bluuebunny/crossref_metadata_2025 huggingface dataset:
HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS
Authors: Rapaport F. T. , Hanaoka T. , Shimada T. , Cannon F. D. , Ferrebee J. W.
Published: June 2004

The establishment of a closely bred colony of beagles with known leukocyte group phenotypes has permitted an assessment of the role of leukocyte group antigens in conditioning the survival of renal allografts in the unmodified host. 22 kidney transplants obtained from leukocyte group-compatible donors were accorded a mean survival time of 25.5 days, as compared with 13.1 days for 27 transplants obtained from incompatible donors. Donor-recipient coefficients of correlation and Swisher erythrocyte group incompatibilities did not appear to affect the observed results. The mean survival time of 21 renal allografts performed in randomly selected mongrel dogs was 9.5 days.

Availability of a carefully characterized and phenotyped canine population may be useful in further studies of the comparative immunogenicity of the major transplantable organs, and of methods designed to facilitate prolonged organ transplant survival in the mammalian host.
INDUCTION OF IMMUNOLOGIC TOLERANCE IN OLDER NEW ZEALAND MICE REPOPULATED WITH YOUNG SPLEEN, BONE MARROW, OR THYMUS
Authors: Staples Parker J. , Steinberg Alfred D. , Talal Norman
Published: June 2004

Newborn, 7–9 day, and 16–18 day old NZB and B/W mice were, unlike older New Zealand mice, rendered tolerant to single doses of 8–10 mg of soluble BGG. After challenge, this tolerance was of short duration and escape occurred rapidly. Age-matched and similarly treated C3H, Balb/c and C57Bl mice did not escape from tolerance. Partial tolerance could be maintained by repeated injections of BGG.

Biofiltration ruled out hyperphagocytosis as an explanation for this resistance to tolerance. Tolerance could be induced in older B/W mice if they were thymectomized, irradiated, and repopulated with young (12–15 day), but not old (2–3 month), spleen or bone marrow cells. Old bone marrow cells gave a non-tolerant response even when combined with young thymic grafts. Young bone marrow gave a tolerant response which was followed by the expected rapid escape only if a young thymus graft was also present. Escape was retarded if old thymus, or old irradiated thymus, was combined with young bone marrow. These results are best explained by abnormalities of both lymphoid precursors and thymic regulation.
IN VITRO INDUCTION OF LYSOSOMAL ENZYMES BY PHAGOCYTOSIS
Authors: Axline Stanton G. , Cohn Zanvil A.
Published: June 2004

The in vitro induction of lysosomal enzymes by phagocytosis was demonstrated in cultivated mouse peritoneal macrophages. The contribution of each of several steps in the endocytic process to enzyme induction was examined. The enzymatic response after the uptake of equal numbers of erythrocytes (RBC) and nondigestible particles were compared. Phagocytosis of RBC produced a marked increase in the levels of acid phosphatase, ß-glucuronidase, and cathepsin D. Puromycin (1 µg/ml) inhibited the enzyme response. In contrast, phagocytosis of polyvinyl toluene, polystyrene, and insoluble starch particles produced no increase in macrophage lysosomal enzymes, although fusion of phagosomes with preexisting lysosomes occurred normally. The endocytic stimulus to synthesis of inducible lysosomal enzymes, therefore, occurred at or beyond the stage of digestion. Purified protein (bovine gamma globulin) aggregates and homopolymer coacervates of poly-l-glutamic acid: poly-l-lysine were effective inducers of lysosomal acid phosphatase, ß-glucuronidase, and cathepsin D, whereas homopolymers of the same D-amino acids were ineffective as inducers. Both the quantity of phagocytized substrate and its rate of enzymatic hydrolysis appear to control the level and persistance of lysosomal hydrolases.
STUDIES ON THE REGULATION OF AVIDITY AT THE LEVEL OF THE SINGLE ANTIBODY-FORMING CELL
Authors: Andersson Birger
Published: June 2004

The hemolytic plaque formation of cells producing antibody against heterologous albumins was tested for sensitivity to specific inhibition by free antigen. The inhibition characteristics of plaques in this system were found to be a measure for the avidity of the antibody produced by the plaque-forming cells (PFC:s). High avidity-producing PFC:s were more sensitive to inhibition than low avidity PFC:s. Immunization with a high dose of antigen induced PFC:s that produced antibody with a lower avidity as compared to PFC:s from animals immunized with a low dose. The avidity was increased with time. Determinations of avidity at the serum level were also made, and the results were in agreement with the findings at the cellular level.

The present method made it possible to demonstrate differences in avidity of antibody at the level of the single antibody-forming cell. It may also constitute a useful tool for the analysis of the cellular events leading to the production of antibodies with varying affinities during the immune response.
HUMAN PLASMA ALPHA 2-MACROGLOBULIN
Authors: Harpel Peter C.
Published: June 2004

Activation of plasma kallikrein arginine esterase activity by kaolin resulted in peak activity at 1 min of incubation and a 50% reduction in activity at 5 min in normal plasma, and 30% reduction in the plasma of patients with hereditary angioneurotic edema who lacked the C1 inactivator. The peak esterolytic activity was inhibited by soybean trypsin inhibitor whereas the 5 min activity was resistant to this inhibitor. Acid treatment of normal and hereditary angioneurotic edema plasma destroyed the factor responsible for the fall in esterase activity at 5 min and the factor which rendered the esterase resistant to soybean trypsin inhibitor.

Purified α2-macroglobulin inhibited approximately 50% of the TAMe esterase activity of purified plasma kallikrein without changing its activity toward basic amino acid esters. The interaction between the α2-macroglobulin and kallikrein resulted in alterations in the gel filtration chromatographic pattern of the TAMe esterase and biologic activity of kallikrein, indicating that kallikrein was bound to the α2-macroglobulin. The TAMe esterase activity of this complex, isolated by column chromatography, was resistant to C1 inactivator and SBTI. Studies of incubation mixtures of kallikrein, α2-macroglobulin and C1 inactivator suggested that these inhibitors compete for the enzyme, and that the α2-macroglobulin partially protects the esterase activity of kallikrein from C1 inactivator. The α2-macroglobulin isolated from kaolin-activated plasma possessed 240 times the esterolytic activity of the α2-macroglobulin purified from plasma treated with inhibitors of kallikrein and of its activation. The α2-macroglobulin blocked the uterine-containing activity and vascular permeability-inducing effects of plasma kallikrein. These studies suggest that the α2-macroglobulin is a major plasma inhibitor of kallikrein and provide a new example of an interrelationship between the coagulation, fibrinolytic, and kallikrein enzyme systems.
THE IN VITRO TRANSFORMATION OF FROZEN-STORED LYMPHOCYTES IN THE MIXED LYMPHOCYTE REACTION AND IN CULTURE WITH PHYTOHEMAGGLUTININ AND SPECIFIC ANTIGENS
Authors: Mangi Richard J. , Mardiney Michael R.
Published: June 2004

We have investigated the in vitro transformation of lymphocytes that have been frozen and stored at low temperatures. Cells frozen at different times and stored for various times do transform in a reproducible manner when placed in culture with PHA or as one population of the two-way or the one-way MLR.

When frozen-stored lymphocytes are cultured with specific antigen or as both partners in the MLR the response is minimal.

The freezing process destroys neutrophils, and the remaining population transforms in a manner similar to cultures of purified lymphocytes.

Practical aspects of the technique are discussed and we have suggested possible practical applications for future investigation.
CHRONIC ALLOGENEIC DISEASE
Authors: Armstrong Martine Y. K. , Gleichmann Ernst , Gleichmann Helga , Beldotti Lorraine , Andre-Schwartz Janine , Schwartz Robert S.
Published: June 2004

The incidence of lymphomas in 371 CAF1 mice injected with BALB/c spleen cells was compared with that in 324 control CAF1 mice. A high incidence of lymphomas was found in the treated mice, but not in the control animals. The development of the neoplasms was a function of the number of parental cells administered. Analyses of the injected mice for the presence of donor cells indicated that the majority of the injected parental cells lost antihost activity, probably within 24 hr of their administration. The tumors were of host origin, as judged by transplantation tests and antigenic analysis of tumor cells.
TOLERANCE AND IMMUNITY TO MATERNALLY DERIVED INCOMPATIBLE IgG2a-GLOBULIN IN MICE
Authors: Warner Noel L. , Herzenberg Leonore A.
Published: June 2004

Progeny mice were confronted with maternal γ-globulin of a different allotype by either back-cross mating, intercross mating, or by foster nursing. In all cases, many mice subsequently produced alloantibodies directed against the incompatible maternal type of IgG2a-globulin.

In one series of experiments, immunologic tolerance to the maternally derived γ-globulin was demonstrated to exist in the period before formation of spontaneous antibody. The state of tolerance was then lost, unless maintenance injections of foreign γ-globulin were given.

These studies demonstrate in a natural situation that maternally derived foreign proteins can first induce a state of immunological tolerance which is followed, after disappearance of the antigen, by a state of immunity. As such, this parallels the experimental induction of tolerance to foreign proteins by neonatal injections.
STUDIES ON ANTIBODY-PRODUCING CELLS
Authors: Gudat Fred G. , Harris T. N. , Harris Susanna , Hummeler Klaus
Published: June 2004

Antibody-bearing cells of spleen and lymph node of the mouse and rabbit detected by rosette formation with the antigenic red blood cells were collected by micropipet and studied by electron microscopy. More than 300 such cells were examined. In the lymph nodes, rosette-forming cells were all in the lymphocytic and plasmacytic categories. In cells of the mouse spleen, macrophages were also found among the RFC, especially in the later days after immunization.

The great majority of the RFC, 70–100%, were of the lymphocytic category. These included small, medium, and large lymphocytes with fine gradations of differentiation, and blast forms with little heterochromatin. The endoplasmic reticulum of these cells occurred in short, very narrow pieces, usually in contact with a mitochondrion. The cells of the plasmacytic category also showed fine gradations from plasmablasts to typical mature plasma cells.

Plaque-forming cells of mouse and rabbit were also collected by micropipet. Of 162 such cells, fine gradations were also found throughout the lymphocytic and plasmacytic categories, but in this case the great majority were in the plasmacytic group, and more plasma cells showed amorphous nuclear chromatin.

Among antibody-forming cells detected by both reactions, some of the more highly differentiated large lymphocytes contained ER which differed from that in the other large lymphocytes in that the channels were slightly and variably distended, with deposition of some precipitate, and with some tendency to a more nearly parallel orientation of the few channels seen. These were considered transitional cells.

Of 10 RFC found in mitosis, all were in the lymphocytic category, in various stages of differentiation, the most advanced of which (in 2 of the 10 cells) was that of the transitional lymphocyte described here.

Cells producing plaques facilitated by antisera vs. IgG of the mouse or rabbit (7S) showed the same distribution between cell categories and the same fine gradations as the direct (19S) PFC.

Cells producing rosettes which were resistant to lysis in the presence of complement, and were thus presumably producing 7S antibody, showed a distribution similar to that found generally with rosette-forming cells, approximately 80–90% in the lymphocytic category.
THE TOXOPLASMA GONDII OOCYST FROM CAT FECES
Authors: Dubey J. P. , Miller Nancy L. , Frenkel J. K.
Published: June 2004

Coccidian oocysts resembling those of Isospora bigemina were excreted by cats fed Toxoplasma. In order to identify these oocysts with Toxoplasma infectivity a number of critical comparisons were made. The appearance of oocysts and Toxoplasma infectivity was simultaneous in the feces of 23 of 24 adult cats, 3–5 days after feeding of Toxoplasma cysts; in the feces of 4 out of 9 cats, 7–10 days after feeding of trophozoites; and in 8 out of 17 cats, 20–24 days after feeding of cat feces containing oocysts. Oocysts and infectivity were present in similar numbers, and they disappeared simultaneously from the feces of cats. Oocysts and infectivity were also observed simultaneously in the feces of 9 kittens, 1–2 days old, fed Toxoplasma cysts. Oocysts could not be separated from infectivity by filtration, by continuous particle electrophoresis, or by density gradient centrifugation. Excystation of oocysts was followed by an increase in titer of Toxoplasma infectivity.

Unsporulated oocysts in fresh cat feces were noninfectious to mice, but oocyst sporulation was associated quantitatively with the development of infectivity at different temperatures and conditions of oxygenation. Maximum oocyst sporulation at 48 hr correlated with the development of maximum Toxoplasma infectivity.

1 and 2% sulfuric acid, and 2.5% potassium dichromate were found to be the best preservatives for sporulation of oocysts and for the development of Toxoplasma infectivity. Low sporulation rates in 0.1% formalin, 20% ethanol, and in water were associated with low infectivity in these reagents. Neither Toxoplasma infectivity nor oocysts developed in 0.3% formalin, 1% ammonium hydroxide, or 1% iodine in 20% ethanol.

Oocysts, sporocysts, and sporozoites were stained specifically with Toxoplasma antibody in the indirect fluorescent antibody test. Typical coccidian stages, schizonts, and male and female gametocytes were found in the epithelium of the small intestine of kittens fed Toxoplasma cysts. The classification of T. gondii is discussed in relation to that of other isosporan coccidia of cats and dogs. The term "Toxoplasma oocyst" is introduced and Toxoplasma is classified in the family Toxoplasmidae of the suborder Eimeriina. The species Isospora bigemina is restricted to dogs, and I. cati to cats. I. felis and so-called I. rivolta from cats were noninfectious to dogs, and did not confer immunity to subsequent infection with I. canis and I. rivolta from dogs.
STUDIES OF THE RELATIONSHIP BETWEEN THE PRODUCTION OF BACTERIOCINES BY GROUP A STREPTOCOCCI AND ACUTE GLOMERULONEPHRITIS
Authors: Overturf Gary D. , Mortimer Edward A.
Published: June 2004

The previously reported relationship between nephritogenicity and bacteriocine production among Group A streptococci has been examined. Using techniques comparable to the earlier study, the present study did not reveal any such relationship. Among 73 strains tested, 53% produced bacteriocines; no significant difference was noted between bacteriocines from strains isolated from cases of nephritis and those from a group of strains recovered from patients with other conditions. In addition, no correlation between type and bacteriocine production was observed.
COMMON INDIVIDUAL ANTIGENIC DETERMINANTS IN FIVE OF EIGHT BALB/c IGA MYELOMA PROTEINS THAT BIND PHOSPHORYL CHOLINE
Authors: Potter Michael , Lieberman Rose
Published: June 2004

Eight IgA myeloma proteins derived from independently induced plasma-cytomas in genetically similar inbred BALB/c mice are functionally related by their binding of phosphoryl choline-containing antigens (Pneumococcus C polysaccharide or Lactobacillus antigen). Each protein resembles a single species of immunoglobulin in antibody. The proteins are characterized by highly sensitive myeloma-specific antisera prepared by immunizing mice of other inbred strains with the BALB/c myeloma proteins. Individual or myeloma-specific determinants located on Fab fragments were found on three of the proteins that were unique for that protein and did not react with any other IgA protein among over 70 tested. Remarkably, five of the proteins shared two common myeloma-specific determinants which were specific for this group of five proteins. These results suggest that the five functionally and genetically related proteins sharing the same myeloma-specific determinants might also be structurally similar.
THE REACTION MECHANISM OF HUMAN C5 IN IMMUNE HEMOLYSIS
Authors: Cooper Neil R. , Müller-Eberhard Hans J.
Published: June 2004

The data presented here indicate that the C5 reaction step may proceed via the specific attachment of C5 to EAC1,4,2,3 and the formation of a hemolytically active C5 intermediate complex. During this process only a minor proportion (less than 4%) of C5 offered to EAC1,4,2,3 becomes bound, although the remaining C5 also participates in the reaction as evidenced by its inactivation in the fluid phase. Once bound, C5 is exceptionally efficient in producing hemolysis, requiring less than seven specifically bound molecules per cell for the production of a hemolytic lesion. The extent of formation of the C5 intermediate complex is primarily dependent on the number of molecules of C4, 2 and C3 present on the cells employed for its generation. In these respects, the mode of action of C5 is completely analogous to that of the other components of complement thus far investigated. The C5 step differs, however, in other aspects. The binding of C5 is influenced by C6 and C7, components which are thought to act subsequent to it in the complement sequence. In addition, the hemolytic activity of the isolated C5 intermediate complex is exceedingly labile, having an average half-life at 30°C of only 9 min. This characteristic distinguishes the C5 step, along with the C2 step, as potentially rate-limiting in the complement reaction. However, unlike C2, C5 remains firmly cell-bound during the decay process and apparently undergoes an alteration in situ which renders it hemolytically unreactive. Finally, C5 is unique in that it readily adsorbs in native form to unsensitized erythrocytes. This nonspecifically bound C5 remains firmly attached, although it may be specifically utilized as a source of C5 by an ongoing complement reaction. The significance of the marked affinity of native C5 for cell-surface receptors remains to be determined.
THE ABROGATION OF SHEEP ERYTHROCYTE TOLERANCE IN RATS BY MEANS OF THE TRANSFER OF ALLOGENEIC LYMPHOCYTES
Authors: McCullagh Peter J.
Published: June 2004

Whereas the transfer of lymphocytes from normal syngeneic donors fails to abrogate tolerance of sheep erythrocytes in rats, lymphocytes from allogeneic donors are effective. When tolerance is abrogated in this situation, the hemolysin-forming cells are predominantly of host origin. Immunological interaction between transfused lymphocytes and host cells is a prerequisite for the abrogation of tolerance. From the time required for abrogation to occur after transfer of the allogeneic cells, it is suggested that tolerance of sheep erythrocytes in rats represents the repression of a specific reactivity in cells rather than the elimination or irreversible inactivation of reactive cells. This explanation implies the existence of specifically tolerant cells.
THE EFFECT OF HETEROLOGOUS ANTI-LYMPHOCYTE SERUM ON LYMPHOCYTES OF THYMUS AND MARROW ORIGIN
Authors: Jeejeebhoy H. F.
Published: June 2004

When CY-treated mice were given sheep red blood cells the serum hemagglutinin titers produced were significantly lower than those found when mice received SRBC but not CY. Titers could be raised to the levels found in the latter group if, in addition to SRBC, the CY-treated mice received 2 x 107 normal syngeneic spleen cells or a mixture containing 1.2 x 108 normal thymus and 1.2 x 108 normal marrow cells. Inocula which contained fewer cells produced correspondingly smaller amounts of antibody. A synergistic interaction between normal thymus and marrow cells was always demonstrable in these experiments.

Hemagglutinin titers produced by CY-treated mice given SRBC and 2 x 107 normal syngeneic spleen cells were always much higher than those found when the spleen cells were obtained from animals previously given ALS. Titers could be raised to normal levels if the animals in this latter group received additional injections containing mixtures of normal syngeneic thymus and marrow cells. Marrow cells alone were completely ineffective, while inocula which only contained thymus cells were much less effective than mixtures of thymus and marrow cells. These results suggest that immunosuppression by ALS is associated with the inactivation of both thymus and marrow-derived lymphocytes.

In other experiments CY-treated mice received SRBC and mixtures of thymus and marrow cells from both untreated and ALS-treated donors. No decrease in the immunological competence of cells located within the thymus of ALS-treated donors was demonstrable in these experiments. Marrow cells were slightly affected but to a markedly lesser degree than were spleen cells of ALS-treated animals. In a final experiment, it was possible to show that the thymus and marrow cells of ALS-treated animals could repair the immunological defects which were present in their own spleen cell populations.
THE INTERACTION BETWEEN HUMAN MONOCYTES AND RED CELLS
Authors: Abramson N. , Lo Buglio A. F. , Jandl J. H. , Cotran R. S.
Published: June 2004

Red cells coated with IgG globulin were bound firmly to human mononuclear cells and formed rosettes. Rosette formation occurred when red cells were coated with IgG attached either immunologically (anti-D, anti-penicillin, or Donath-Landsteiner antibodies) or nonimmunologically with chromic chloride; no attachment was observed with cells coated with albumin. Rosette formation was blocked by pretreatment of white cells with sulfhydryl-binding reagents. Metabolic inhibitors did not prevent red cell adherence. White cells of other primates demonstrated a high degree of species specificity. Ultrastructural studies showed that the predominant leukocytes involved in rosette formation were monocytes, but some cells with characteristics of lymphocytes also formed rosettes. Considerable interdigitation of cell surfaces occurred at attachment sites and bound red cells appeared deformed. Thus, these studies confirm the presence of specific surface receptors for IgG on human monocytes and suggest that such receptors may provide a mechanism by which large numbers of red cells are eventually destroyed.
THE INTERACTION BETWEEN HUMAN MONOCYTES AND RED CELLS
Authors: Abramson N. , Gelfand E. W. , Jandl J. H. , Rosen F. S.
Published: June 2004

Studies were carried out in order to characterize the specificity of IgG sub-classes and IgG fragments for rosette formation using red cells and human mononuclear cells. Rosette formation of red cells coated with anti-D was inhibited by free IgG1 and IgG3; less inhibition occurred with IgG2 and IgG4. Red cells specifically coated with IgG1 and IgG3 by chromic chloride were bound to monocytes. Rosette inhibition of anti-D-coated red cells occurred with free Fc fragment of IgG globulin, and only partly with F(ab')2. Inhibitory capacity of Fc fragments of IgG and γ1 heavy chain from heavy chain disease was reversed by the cleavage of disulfide bonds. No inhibition was noted with Fab, or with pepsin components II, III, or IV. These studies indicated that the mononuclear receptor was specific for IgG1 and IgG3. The peptide portion of IgG globulin which attached to the mononuclear cell appeared to reside in the N-terminal portion of the Fc fragment and also appeared to require the integrity of the inter-heavy chain disulfide bond. A specific receptor for C3 was not confirmed.
IMMUNOHISTOLOGICAL AND ELUTION STUDIES OF THE HUMAN PLACENTA
Authors: McCormick J. N. , Faulk W. Page , Fox H. , Fudenberg H. H.
Published: June 2004

An immunohistological survey of 28 full-term human placentas has demonstrated deposits of IgG, ß1C, ß1E, and fibrinogen/fibrin in areas of fibrinoid necrosis and on the trophoblast basement membrane in approximately 35% of placental villi. Traces of IgM were detected at similar sites in 18 of 28 full-term placentas. In 11 specimens of immature placentas (10–18 wk gestation) traces of IgG and ß1C and deposits of fibrinogen/fibrin were also present, but IgM was not detected in this material.

IgG was recovered in acidic eluates from an homogenized placenta which behaved as an antibody reactive with unidentified material present in fibrinoid deposits and on the thickened trophoblast basement membrane of some villi. It could not be determined whether this IgG was derived from the maternal or fetal circulation.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Lee Chi-Jen , Dubos René
Published: June 2004

Specific pathogen-free mice were exposed to three different kinds of environmental stress during early life: (a) by infecting them with a mouse enterovirus on the second day after birth; (b) by placing the mother during pregnancy and lactation on a mildly deficient diet containing wheat gluten supplemented with

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small amounts of lysine and threonine; (c) by combining a (neonatal infection) and b (early malnutrition).

All animals survived the three types of stresses, but all exhibited marked depressions of metabolic activity, and of body weights and organ weights. These depressions lasted throughout the experimental period even though all animals were placed under optimum conditions of nutrition and husbandry after weaning, and maintained under these same conditions thereafter.

Metabolic activity was determined by measuring the turnover of 14C-acetate and 14C-glucose in respiratory CO2, and their incorporation in total lipids of liver and brain.

The utilization of 14C-acetate was profoundly depressed in all experimental groups with regard to both elimination in respiratory CO2 and their incorporation in total lipids of liver and brain.

In contrast, the utilization of 14C-glucose was much less affected; its incorporation into lipids was not decreased and its elimination in respiratory CO2 was depressed only in animals having experienced both neonatal infection and early malnutrition.

The extent of weight depression per 100 g of body weight differed according to the organ and the type of stress. Irrespective of the organ, however, depression of weight was largest in animals having experienced both neonatal infection and early malnutrition. And irrespective of the type of stress, the brain exhibited the smallest depression of weight relative to total body weight.
IMMUNOGLOBULINS ON THE SURFACE OF LYMPHOCYTES
Authors: Rabellino Enrique , Colon Sonia , Grey Howard M. , Unanue Emil R.
Published: June 2004

The distribution, and quantity of immunoglobulins on the surface of lymphocytes has been studied by means of immunofluorescence and a quantitative radio-immunoassay. Surface immunoglobulins were found on approximately 45% of spleen and marrow lymphocytes and 7–14% of lymphocytes from lymph nodes, peripheral blood, and peritoneal exudate. Thymic lymphocytes contained undetectable amounts of immunoglobulin. In the spleen the different immunoglobulins were present in the following order: γG2 > γG1 > M > γA > γG3. The surface immunoglobulin was largely removable by brief treatment with trypsin. Quantitative analysis indicated that 50,000–150,000 molecules of immunoglobulin were present on an individual cell. A variety of observations make it likely that this lymphocyte-associated immunoglobulin. is a product of the cell to which it is attached rather than a form of cytophilic antibody.
IMMUNOSUPPRESSIVE AND GRAFT-REJECTING ANTIBODIES IN HETEROLOGOUS ANTI-LYMPHOCYTIC SERUM
Authors: Cinader B. , Jeejeebhoy H. F. , Koh S. W. , Rabbat A. G.
Published: June 2004

Skin allografts survived longer on ALS-treated, complement-deficient (C5 negative) recipients than on ALS-treated, complement-competent (C5 positive) recipients. Administration of C5-positive serum to C5-negative, ALS-treated recipients resulted in reduced graft survival. A percentage of grafts from ALS-treated, C5-positive donors was rejected when transferred to untreated syngeneic recipients; this was not observed when C5-negative, syngeneic animals served as ALS-treated donors and untreated recipients. It was concluded that ALS has graft-rejecting properties which are promoted by late acting complement components. Unlike ALS-mediated graft rejection, ALS-mediated immunosuppression appeared to be independent of the late acting complement components.

The effect of ALS on the humoral response to sheep erythrocytes was examined in complement-deficient and complement-competent mice. Immune-suppression was determined by ALS treatment of C5-competent and C5-deficient mice and also by transfer of in vitro ALS-treated spleen cells from C5-negative and C5-positive donors to cyclophosphamide-treated recipients. The ability of ALS to depress the humoral response to sheep cells and to decrease immunological competence of spleen cells was the same in the presence as in the absence of C5.
HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS
Authors: Rapaport Felix T. , Boyd Arthur D. , Spencer Frank C. , Lower Richard R. , Dausset Jean , Cannon Florence D. , Ferrebee Joseph W.
Published: June 2004

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days.

Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens.

Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions.

The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration.
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: Koster F. T. , McGregor D. D. , Mackaness G. B.
Published: June 2004

Peritoneal exudates from rats which have survived an infection with L. monocytogenes can protect cyclophosphamide-treated recipients against a Listeria challenge. They are more effective in this respect than cells obtained from the spleen or thoracic duct lymph. Since exudate cells from normal rats and inocula prepared from the resident peritoneal cell populations of infected donors are unable to inhibit the challenge infection, the protective cells must belong to a class of lymphocytes that emerges from the blood in response to inflammation. It is significant therefore that thoracic duct lymphocytes formed during an acute Listeria infection can move into exudates induced by a variety of inflammatory stimuli. The affinity of newly formed lymphocytes for inflamed tissue points to a mechanism whereby the host marshalls its cellular defenses at sites of bacterial invasion. The tendency of short-lived lymphocytes to leave inflamed vessels might also explain their short-circulating life-span.
THE IMMUNOGENICITY OF HUMAN HL-A HAPLOTYPES AS MEASURED BY SKIN GRAFT SURVIVAL TIMES AND MIXED LEUKOCYTE REACTIONS
Authors: Seigler H. F. , Ward F. E. , Amos D. B. , Phaup M. B. , Stickel D. L.
Published: June 2004

The immunogenicity of the haplotypes in 30 families was measured by survival of skin grafts between selected paired family members. These families were genotyped for HL-A using 57 selected cytotoxic alloantisera defining HL-A 1–12 as well as other nondefined specificities. Mixed leukocyte reactions were also studied in this series and the correlations between the mixed leukocyte reactions with skin graft survival times, individual HL-A specificities, and the number of incompatible HL-A alleles are reported. Comments concerning the interpretation and quantitation of the mixed leukocyte reactions are discussed.
PATHOGENESIS OF H-1 VIRUS INFECTION OF EMBRYONIC HAMSTER BONE IN ORGAN CULTURE
Authors: Heggie Alfred D.
Published: June 2004

H-1 virus infection of hamsters has been shown to produce runting, microcephaly, cranial lacunae, and deformed teeth in animals inoculated during the suckling period and to cause various abnormalities, including skeletal defects, in embryos infected transplacentally. To explore the pathogenesis of these effects of viral infection on bone, the response of embryonic hamster tibiae in organ culture to inoculation with the H-1 strain of picodna virus was studied. This system made possible the direct observation of the reaction of bone to virus in a regulated environment. During a period of 7–17 days after inoculation the following observations were made: (a) H-1 virus was found to infect and replicate in bone. (b) Infected bones became more translucent, slender, and elongated than control bones. (c) Bone growth as measured by increase in wet weight was reduced in infected tibiae. (d) Infected bones showed periosteal and perichondral degeneration and diminished deposits of subperiosteal bone. It was concluded that the skeletal abnormalities which develop in embryonic and suckling hamsters after H-1 virus inoculation are the direct result of viral replication in bone, and that indirect phenomena such as those associated with chronic infection need not be postulated to explain the deformities seen in these animals.
THE LYMPHATIC STATUS OF HAMSTER CHEEK POUCH TISSUE IN RELATION TO ITS PROPERTIES AS A GRAFT AND AS A GRAFT SITE
Authors: Barker Clyde F. , Billingham R. E.
Published: June 2004

Hamster cheek pouch skin, transplanted to the side of an isogenic host's chest wall, retains its immunologically privileged status as evidenced by the prolonged survival of inlaid homografts of ordinary skin.

Various findings sustain the premise that exemption from rejection by otherwise susceptible homografts in both intact pouch tissue and in established pouch skin isografts is due to an impediment in the afferent pathway of the immunologic reflex, i.e., to deficient lymphatic drainage. Although lymphatics were not apparent when dye was injected into pouch skin grafts or into grafts of ordinary skin sustained by them, lymph vessels were readily and consistently revealed by dye injected into intact trunk skin or established isografts of trunk skin. When suspensions of viable lymph node cells from specifically sensitized parental strain donors were injected superficially into either the intact skin or established grafts of normal skin on F1 hybrid hamsters, a striking hypertrophy of the regional lymph nodes occurred, due to graft-versus-host reactivity. However, similar cell suspensions inoculated into intact pouch tissue or into pouch skin grafts on F1 hamsters incited no regional lymphadenopathy, indicating the lack of appropriate pathways to the nodes.

When skin homografts were inlaid eccentrically into pouch skin isografts, so that they were in contact with host skin at one edge, rejection occurred. Furthermore, rejection of long-established intrapouch skin homografts resulted if the hosts received: (a) small homografts of ordinary skin transplanted to conventional beds; (b) suspensions of donor strain pouch skin epidermal cells, injected intracutaneously; (c) lymph node cells from specifically sensitized donors of the same strain, i.e. adoptive immunization; or, (d) if a portion of the target homograft's perimeter was surgically approximated to body skin.

Treatment of normal hamsters with two closely spaced pulses of ALS, although only marginally effective in prolonging the lives of homografts of trunk skin, enabled pouch skin homografts to survive for very long periods. The influence of this brief treatment with immunosuppressant was still demonstrable if challenge of hosts with the weakly immunogenic pouch skin homografts was delayed for 100 days.
AN EXPERIMENTAL SYSTEM FOR THE SIMULTANEOUS ESTIMATION OF MITOSTATIC AND LYMPHOTOXIC EFFECTS OF IMMUNOSUPPRESSANTS AND CYTOSTATICS
Authors: Petrov R. V. , Manyko V. M. , Khaitov R. M. , Seslavina L. S.
Published: June 2004

Sublethally (600 R) irradiated (CBA x C57BL)F1 mice were grafted intravenously with parental lymph node cells in doses ranging from 0.2 x 106 to 12 x 106. The transplantation of these lymphoid cells leads to inactivation of the recipient's endogenous CFU (as measured by the diminution of the number of colonies registered on the 10th day after irradiation). A 50% inactivation was observed when the graft size of the CBA cells was 0.52 x 106. This figure for C57BL cells was 10 times more. This experimental system evaluates two simultaneously developing processes: the multiplication of endogenous CFU and the homograft reaction of transplanted lymphocytes against them. Both processes can be quantitatively estimated simultaneously in the same experiment by the determination of the number of colonies in corresponding experimental groups. Thus it was possible in a single experiment to compare quantitatively the effect of immunosuppressants on two points: (a) mitostatic action (suppression of CFU) and (b) lymphotoxic action. The latter, a true immunosuppressive effect, represents suppression of GVH activity of lymphoid cells and is demonstrated by abolition of the inhibition of endogenous colony formation. In the present system we have tested 6-MP, ALS, cyclophosphamide, hydrocortisone, and other drugs. The definite mitostatic and lymphotoxic doses of drugs are ascertained. Cyclophosphamide and ALS proved to be drugs with high dose ranges of selective lymphotoxic action. Hydrocortisone acetate had a more narrow range of selective lymphotoxic effect. 6-MP and Imuran (azathioprine) failed to exert any selective action on lymphoid elements. They possessed pronounced mitostatic efficiency, however.
IGE AND IGGA ANTIBODY-MEDIATED RELEASE OF HISTAMINE FROM RAT PERITONEAL CELLS
Authors: Bach Michael K. , Bloch Kurt J. , Austen K. Frank
Published: June 2004

The optimum conditions for antigen-induced release of histamine in the rat IgE and IgGa antibody-mediated systems were studied in vitro. The IgE antibody-mediated reaction could be separated into two steps: preparation of target cells with antibody and challenge with antigen. The optimal conditions for these two steps were distinctly different. Release of histamine by IgGa antibody and antigen could not be separated into two steps, and the optimal conditions for the total reaction were identical to those of the antigen challenge step of the IgE antibody-mediated system.
IGE AND IGGA ANTIBODY-MEDIATED RELEASE OF HISTAMINE FROM RAT PERITONEAL CELLS
Authors: Bach Michael K. , Bloch Kurt J. , Austen K. Frank
Published: June 2004

IgGa, in contrast to IgE, antibodies mediated the antigen-induced release of histamine from rat peritoneal mast cells without a requirement for a latent period and without the capacity to bind firmly to the target cell. Nonetheless, IgGa anti-DNP antibody interfered with the capacity of rat anti-N. brasiliensis antiserum rich in IgE antibodies to prepare the target cells for histamine release by worm antigen. Further, interaction of IgE antibody-prepared cells with IgGa anti-DNP antibody and DNP-BSA at 0°C so as to achieve sterile activation, or at 30°C to permit histamine release, inactivated such cells as determined by the subsequent failure to release histamine upon challenge with worm antigen. Thus, although IgE and IgGa antibodies are immunochemically distinct homologous immunoglobulins and exhibit different functional characteristics, their interaction at the target cell involves a common receptor and at least one common point in the pathway to the release of pharmacologic agents from the cell.
MACROPHAGE PLASMA MEMBRANE
Authors: Nachman Ralph L. , Ferris Barbara , Hirsch James G.
Published: June 2004

Rabbit alveolar macrophages were incubated in vitro with radioactive protein precursors. Plasma membranes were isolated from these cells, dissolved in phenol-urea-acetic acid, and separated by acrylamide gel electrophoresis. 3H-leucine was rapidly incorporated into membrane protein. The rate of labeling with 3H-leucine was markedly different from one protein band to another, indicating heterogeneous or multistep synthesis and assembly of proteins in the alveolar macrophage plasma membrane.

Cells incubated with 3H-choline incorporated this compound into membrane lecithin. On gel electrophoresis the label derived from choline was located in the two bands migrating most rapidly towards the cathode. Studies on cells incubated with 3H-glucosamine revealed incorporation of label into two protein bands, one located near the origin and the other migrating rapidly towards the cathode.

The in vitro techniques were also employed for pulse-chase studies to gain information on rate of turnover of macrophage plasma membrane proteins. This turnover rate was rapid, with a half-life of approximately 8 hr. The radioactivity disappeared from the several protein bands at the same rate, suggesting bulk removal of membrane rather than catabolism of the individual proteins in situ. Endocytosis seems a likely mechanism to account for a major part of the plasma membrane removal.

Studies on the protein components of phagolysosomal membranes from cells which had been labeled with 3H-leucine revealed the presence of all of the major labeled protein bands characteristic of the plasma membrane except one, thus confirming the bulk interiorization of large segments or units of plasma membrane by endocytic processes.
AUTOSENSITIZATION IN VITRO
Authors: Cohen Irun R. , Globerson Amiela , Feldman Michael
Published: June 2004

Autosensitization of rat or mouse lymphoid cells against syngeneic fibroblast antigens was induced in cell culture. Rat lymphoid cells autosensitized by this method were able to produce immunospecific lysis of syngeneic target fibroblasts in vitro or GvH reactions in newborn rats. Autosensitized mouse spleen cells mediated similar GvH reactions when injected into newborn mice.

The nature of the system used to induce immunity in vitro appears to argue against the possibility that lymphocytes capable of reacting against self-antigens could arise by mutation in cell culture. Hence, it is likely that cells potentially reactive against self-antigens preexisted in the lymphoid cell donors. The ability of autosensitized cells to mediate immune reactions in vivo suggests that the immunogenic self-antigens present on sensitizing fibroblasts also were accessible in the intact animals.

Loss of natural self-tolerance in vitro, therefore, can be explained most simply by the existence of lymphocytes which are reversibly tolerant to self. Hence, ontogenic elimination of potentially self-reactive cells may not be the only basis for natural tolerance. Regulatory mechanisms, such as antigen excess, may have to function in vivo to prevent differentiation of self-tolerant lymphocytes. These regulatory mechanisms appear to be annulled in the cell-culture system. The present system thus may offer a new approach to studies of tolerance and regulation of cellular immunity.
IMMUNOGLOBULIN SYNTHESIS AND SECRETION
Authors: Sherr Charles J. , Uhr Jonathan W.
Published: June 2004

Cells from an established line of Burkitt's lymphoma (Daudi) and a mouse myeloma (P3K) were pulse-labeled in vitro with 3H-leucine, and immunoglobulin was immunologically precipitated from cell lysates and secretions. In contrast to P3K cells, Daudi cells synthesize a small amount of Ig which is not secreted. Subcellular fractionation experiments indicated that Ig of Daudi cells is synthesized on membrane-bound polyribosomes and enters the cisternae of the microsomes. Ig in the microsomes could be labeled with either 3H-galactose or 3H-fucose suggesting that transport proceeds to the Golgi complex. Additional evidence indicates that Ig molecules are transported to the plasma membrane but are not cleaved from the cell surface. These results together with other studies of Burkitt lymphoma cells suggest that the Daudi line may represent a clone of neoplastic cells derived from normal lymphocytes which synthesize but do not secrete Ig. Similarities between lymphoma cells and antigen-binding cells are discussed.
ANTIGEN-BINDING CELLS IN MICE IMMUNE OR TOLERANT TO ESCHERICHIA COLI POLYSACCHARIDE
Authors: Sjöberg Olof
Published: June 2004

The number of PFC and of RFC was studied in mice which were unimmunized, immunized, or tolerant against lipopolysaccharide of E. coli 055:B5 origin. The number of PFC/106 spleen cells increased from 0.5 in normal to 209 in immunized mice. The corresponding figures for RFC were 93 and 513 RFC/106 spleen cells. In tolerant animals, which contained few or no PFC, the number of RFC was increased as compared to that found in unimmunized mice. The formation of rosettes was specific, since their formation was inhibited by soluble coli polysaccharide and by rabbit antisera against mouse immunoglobulins. The antigen-binding cells were not derived from thymus, neither in immune or tolerant mice, because they did not carry the theta antigen. It is suggested that the majority of antigen-binding cells present in tolerant animals are cells having receptors for the antigen of rather low affinity. The relevance of these findings for the induction of high and low zone tolerance is discussed.
IMMUNOGLOBULINS ON THE SURFACE OF LYMPHOCYTES
Authors: Unanue Emil R. , Grey Howard M. , Rabellino Enrique , Campbell Priscilla , Schmidtke Jon
Published: June 2004

Immunofluorescent studies using live cells from antibody-forming organs and anti-immunoglobulin antibodies demonstrate two populations of small lymphocytes which are differentiated by the presence or absence of Ig on their surface membranes. Most of the lymphocytes with detectable surface Ig appear to derive from cells of the bone marrow, while most of the Ig-negative lymphocytes derive from the thymus. Thus, adult mice thymectomized, lethally irradiated, and transplanted with bone marrow cells showed a normal number of lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes. Injection of thymocytes into these mice did not result in an increase in the number of lymphocytes with surface Ig in spleen and lymph nodes. Most of the injected thymocytes could be identified by means of histocompatibility markers. Also, the spleen and lymph nodes of neonatally thymectomized mice contained lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes.

Attempts were made to identify light chains on thymocytes by a sensitive radioimmunoassay. In some experiments no light chains were detected and in others a small amount, i.e. no more than 2.6% of the amount present on spleen lymphocytes, could be detected. Whether these low figures are significant or represent a small amount of serum contamination is not clear as yet.
A MAJOR GENETIC LOCUS AFFECTING RESISTANCE TO INFECTION WITH MURINE LEUKEMIA VIRUSES
Authors: Pincus Theodore , Rowe Wallace P. , Lilly Frank
Published: June 2004

The N-B locus affecting tissue culture infectivity with naturally occurring murine leukemia viruses appears to be identical to the Fv-1 locus described for sensitivity to Friend leukemia virus. Results of tissue culture studies were parallel to results of studies in vivo and indicate that the F-S virus is N-tropic and the F-B virus is NB-tropic. Inbred and partially congenic mouse strains sensitive at Fv-1 show N-type sensitivity; strains resistant at Fv-1 show B-type sensitivity. The Fv-2 locus does not appear to exert significant effect in tissue culture. Knowledge of N-B type has been useful in predicting Fv-1 sensitivity.