bluuebunny/crossref_metadata_2025 huggingface dataset:
REACTIVATION IN VITRO OF IMMUNOCOMPETENCE IN IRRADIATED MOUSE SPLEEN
Authors: Globerson Amiela , Auerbach Robert
Published: June 2004

The restoration of immunological competence to irradiated adult mouse spleen was studied using an in vitro assay system. Competence of the spleen to evoke a graft versus host reaction in vitro was lost upon sublethal irradiation (550 R). Regeneration of immune competence occurred when such spleens were grown for 2–3 days in the presence of thymus tissue, but not when grown in the presence of a variety of other tissues. This thymic activity was demonstrated to occur across an intervening Millipore filter barrier. When lethal doses of irradiation were used, reactivation of immune competence did not occur unless both thymus and bone marrow were present. In this experimental situation the bone marrow appeared to supply the immunocompetent cells.
RELEASE OF AN ENDOGENOUS PYROGEN IN VITRO FROM RABBIT MONONUCLEAR CELLS
Authors: Atkins Elisha , Bodel Phyllis , Francis Lorraine
Published: June 2004

The capacity of rabbit mononuclear cells to release an endogenous pyrogen (EP) in vitro has been studied.

After incubation with tuberculin, preparations of predominantly monocytic cells, derived from the respiratory passages of the lungs of rabbits sensitized with BCG, were activated to release EP. Pyrogen production occurred more slowly with lung monocytes than with blood leukocytes of similarly sensitized rabbits and 9 to 10 hr incubation in a fully supportive medium was required to produce clear-cut results. As previously reported with blood leukocytes, mononuclear cells from the lungs of normal animals were also activated by tuberculin but to a lesser degree than were those from specifically sensitized rabbits.

Under a variety of conditions, mononuclear cells from either spleen or lymph nodes of the same sensitized rabbits failed to release detectable amounts of pyrogen when incubated with tuberculin in vitro but were activated in a majority of instances when phagocytosis of heat-killed staphylococci was used as the stimulus.

Release of pyrogen from lung monocytes appears to be an active process that is both temperature-dependent and requires protein synthesis. Neither serum antibody nor complement appears to play a role in this process.

Evidence is presented that the granulocyte is the main source of pyrogen evolved by blood leukocytes incubated in vitro with OT or heat-killed staphylococci, whereas the lung macrophage and/or monocyte is responsible for most of the pyrogen released from the lung cell preparations.

From these studies, it is concluded that mononuclear cells can be activated in vitro by several microbial stimuli and must be considered an additional cellular source of EP. The clinical implications of these findings for the pathogenesis of fever in granulomatous diseases where the monocyte is the predominant cell are discussed.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Hahn Helmut H. , Char David C. , Postel Wilfred B. , Wood W. Barry
Published: June 2004

Macrophages from oil-induced peritoneal exudates in rabbits produce endogenous pyrogen when first activated by incubation in 4 hr exudate fluid and then stimulated by incubation in potassium-free isotonic sodium chloride solution. The failure of earlier investigators to obtain pyrogen from macrophages is explained, and the relevance of macrophage pyrogen to fevers of agranulocytosis and other diseases, in which mononuclear rather than granulocytic exudates predominate, is discussed.
CYTOTOXICITY BY NONIMMUNE ALLOGENEIC LYMPHOID CELLS
Authors: Möller Erna
Published: June 2004

Nonimmune lymphoid cells were capable of causing cytotoxicity of H-2 incompatible mouse tumor cells in vitro in the presence of PHA, whereas syngeneic cells were not. Semisyngeneic and X-irradiated (1500–3000 R) F1 hybrid lymphoid cells were cytotoxic for target cells derived from one of the parental strains. In addition, parental nonimmune and X-irradiated lymphoid cells damaged hybrid target cells. It was concluded that one component of cytotoxicity was not related to an induction of a primary immune response in vitro, since F1 hybrid cells are not capable of reacting immunologically against parental type target cells. It seemed probable that cytotoxicity was caused by target cell confrontation with antigenically and/or structurally incompatible lymphoid cells. This conclusion was strengthened by the demonstration that isoantibodies produced in the target strain and directed against the allogeneic lymphoid cells specifically suppressed cytotoxicity. Isoantibodies reacting against some but not all of the antigenic determinants of the lymphoid cells differentiating them from the target cells did not suppress cytotoxicity. The specific suppression of cytotoxicity by specific isoantibodies against the lymphoid cells support the allogeneic inhibition concept.
THE RESPONSE OF CULTURED MAMMALIAN CELLS TO DIPHTHERIA TOXIN
Authors: Moehring Thomas J. , Moehring Joan M. , Kuchler Robert J. , Solotorovsky Morris
Published: June 2004

The response to diphtheria toxin of two sensitive cell lines, KB and HeLa, was investigated. Inhibition of the incorporation of radioactively labeled amino acids into protein was the earliest detectable effect of diphtheria toxin. It was observed that, during the period of intoxication, the cell membrane was morphologically intact and retained its semi-permeable character, although it was rendered fragile and more easily disrupted by mechanical manipulations than the normal cell. The transport of amino acids continued even after intoxicated cells had ceased to synthesize protein, and the levels accumulated were equal to those of control cells. It was observed that cultural conditions, age, and handling of cells affected their response to toxin. In early log phase cells subjected to a minimum of handling before application of the toxin, the normally observed latent period preceding detectable effects was reduced to 15 min for KB cells and 30 min for HeLa cells, shorter times than previously reported. The data are consistent with the hypothesis that diphtheria toxin enters susceptible cells, possibly by pinocytosis, and there acts upon cytoplasmic sites of protein synthesis.
THE RELATIONSHIP OF POLYMORPHONUCLEAR LEUKOCYTES TO INFERTILITY IN UTERI CONTAINING FOREIGN BODIES
Authors: Parr Earl L. , Schaedler Russell W. , Hirsch James G.
Published: June 2004

A chronic infiltration of polymorphonuclear leukocytes was invariably found in the infertile regions of uteri containing foreign bodies in conventional rats, germfree rats, mice, and rabbits. Polymorphonuclear leukocytes were never found in the fertile regions of these uteri.

A foreign body in the uterus of the rat, and probably also the mouse, was associated with a bacterial infection which spread the inflammatory response throughout the horn containing the foreign body, and in the mouse occasionally into the control horn as well. No bacteria could be cultured from the rabbit uterine horn containing a foreign body.

In the germfree rat, both the infiltration of polymorphonuclear leukocytes into the uterus and fertility were significantly different from that observed in the conventional rat. Whereas in the conventional rat the inflammation and infertility extended along the entire length of the uterine horn containing a small foreign body, in the germfree rat the inflammation and infertility were closely correlated to the position of the foreign body.

As judged by measurements of lysozyme in the uterine lumens of rats and rabbits, polymorphonuclear leukocytes released their contents into solution in the uterine lumen. It is concluded that some substance derived from polymorphonuclear leukocytes may exert toxic effects on fertilized ova or on spermatozoa and thus be responsible for the infertility of uteri containing foreign bodies.
STUDIES ON THE NONSPECIFIC DEPRESSION OF THE IMMUNE RESPONSE
Authors: Jennings John F. , Oates Carolyn M.
Published: June 2004

Calf serum has been shown to suppress the primary immune response to erythrocytes and some bacterial antigens in mice if administered prior to and not after immunization. The importance of the route of iniection of antigens and immunosuppressant is indicated. It is suggested that immunosuppression is achieved by phagocytosis and enyzmatic destruction of the injected antigen by peritoneal macrophages. A similar mechanism is probably involved in the type of immunosuppression induced by PHA.
ALLOGRAFT REJECTION IN C'6 DEFECTIVE RABBITS
Authors: Rother Ursula , Ballantyne Donald L. , Cohen Carl , Rother Klaus
Published: June 2004

27 skin allografts were transplanted in duplicate to 13 rabbits defective in the sixth component (C'6) of complement (C'). 14 were rejected within the normal period of time and 9 only after a significant delay. In four grafts, no rejection was observed. Grafts exchanged between C' active and C' defective littermates tended to persist viable longer on the C' defective partners.

It is concluded that in a species of higher vertebrates, the rabbit, allograft rejection can proceed in the absence of C'6 and the biological functions depending on it. This includes the cytotoxic function of complement. However, the prolonged survival in C'6 defective rabbits of some allografts strongly suggests that two pathways may be operative in the rejection reaction. The results are consistent with the view that a mechanism independent of C'6 was alone fully effective in the majority of the donor-host combinations. A C'6-dependent mechanism became influential only in some specific donor-host combinations.
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Wilson Darcy B.
Published: June 2004

Some of the conditions and parameters of the proliferative response in the mixed lymphocyte interaction have been studied with the use of culture inocula consisting of lymphoid cells from various immunogenetically diverse, isogenic strains of rats. Procedures are described by which consistent culture responses can be obtained which are measurable in terms of incorporation of radioactive thymidine into a trichloroacetic acid precipitable cell fraction. Results of experiments with this "mixed lymphocyte interaction" show that

(a) Incorporation of thymidine into the mixed cultures is detectable only during and after the 4th day of incubation. Use of culture inocula derived from the thoracic duct or partially purified suspensions of lymphocytes from the peripheral blood provides further evidence that it is the small lymphocyte which synthesizes DNA in these cultures. The addition of peritoneal exudate cells, presumably containing some macrophages, to the mixed lymphocyte cultures does not alter the kinetics of the response.

(b) Proliferative responses occur in mixed cultures of cells only when the donors differ by alleles at the important Ag-B histocompatibility locus.

(c) Proliferative reactivity in mixed cultures of lymphocytes from parental and hybrid donors is unidirectional. With the use of chromosomally marked cells from donors of different sexes, it was established that only parental lymphocytes are dividing in mixed cultures of parental and hybrid cells.

The results of these experiments strongly support the premise that the proliferative response in mixed cultures of lymphocytes represents a de novo immunologic reaction on the cellular level against histocompatibility antigens.
M ANTIGENS AMONG GROUP A STREPTOCOCCI ISOLATED FROM SKIN LESIONS
Authors: Top Franklin H. , Wannamaker Lewis W. , Maxted W. R. , Anthony Bascom F.
Published: June 2004

Three new provisional types of Group A streptococci have been identified among strains isolated from skin infections of American Indian children. A previously established type, Type 41, was also recognized among the pyoderma strains.

Most of the skin streptococci with T-agglutination pattern 3/13/B3264 could be identified as Type 41 or as one of two new provisional types, Schoenborn (Type 52) and Hanson (proposed Type 53). Strains of the third new provisional type, Kingbird (proposed Type 54), agglutinated as 15/17/19/23/47, a T pattern not associated with skin infections in studies of other populations.

Approximately half of the pyoderma strains examined were found to produce an M antigen; the proportion of M-typable strains from skin infections was found to be similar to that currently found in throat cultures of children with pharyngitis. The demonstration of M antigens in streptococci from skin lesions provides evidence of their potential virulence and should facilitate their classification in subsequent epidemiological studies.
IMMUNOGLOBULIN SYNTHESIS IN MICE
Authors: Herzenberg Leonore A. , Herzenberg Leonard A. , Goodlin Robert C. , Rivera Edna C.
Published: June 2004

In the mouse, antibody directed against an immunoglobulin allotype, Ig-1b, passed from mother to offspring or injected into neonates, suppresses synthesis of immunoglobulin carrying Ig-1b. In allotype homozygotes as well as heterozygotes the allotype suppression is manifested both by a delay of several weeks in attaining initial detectable allotype levels and a reduction in allotype level continuing into adulthood. A possible mechanism for the differentiation of the immune system consistent with both the kinetics of suppression reported here for the mouse and the comparatively longer lived and more complete allotype suppression described for the rabbit is discussed.

Evidence for a strong intralitter (as opposed to interlitter) correlation of age of onset of immunoglobulin allotype synthesis is presented.
AN ASSAY METHOD FOR LEUKOCYTE PYROGEN
Authors: Murphy P. A.
Published: June 2004

A method for assaying leukocyte pyrogen is described which is shown to remain valid despite the presence of very large amounts of bacterial endotoxin. It uses a combination of two procedures to inactivate endotoxin: incubation in normal rabbit plasma for 24 hr at 37°C, and injection into rabbits rendered refractory to endotoxin. The validity of the assay was confirmed by formal statistical methods. A simplified assay method is also described which lacks full statistical validity, but is more suitable for routine use.
THE RATE OF RELEASE OF LEUKOCYTE PYROGEN FROM RABBIT BLOOD INCUBATED WITH ENDOTOXIN
Authors: Murphy P. A.
Published: June 2004

The time course of leukocyte pyrogen liberation from whole rabbit blood incubated at 37°C with various concentrations of proteus endotoxin was studied. The kinetics of the process provide further evidence for the view that leukocyte pyrogen is an independent entity. It was shown that complete liberation of all available leukocyte pyrogen from blood is too slow a process to account for the fevers seen when rabbits are injected with endotoxin. However, very small quantities of leukocyte pyrogen were demonstrated after short periods of incubation which are adequate to account for endotoxin fevers. It was also found that small, but definite, quantities of leukocyte pyrogen are liberated from rabbit blood incubated without endotoxin.
THE INTERACTION IN VITRO BETWEEN GROUP B MENINGOCOCCI AND RABBIT POLYMORPHONUCLEAR LEUKOCYTES
Authors: Roberts Richard B.
Published: June 2004

The interaction in vitro between group B meningococci and rabbit polymorphonuclear leukocytes has been described. Phagocytosis did not occur in the presence of normal rabbit serum. Antiserum collected 12–21 days following one subcutaneous inoculation of living log phase meningococci exhibited opsonic activity with type specificity; this opsonic action depended on both heat-labile and heat-stable factors. Following ingestion by granulocytes, meningococci were rapidly killed. These studies suggest that group B meningococcal strains contain specific antiphagocytic surface factors of an as yet unknown chemical nature.

Antisera obtained 4 or more wk after immunization showed bactericidal activity with the same type specificity as opsonic activity. This bactericidal activity was also lost after heating and restored by the addition of normal serum.

Further studies on opsonins and bactericidins for meningococci may shed light on virulence factors in these microorganisms, and may prove useful for a more precise classification of meningococci according to type rather than group specificity.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Goor Ronald S. , Pappenheimer A. M.
Published: June 2004

Extracts from HeLa cells treated with excess diphtheria toxin for several hours, until all protein synthesis has been arrested, are still able to stimulate the poly U-directed incorporation of phenylalanine into polypeptides at a moderate rate. Activity may be restored to normal levels or above by addition of a soluble enzyme fraction containing transferase II. Our results are in agreement with those of Collier who has recently shown that toxin inactivates transferase II in extracts from rabbit reticulocytes. We have further demonstrated that amino acid incorporation in extracts from intoxicated HeLa cells is limited by their transferase II content whereas, in extracts from normal cells, it is the ribosomes and to a lesser extent sRNA that are limiting. We have found that only soluble transferase II is inactivated by toxin; the ribosome-bound enzyme is resistant.
FURTHER OBSERVATIONS ON THE SIGNIFICANCE OF A/EQUINE-2/63 ANTIBODIES IN MAN
Authors: Davenport F. M. , Hennessy A. V. , Minuse Elva
Published: June 2004

The antibody pattern of equine-2/63 viruses has been more sharply defined using a large number of human sera collected in 1964. The birth dates of persons exhibiting the richest experience with equine-2/63-like viruses delineate a period of past prevalence in man of equine-2/63-like viruses. The period is believed to have begun in the mid-1870's and to have terminated in 1889–1890 at the time of the first Asian pandemic. The equine-2/63 antibodies found in human sera react specifically in the photometric test of Drescher. The equine-2/63 antibody pattern advances along the age scale in exact concordance with the passage of time. The homologous antibody response of the older subjects to equine-2/63 vaccine is more vigorous, reflecting the conditioning effects of prior exposures to equine-2/63 antigens. A "one-way cross" between equine-2/63 virus and A2 and A1 strains has been demonstrated. The antigenic ties between strains of influenza A isolated from humans, swine, horses, and birds is recognized and discussed. It is apparent that horses do not constitute an active reservoir for strains of human involvement. The epidemiologic significance of the antigenic linkages between strains isolated from different species remains obscure.
RENAL TRANSPLANTATION IN THE INBRED RAT
Authors: Guttmann R. D. , Carpenter C. B. , Lindquist R. R. , Merrill J. P.
Published: June 2004

Heterologous rabbit anti-rat thymocyte sera, its immunoglobulin G fraction, and the bivalent and univalent antibody fragments obtained by pepsin digestion are potent immunosuppressive reagents when tested in a system of renal allotransplantation between the LBN F1 hybrid and Lewis rat strains.

The AT F(ab')2 is not lymphocytotoxic in vitro but has agglutinating ability, while the AT Fab' neither agglutinates nor is cytotoxic to rat lymphocytes, but will inhibit the in vitro reaction. The AT IgG and the F(ab')2 are more immunogenic in their host than normal rabbit IgG and F(ab')2, probably due to increased delivery of the antibody to the immune system.

Donor pretreatment studies demonstrate that a cross-reacting, highly immunogenic antibody with anti-lymphocyte specificity may bind to renal sites and be transferred to the new host after transplantation. In addition, the crude unabsorbed anti-thymocyte antisera may induce a nephritis characteristic of immune complex disease which can be eliminated by complete absorption with serum proteins. Further in vivo and in vitro evidence is presented that the AT IgG contains small amounts of antibody to glomerular basement membrane antigens and may induce an autologous phase-nephrotoxic nephritis. The amount of in vivo binding by AT IgG to GBM was reduced by subcutaneous rather than intravenous administration.

Most of the rabbit antisera tested contain antibody in low titer to sheep erythrocytes and in vivo experiments indicate that the nature of the immunodepressive effect of AT globulin to sheep erythrocytes is due in part to the passive transfer of antibody and is not necessarily due to a specific anti-lymphocyte effect.
SEQUENTIAL CHANGES IN THE RELATIVE AFFINITY OF ANTIBODIES SYNTHESIZED DURING THE IMMUNE RESPONSE
Authors: Steiner Lisa A. , Eisen Herman N.
Published: June 2004

The anti-2,4-dinitrophenyl (DNP) antibodies synthesized by suspensions of lymph node cells obtained at various intervals from rabbits that had been immunized with DNP-bovine γ-globulin increased progressively in their affinity for the dinitrophenyl determinant. This change accompanied and was apparently responsible for a similar change in the binding properties of anti-DNP antibodies isolated from the serum. The rate of change in affinity was related to the dose of immunogen: increasing the dose delayed the change.

The antibodies formed during a brief (5 hr) incubation in vitro were heterogeneous in their binding properties. Therefore, the mixing in the circulation of molecules synthesized at different times may contribute to, but is not alone responsible for, the heterogeneity in the serum antibodies.

Variability in binding did not appear to be related to heterogeneity in immunoglobulin class. Indeed, the variations in relative affinity occurred entirely within the γG-immunoglobulins.
THE RELATIVE AFFINITY OF ANTIBODIES SYNTHESIZED IN THE SECONDARY RESPONSE
Authors: Steiner Lisa A. , Eisen Herman N.
Published: June 2004

In response to a second injection of rabbits with a dinitrophenylated antigen, given 2 months to 2 yr after the first injection, there was rapid synthesis of large amounts of antibody high in relative affinity for the dinitrophenyl (DNP) determinant. The antibodies formed 3 days after restimulation were already high in affinity.

Amounts of antigen too small to elicit detectable antibody production may prime the animal for a partial secondary response characterized by the formation of antibody of intermediate affinity after a second antigenic stimulus.

Investigations into the specificity requirements for the secondary response indicated that variation in the carrier protein and in the haptenic determinant could be tolerated. Thus, after immunization with DNP-bovine γ-globulin, DNP-hemocyanin elicited the vigorous production of high affinity anti-DNP antibodies. However, DNP serum albumin was much less effective: it elicited a secondary response in some animals primed with DNP-bovine γ-globulin only when the interval between injections was increased from 10 to 28 wk. A secondary response was also evoked when the haptenic determinent of the second immunogen differed slightly from that of the one injected initially (i.e., 2,4,6-trinitrophenyl versus 2,4-dinitrophenyl).
THE LOCALIZATION OF CIRCULATING IMMUNE COMPLEXES IN EXPERIMENTAL SERUM SICKNESS
Authors: Kniker William T. , Cochrane Charles G.
Published: June 2004

In serum sickness, mechanisms by which circulating immune complexes become localized in the walls of vessels and glomeruli have been studied. In affected arteries, morphologic observations showed that circulating marker particles of carbon would rapidly deposit along the luminal surface of the internal elastic lamina. This, as in previous studies, suggested an increase in vascular permeability during which large molecules were capable of being trapped by a filtering membrane in the vessel wall.

In attempts to prevent the increase in vascular permeability, rabbits were treated with antagonists of histamine and serotonin. Such treatment markedly inhibited the localization of immune complexes in glomeruli, the development of proteinuria, and glomerular endothelial proliferation. Cardiovascular lesions also were largely prevented from developing. Depletion of platelets, the principal reservoir of vasoactive amines, had a similar though less pronounced effect. While the deposition of immune complexes was inhibited, allergic inflammation in general was not, since normal rabbits treated as above were found capable of developing full Arthus reactions and acute nephrotoxic nephritis.

Hydrodynamic factors were noted to be important in determining the location of arterial lesions. Studies of aortas from unmodified rabbits and from those with surgically induced coarctations of the abdominal aorta revealed intimal lesions concentrated at areas of high turbulence, such as at branches, bifurcations, outflows and zones of configurational change. Lesions in these areas were also largely inhibitable by depletion of platelets or by antagonists of histamine and serotonin.
ANTIGENIC COMPETITION BETWEEN POLYPEPTIDYL DETERMINANTS IN NORMAL AND TOLERANT RABBITS
Authors: Schechter Israel
Published: June 2004

Competition between two polypeptidyl determinants was studied in normal rabbits and rabbits made tolerant to the competing antigen. The capacity of poly-DL-phenylalanyl protein conjugate to inhibit the formation of antibodies specific to the poly-DL-alanyl determinant was dependent on the nature of the protein carrier of the singly substituted antigens. Competition occurred only when the peptidyl determinants were attached to identical or similar (RSA and HSA) carriers. Thus, the immune response toward the poly-DL-alanyl determinant was impaired by injecting the pairs p-DL-PheRSA and p-DL-AlaHSA, or p-DL-PheRNase and p-DL-AlaRNase. Suppression of the formation of antibodies with poly-DL-alanyl specificity was not observed, however, upon administration of p-DL-PheRSA together with p-DL-AlaRNase or of p-DL-PheRNase with p-DL-AlaHSA.

Tolerance to p-DL-PheRSA was induced by injecting this material into newborn rabbits. The tolerant animals retained their capacity to produce anti-poly-DL-alanyl antibodies upon injection of p-DL-AlaRSA or p-DL-AlaHSA. However, when these poly-DL-alanyl proteins were administered together with p-DL-PheRSA, antibodies against the poly-DL-alanyl determinant were not formed even though no antibodies with poly-DL-phenylalanyl specificity were produced.

These results indicate that in competition experiments the preference in the immune response against a given determinant is dependent not only on the nature of the competing determinants, but it is also governed to a large extent by the over-all properties of the antigenic molecules. This suggests that at the stage at which the competition occurs the competing molecules had not undergone considerable degradation.

On the basis of experiments with tolerant animals, it is suggested that in normal animals antibody formation to the competing antigen is not the cause of its inhibitory action on the response against the other antigen.

The competition experiments described suggest that an antibody-forming cell is multipotent.
DELAYED HYPERSENSITIVITY
Authors: Kantor Fred S.
Published: June 2004

Exposure to picryl guinea pig albumin with 3–6 picryl groups per mole failed to affect the ability of peritoneal exudate or peripheral blood leukocytes from sensitized donors to transfer delayed sensitivity to normal recipients. In contrast, conjugates containing 40–48 picryl groups per mole altered the ability of exposed leukocytes to transfer delayed sensitivity. Evidence is presented that highly conjugated guinea pig albumin is self-aggregating. Lightly conjugated albumin, previously heat-aggregated, also was effective in "desensitization." The properties of antigen size, cell association of antigen after exposure, and desensitization appear to be associated.
THE ULTRASTRUCTURE OF NORMAL AND PATHOLOGICAL IGM IMMUNOGLOBULINS
Authors: Chesebro B. , Bloth B. , Svehag S-E.
Published: June 2004

Free IgM immunoglobulins were examined in the electron microscope using the negative contrast technique. Normal human and rabbit IgM and Waldenström macroglobulins were indistinguishable from one another and revealed flexible spider-like particles with five appendages joining a central ring. The average total span of the molecules was 300 A. The appendages were about 125 x 30 A; the central ring had an outer diameter of approximately 100 A and an inner diameter of 40 A.

Some purified 19S IgM preparations tended to form massive aggregates (≥50S) which, when examined in the electron microscope, revealed enormous clumps of IgM molecules whose appendages were entangled with one another.

Electron microscopy of reduced-alkylated IgM revealed total absence of intact spider-like molecules. The predominating structure observed was a round electron-dense knob about 50 A in diameter which in some cases had a fine fiber-like extension with approximate dimensions 100 x 15 A.

Rabbit and human IgM molecules with antibody activity to poliovirus dried in sodium tungstosilicate on a carbon film as in preparation for electron microscopy were shown to retain nearly 100% of their poliovirus neutralizing activity after redissolving in a physiological buffer.
THE EFFECT OF HISTOCOMPATIBILITY-2 TYPE ON RESPONSE TO THE FRIEND LEUKEMIA VIRUS IN MICE
Authors: Lilly Frank
Published: June 2004

Two types of quantitative response to the F-B strain of Friend virus in segregating generations of a cross involving a susceptible (DBA/2 or BALB/c; H-22) and a resistant (C57BL/6; H-2b) mouse strain show a marked correlation with the H-2 type of the mice. Essential susceptibility, as determined by the splenomegalic response to high virus doses, is controlled by a single pair of alleles which segregates independently with respect to the H-2 locus. However, relative susceptibility, as determined by the incidence of the splenomegalic response at moderate or low levels of virus dosage, is significantly greater among mice homozygous or heterozygous for the H-2d allele than among H-2b homozygotes in these populations. In addition, the incidence of recovery from splenomegaly induced by a given level of virus dosage is significantly greater in H-2b homozygotes than in segregants of other H-2 types among their littermates. Possible mechanisms responsible for these effects are discussed.
AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS INDUCED WITH RENAL TUBULAR ANTIGEN
Authors: Edgington Thomas S. , Glassock Richard J. , Dixon Frank J.
Published: June 2004

The nephritogenic antigen, responsible for the immunogenic stimulus in experimental allergic glomerulonephritis induced with tubular antigen, has been identified as a renal tubular epithelial (RTE)-specific antigen and has been isolated in a relatively purified form. This antigen, RTE-α5, is a distinct and antigenically specific lipoprotein of high density which is derived primarily from the brush border of proximal convoluted tubular epthelium of the rat kidney. It has been suggested that this molecule may be a plasma membrane subunit. Immunization of rats with as little as 3 µg N of RTE-α5 in complete Freund's adjuvant has effectively induced this form of membranous glomerulonephritis. RTE-α5 is not a constituent of normal rat glomeruli; however, with the onset of autologous immune complex nephritis it is deposited in a granular fashion along glomerular capillary walls indistinguishable from the deposits of γ-globulin and complement. The antigenic specificity of this antigen and its tissue derivation has been explored, and the observations support the autologous immune complex pathogenesis of the glomerulonephritis induced in rats by immunization with renal tubular antigen.
CARDIAC AUTOANTIBODIES
Authors: Halbert S. P. , Holm S. E. , Thompson A.
Published: June 2004

1. A high proportion of rabbits immunized with pooled rabbit heart homogenates in complete Freund's adjuvant responded with the production of multiple precipitating antibodies to soluble rabbit heart antigens. The most potent antisera revealed at least five distinct antigens.

2. Rabbit anti-rabbit heart antibodies reacted with similar antigens in other mammalian hearts, (human, rat, guinea pig, and bovine) with apparent "reactions of identity" by immunodiffusion.

3. Rabbits immunized with human, rat, or guinea pig heart homogenates also responded with multiple precipitating antibodies directed against rabbit cardiac antigens, although somewhat less intensively than animals immunized homologously. The specificities of these antibodies appeared to be the same as those evoked homologously.

4. The autoantibody nature of the homologously and heterologously induced responses was unequivocally demonstrated in several instances by reactions between the sera from immunized rabbits and their own hearts.

5. Many of the autoantibodies appeared to be directed against antigens restricted to the heart, judging by comparative immunodiffusion tests with other rabbit tissue extracts. This was convincingly confirmed by multiple absorption of potent antisera with several rabbit tissues. The cardiac-restricted antigens were also present in heart extracts of other mammalian species. In those instances where some of the cardiac-evoked autoantibodies reacted with other rabbit tissues, the tissue cross-reactions were quite variable.

6. Rabbits immunized with guinea pig heart homogenate suffered a high early mortality of undetermined cause, compared to animals immunized with rabbit, human, or rat hearts.

7. A small proportion of the anti-heart sera revealed immunodiffusion reactions with Group A streptococcal products, derived from organisms grown in antigen-free media. In these few instances, the reactions appeared unrelated to cardiac autoantibody responses.
THE DEACTIVATION OF RABBIT NEUTROPHILS BY CHEMOTACTIC FACTOR AND THE NATURE OF THE ACTIVATABLE ESTERASE
Authors: Ward Peter A. , Becker Elmer L.
Published: June 2004

As shown previously, immune complexes engender in rabbit serum a factor capable of inducing chemotaxis of rabbit polymorphonuclear leukocytes. This chemotactic factor consists of a complex of the fifth, sixth, and seventh components of complement. As demonstrated here, the polymorphonuclear leukocytes incubated with such treated rabbit serum lose their ability to respond chemotactically to the chemotactic factor. They are "deactivated."

The process of "deactivation" is a function of the duration of contact of the cells with, and the concentration of, the treated serum. There is a parallelism between the time course of deactivation and of chemotaxis, as well as the dose-response curves for the two processes. Chemotactic factor purified by isoelectric precipitation and ion-exchange chromatography produces deactivation in the same manner as the treated serum. The deactivating activity requires, as does the chemotactic factor, the sixth component of complement; like the chemotactic factor, it is heat-stable and nondialyzable. Deactivation is prevented by the same phosphonate esters shown previously to prevent chemotaxis by the complement-associated chemotactic factor. The profiles of the phosphonates in protecting against deactivation are the same as the profiles for the chemotactic factor-dependent inhibition of chemotaxis. Aromatic amino acid derivatives prevent both chemotaxis and deactivation. We conclude from this evidence that the chemotactic factor is able to deactivate or induce chemotaxis depending upon experimental conditions.

The fact that the profiles given by the phosphonates for protection against chemotactic factor-dependent deactivation and for chemotactic factor-dependent inhibition of chemotaxis are the same indicates that the "activatable esterase" is involved in both processes. Acetate esters such as ethyl acetate and others shown previously to prevent chemotaxis by inhibiting the "activated esterase" do not prevent deactivation. This indicates that deactivation can occur without participation of the latter enzyme, implying that deactivation involves only a part of the biochemical mechanism of chemotaxis.

The protection against deactivation afforded by aromatic amino acid derivatives is specific, insofar as nonaromatic amino compounds and simple acetate esters have no effect. In addition, as stated, the aromatic amino acid derivatives inhibit deactivation and chemotaxis by the chemotactic factor. This latter finding, together with the demonstration of the involvement of the activatable esterase in both deactivation and chemotaxis, suggests that the activatable esterase of the rabbit polymorphonuclear leukocyte is a serine esterase with a special affinity for aromatic amino acid derivatives.
HETEROLOGOUS CARRIERS IN THE ANAMNESTIC ANTIHAPTEN RESPONSE
Authors: Rittenberg Marvin B. , Campbell Dan H.
Published: June 2004

Anamnestic antihapten responses were obtained to trinitrophenyl (TNP) when rabbits sensitized to trinitrophenyl-hemocyanin (TNP-KLH) were challenged with TNP-heterologous protein conjugates. Hapten-heterologous carrier conjugates elicited antihapten titers similar in magnitude to those elicited by the homologous carrier conjugate. Hapten-heterologous carrier recall of antihapten was successful as early as 37 days and as late as 11 months after sensitization. There was no correlation between anti-TNP-precipitating antibody titer after sensitization and the ability to respond to challenge by hapten-heterologous carrier. The results are discussed in terms of immunogenicity of sensitization, suppressive effects of persisting postsensitization antibody, and submolecular haptenic environment as factors possibly affecting the heterologous recall process.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Seravalli Egilde , Dubos René
Published: June 2004

Certain specific-pathogen-free (SPF) mice bred and maintained under semiprotected conditions have an intestinal flora which is qualitatively simpler (although not quantitatively smaller) than that of mice of the same genetic stock produced under ordinary conditions. They are also heavier at weaning time, grow at a faster rate, and reach a greater adult weight than ordinary mice.

When SPF mice are contaminated per os shortly after birth with certain bacterial cultures isolated from the intestinal contents of adult ordinary mice, these bacteria multiply extensively throughout the gastrointestinal tract and persist at extremely high levels until weaning time. Such bacterial infections do not affect significantly either weaning weight, growth rate, or maximum adult weight.

In contrast, weight depression could be consistently brought about by contaminating newborn SPF mice per os with bacteria-free filtrates of homogenates of intestines from ordinary mice.

The weight-depressing agent passed through Millipore discs of 0.45 and 0.22 µ porosity, but was held back at 0.10 µ porosity.

The depression of weight caused by either intestine homogenate or filtrates thereof could be detected within a few days after contamination (of 2 day old mice) and persisted throughout the adult life of the contaminated animals. When intestine homogenate of the SPF mice used in this study were introduced per os into newborn SPF mice, they did not affect their growth rate or adult weight.

On several occasions, but not consistently, bacteria-free filtrates capable of depressing the weight curve of SPF mice produced alterations in the appearance of tissue cultures of BHK-21 and mouse embryo cells. When tissue cultures so infected were introduced into newborn SPF mice, the weight of these animals was depressed early and lastingly.

An agent exhibiting weight-depressing activity has been transferred from mouse to mouse over many passages by contaminating newborn SPF animals per os.

Weight depression was achieved with extremely small doses of material (10–5 ml of intestine homogenate of 10–4 of mouse embryo culture). Under these conditions, none of the animals showed obvious signs of disease except reduced weight.

Only very young SPF mice (preferably less than 3 days old) proved susceptible to the weight-depressing effect of the filtrates of intestine homogenates or of infected tissue cultures prepared therefrom. After oral contamination, it took approximately 1 wk before the intestinal homogenate obtained from contaminated animals exhibited a high level of weight-depressing activity.

The growth-depressing effect could be transmitted from one generation to the next by mating SPF mice that had been contaminated shortly after birth and that were consequently smaller than control SPF animals.
FACTORS MODIFYING HOST RESISTANCE TO VIRAL INFECTION
Authors: Murphy Brian R. , Glasgow Lowell A.
Published: June 2004

The resistance of mice to encephalomyocarditis (EMC) virus was markedly decreased by prior exposure to whole body X-irradiation. In contrast to non-irradiated controls, the course of EMC virus infection in X-irradiated animals was characterized by (a) an enhanced mortality, (b) shortening of the incubation period, (c) higher levels of virus in the blood during the viremic phase and persistence of the viremia until death, (d) failure to develop detectable serum levels of neutralizing antibody, and (e) the earlier appearance and higher levels of virus in brain and heart tissue. The level of interferon in the serum during the course of infection was similar in both groups. The administration of relatively small quantities of anti-EMC virus neutralizing antibody to X-irradiated mice during the early phases of the infection with EMC virus restored their resistance to levels comparable to nonirradiated animals. An alteration of local organ defense mechanisms in the central nervous system could not be demonstrated. It is proposed that (a) the inability of the X-irradiated animal to elaborate specific neutralizing antibody was a critical determinant in their failure to clear the viremia, (b) this increase in the level and duration of the viremic phase resulted in the exposure of target organs to a greater inoculum of virus, and (c) the enhanced mortality observed in irradiated mice reflected this greater target organ involvement. The experimental model presented, therefore, suggests that the immunologic response is a critical determinant of host resistance during this primary systemic virus infection.
THE MIXED LYMPHOCYTE REACTION: AN IN VITRO TEST FOR TOLERANCE
Authors: Schwarz M. Roy
Published: June 2004

Tolerance, as defined by an inability to produce runt disease and the failure to elicit a normal lymphocyte transfer reaction, was induced in Lewis and Brown Norway rats by the neonatal injection of bone marrow from the opposite strain. When thymus, thoracic duct lymph, or lymph node cells from such tolerant Lewis and Brown Norway rats were cultured together, or were individually cultured with similar cells from an F1 hybrid of these strains, transformation was suppressed to the levels observed in nonmixed control cultures. In contrast, mixtures of cells involving nontolerant donors demonstrated significant transformation as measured by per cent enlarged cells and thymidine-3H uptake. The specificity of the tolerance was confirmed by the presence of transformed cells in mixtures involving cells from a tolerant donor and an unrelated or a partially related third strain of rats. From these results, it is suggested that the mixed lymphocyte reaction may be used as a simple test for tolerance and that it most likely represents an in vitro immune response.
PHYLOGENETIC ORIGINS OF ANTIBODY STRUCTURE
Authors: Marchalonis John J. , Edelman Gerald M.
Published: June 2004

The sea lamprey, Petromyzon marinus, has been found to produce specific antibodies after immunization with bacteriophage f2. Antibody activity is localized in 6.6S and 14S fractions of lamprey serum. The 6.6S antibodies were purified by a combination of zone electrophoresis, ion exchange chromatography, and gel filtration. Antigenic analysis of the 6.6S antibodies showed them to be free of other serum proteins and antigenically similar or identical to the 14S fraction. Evidence has been obtained which suggests that the 6.6S immunoglobulins consist of light components (molecular weight 25,000) and heavy components (molecular weight 70,000). In the immunoglobulin, these polypeptides appear to be linked via weak interactions but not by interchain disulfide bonds. Molecular weight analyses support the view that the chains can undergo concentration-dependent dissociation in aqueous solutions. Amino acid analyses showed that the compositions of the light and heavy components were similar and that aspartic acid or asparagine was the predominant amino terminal residue. Starch gel electrophoresis indicated that the subunits of lamprey antibodies are diffusely heterogeneous. The heavy chain mobility corresponded to that of µ-chains and resembled that of heavy chains of shark and sting ray immunoglobulins.

In the course of the fractionation a 46S natural hemagglutinin composed of lower molecular weight subunits was isolated. This hemagglutinin did not resemble the lamprey immunoglobulin although it had a similar zone electrophoretic mobility in the ß-region.

These studies are consistent with the hypothesis that µ-chains were the earliest of the heavy chain classes to emerge and further support the view that the multichain structure of immunoglobulins is a fundamental feature of antibody molecules.
BONE MARROW ORIGIN OF IMMUNOLOGICALLY COMPETENT LYMPHOCYTES IN THE RAT
Authors: McGregor Douglas D.
Published: June 2004

Rat bone marrow is deficient in immunologically competent cells when compared with the peripheral pool of circulating small lymphocytes. However, circulating lymphocytes capable of initiating a lethal graft vs. host reaction can develop from myeloid precursors. In adult rats inoculated at birth with parental strain bone marrow cells, the thoracic duct lymph contains cells having the immunological capability of the marrow donor. The evidence suggests that immunologically competent lymphocytes derive from cells normally resident in bone marrow and probably not from precursors in the peripheral lymphocyte pool.
THE SUBUNITS IN RABBIT ANTI-FORSSMAN IGM ANTIBODY
Authors: Frank Michael M. , Humphrey John H.
Published: June 2004

Rabbit IgM anti-Forssman antibody was highly purified and the subunits obtained on reduction and alkylation were labeled radioactively and isolated by two different and unrelated methods. In both cases the subunits were found to have a molecular weight of about 90,000, based on their behavior on density gradient centrifugation and gel filtration, and evidence is given that they contained one light and one heavy chain. The subunits bound only weakly to sheep erythrocyte stroma, and only half could be shown to possess antigen specific sites. The data are consistent with the concept that each anti-Forssman IgM molecule has five effective binding sites, but it is uncertain whether the ineffectiveness of the remaining five H-L chain pairs is inherent in the structure of the IgM molecule or an artifact due to the isolation procedure. Intact IgM anti-Forssman antibody binds very firmly to structures containing multiple repeating antigen sites, and it appears that this is due to the presence of multiple binding sites on the molecule.