.
Spleen cells alone or bone marrow cells alone produced an insignificant and a moderate peritoneal eosinophil response, respectively, to antigen.
In the presence of bone marrow cells, normal spleen cells augment the capacity of recipient animals to mount an eosinophil response to antigen. A much greater augmentation occurs in animals reconstituted with splenic or thymic cells from primed animals.
The increase in antitoxin titers appears to be independent of the response of eosinophils since: (a) marked accumulation of eosinophils can occur in animals with no measurable humoral antitoxin, and (b) high antitoxin titers can occur in animals which do not have marked eosinophil responses.
It is suggested that a thymic-derived or thymic-dependent mononuclear cell population is necessary for optimal eosinophil response to antigen. The neutrophil and mononuclear cell responses to antigen are determined by different mechanisms from those which determine the eosinophil response. These studies together with earlier findings strongly indicate that the eosinophil granulocytes play a role in the immune response to antigen.