bluuebunny/crossref_metadata_2025 huggingface dataset:
THE IMMUNE RESPONSE TO SHEEP ERYTHROCYTES IN THE MOUSE
Authors: Eidinger David , Pross Hugh F.
Published: June 2004

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level.

The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1–2 days and 2–3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2–3 days.

The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr.

The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus.

Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy.

The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody.

Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.
BENIGN AND MALIGNANT HYPERTENSION AFTER ADRENAL ENUCLEATION IN THE RAT
Authors: Hall C. E. , Holland O. B. , Hall O.
Published: June 2004

Adrenal-enucleated, mononephrectomized rats given a high salt diet rapidly develop malignant hypertension, characterized by the presence of necrotizing vascular lesions in a number of organs and tissues. If a normal salt intake is provided, or if hydrochlorothiazide is given together with a high salt diet, there is, instead, the delayed onset of benign hypertension which either stabilizes or increases in intensity extremely slowly; Such animals display few, if any, pathologic vascular changes other than occasional focal glomerular hyalinization, show insignificant cardiac enlargement, and do not exhibit alterations in the serum sodium or potassium. Occasional animals behave atypically and develop malignant hypertension despite normal salt consumption, demonstrating that in susceptible rats excess salt is not essential to this disorder. Hydrochlorothiazide given to rats that imbibed distilled water postoperatively prevented hypertension entirely for 97 days, when one of eight rats developed mild hypertension and some others reached what is regarded as a prehypertensive range.

It is concluded that adrenal regeneration provides a physiological milieu favorable to the development of benign hypertension, which is not, as a rule, manifest until regeneration is complete. Salt excess converts the response into one in which malignant hypertension begins during regeneration and worsens rapidly thereafter until death. The course and findings are compared with those of the benign and malignant phases of clinical essential hypertension, and the implications of the similarities are discussed.
AN ULTRASTRUCTURAL STUDY OF THE MECHANISMS OF PLATELET-ENDOTOXIN INTERACTION
Authors: Spielvogel Arthur R.
Published: June 2004

Electron microscopy has confirmed previous studies and has provided much new information on the mechanism of endotoxin-platelet interaction. The Boivin lipopolysaccharide preparation is particulate, and on electron microscope examination appears as a three-layered structure, morphologically similar to bacterial cell wall.

In vitro and in vivo experiments have demonstrated that these endotoxin particles adhere to platelets. In some species, particularly the rabbit, this is associated with loss of platelet contents, due to lysosomal and cell membrane lysis, resulting in platelet sphering and apparent cell death. Serial observation of degranulating platelets and metabolic studies indicate that although some platelet engulfment of endotoxin occurs, degranulation is not dependent upon phagocytosis.

Several observations suggest that these endotoxin effects are mediated through immune mechanisms: (1) Inactivation of complement in the suspending plasma by heating to 56°C, anticoagulation with EDTA, a reaction temperature of 5°C, ammonium hydroxide incubation, and adsorption with either zymosan or washed antigen-antibody complexes, inhibits both endotoxin adherence and platelet degranulation. (2) The reaction requires a plasma cofactor, possibly antibody, which can be adsorbed out by endotoxin. (3) Endotoxin adheres selectively to nonprimate platelets and primate red cells, a pattern conforming to immune adherence, a phenomenon requiring antigen, antibody, and complement.

It is suggested that endotoxin-induced platelet damage is dependent upon the intimate contact provided by immune adherence. We have not established whether degranulation is an endotoxin or complement effect. The species variation in susceptibility to endotoxin also merits further investigation.
MITOCHONDRIAL ANTIBODIES IN PRIMARY BILIARY CIRRHOSIS
Authors: Berg Peter A. , Doniach Deborah , Roitt Ivan M.
Published: June 2004

The antigen reacting with complement-fixing antibodies in the sera of patients with primary biliary cirrhosis was localized predominantly in the mitochondrial fraction of tissue homogenates obtained by differential centrifugation. Purified mitochondrial preparations had a high content of the antigen whereas purified lysosomes failed to fix complement with PBC sera. Analysis of a number of fractionation experiments showed a high correlation between antigen content and the mitochondrial enzyme succinic dehydrogenase in all fractions. There was much poorer correlation with lysosomal and micrososomal enzyme markers. The patterns of staining obtained with a fluorescein conjugate of IgG from a PBC patient closely paralleled those obtained with a histochemical method for the demonstration of succinic dehydrogenase, further confirming the mitochondrial localization of the antigen. Staining was brightest in cells containing mitochondria with well-developed cristae. Studies on mitochondria fragmented by osmotic lysis, hexane, lysolecithin, and ultrasound suggest that the antigen is associated with the mitochondrial inner membranes.
THE SEROLOGIC SPECIFICITY OF TROPOCOLLAGEN TELOPEPTIDES
Authors: Davison Peter F. , Levine Lawrence , Drake Maurice P. , Rubin Albert , Bump Susan
Published: June 2004

Tropocollagen preparations from carp, buffalo fish, rats, calves, sheep, and humans have been studied by electron microscopy and serologic methods. Tropocollagens from each species appeared identical by electron microscopy but they were readily distinguished (except between sheep and calves) by C'-fixation tests with rabbit antisera against the various tropocollagens. Tests with calf tropocollagen antiserum showed no distinction between tropocollagen isolated from different tissues nor between individuals of the same or different strains.

The major immunogenic sites in native tropocollagen are the telopeptides, and these are present on both α1- and α2-chains. The C'-fixing activity was lost with heat denaturation of the tropocollagen, but could be recovered in a concentration-dependent process on cooling.

The fact that pure and enzyme-treated collagen can provoke serologic reaction implies that collagenous sutures and prostheses used in surgery may lead to sensitization and rejection, a fact which may merit clinical concern.
CUTANEOUS HYPERSENSITIVITY REACTIONS TO CELLULAR ISOANTIGENS IN RATS
Authors: Streilein J. W. , Billingham R. E.
Published: June 2004

Rats have been shown to be capable of displaying the various kinds of delayed cutaneous hypersensitivity reactions attributable to transplantation immunity previously described in guinea pigs, hamsters, rabbits, dogs, and man. The rat is unlike most other species in that much larger numbers of lymphoid cells are needed to incite these cutaneous reactions.

With direct, transfer, or normal lymphocyte transfer reactions, the cutaneous responses were greater when donor and recipient differed at the Ag-B histocompatibility locus than when donor and recipient shared the same Ag-B alleles.

An experiment was performed in which adult rats of a genetically defined backcross population, resulting from matings between DA and (DA x Lewis) F1 hybrid rats, were inoculated intradermally with lymph node cells from DA rats sensitized against tissues from Lewis-strain donors. Some of the R2 animals gave a biphasic transfer reaction with peak reactivities occurring first at 48 hr and recurring at 96–120 hr, while the others lacked this second component. Hemagglutination tests revealed that the R2 rats giving the biphasic response possessed the Ag-B,1 antigen, which is also present in Lewis rats, whereas rats which gave monophasic reactions were homozygous for the Ag-B,4 antigenic determinant which is present in the DA strain. This suggested that the recall flare at 96–120 hr reflects proliferative activity on the part of the inoculated cells confronted by the disparate Ag-B isoantigen in the host's dermis. Skin homografts from R1 animals bearing the Ag-B,1 antigen were uniformly rejected by DA hosts in 11 days or less, while grafts from backcross animals homozygous for the Ag-B,4 antigen usually lived longer, being rejected in 9 to 27 days.

Evidence is also presented which suggests that specific isoantibodies may act synergistically with immune lymphocytes to bring about cutaneous inflammatory reactions in the rat.
STREPTOCOCCAL NUCLEASES
Authors: Wannamaker Lewis W. , Yasmineh Walid
Published: June 2004

Streptococcal DNAse C is more resistant to heat inactivation than the A or B enzyme. DNAses A and C are indifferent to the bacterial ribonucleic acid inhibitor whereas the B enzyme is markedly inhibited. Prolonged digestion with relatively large amounts of DNAse B results in chemical and biological destruction of the inhibitor.

Ribonuclease as well as deoxyribonuclease activity is associated with the B enzyme. Both activities require divalent cations and both are inhibited by bacterial ribonucleic acid. The ratios of the two activities are constant in various preparations and after partial heat inactivation. Mutual inhibition of the two activities can be demonstrated in mixed substrate systems. The evidence presented is consistent with the view that the B enzyme is a single nuclease which can attack both deoxyribonucleic and ribonucleic acids.
RENAL HOMOTRANSPLANTATION IN RATS
Authors: Feldman Joseph D. , Lee Sun
Published: June 2004

Within 3–6 hr after the reestablishment of the circulation, a characteristic pathology developed in renal homotransplants. Blood monocytes and lymphocytes adhered to large thin-walled vessels of the septa carrying interlobular arteries, traversed their walls, and aggregated in the connective tissue spaces around them. Within 3 days, the number and size of the extravascular cells markedly increased, filling the septa completely and spreading from them centrifugally to occupy the intertubular spaces throughout the cortex. The composition of these aggregates at first was a mixture of lymphocytes and monocytes, and later consisted of large blast cells, macrophages, a few plasma cells, and polymorphonuclear leukocytes. Mitotic activity was seen 2 days after surgery among the large blast cells and increased to a maximal level a day later. Coevally with these changes, the thin-walled septal vessels, intertubular veins and capillaries, and finally, arteries and arterioles, in that order, were damaged. Focal injury of tubules was slight 24 hr after homografting; widespread cortical necrosis had developed 5–7 days later. At no time up to 7 days were concentrations of immunoglobulins detected by fluorescence microscopy in the transplanted kidneys.

The morphologic manifestations and temporal sequences of renal homograft destruction suggested that several mechanisms acted synergistically to eliminate the transplant. The initial injury appeared to be the result of an interaction between host lymphoid cells and target endothelium, a phenomenon akin to allogeneic inhibition; followed by spreading ischemia; additional contact injury to tubules; and nonspecific inflammation associated with necrobiotic tissue.
FACTORS INFLUENCING HEMATOPOIETIC SPLEEN COLONY FORMATION IN IRRADIATED MICE
Authors: Marsh John C. , Boggs Dane R. , Bishop Carter R. , Chervenick Paul A. , Cartwright George E. , Wintrobe Maxwell M.
Published: June 2004

Data pertaining to the endogenous mouse spleen colony system, 10 days postirradiation, are presented. The Do for visible colonies is 78 R, while that for 6 hr iron uptake over a range of 600–800 R is 50 R. The Do for spleen weight is 196 R and that for IUdR uptake is 193 R. These measurements increase with the age of the mouse. Hypertransfusion decreases spleen iron uptake and colony number. DF-32P and sodium sulfate-35S are not useful indicators of splenic hematopoiesis in this system. Visible hematopoietic colonies in the spleen are not produced by vinblastine, nitrogen mustard, methotrexate, or cyclophosphamide.
FACTORS INFLUENCING HEMATOPOIETIC SPLEEN COLONY FORMATION IN IRRADIATED MICE
Authors: Boggs Dane R. , Marsh John C. , Chervenick Paul A. , Bishop Carter R. , Cartwright George E. , Wintrobe Maxwell M.
Published: June 2004

Normal dog plasma and serum, human, rat, and Swiss-Webster mouse plasma, phytohemagglutinin, sheep red cells, mumps and influenza vaccine, fibrinogen, and endotoxin injected before irradiation led to an increased number of endogenously derived spleen colonies in irradiated mice. Spleen weight and uptake of radioactive iron and iododeoxyuridine into such spleens were also increased. The relationship between these parameters of splenic hematopoiesis was unchanged by plasma injection suggesting that, while the number of colonies was increased, the composition of individual colonies was unchanged. This conclusion was supported by studies on plethoric mice in which splenic erythropoiesis is abolished. Increased splenic hematopoiesis was accompanied by an increase in the volume of packed red blood cells 10 days after irradiation.

The total volume of plasma injected, the number of days of plasma injection preceding irradiation, and the route of administration were all important variables influencing the effect of plasma injections.

Crude fractions of human albumin and gamma globulin, cortisol, C57BL (maternal) and DBA (paternal) mouse plasma, and isogeneic plasma were without effect. The ineffectiveness of isogeneic and closely related allogeneic plasma rendered unlikely the hypothesis that this effect represented the presence of homeostatic hematopoietic regulating factors in plasma.

The increased hematopoiesis induced with plasma appeared to be limited to the spleen, for increased bone marrow hematopoiesis was not detected.

Certain observations suggested that the effect of plasma may not be due to an antigenic or an inflammatory effect. From current observations, it was unclear whether the increased colonies induced by plasma were representative of expansion of the colony-forming cell pool or of increased efficiency of growth of the fraction surviving irradiation.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Goor Ronald S. , Pappenheimer A. M.
Published: June 2004

The ability of a number of nucleotides related to NAD to replace NAD as cofactors for inhibition by diphtheria toxin of peptide bond formation has been examined. Neither NADH nor NADP are active. Of some 14 analogues closely related structurally to NAD that have been tested, only 3-thiocarboxamide pyridine-AD is as active as NAD itself. Replacement of the 3-carboxamide group on the pyridine ring by an acetyl group, or deamination of the purine ring, resulted in derivatives with reduced activity. The results were interpreted as suggesting that NAD and certain related nucleotides are capable of specific interaction with diphtheria toxin. Using the method of equilibrium dialysis, reversible binding of 1 mole of NAD per mole of toxin has been demonstrated. Toxoid does not interact with NAD.
GENETIC CONTROL OF THE ANTIBODY RESPONSE
Authors: McDevitt Hugh O. , Sela Michael
Published: June 2004

CBA and C57 mice were tested for their ability to make an immune response to a related series of branched, multichain synthetic polypeptide antigens in which the antigenic determinants on the amino termini of the branched side chains were systematically varied. Neither strain responded to the polyglutamic acid determinant. Both strains responded well and equally to the poly(phenylalanine, glutamic acid) determinants. CBA mice responded poorly, and C57 mice responded well to two different antigens bearing poly(tyrosine, glutamic acid) determinants. CBA mice responded well, and CS7 mice responded poorly to two different antigens bearing poly(histidine, glutamic acid) determinants.

The genetic control of the immune response to (H,G)-A--L appears to be dominant and polygenic, as it has been shown to be for (T,G)-A--L.

The related antigens used in this study show extensive cross-reactions with antisera against other members of the related series.
STAPHYLOCOCCAL CLUMPING WITH SOLUBLE FIBRIN MONOMER COMPLEXES
Authors: Lipiński B. , Hawiger J. , Jeljaszewicz J.
Published: June 2004

Clumping reaction, using standard suspension of Staph. aureus Newman D-2-C strain and various substrates, was quantitatively tested. It has been shown that clumping occurs in fibrin lysate containing soluble fibrin monomer complexes unclottable by thrombin. The reaction was positive with staphylococcal strains possessing clumping factor regardless of staphylocoagulase production. Clumping reaction is similar to paracoagulation reaction induced by protamine sulfate. The substrate for both reactions is stable at 56°C but is destroyed at 60°C. The kinetics of substrate formation for both reactions during fibrin clot lysis is also similar. Clumping reaction with a strain of Staph. epidermidis possessing no clumping factor was positive when these bacteria were coated with protamine sulfate. The effect of heparin, sodium citrate, urea, 2-mercaptoethanol, merthiolate, and mucin on both reactions was tested. The present findings explain the clumping reaction in serum and emphasize the role of blood clotting and fibrinolytic systems in this phenomenon.
CARTILAGE MATRIX DEPLETION BY RHEUMATOID SYNOVIAL CELLS IN TISSUE CULTURE
Authors: Hamerman David , Janis Rosamond , Smith Carol
Published: June 2004

Articular cartilage fragments were added to monolayer cultures of synovial membrane cells. After 3 wk of incubation, the cartilage fragments were examined histologically for metachromasia and basophilia, and for fluorescent staining using a rabbit antiserum to cartilage protein-polysaccharide. Cartilage incubated with cells derived from rheumatoid synovial membranes showed striking loss of metachromasia and basophilia as well as diminished to absent fluorescent staining. Cartilage fragments incubated with cells from normal synovia, or with cells from the synovial membrane of a patient with Reiter's syndrome, did not show these changes and resembled control cartilage incubated in tissue culture medium alone. It appears, therefore, that rheumatoid synovial cells in tissue culture are able to deplete the matrix of articular cartilage.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Bonventre Peter F. , Imhoff John G.
Published: June 2004

Primary heart cell cultures of embryonic guinea pigs and the neonatal rat were established and incubated with purified diphtheria toxin. The rat heart cell cultures were refractory to the effects of the toxin; protein synthesis proceeded normally as measured by the incorporation of tritiated leucine into cell proteins; beating heart cells continued to contract; and the cell monolayers remained intact after exposure to the toxin for periods as long as 72 hr. These findings are compatible with the species resistance of the rat to diphtheria toxin. The guinea pig heart cell cultures were found to be extremely sensitive to the toxin. Protein synthesis was inhibited by approximately 50% after incubation with small quantities of toxin for 3 hr. Increasing the concentration of the length of exposure to the toxin did not increase this inhibition significantly. In addition, diphtheria toxin exerted a true cytopathic effect on the guinea pig heart cells. Monolayers were destroyed when incubated with the toxin for 2 to 3 days.

The results show that the heart cells reflect species resistance or sensitivity to diphtheria toxin in the absence of neural or endocrine influences and suggest further that the toxin exerts a direct toxicity to muscle cells of the heart. It is not yet possible to explain in biochemical terms why the toxin seems to act specifically on cardiac tissues.
EVALUATION OF A STROMA-FREE HEMOGLOBIN SOLUTION FOR USE AS A PLASMA EXPANDER
Authors: Rabiner S. Frederick , Helbert J. Raymond , Lopas Harry , Friedman Lila H.
Published: June 2004

The preparation of large quantities of a stable, stroma-free hemoglobin solution without coagulant activity is described. Following infusion of this solution into phlebotomized dogs, there is no methemoglobin formation, no adverse effects on vital signs, and no demonstrable activation of blood coagulation. The hemoglobin maintains its oxygen-carrying capacity and liberates oxygen into tissues. Acute and chronic effects on renal function following infusion of this preparation were also studied and no effect on clearance of urea, creatinine, or P.A.H. could be demonstrated. There was no change in urinary output and histological sections revealed no lesions attributable to hemoglobin toxicity. It is concluded that a stroma-free hemoglobin solution may have use as a plasma expander.
IMMUNOGLOBULINS IN NZB/BL MICE
Authors: Warner Noel L. , Wistar Richard
Published: June 2004

Determination of serum immunoglobulin levels in NZB and normal mice has indicated that an elevation of the γM-globulin level occurs in NZB mice. This can be demonstrated in young NZB mice well before other autoimmune manifestations are observed. A slight elevation of γM-globulin was also observed in NZB hybrid mice.

Erythrocyte autoantibodies were analyzed by the direct Coombs' test with specific antiimmunoglobulin reagents. Autoantibodies in NZB mice can be of all immunoglobulin classes, although predominantly of γG1-class. In (NZB x NZC)F1 hybrid mice, although Coombs' positivity develops around the same age as in NZB mice, there is a greater restriction of the autoantibodies into γM- and γG1-classes.

Preliminary attempts to quantitate immunoglobulins coating NZB red cells have shown that there are approximately 400 molecules of γM and 5000 molecules of γG-globulin per NZB mouse red cell.
IMMUNOLOGICAL ANALYSIS OF RABBIT ANTI-ANTIBODY SYSTEMS
Authors: Kelus Andrew S. , Cell Philip G. H.
Published: June 2004

A study has been made of the production of antiidiotypic antibodies (anti-antibodies) arising during the immunization of 39 rabbits with 19 individual samples of rabbit anti-Proteus vulgaris x 19 antibodies adsorbed onto bacilli. In addition to the regular demonstration of antiidiotypic antibodies attention is drawn to the frequent occurrence of antiallotypic antibodies against molecules of immunoglobulin classes other than IgG, especially macroglobulins, which may arise during such immunization. In four cases attempts to raise autoantiidiotypic antibodies were unsuccessful, as expected.

The idiotypic specificities (antigenic determinants) have been found mainly on IgG but also sometimes on IgM molecules. The individual specificity of the antiidiotypic antibodies appears to be absolute, as long as the antiallotypic antibodies are recognized and excluded; e.g., each idiotypic specificity is characteristic of only one single rabbit and of a single kind of antibody within that rabbit. These principles hold even when antibodies of rabbit families are examined: the parental idiotypic determinants could not be found in the offspring.

In two samples tested the idiotypic specificities were found on the Fab fragment of IgG molecule but not on its antibody-combining site.
HAPTEN CARRIER RELATIONSHIPS IN THE DNP-PLL·FOREIGN ALBUMIN COMPLEX SYSTEM: INDUCTION OF TOLERANCE AND STIMULATION OF CELLS IN VITRO
Authors: Green Ira , Paul William E. , Benacerraf Baruj
Published: June 2004

Genetic nonresponder guinea pigs made tolerant to BSA and then immunized with DNP-PLL·BSA failed to make anti-DNP-PLL antibodies. Thus, tolerance to a carrier protein renders animals unresponsive to the hapten which it bears.

The addition in vitro of DNP-PLL or DNP-GL to lymph node cell cultures derived from genetic responder animals immunized with these materials led to a significant stimulation of 3H-thymidine incorporation into DNA. However, the addition of DNP-PLL or DNP-GL to lymph node cell cultures from nonresponder animals immunized with these materials failed to produce any stimulation of DNA synthesis. Furthermore, the addition of DNP-PLL to lymph node cell cultures from nonresponder animals immunized with DNP-PLL·BSA or DNP-PLL·OVA also failed to stimulate cell proliferation in spite of the fact that the lymph node cells of these animals were producing anti-DNP-PLL antibodies.

The above facts suggest that the function of the PLL gene product is to act at an early crucial step in the immune mechanism to form an antigen-inducer complex. The specificity of this early step may be of a simple order and different than that of the antibody which is later produced in the immune response.
STUDIES ON THE CONTROL OF ANTIBODY SYNTHESIS
Authors: Siskind Gregory W. , Dunn Philip , Walker J. Geoffrey
Published: June 2004

The effect of antigen dose on the kinetics of circulating antibody synthesis and on antibody affinity was studied in a haptenic system. High doses of antigen resulted, early in immunization, in higher concentrations of antibody followed later in the immune response by decreased serum levels of antibody as compared with lower doses of antigen. The affinity of the initial antibody synthesized was very similar over a wide antigen dose range. Subsequently, however, a rapid rise in affinity was seen in animals immunized with low doses of antigen, while relatively little change in affinity was seen in animals immunized with higher antigen doses. Suppression of active antibody formation by passive antiserum led to an increase in antibody affinity.

The results are discussed in terms of the mechanisms involved in the selection of a population of cells to participate in the immune response and the mechanisms whereby antigen dose and circulating antibody function to control antibody synthesis.
MECHANISMS OF ACTIVATION OF C'1 ESTERASE IN HEREDITARY ANGIONEUROTIC EDEMA PLASMA IN VITRO
Authors: Donaldson Virginia H.
Published: June 2004

The generation of C'1 esterase activity in siliconed plasma obtained from individuals with hereditary angioneurotic edema in remission tends to occur spontaneously, but can be hastened during its incubation with preparations of activated Hageman factor. This effect of activated Hageman factor could not be shown during its incubation with normal siliconed plasma, nor could consumption of normal serum inhibition of C'1 esterase be clearly shown.

Soy bean trypsin inhibitor and heparin could impair this enhanced generation of C'1 esterase but neither inhibits the esterolytic function of C'1 esterase once formed. Trasylol was less effective in blocking this effect of activated Hageman factor.

While the mechanism of the effect of activated Hageman factor upon C'1 activation remains obscure, it is apparent that some intermediate steps, possibly involving a kinin-forming system of plasma, may play a role.
STUDIES ON STREPTOCOCCAL BACTERIOPHAGES
Authors: Fischetti Vincent A. , Barron Bruce , Zabriskie John B.
Published: June 2004

Evidence has been presented that the burst size in the Group A and Group C streptococcal phage-host systems are in general similar producing approximately 13 phage particles per infected coccus. The exception was the C1 phage which produced 10 times more virus particles than all the other phages tested. The eclipse period for the A25 phage-host system was found to extend for 34 min, while the C1 phage were found as early as 10 min after infection. Conclusive evidence has been presented indicating that mercuric ions at 2.5 x 10–6 M concentration have the ability to halt intracellular phage production at any point during the infective cycle of A25 bacteriophages. This blocking action can then be quickly reversed with the addition of reduced glutathione with subsequent completion of the viral cycle.
STUDIES ON STREPTOCOCCAL BACTERIOPHAGES
Authors: Fischetti Vincent A. , Zabriskie John B.
Published: June 2004

Evidence has been presented that Group C bacteriophages differ as to their inactivating site on the streptococcal cell wall. While all three phages adsorb to isolated cell walls, only the C1 phage was inactivated by enzymatically prepared group-specific carbohydrate. None of the Group C phages were inactivated by chemically extracted group-specific carbohydrate. In contrast, all virulent Group A streptococcal bacteriophages adsorbed only to living Group A streptococci. However, Group A temperate phages were able to adsorb to isolated cell walls but not to group-specific carbohydrate.

While it has not been possible to identify the specific inactivating substance for the Group A virulent phages, certain pieces of evidence indirectly implicate the group-specific carbohydrate, specifically the N-acetylglucosamine moiety. The fact that Group A virulent phages failed to adsorb to heat-killed Group A streptococcal cells suggests that additional factors produced by the living cell are needed for complete viral inactivation.
ENHANCED ERYTHROPOIESIS WITH CONCOMITANT DIMINISHED GRANULOPOIESIS IN PREIRRADIATED RECIPIENT MICE
Authors: Hellman Samuel , Grate Helen E.
Published: June 2004

Three different methods of measuring the proliferative capacity of transplanted mouse bone marrow were used to study the effects of preirradiation of the recipient. Recipient mice were exposed to 700 R and given graded numbers of syngeneic bone marrow. 7 days were allowed for proliferation of these cells, and then the granulocytic or erythrocytic progeny was measured. The former was determined by the response to endotoxin, and the latter by the incorporation of radioactive iron into newly formed red blood cells. Erythropoiesis, therefore, could be measured independently from granulopoiesis by these techniques. The third method used was the spleen colony method of Till and McCulloch (5).

Recipient animals exposed to 150 R preirradiation, 7 days before 700 R and bone marrow transplantation, demonstrated an increase in erythropoiesis with a concommittant decrease in granulopoiesis compared to similar recipients not preirradiated. The spleen colony technique showed that while the number of colonies were the same in both groups, the colonies themselves were significantly larger in the preirradiated animals. Since such colonies are primarily erythropoietic, this finding is consistent with the other methods. The results can be explained by assuming the presence of a hematopoietic stem cell which, in these preirradiated recipients, is directed towards erythropoiesis at the expense of granulopoiesis.
THE PHYSICAL STATE OF HEMOGLOBIN IN SICKLE-CELL ANEMIA ERYTHROCYTES IN VIVO
Authors: Döbler Johanna , Bertles John F.
Published: June 2004

Venous blood removed anaerobically from patients with sickle-cell anemia was transferred immediately into fixative, thus precluding significant loss or gain of oxygen by the cells. Electron microscopy demonstrated an intraerythrocytic fibrillar fine structure similar to that described in prior studies on erythrocytes sickled by deoxygenation in vitro. Observations reported here lead to these conclusions: (a) explanations of the sickling process derived from in vitro experimentation may with validity be applied to sickling in vivo; and (b) the term "sickled" must be used with caution: a sickle-shaped membrane does not necessarily endose Hb S in filamentous form.
ANTIGEN-INDUCED RELEASE OF SLOW REACTING SUBSTANCE OF ANAPHYLAXIS (SRS-ARAT) IN RATS PREPARED WITH HOMOLOGOUS ANTIBODY
Authors: Orange Robert P. , Valentine Martin D. , Austen K. Frank
Published: June 2004

The polymorphonuclear leukocyte appears to be an essential cellular prerequisite for the antigen-induced release of SRS-Arat in the peritoneal cavity of rats prepared with homologous, hyperimmune antisera. Depletion of PMN leukocytes is associated with a marked suppression of SRS-Arat release, whereas depletion of circulating lymphocytes or peritoneal mast cells does not influence the antigen-induced release of SRS-Arat. A local increase in the number of PMN leukocytes produced by the induction of a peritoneal exudate was associated with an enhanced release of SRS-Arat.

A distinct difference in the cellular requirements for the antigen-induced release of histamine and SRS-Arat in the rat was observed. Homocytotropic antibody-mediated histamine release could be achieved in leukopenic rats but not in mast cell-depleted animals. Conversely, SRS-Arat release was suppressed in leukopenic rats but was unaffected by mast cell depletion.

Diethylcarbamazine inhibited the antigen-induced release of SRS-Arat following preparation with homologous, hyperimmune antisera but did not interfere with homocytotropic antibody-mediated histamine release. In preventing SRS-Arat release, diethylcarbamazine did not interfere with antigen-antibody interaction since desensitization of tissues was possible in the presence of this inhibitor. This observation is consistent with the view that diethylcarbamazine inhibits the reaction sequence leading to the formation and release of SRS-Arat at some step subsequent to antigen-antibody interaction.

These studies support the view that the immunologic pathways leading to the release of SRS-Arat and histamine in the rat are distinctly different in terms of the immunoglobulins involved, the cellular prerequisites, and the effective pharmacologic inhibitors.
CELLULAR IMMUNITY IN VACCINIA INFECTION OF MICE
Authors: Hirsch Martin S. , Nahmias André J. , Murphy Frederick A. , Kramer Joel H.
Published: June 2004

Rabbit anti-mouse thymocyte serum suppressed host cell-mediated responsiveness to intravenously administered vaccinia virus, thereby augmenting the morbidity and mortality of this infection. It did not affect either humoral antibody or interferon production in response to vaccinia virus. No effects were noted on primary or secondary immunity to intracerebral virus inoculation.
STUDIES ON THE COMPETENCE OF SINGLE CELLS TO PRODUCE ANTIBODIES OF TWO SPECIFICITIES
Authors: Gershon Harriet , Bauminger Sara , Sela Michael , Feldman Michael
Published: June 2004

Two series of experiments were performed, utilizing a modification of the hemolysin plaque technique which registers 19S antibody, in an attempt to determine the frequency of cells capable of simultaneously producing antibody to two non-cross-reacting antigens. Mice were immunized i.v. with rabbit and camel RBC and their spleens assayed for cells producing antibody against both antigens. 16,904 cells producing antibody of one or the other specificity, from 26 mice, were counted. Not one cell was detected which produced antibody of two specificities. Rabbits were immunized intradermally with HSA to which polyalanyl and p-azobenzenearsonate groups were chemically attached. The individual haptens, polyalanyl, and p-azobenzenearsonate groups were coupled to separate aliquots of SRBC, and the lymph nodes of immunized rabbits were assayed for cells releasing antibody against both haptens. In a study of 11 rabbits, after counting 27,845 cells producing antibody, we detected no "double" plaques.
RADIOAUTOGRAPHIC STUDIES OF PLAQUE-FORMING CELLS
Authors: Koros Aurelia M. C. , Mazur John M. , Mowery Margaret J.
Published: June 2004

A method has been described for obtaining radioautographs of plaque-forming cells. The method permits radioautographic analyses of small numbers of plaque-forming cells amidst large populations of non-plaque-forming cells. Spleen cells that were pulse-labeled with tritiated thymidine could be categorized readily as labeled or not labeled.

Using this method it was found that (a) at least 55% of plaque-forming cells which appear 3 days after a maximal stimulus of 4 x 108 sheep red cells are still capable of DNA synthesis, and must have arisen by cell proliferation; (b) the rate of proliferation of plaque-forming cells is proportional to the log of the dose of antigen; (c) the S period of plaque-forming cells is at least 2 hr, appears to be constant, and is not influenced by antigen dose. The results suggest that antigen stimulates proliferation of plaque-forming cells by hastening their transit through the G1 phase of the generative cycle.
INTERACTIONS OF THE COMPLEMENT SYSTEM WITH ENDOTOXIC LIPOPOLYSACCHARIDE
Authors: Snyderman R. , Gewurz H. , Mergenhagen S. E.
Published: June 2004

Endotoxic lipopolysaccharide has recently been shown to fix large amounts of the complement components related to the biologic activities mediated by that system. The present study sought to determine whether the generation of chemotactic factor by endotoxin in serum was dependent upon complement system activation.

Preheating serum, incubating at 0°C, or incubating in the presence of EDTA, all prevented chemotactic factor generation as well as complement fixation by endotoxin. "Endotoxoids" deficient in complement-firing activity were also deficient in chemotactic factor generation. Chemotactic factor could not be generated by endotoxin in sera of mice congenitally deficient in the C'S component of complement, while chemotactic factor was generated by endotoxin in the sera of coisogenic mice with normal complement levels for that species.

The chemotactic factor induced by endotoxin was heat stable and nondialyzable. Molecular sieve chromatography and sucrose density gradient ultracentrifugation demonstrated that the chemotactic factor was a relatively low molecular weight product (15,000–30,000) and as such different from previously scribed C' system-derived chemotactic factors.

These experiments demonstrate that generation of chemotactic factor by endotoxin in serum is dependent upon C' system activation involving at least C'5. Furthermore, the relatively low molecular weight of this factor suggests that it might be derived from activation of a single complement component rather than from complexing of multiple complement components.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart
Published: June 2004

The number of lymphocytes transformed in vitro by antiallotype sera in cultures obtained from allotypically suppressed rabbits is significantly less than that induced in cultures from normal rabbits. There is a compensatory increase in the amount of transformation induced by antiallotype sera directed toward the unsuppressed allotype. Thus the control of allotypic expression is suppressed rabbits appears to be the same for lymphocytes and for plasma cells.
PHYSICOCHEMICAL STUDIES OF THE CARCINOEMBRYONIC ANTIGENS OF THE HUMAN DIGESTIVE SYSTEM
Authors: Krupey John , Gold Phil , Freedman Samuel O.
Published: June 2004

A procedure has been described for the purification of the carcinoembryonic antigens (CEA) of the human digestive system. Tumor tissue extraction in 0.6 M perchloric acid followed by paper block electrophoresis and column chromatography on Sephadex G-200 resulted in highly purified CEA preparations as determined by both immunological and physicochemical criteria.

The properties and composition of five different purified CEA preparations derived from digestive system cancer metastases were examined. The findings demonstrated a high degree of uniformity amongst these samples. Sedimentation coefficients ranged from 6.9 to 8S. Each sample showed the presence of 14 different amino acid residues and six different carbohydrate constituents (four of which could be quantitated with the amount of material available for analyis). Studies of a purified CEA preparation from a primary hepatoma yielded results which, in some respects, differed from those obtained with the CEA samples of metastatic tumor origin. The implications of these variations were discussed with regard to the probable presence of non-CEA components in the hepatoma preparation.

Of primary importance was the observation that the few normal adult digestive system tissues tested failed to show the presence of constituents similar to the CEA. This finding would seem to indicate that, in the adult, the carcinoembryonic antigens of the human digestive system are qualitatively tumor-specific and are not dectectable in comparable normal tissues.
ROLE OF MACROPHAGES IN IMMUNOLOGICAL MATURATION
Authors: Argyris Bertie F.
Published: June 2004

1. Transplantation of peritoneal macrophages from thioglycollate-stimulated adult C3H donor mice, into 3-day-old C3H mice results in an enhanced antibody response to simultaneously injected SRBC. The increase in immuno-competence is even more pronounced when 1-day-old C3H mice are pretreated with adult macrophages and sensitized 3 days later with SRBC. Nonviable macrophages or nonviable spleen cells are ineffective.

2. There is a critical period in the development of the neonatal mouse during which the spleen cells benefit from the addition of adult macrophages. Treatment before or beyond this stage is ineffective.

3. Very high doses (20 million) of macrophages are less effective in stimulating antibody synthesis to SRBC than doses of 5 or 10 million, suggesting that a critical ratio of macrophages to immunocompetent cells may be required for enhancing antibody synthesis in young mice.

4. The results are discussed in the light of the hypothesis that newborn mice are immunologically deficient not because they lack immunocompetent cells but because they lack an antigen recognition or antigen-processing system in the form of functional macrophages.
THE INITIAL LESION IN EXPERIMENTAL ALLERGIC NEURITIS
Authors: Åström Karl E. , Webster Henry de F. , Arnason Barry G.
Published: June 2004

Experimental allergic neuritis (EAN) was produced in rats by the intradermal injection of an emulsion of peripheral nerve in Freund's adjuvant. Early lesions in perfused sciatic nerves were studied by phase, light, and electron microscopy at intervals up to 15 days following immunization.

Circulating lymphocytes attached focally to the inner surface of blood vessels, primarily venules, to initiate parenchymal lesion formation. Attached cells had the hand mirror configuration typical of the motile lymphocyte. They subsequently flattened against the endothelial surface and then traversed the vascular wall by sinking into and passing through the cytoplasm of endothelial cells. The transgressor and transgressed cell membranes were intact and both cells retained their integrity.

Lymphocytes began to transform and divide intravascularly; these events accelerated extravascularly. Although the migrating cells became larger and more pleomorphic in the perivascular regions, their essential character was in keeping with an origin from circulating lymphocytes. In many lesions, there was fluid with protein, possibly produced by the transformed extravascular cells. The described cellular events precede tissue damage and are likely instrumental in the myelin destruction which follows
THE ENZYMATIC NATURE OF C'1r
Authors: Naff George B. , Ratnoff Oscar D.
Published: June 2004

Human C'1, a macromolecular complex composed of three subunits, is the zymogen for at least two distinct enzymes. Preparations of one subunit, C'1r, functioned as a protease which converted another subunit, C'1s, to C'1 esterase. The conversion of C'1s to C'1 esterase by C'1r was blocked by Liquoid, phenyl methylsulfonyl fluoride, and calcium ions, but not by soybean trypsin inhibitor, hirudin, or heparin.

Preparations of C'1r also possessed two additional functions, i.e., the ability to hydrolyze certain synthetic amino acid esters and to participate in immune hemolysis. Evidence was presented which indicates that these three functions are properties of a single entity, C'1r, but not of the same portion of its molecular structure. These observations suggest that C'1r has at least two active sites, one for its reaction with C'1q, an additional subunit of C'1, and one for its reaction with C'1s; together, the three subcomponents, C'1q, C'1r, and C'1s, form a single functional unit, the first component of complement.
THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION
Authors: Byers Vera S. , Sercarz Eli E.
Published: June 2004

A concentration of 5 mg/ml bovine serum albumin (BSA) prevents the in vitro elicitation of a secondary response in primed rabbit popliteal lymph nodes, if it is left in contact with the node fragments for the first 6 days of culture. No antibody formation can be detected at any time during the culture period in most cases, although occasional fragments are resistant to inhibition. Reducing the exposure time to the first 3 days of culture delays the peak of the antibody response. The inhibition is antigen specific.

Reconstruction experiments demonstrate that the inhibition is not due to antigen masking of the antibody. Even shortly after optimal stimulation, the addition of 5 mg/ml BSA to the fragments was not able to prevent a normal antibody response.

The implications of these findings are that (a) a high antigen concentration suspends the memory cell in a reversibly paralyzed state, (b) memory cells have a heterogeneous susceptibility to inhibition, (c) once induced, the antibody response cannot be inhibited by antigen overloading, (d) unresponsiveness in a primed animal can be due to either exhaustion of the memory cell population or paralysis of the memory cell.