bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMMUNOLOGICAL SPECIFICITY OF DELAYED AND IMMEDIATE HYPERSENSITIVITY REACTIONS
Authors: Benacerraf B. , Levine B. B. 
Published: June 2004

The effects of the following parameters on the immunologic specificity of delayed and immediate hypersensitivity reactions were investigated in the guinea pig using the picryl and p-toluenesulfonyl systems: (a) the contribution of the carrier protein, (b) the effect of the number of hapten groups per molecule of the immunizing and challenging antigens, and (c) the effect of interposing a 6 carbon chain (ϵ-aminocaproic acid) between the hapten and its usual attachment to the lysine ϵ-NH2 groups of the carrier protein.
It was found that induction of delayed hypersensitivity was accomplished equally well with both lightly and heavily coupled conjugates. Sensitized animals which gave strong delayed reactions to the immunizing conjugate cross-reacted poorly or not at all to (a) conjugates of the same hapten with a different carrier protein, or (b) conjugates differing from the immunizing conjugate by having an ϵ-aminocaproyl chain interposed between hapten and its attachment onto the carrier protein. Animals sensitized with either lightly or heavily substituted conjugates exhibited strong delayed reactions to both conjugates, but more intense reactions to the immunizing conjugate were always observed.
In contrast to the marker carrier specificity exhibited by the delayed hypersensitivity reactions, immediate hypersensitivity reactions, (specific precipitation, Arthus, and PCA reactions) could be elicited equally well with hapten conjugates of all carrier proteins, as well as with conjugates containing ϵ-aminocaproyl chains interposed between hapten and the carrier protein, provided the number of hapten groups per molecule conjugate was sufficiently high. Both in inducing antibody response and in provoking immediate hypersensitivity reactions, heavily substituted conjugates were considerably more effective than were lightly substituted conjugates.
Alternative explanations for these observed differences in specificity between immediate and delayed hypersensitivity reactions are discussed.
DELAYED HYPERSENSITIVITY TO HAPTEN-PROTEIN CONJUGATES
Authors: Cell P. G. H. , Silverstein Arthur M. 
Published: June 2004

Further data have been presented showing that the specificity of the delayed hypersensitivity reaction in the guinea pig to hapten-protein conjugates involves to a considerable degree a contribution by the protein carrier. The carrier contribution is such that sensitization to guinea pig albumin-m-azobenzenesulfonate, for example, does not result in cross-reaction with conjugates of the same hapten with unrelated proteins such as ovalbumin or human gamma globulin, nor were cross-reactions observed between conjugates prepared with the same hapten, coupled to the same protein, but by two different chemical routes, such that the point of attachment of the hapten to the protein differed. It thus appears that in this system both hapten and carrier protein are necessary, but that neither alone is in general sufficient to stimulate the delayed sensitive cell.
Desensitization experiments with cross-reacting hapten-protein conjugates have suggested the presence of a multiplicity of antigenic determinants participating in the elicitation of the delayed lesion, and of a concomitant development of a heterogeneity of specificities in the population of delayed sensitive cells in the sensitized animal.
The data are discussed in terms of the apparent requirement of the delayed sensitivity mechanism for a larger functional antigenic determinant than that required for interaction with circulating antibodies. Some possible explanations for this difference, and some of its consequences, are discussed.
IMMUNOHISTOLOGIC STUDIES ON ANTIGEN-ANTIBODY REACTIONS IN THE AVASCULAR CORNEA
Authors: Germuth Frederick G. , Maumenee A. Edward , Senterfit Laurence B. , Pollack Abou D. 
Published: June 2004

The injection of antigen into the center of the avascular cornea of homologously sensitized animals induced a ring of opacification between the center of the cornea and the limbus. This ring of opacification was composed of a line of deeply eosinophilic amorphous material in a matrix of swollen collagen fibers, palisaded by polymorphonuclear leucocytes. By use of fluor-tagged antigen, it was shown that the line of damage in the cornea coincided with the precipitation of antigen presumably by antibody entering the cornea from the limbal vessels. With the passage of time, the antigen-antibody precipitates were removed, at least in part by phagocytosis, and the ring of opacification was replaced by ingrowing blood vessels surrounded by plasma cells.
Treatment of sensitized animals with nitrogen mustard showed that antigen-antibody interaction could injure the corneal stroma in the relative absence of polymorphonuclear leucocytes.
THE HISTOLOGICAL DISTRIBUTION OF THE BLOOD GROUP SUBSTANCES IN MAN AS DISCLOSED BY IMMUNOFLUORESCENCE
Authors: Szulman Aron E. 
Published: June 2004

The H antigen was mapped out by immunofluorescence in human tissues (including those of fetuses from 15 cm crown-heel length) from individuals of the various groups within the ABO system, both secretors and non-secretors. The distribution of the antigen can be summarized under the following headings:
Cell walls of endothelium: present throughout the cardiovascular system;
Cell walls of stratified epithelia: in skin, non-cornifying squamous stratified membranes, transitional epithelia;
Mucus: occurring wherever the latter is produced in secretor individuals and confined to a few special topographical areas in non-secretors;
Secretions and excretions: the pancreatic and sudoriferous (independent of secretor status), and mammary and uterine (governed by the secretor makeup) all contain it.
The distribution of the H antigen is most fully represented in tissues of group O. It follows an over-all universal pattern, characteristically modified in non-secretors, equally valid for antigens A and B described in a preceding study. Within this pattern, in tissues of the non-O groups, the complement of the H substance in its various forms wanes in a manner consistent with the hypothesis that it serves as a substrate for the A1, A2, B genes, exerting their action with different degrees of efficiency.
The secretor:non-secretor phenomena can be most simply interpreted by viewing the non-secretor, recessive gene (in the homozygous, ss condition) as inhibiting the production of some of the water-soluble forms of the blood group substances. Since the gene was never found responsible for dissociation of the H and A, B antigens its inhibitory action is thought to be wrought at the point of formation of the basic H substance or its precursor.
THE NATURE OF BENCE-JONES PROTEINS
Authors: Delman G. M. , Gally J. A. 
Published: June 2004

The chemical relations among Bence-Jones proteins, myeloma proteins, and normal γ-globulins have been investigated by a variety of means. Starch gel electrophoresis in 8 M urea of reduced alkylated Bence-Jones proteins yielded patterns of bands corresponding to those of the light (L) polypeptide chains of the dissociated myeloma protein from the same patient.
One instance in which this correspondence was found was chosen for extensive study. Chromatography on carboxymethylcellulose in 6 M urea was employed to isolate the light (L) polypeptide chains and heavy (H) polypeptide chains of the completely reduced and alkylated myeloma protein. Isolation of similarly treated Bence-Jones protein from the same patient corroborated the correspondence to the L chains of the myeloma protein. Amino acid analyses indicated that the compositions of the Bence-Jones protein and the L chains of the myeloma protein were identical. Moreover, the thermosolubility properties and spectrofluorometric behavior of the isolated L chains and Bence-Jones protein were similar.
Ultracentrifugal analyses of the L chains of normal human 7S γ-globulin showed that their molecular weight in 6 M urea was 20,000. In aqueous solution their molecular weight was 41,000, suggesting that they exist as dimers under these conditions. The L chains of normal human γ-globulin were found to have reversible thermosolubility properties similar to those of Bence-Jones proteins. The H chains of normal human γ-globulin did not share these properties.
Using spectrofluorometric methods, characteristic molecular transitions were found upon heating Bence-Jones proteins and L chains. These transitions were indicated by an increase in the intensity of fluorescence at well defined temperatures as well as by reversible shifts in the wavelength of maximal emission.
The findings suggest that Bence-Jones proteins are composed of L chains of the type found in normal and pathological γ-globu]ins.
THE EFFECT OF HYDROCORTISONE ON THE RESPONSE OF FETAL RAT SKIN IN CULTURE TO ULTRAVIOLET IRRADIATION
Authors: Weissmann Gerald , Fell Honor B. 
Published: June 2004

1. The effect of hydrocortisone on the development of fetal rat skin in organ culture, and on its repair after exposure to a mixed beam from a mercury lamp, are described.
2. The addition of hydrocortisone (7.5 µg/ml) to the culture medium (HC medium) caused accelerated differentiation and keratinisation of the epidermis followed by atrophic changes as in vivo.
3. Explants were grown for 2 days in either normal or HC medium and then irradiated with light from an Hanovia lamp.
4. Irradiation of the control explants produced severe necrosis in both epidermis and dermis and much disorganisation of the dermal intercellular material; 2 days after exposure the s. corneum with adherent cellular debris had become either completely detached from the denuded dermis, or raised to form a fluid-filled blister. Epidermal regeneration had begun by the 4th day after irradiation and was usually complete by the 6th day.
5. Hydrocortisone modified the response to irradiation as follows: (1) reduced and retarded cellular breakdown, (2) prevented vesication, (3) preserved the organisation of the dermal intercellular material, (4) hastened epithelialisation, (5) accelerated the differentiation of the new epidermis. Effects (2), (3), and (4) were probably secondary to (1).
6. Experiments with various light filters showed that the effective wavelengths for producing lesions in the skin explants were those below 3000 A.
7. It is suggested that the beneficial effect of hydrocortisone on the repair of irradiated skin explants might be due, at least in part, to a reduced proteolytic activity in the damaged tissue through a stabilising action of the hormone on the lysosomes.
8. The relationship of these findings to clinical observations is discussed.
INTRACELLULAR LOCALIZATION AND QUANTITATION OF TRITIATED ANTIGENS IN RETICULOENDOTHELIAL TISSUES OF MICE DURING SECONDARY AND HYPERIMMUNE RESPONSES
Authors: Roberts Audrey N. , Haurowitz Felix 
Published: June 2004

Autoradiography and quantitative radiochemical techniques have been used to determine intracellular localization of tritium and the quantity of tissue-bound tritium, respectively, following injections of H3-aniline azo PGG or H3-arsanilazo PGG to yield hyperimmune or secondary response stimulation in mice. Autoradiography revealed intracytoplasmic localization of grains in macrophages of spleen and lung sections, and in Kupffer cells of liver sections following intravenous and subcutaneous injections of H3-aniline azo PGG. Quantitation of tissue section surface radioactivities in the windowless flow counter and scintillation counter, and of dissolved tissue section activities in the scintillation counter, showed that greatest radioactivity was present in lung tissue, with less in spleen, liver, and mesenteric lymph nodes from these hyperimmunized mice.
Autoradiographic studies on tissue sections from mice in secondary response stimulation after subcutaneous foot-pad injections of H3-arsanilazo PGG, showed intracellular and extracellular grains over regional popliteal node sections, with intracytoplasmic grain localization over macrophages and pyroninophilic plasmacytes. Scattered macrophages in spleen and lung sections also contained intracytoplasmic radioactivity. Clusters of antibody-synthesizing cells in the regional lymph nodes were demonstrated with fluorescence microscopy, and these cells were compared to similar cells possessing radioactivity as observed in the section autoradiographs. An occasional Russell body plasma cell containing specific antibody was observed in splenic impressions. Windowless flow counting showed that greatest radioactivity was in regional node sections, with less in spleen and lung, and none in contralateral lymph nodes.
A quantitative comparison between windowless flow counting and autoradiography revealed that 20 counts were required to yield one silver grain.
STUDIES ON LYSOSOMES
Authors: Weissmann Gerald , Thomas Lewis 
Published: June 2004

Granular fractions sedimenting between 800 g and 15,000 g have been prepared in 0.25 M sucrose from the livers of normal young rabbits and from the livers of rabbits injected with A. aerogenes endotoxin. As early as 5 minutes after endotoxin, there was an augmented release of two enzymes, beta glucuronidase and cathepsin, into the supernatant of fractions which had been incubated or incubated and irradiated with a mercury vapor lamp at 37°C. These effects were maximum at 30 minutes after endotoxin and were associated with a depletion of the total activities of the two enzymes within the granules. Concurrently there was a rise in the activity of the two enzymes in fractions of the homogenate which were unsedimentable at 15,000 g. Fractions prepared from animals made tolerant to endotoxin no longer responded to incubation and irradiation by an augmented release of these two hydrolases, nor did fractions prepared from animals pretreated with glucocorticoids. Pretreatment with DOCA did not prevent release of enzymes after endotoxin.
The results have been interpreted to indicate that one consequence of the injection of endotoxin is an effect upon the stability of lysosomes, with subsequent release of acid hydrolases into the cell sap or surrounding tissue. Glucocorticoids may exert their pharmacologic effects through the protection of these subcellular particles against a variety of injurious agents.
ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)
Authors: Maurer Paul H. , Gerulat Bernard F. , Pinchuck Paul 
Published: June 2004

It has been shown that the polymers GLA5, GLT, GLA40, and GLAT are antigenic in human beings. Both immediate skin reactions and delayed (cellular) reactions were observed.
The antibody produced reacted well in the precipitin reaction, agglutinated antigen coated tanned sheep cells, was less effective in inducing PCA reactions, and failed to sensitize guinea pigs for passive systemic anaphylaxis.
The immediate skin reactivity appeared not to be related to the P-K antibody. The delayed reaction was histologically distinct from the immediate reaction and consisted of perivascular lymphocytic infiltration in contrast to the predominantly polymorphonuclear cells in the latter reaction. The antigenic response against the polymers resembled that observed with proteins. From cross-reactions it appears that the response is heterogeneous in the sense that not all individuals react against the same groupings in the complex polymers.
SIGNIFICANCE OF CRYOPROFIBRIN IN FIBRINOGEN-FIBRIN CONVERSION
Authors: Shainoff John R. , Page Irvine H. 
Published: June 2004

Fibrinogen altered by thrombin-catalyzed liberation of fibrinopeptide A was found to combine with native fibrinogen to form a cold-precipitable complex we have called "cryoprofibrin." The altered fibrinogen lacking fibrino-peptide A polymerized into fibrin, but not until conditions for equilibrium between its incorporation into both cryoprofibrin and fibrin were satisfied. At equilibrium, the concentration of cryoprofibrin was maintained at a threshold proportional to the concentration of fibrinogen. When the concentration of cryoprofibrin was below threshold, fibrin could be depolymerized and solubilized by fibrinogen with resultant formation of cryoprofibrin. Since threshold concentrations of cryoprofibrin appear necessary for precipitation of fibrin, the concentration of cryoprofibrin in plasma provides a basis for determining intravascular deposition of fibrin. Intravascular deposition of fibrin does not appear to occur normally in rabbits, because the concentration of cryoprofibrin in plasma from normal rabbits is far below the threshold for precipitation of fibrin. The applicability of cryoprofibrin as an indicator of fibrin deposition is demonstrated by the occurrence of levels of cryoprofibrin approaching the threshold for precipitation of fibrin in plasma from endotoxin-treated rabbits.
The current concept that the fibrinogen molecule can dissociate into subunits can be used to explain the conversion of fibrinogen to cryoprofibrin. As one possibility, the two residues of fibrinopeptide A contained in fibrinogen may be located on two separate subunits of the molecule; cryoprofibrin is produced when one of these subunits is replaced by a subunit altered by loss of fibrinopeptide A. Recombination of native subunits with subunits altered by loss of A would counter dissociation of cryoprofibrin and inhibit polymerization of subunits lacking fibrinopeptide A. As an alternate mechanism, two residues of A may be liberated concurrently from a single subunit. Cryoprofibrin would then correspond to a fibrinogen molecule, containing a subunit with two residues of A, in combination with an altered molecule containing a subunit lacking two residues of A.
Liberation of fibrinopeptide B did not contribute measurably to production of fibrin resulting from limited action of thrombin on rabbit fibrinogen. Both fibrin containing B but not A, and fibrin containing neither B nor A, as is produced by extensive action of thrombin, could be solubilized by fibrinogen.
Thrombin, or another enzyme utilizing tosyl-L-arginine methyl ester as substrate, appeared reversibly to inhibit polymerization of fibrin containing fibrinopeptide B. This enzyme and fibrinogen were the only proteins appearing to inhibit polymerization in plasma from normal rabbits.
ANTIBODY STUDIES IN RABBIT ENCEPHALOMYELITIS INDUCED BY A WATER-SOLUBLE PROTEIN FRACTION OF RABBIT CORD
Authors: Kibler Robert F. , Barnes Arthur E. 
Published: June 2004

A water-soluble protein fraction of nervous tissue was prepared by extraction of rabbit spinal cord with sodium citrate at pH 4.3. Characterization by nitrogen content and paper electrophoresis showed it to be a mixture of basic proteins. This extract demonstrated encephalitogenic activity when injected into rabbits.
The most suitable technique for the measurement of serum antibody to the rabbit cord antigen proved to be the precipitation of antigen-antibody complexes by 40 per cent saturated ammonium sulfate. Antibody could not be demonstrated by the techniques of complement fixation, quantitative precipitation, and Ouchterlony plates.
The early appearance of circulating antibody occurred almost exclusively in rabbits that subsequently developed EAE. Specificity of the antibodies for nervous tissue was demonstrated by appropriate blocking and adsorption experiments.
MEASUREMENT OF RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN MICE
Authors: Costello Richard , Dubos Rene , Schaedler Russell W. 
Published: June 2004

NCS mice were found to be susceptible to a hyperacute form of disease induced by injection of relatively large doses of Mycobacterium tuberculosis. Susceptibility to this type of disease was conditioned by the sex, age, and dietary history of the animals. Unlike the more usual response of mice to mycobacterial disease, these conditions affected primarily the relative occurrence of early-acute deaths rather than average survival time.
Resistance to this form of disease was increased by previous exposure of the animals to Gram-negative bacteria, to their endotoxin, or to various preparations of killed mycobacterial cells.
DISSOCIATION OF THE BIOLOGICAL PROPERTIES OF BACTERIAL ENDOTOXIN BY CHEMICAL MODIFICATION OF THE MOLECULE
Authors: Freedman Henry H. , Sultzer Barnet M. 
Published: June 2004

The preparation and properties of three fractions isolated from the acetylation of endotoxin by acetic anhydride in the presence of anhydrous sodium acetate are described. One fraction is of primary interest for it allows the experimental dissociation of some of the myriad biological activities of the parent endotoxin. Pyrogenicity and acute toxicity are markedly reduced, and ability to confer tolerance to the lethality and pyrogenicity of homologous or heterologous endotoxins is equivalently diminished. In contrast, this acetylated derivative retains the ability to stimulate phagocytosis and, as shown in the following paper, to enhance non-specific host resistance to infection. Detoxification is reversible, the original toxicity and pyrogenicity being recovered following mild saponification.
The implications of the findings are discussed, and it is suggested that the observed dissociation of biological properties is explained neither by deacetylation of the derivative in vivo nor by the observable alteration of physical state in the gross.
THE SPECIFICITY OF ALLERGIC REACTIONS
Authors: Coe John E. , Salvin S. B. 
Published: June 2004

"Gastric feeding" of adult guinea pigs with dinitrochlorobenzene (DCB) resulted in a specific unresponsiveness to sensitization with the specific contact hapten. The more DCB gastric-fed to a guinea pig, the more complete the unresponsiveness to the hapten. When mycobacteria were incorporated into the sensitizing emulsion, the state of unresponsiveness to the dinitrophenyl (DNP) group was less apparent. When animals gastric-fed with DCB were later sensitized with an in vitro conjugate of the hapten combined with a heterologous protein such as dinitrophenyl-hen egg albumin (DNP·HEA), an immune response similar to that in the controls occurred both to the hapten and to the protein carrier. However, when the tolerant animals were sensitized with a conjugate containing a homologous protein carrier such as dinitrophenyl guinea pig serum (DNP·GPS), they showed diminished immune responses in comparison with those in the non-tolerant controls. The presence of circulating anti-DNP antibodies from sensitization with DNP-HEA did not affect the unresponsiveness to the specific contact hapten, regardless of whether these antibodies are present before or after induction of tolerance. Sensitization with picryl chloride (PiCl) (a cross-reacting hapten), either before or after gastric feeding of DCB, did not affect the state of unresponsiveness to DNP. Similarly when the DNP-tolerant animal was sensitized with PiCl, the subsequent immune response was similar to that in the controls; cross-reactions with the DNP group both in the contact and circulating antibody phase occurred at a rate similar to that in the controls.
The foregoing relationships can be explained by presuming that, upon the gastric feeding of DCB, an in vivo conjugate is formed with a somatic protein, which determines the basic specificity of the tolerance. Acquired tolerance seems to manifest an immunologic specificity similar to that of delayed hypersensitivity, a relationship not unexpected if delayed hypersensitivity is an early phase of the immune response.