bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternate Complement Pathway: Factors Involved in Cobra Venom Factor (CoVF) Activation of the Third Component of Complement (C3)
Authors: Hunsicker L. G. , Ruddy S. , Austen K. F.
Published: December 2022

An immunochemically pure plasma protein, β2II, possessed properdin factor B activity. On the other hand, purification of this protein was associated with loss of the ability to interact with cobra venom factor (CoVF) so as to inactivate the third complement component (C3) or activate the terminal complement sequence as assessed by the lysis of unsensitized erythrocytes. C3 inactivation was restored, and terminal component activation partially restored, by combining with β2II and CoVF a 35,000 molecular weight protein isolated from euglobulin, termed factor D. An additional factor of approximately 160,000 m.w., termed factor E, also obtained from euglobulin, was required for complete reconstitution of CoVF-induced terminal component activation. Addition of radioiodinated CoVF to serum, EDTA-plasma, or serum rendered deficient in β2II, resulted in an apparent increase in the molecular weight of CoVF from 144,000 to 220,000 indicating that the interaction of CoVF with a binding protein can occur independently of magnesium ions or β2II. Complexing of CoVF was not seen with β2II, factor D, or a mixture of the two but was observed with preparations of factor E.
Hapten-Specific Tolerance: Depressed Humoral and Normal Cellular Immune Responses
Authors: Cohen Benjamin E. , Davie Joseph M. , Paul William E.
Published: December 2022

A profound depression of the anti-DNP antibody response to DNP-guinea pig albumin (GPA) is induced by pretreatment of guinea pigs with the DNP conjugate of the copolymer of d-glutamic acid and d-lysine (DNP-d-GL). This tolerance is hapten-specific and previous studies have indicated that the number of precursors of anti-DNP antibody-secreting cells is diminished as a result of the tolerance induction. Thus, the tolerant state appears to be due to an immune paralysis within the precursors of antibody-secreting cells (bone marrow-derived cells). In this study, it is shown that animals tolerized with DNP-d-GL, although manifesting a marked depression in the humoral response after immunization with DNP-guinea pig albumin, display a normal delayed hypersensitivity response to DNP-guinea pig albumin. Furthermore, lymph node cells from tolerized animals incorporate thymidine into DNA when stimulated with antigen in amounts equivalent to cells from normal immune animals. Thus, cellular immune responses (thymus-derived cell mediated functions) to DNP-GPA are normal in guinea pigs pretreated with DNP-d-GL. These studies strongly reinforce the concept that a basic specificity distinction exists between receptors on precursors of antibody-secreting cells and those on cells participating in cellular immune responses.
Antibody-Binding Characteristics at the Cellular Level
Authors: Claflin Latham , Merchant Bruce
Published: December 2022

The development of immune plaque-forming cell (PFC) populations producing IgG antibody of high affinity for the hapten, N-(2,4-dinitrophenyl)-β-alanylglycylglycine (DnpAGG) was studied in BALB/c mice. DnpAGG-specific PFC subpopulations differing in the affinity of their secreted antibodies were identified by the hapten-specific plaque inhibition technique. Immunization procedures were used which selected for or against the early appearance of high affinity PFC. With most procedures the main response late after antigen injection resided typically among high affinity PFC. Subpopulation profile analysis indicated that each of these procedures yielded the same high affinity PFC subpopulations. Population dominance by high affinity PFC was ordinarily reached 26 to 33 days after immunization, after which time no new PFC were detected which secreted antibody of any affinity higher than that previously observed. Under the influence of special immunization procedures these high affinity PFC could be readily detected, in reduced but significant numbers, as early as 4.5 days after immunization when IgG-secreting cells were first marking their appearance. These data indicate that in IgG, as in IgM, bone marrow-derived cell commitment to the synthesis of an antibody molecule having a given specificity and affinity commonly occurs before specific antigenic insult.
Immunochemical Similarity Between Polysaccharide Antigens of Escherichia Coli 07:K1(L):NM and Group B Neisseria Meningitidis
Authors: Kasper Dennis L. , Winkelhake Jeffrey L. , Zollinger Wendell D. , Brandt Brenda L. , Artenstein Malcolm S.
Published: December 2022

Polysaccharide antigens from Escherichia coli 07:K1(L):NM and group B Neisseria meningitidis have been isolated and purified. Like the meningococcal group B polysaccharide, the sialic acid antigen from E. coli was acidic in nature, was susceptible to neuraminidase degradation and lacked O-acetyl groups. Immunologically these two polysaccharides were indistinguishable in assays of hemagglutination inhibition and they produced lines of identity by immunodiffusion. Investigation of the immunogenicity of the E. coli polysaccharide showed that it induced antibody in rabbits after multiple injections but not in human volunteers given one or two injections of 50 µg each.
In Vitro Kinetics of Intestinal Secretory IgA Secretion
Authors: Kagnoff Martin F. , Serfilippi Delchi , Donaldson Robert M.
Published: December 2022

Locally synthesized secretory IgA (sIgA)3 is the predominant immunoglobulin in most mammalian external secretions (1). In the intestinal tract, the sIgA molecule is thought to be a synthetic product of lamina propria plasma cells (i.e., heavy (H) and light (L) chains, and J chain) and mucosal epithelial cells (i.e., secretory component) (1–3). Because appropriate models have not been available, it has not been possible to examine directly the kinetics of sIgA secretion.

We have recently shown (4) that biopsies of rabbit small intestine maintained in organ culture synthesized and secreted protein in vitro under steady-state conditions for at least 24 hr. Furthermore, these biopsies synthesized sIgA de novo and secreted intact sIgA into the organ culture medium. The present paper describes the kinetics of sIgA secretion by rabbit intestinal mucosa in vitro.

Rabbit small intestinal biopsies consisting largely of mucosa and submucosa were placed in organ culture as described in detail previously (4, 5).
The Role of Humoral Factors in the Initiation of in Vitro Primary Immune Responses
Authors: Watson James , Epstein Ruth , Nakoinz Ilona , Ralph Peter
Published: December 2022

Lymphocyte mitogens were used to analyze the induction of in vitro primary immune responses. Bacterial lipopolysaccharide (LPS), concanavalin A (Con A), pokeweed mitogen (PWM) and phytohemagglutinin (PHA) stimulated DNA synthesis but inhibited primary immune responses to sheep erythrocytes (SRBC) in normal mouse spleen cultures. In the same concentration range LPS, Con A and PWM stimulated immune responses to SRBC in spleen cultures depleted of thymus-derived cells by treatment with anti-θ C3H serum. Spleen cultures prepared from congenitally athymic (nude) mice did not support in vitro primary immune responses to SRBC. LPS, but not Con A or PWM, stimulated both DNA synthesis and primary immune responses to SRBC in spleen cultures from athymic mice. Con A and PWM appear to require the presence of thymus-derived cells to exert their inhibitory or stimulatory effects on immune responses. In contrast LPS replaces the requirement for thymusderived cells in the induction of primary immune responses.
Suppression of Delayed Hypersensitivity Reactions in Bursectomized Chickens by Passively Administered Anti-Immunoglobulin Antisera
Authors: Theis Gail A. , Thorbecke G. Jeanette
Published: December 2022

Intravenous injection of rabbit anti-chicken immunoglobulin antisera (R anti-Ch IgG and R anti-Ch IgM) resulted in inhibition of delayed hypersensitivity (DH) reactions in bursectomized agammaglobulinemic chickens. Persistence of a high titer of circulating anti-Ig over the first 48 hr after challenge of sensitized chickens was correlated with effective inhibition of DH responses. Since both the R anti-Ch IgG and R anti-Ch IgM antisera had inhibitory effect, it is suggested that the anti-Ch L-chain component common to both antisera is responsible for inhibition. Mechanisms through which anti-Ig antibody might interfere with DH reactions are discussed.
Alteration of Macrophage Interfacial Tension by Supernatants of Antigen-Activated Lymphocyte Cultures
Authors: Thrasher Susan G. , Yoshida Takeshi , van Oss Carel J. , Cohen Stanley , Rose Noel R.
Published: December 2022

Supernatant fluids from cultures of sensitized lymphocytes incubated with specific antigen contain a soluble factor which lowers the contact angle between a sessile drop of buffered saline and macrophage monolayers. This effect, which reflects a reduction in the interfacial energy of the cell surface, is carrier specific and is not due to antibody or antigen in the culture fluids. This factor appears concomitantly with MIF production. The lowering of contact angle is associated with enhanced phagocytosis, in a system involving opsonized erythrocytes. Aside from providing information about interactions between sensitized lymphocytes and macrophages, this system may serve as a rapid assay for detecting lymphokine activity.
The Localization of IgE in Canine Skin: An Immunofluorescent Study
Authors: Halliwell R. E. W.
Published: December 2022

The distribution of IgE in canine skin was studied by immunofluorescence. The antibody was found to be associated exclusively with mast cells and to be largely cytoplasmically located. No other recognized immunoglobulin had a similar association. Immunofluorescent localization of Ascaris-binding antibodies gave parallel results to the IgE system. The amounts of IgE and of Ascaris-binding antibody in the skin of eight dogs were assessed semiquantitatively and showed a positive correlation with the results of intradermal skin tests with Ascaris extract and with anti-IgE (reversed cutaneous anaphylaxis). There was a poorer correlation between the amount of cutaneous IgE and the levels in the sera of the same eight dogs.
Platelet Injury Due to Activation of the Alternate Complement Pathway
Authors: Siraganian R. P. , Sandberg A. L. , Alexander A. , Osler A. G.
Published: December 2022

Allergic histamine release from rabbit platelets can be initiated through the alternate pathway of C activation. The release reaction proceeds in the absence of the Fc portion of the antibody molecule. The time course of release due to this pathway is slower than that after activation of the classical C sequence. Platelet injury due to immune complexes through both pathways requires the sixth C component.
Polycarbonate Sieve Filtration of Lymph Node Cells: Selective Depletion of Immunoglobulin-Bearing Lymphocytes
Authors: Harrison Michael R. , Elfenbein Gerald J. , Green Ira
Published: December 2022

The physical properties of lymphocytes are likely to be heterogeneous as are their functional properties. Thus, thymus-derived (T)1 lymphocytes are functionally distinct from bone marrow-derived (B) lymphocytes and this distinction is reflected not only in the presence or absence of easily detectable immunoglobulin on the cell surface (1), but also in the buoyant density of these cells as determined by velocity sedimentation (2) and their surface charge as measured by electrophoretic mobility (3, 4).

The lymphocyte's ability to migrate across post-capillary venules (5) may depend on general physical properties such as cell size and membrane charge adhesiveness and deformability. T lymphocytes differ from B lymphocytes in their migration and recirculation patterns (2, 6). T cells gain access to extravascular spaces such as chylous effusions more easily than B cells (7). The elegant studies of erythrocyte deformability as measured by passive filtration through polycarbonate sieves of defined pore size (8–11) led us to adapt this technique to the study of lymphocytes.
Characteristics of Disparate Histocompatibility Barriers in Congenic Strains of Mice
Authors: Cantrell J. L. , Hildemann W. H.
Published: December 2022

Characteristics of specific immunologic suppression were investigated in C57BL/10 congenic mouse strain combinations disparate at non-H-2 loci as a function of strong, moderate, and weak incompatibilities. These immunogenetic barriers were defined by both graft-vs-host reactivity and distinctive skin allograft survival times. Intraperitoneal injection of neonates with varying doses (2 × 106 to 20 × 106) of allogeneic spleen cells led to degrees of subsequent donor skin allograft acceptance which were closely dependent upon the interallelic combination. However, long-term skin allograft acceptors consistently produced serum alloantibodies against donor cells detectable in vitro by both cytotoxicity and hemagglutination-migration assays. The effectiveness of this specific antibody-associated suppression of transplantation immunity suggestive of enhancement was inversely proportional to the strength of the immunogenetic barrier and directly proportional to donor cell dosage. Increased immunogenetic incompatibility required increased dosage of allogeneic cells to induce specific suppression. The weaker the incompatibility the higher the incidence of effective allogeneic suppression and of concomitant alloantibody production obtained at lower antigen dosage. Coexistence of suppression of transplantation immunity (thymus-derived cell pathway blocked) with continuing anti-donor alloantibody production (bone marrow-derived cell pathway open) was found to be characteristic of the allograft-tolerant state.
Isolation of an Immunosuppressive Peptide Fraction from Human Plasma
Authors: Occhino Joseph C. , Glasgow Arthur H. , Cooperband Sidney R. , Mannick John A. , Schmid Karl
Published: December 2022

An immunosuppressive peptide fraction was isolated from Cohn fraction IV of normal human plasma by employing the low temperature-low salt-ethanol procedure of Cohn, fractional precipitation with ammonium sulfate, dialysis and ultrafiltration. The dissociation of the active peptide from an enriched protein fraction was found to be dependent upon high ionic strength and low pH. The resulting peptide fraction was electrophoretically heterogeneous although it appeared monodisperse by ultracentrifugation sedimenting with a coefficient of 0.6S. The peptide fraction was found to suppress both phytohemagglutinin-induced lymphocyte proliferation in vitro and the in vivo induction of splenic plaque-forming cells in mice immunized with sheep erythrocytes. The specific activity of this fraction was increased approximately 10-fold over that of Cohn fraction IV.
Particle Recognition by Cultivated Macrophages
Authors: Rabinovitch M. , De Stefano Mary Jo
Published: December 2022

This paper examines the interaction in serum free media of different particles with normal or stimulated mouse macrophages cultivated in the presence or in the absence of serum. Thioglycollate-stimulated macrophages cultivated for 7 weeks with or without serum phagocytized antibody-coated erythrocytes as well as a variety of particles that tested for “non-immunologic” recognition. After different periods of cultivation, however, depending on the media used, these macrophages failed to interact with erythrocytes coated with amboceptor and complement (EAC). Normal macrophages bound EAC after 2 weeks in culture with serum but failed to do so when serum was omitted from the culture medium. It is concluded that receptors for complement in cultivated macrophages are more labile and require serum for their manufacture or maintenance, in contrast to the apparent stability of receptors for immunoglobulin and non-immunologic phagocytosis.
Studies on Antibody Induction in Vitro
Authors: Adler Louise T. , Curley Dennis M. , Fishman Marvin
Published: December 2022

Soluble extracts of T2 phage prepared by detergent treatment (S-T2) stimulate the formation of vigorous primary type responses in suspensions of rabbit spleen cells. Neutralizing antibody activity in the tissue culture fluids is complement-dependent and reaches a peak at 5 days of culture after a 1-day lag period when an optimal immunogenic dose of antigen is used. Responses of spleen cells from individual rabbits vary considerably, but replicate cultures from a single spleen show excellent reproducibility. Antibodies produced in vitro with cells of unprimed rabbits belong predominantly to the IgM class, while the secondary in vitro response is mostly IgG. The suppressive effect of the inhibitors vinblastine and rifampicin on the primary response to S-T2 suggests that both RNA and DNA synthesis are required for antibody formation in this system.
Three New Immunologic Types of Trachoma-Inclusion Conjunctivities Organisms
Authors: Wang San-Pin , Grayston J. Thomas , Gale James L.
Published: December 2022

Trachoma-inclusion conjunctivitis (TRIC) and lymphogranuloma venereum (LGV) organisms are closely related. Utilizing protection of mice from toxic death by prior immunization and more recently an indirect micro immunofluorescence technique, we have described six immunologic types, A through F, of TRIC organisms and three types of LGV. This report describes three new types of TRIC organisms, G, H and I. While H and I are almost completely unique immunologically, type G has cross-reactions with type F and appears to be an immunologic bridge between the previously unique F type and the B-, Ba-, D-, E- and LGV-related types. Strains of the three new types have been isolated almost entirely from the genital tract and biologically resemble the TRIC types D, E and F which have also been associated primarily with genital infection.
Generation by Bacterial Proteinases of Leukotactic Factors from Human Serum, and Human C3 and C5
Authors: Ward P. A. , Chapitis J. , Conroy M. C. , Lepow I. H.
Published: December 2022

Proteinases derived from Serratia marcescens and group A, β-hemolytic Streptococcus are each able to generate, by cleavage, leukotactic fragments from human C3 and C5. In whole human serum, the Serratia enzyme produces a C3-related leukotactic factor, while the streptococcal proteinase produces a C5-related factor. The finding that proteinases derived from bacteria are able to generate complement-dependent leukotactic factors suggests that this may be one mechanism by which bacteria incite and maintain inflammatory reactions in tissues.
Restoration of Immunocompetency in Tolerant Lymphoid Cell Populations by Cellular Supplementation
Authors: Chiller Jacques M. , Weigle William O.
Published: December 2022

Reconstitution experiments demonstrate that in mice the induction of unresponsiveness to human γ globulin (HGG) occurs more rapidly in specific bone marrow-derived (B) cells of the spleen (<3 days) than the previously reported induction period required for unresponsiveness in specific B cells of the bone marrow (8 to 15 days). This temporal variance could not be attributed to a difference in the gross localization of tolerogen in the respective lymphoid tissues. In contrast, the maintenance of the unresponsive state was similar in both B cell populations (40 to 50 days). Accordingly, the restoration of immunocompetency in unresponsive spleens could be accomplished in an adoptive transfer system by the addition of syngeneic thymocytes only at times predictable by the temporal pattern of the spontaneous loss of unresponsiveness described for bone marrow cells. The mere adoptive transfer of syngeneic thymocytes into tolerant animals did not similarly affect the unresponsive state.
Normal Immunosuppressive Protein (N.I.P.)
Authors: Nelken David
Published: December 2022

A number of publications from this and other laboratories have indicated that α-globulinrich fractions isolated from normal mammalian plasma possess immunosuppressive properties both in vivo and in vitro (1–6).

The present communication describes a method for the isolation of a fraction from human plasma which is extremely active in the prolongation of skin allograft suvival times in mice and in the prolongation of survival times of xenografts from rats to mice. This fraction which we call N.I.P., normal immunosuppressive protein, migrates in immunoelectrophoresis and in acrylamide gel electrophoresis with the α-globulin bands.

The plasma of outdated ACD blood was removed and diluted two and a half times with distilled water. It was then adjusted to pH 5 with glacial acetic acid, and left overnight at 4°C. The fine precipitate which formed was removed by centrifugation. The supernatant was applied to a DEAE-cellulose chromatography column (Whatman, Microgranular, preswollen DE52) previously equilibrated with 0.03 M sodium acetate buffer, pH 5.
Peritoneal Exudate Lymphocyte
Authors: Rosenstreich David L. , Rosenthal Alan S.
Published: December 2022

The antigen-induced in vitro lymphocyte proliferative response of peritoneal exudate lymphocytes (PEL) from guines pigs immune to horseradish peroxidase (HRPO) has been studied. PEL can be stimulated after only a brief (60 min) exposure to HRPO in vitro at 37°C, and the amount of measured stimulation is equivalent to that produced by an equal concentration of antigen present continuously in culture. Lymphocyte stimulation is maximal when the short antigen exposure takes place at 37°C, but a small amount of stimulation is produced when PEL are exposed to antigen at 4°C. This reaction appears to require a separate antigen-binding cell rather than direct binding of antigen to the antigen responsive lymphocyte since PEL that have been pulsed with antigen can stimulate non-pulsed PEL when the two are mixed together. This antigenbinding cell does not have to divide in order to function since it is not sensitive to mitomycin-C, but must be viable. The antigen-binding cell does not have immunologic specificity since antigen-pulsed PEL from non-immune animals function as well as PEL from immune animals in inducing lymphocyte proliferation in non-pulsed PEL.

Several different lymphoid populations were analyzed for the presence of cells capable of binding HRPO and activating immune PEL. Two highly purified thymus-derived (T) cell populations, lymph node lymphocytes and thymocytes contained no antigen-binding cells detectable by this technique. In addition, a bone marrow-derived lymphocyte population, guinea pig L2C leukemia cells, contained no detectable HRPO-binding cells. However, both monocyte- and macrophage-enriched populations contained large numbers of HRPO-binding cells. These data suggest that even in a purified lymphocyte population, macrophages or monocytes are the primary antigen-binding cells for the induction of T lymphocyte proliferation, in vitro.
Immunity in Experimental Syphilis
Authors: Miller James N.
Published: December 2022

Twenty-four rabbits, each immunized intravenously over a 37-week period with a total of 3.71 × 109 γ-irradiated, non-infectious Treponema pallidum, Nichols strain, were found to be completely resistant to intradermal challenge with either 1000 or 100,000 homologous treponemes administered 10 days after the last immunizing injection. Persistence of complete immunity was demonstrable in each of 11 vaccinated rabbits challenged intradermally with 1800 T. pallidum, Nichols strain, 1 year after the last immunizing injection. In contrast, only minimal resistance was observed in 10 of the T. pallidum-immunized rabbits challenged intradermally with 1000 Treponema pertenue, Haiti B strain, 14 days after completion of immunization.

Venereal Disease Research Laboratory, Treponema pallidum immobilization (TPI), and Fluorescent Treponemal Antibody-Absorbed antibodies, each of which is important in the diagnosis and control of syphilis, developed during immunization and persisted in some animals for at least 1 year.

Conclusive evidence that TPI antibody is not associated with the immune response was provided by the finding that 8 of the 11 immune rabbits challenged 1 year after vaccination had no TPI antibody before challenge and failed to develop immobilizing antibody during the 3-month period of observation after challenge.
A Rabbit Antiserum to a Thymus Extract Specific for Mouse Thymus-Derived Cells
Authors: Sarkar Siddhartha , Hyman Robert , Masuda Tohru , Herzenberg Leonard A.
Published: December 2022

A heteroantiserum has been prepared in rabbits against an EDTA eluate of mouse thymus. The globulin fraction of the unabsorbed serum precipitates macromolecules of several molecular weights eluted from various lymphomas. It is highly cytotoxic to both Thy-1 (ϑ)-positive lymphomas and normal thymus cells, but is also cytotoxic to some bone marrow cells. After absorption with insolubilized serum proteins and bone marrow cells, the serum is highly specific for mouse thymus-derived cells.

Indirect immunofluorescence of thymus cells assessed by rapid-flow fluorescent measurements gives a single sharp distribution; the activity of thymusderived cells is specifically removed from primed spleen cells by the absorbed serum plus complement when tested in an in vivo transfer system. The antiserum does not discriminate between Thy-1 (ϑ) alleles.
Complementary Genes Controlling Immune Response to ϑ-AKR Antigen in Mice
Authors: Zaleski Marek , Milgrom Felix
Published: December 2022

The primary response of mice to ϑ-AKR antigen was measured by means of plaque assay detecting cells producing antibodies lytic for AKR thymocytes (PFC). It was found that 3 of 12 different F1 hybrids produced significantly more PFC than either parental strain. In segregating populations of C57BL/6J and DBA/2J mice, H-2 homozygotes responded like parental mice, whereas most but not all H-2 heterozygotes responded like F1 hybrids. In the F2 population 7% and in the backcross population to C57BL/6J parent 20% of H-2 heterozygotes responded like parental mice. On the basis of experimental data, a hypothesis was advanced that thre eloci in the IXth linkage group are involved in genetic control of the response to ϑ-AKR antigen. Each locus has at least two alleles, one dominant and one recessive. Dominant alleles complement each other which explains why the response to certain F1 hybrids is higher than the response of their parents. Two of three hypothetical loci are closely linked to each other as well as to the H-2 complex and might be considered components of the Ir-1 system.
Regulation of the Immune Response with Antigen Specific IgM Antibody: A Dual Role
Authors: Wason William M.
Published: December 2022

IgM a-SRBC antibody administered before antigen produced an augmented response to a suboptimal dose of sheep erythrocytes (SRBC) in the mouse; however, this effect was not observed in two strains of rats tested. The same dose of IgM a-SRBC antibody which elicited an augmented response when given before the SRBC caused a significant suppression of the immune response when given 1 or 2 days after the SRBC. In vitro, IgM a-SRBC antibody suppressed the response of cultured mouse spleen cells to all doses of SRBC, whether given before or after immunization. In the intact mouse, IgM a-SRBC antibody apparently augments the primary immune response to low doses of antigen by increasing the number of SRBC localized in the spleen. Antibody must be present at the time of injection of the antigen for this effect to occur. However, IgM antibody can also act to suppress antibody-forming cells after antigen localization has occurred. Thus IgM antibody appears to play a dual role in the regulation of the immune response in the mouse.
Cutaneous Basophil Hypersensitivity
Authors: Colvin Robert B. , Pinn Vivian W. , Simpson Blanche A. , Dvorak Harold F.
Published: December 2022

Sensitization of guinea pigs with any of a variety of protein antigens in saline or incomplete Freund's adjuvant primes them for a form of delayed-onset cutaneous hypersensitivity characterized by the presence of large numbers of basophilic leukocytes. This form of reactivity, designated cutaneous basophil hypersensitivity (CBH), generally may be elicited only at early intervals after sensitization and is superseded by another form of cutaneous reaction with a more rapid time course, termed the “late reaction.” We have shown here that late reactions are composed of three sequential but overlapping phases, including cutaneous anaphylaxis, Arthus reactivity, and a residual CBH component. The distribution and clearance of antigen in guinea pig late reactions were quite similar to that observed in Arthus reactions elicited in hypersensitized rabbits, as judged by autoradiography. Clearance of 125I-peroxidase from rabbit skin was retarded by the presence of an Arthus reaction, regardless of its immunologic specificity. In guinea pig late reactions, 125I-HSA, probably combined with antibody, was concentrated by basophils and less commonly by eosinophils; antigen was more frequently localized in neutrophils and macrophages. The anaphylactic and, to a lesser extent, the Arthus components of late reactions could be passively transferred to normal animals with small amounts of hyperimmune serum. The CBH component was not so transferred, nor did hyperimmune serum administered before immunization interfere with the induction of CBH reactivity. However, large doses of passive antiserum given after immunization did inhibit the expression of CBH reactivity, as measured by basophil infiltration, but this effect was not immunologically specific.
Regional Lymph Node Irradiation: Effect on Local and Distant Generation of Antibody Forming Cells
Authors: Weissman Irving L. , Peacock Margo , Eltringham James R.
Published: December 2022

After footpad injection of sheep erythrocytes into Fisher rats, the major site of appearance of direct and indirect antibody plaque forming cells (direct and indirect) is the regional lymph node. Indirect plaque forming cells are subsequently found in the spleen, but no other lymphoid tissues. Repeated irradiation (days 1, 3, 5, 7, and 9) to the draining lymph node region after antigenic stimulation prevents the appearance of plaque forming cells in the spleen by day 10. Selective irradiation of this node group on days 4 and 5 prevents splenic appearance of indirect plaque forming cells only, whereas contralateral node irradiation does not. Irradiation at a later time (days 7 and 8) did not significantly lower the level of splenic indirect plaque forming cells by day 10. We concluded from these experiments that the appearance of splenic indirect plaque forming cells was dependent on radiosensitive cell populations in the antigen draining lymph nodes, and not on the generation of these cells independently in the spleen.
Physical Association of Two Nuclear Antigens and Mutual Occurrence of Their Antibodies: The Relationship of the Sm and Rnaprotein (MO) Systems in Sle Sera
Authors: Mattioli Martha , Reichlin Morris
Published: December 2022

An unexpected immunologic relationship was encountered when sera from patients with systemic lupus erythematosus directed against two different nuclear antigens in calf thymus extract were found to give a reaction of partial identity when reacted with a mixture of the antigens in agar diffusion experiments. Analysis of this antigenic mixture by absorption of the antigenic activity by monospecific antisera to such antigens has led to the conclusion that these two nuclear antigens designated Sm and Mo exist in calf thymus extract as a molecular complex. In addition to this physical association, human systemic lupus erythematosus sera containing anti-Sm were found to have an inordinately high concurrence of anti-Mo (17 of 19 sera).
Host Defenses During Primary Venezuelan Equine Encephalomyelitis Virus Infection in Mice
Authors: Rabinowitz Stanley G. , Adler William H.
Published: December 2022

The capacity of humoral antibody to confer protection against Venezuelan equine encephalomyelitis (VEE) infection did not require participation of cellular components of the immune response. Likewise, immune spleen cells conferred protection without participation of either preformed antibody or induction of an anamnestic antibody response. Time after donor immunization was a critical factor in determining the antiviral potential of transferred cells, and mice boosted with a second immunization of attenuated VEE virus did not have their antiviral capacity restored. Protection induced by transfer of immune spleen cells was immunospecific but could be inhibited by in vitro treatment of cell preparations with antithymocyte serum or anti-ϑ serum but not by treatment with anti-mouse γ-globulin. There was no evidence that preformed interferon contributed to the protective activity of passively transferred immune cells. Apparently, both humoral antibody and cellular immunity play important roles in protection against VEE virus infection in mice.
Antigen-Binding Lymphocytes in Normal Man and Guinea Pig to Human Encephalitogenic Protein
Authors: Yung Lily L. L. , Diener Erwin , McPherson T. Alexander , Barton Moira A. , Hyde Harry A.
Published: December 2022

Lymph nodes and blood from human subjects without neurologic disease, as well as lymph nodes from normal guinea pigs, contain lymphocytes capable of binding radiolabeled encephalitogenic basic protein of human myelin. In man, the number of such cells is comparable to that of cells binding a foreign antigen, radioiodinated flagellin of Salmonella adelaide. These observations lend support to the opinion that “forbidden clones” of lymphocytes, recognizing autoantigens, do exist in apparently normal animals.
Long-Term Spontaneous Tumor Incidence in Neonatally Thymectomized Mice
Authors: Sanford Barbara H. , Kohn Henry I. , Daly James J. , Soo Sophie F.
Published: December 2022

A number of workers have reported increased susceptibility of neonatally thymectomized mice to virally induced tumors (1–3). In this case, however, the response of the animal to the virus itself may be a critical factor, so that the effect of immunosuppression might be to reduce resistance to viral infection rather than to virally induced cell surface alteration.

The effect of neonatal thymectomy on other forms of carcinogenesis is not at all clear. Trainin et al. (4) have reported a decreased latent period and an increased number of tumor nodules after urethane treatment of mice that had been subjected to thymectomy on the 3rd day of life. Miller and coworkers (5) reported a decreased latent period for tumor induction when early thymectomy was combined with exposure to chemical carcinogens. On the other hand, using a system similar to Miller's, Law (6) observed no effect of neonatal thymectomy on either tumor incidence or latency.
A 51Cr Microassay Technique for Cell-Mediated Immunity to Viruses
Authors: Steele Russell W. , Hensen Sally A. , Vincent Monroe M. , Fuccillo David A. , Bellanti Joseph A.
Published: December 2022

A 51Cr microassay procedure for the in vitro measurement of cell-mediated immunity to rubella virus is described. The technique consists of a lymphocyte target cell interaction employing tissue culture lines chronically infected with rubella virus in which the quantitative release of 51Cr is used as an index of lymphocyte reactivity. Also described in these studies is an apparatus which separates the reacting cells from supernatant fluids and recovers the released 51Cr. Significant release is only observed with lymphocytes from rubella seropositive individuals and the reaction is inhibited by rubella hyperimmune sera. The microassay technique also appears to be applicable for the study of cellular immunity to a wide variety of viral agents.
Stimulation of in Vitro Antibody Responses to Sheep Red Cells by Thymus Cells Activated to Histocompatibility Antigens
Authors: Vann Douglas C. , Galloway Peter C.
Published: December 2022

Thymus cells from parental strain mice were injected into irradiated F1 recipients to produce thymus-dependent (T) cells activated to histocompatibility antigens (ATC). In vitro, the responses of normal spleen cells, expressed as plaque-forming cells (PFC) to sheep erythrocytes, were significantly enhanced by addition of appropriate numbers of ATC reactive with the spleen cell histocompatibility antigens. The enhancement was greatest on day 3 of culture. These effects were observed only when T cells were activated to foreign histocompatibility antigens and the responding spleen cells possessed the histocompatibility antigens to which the T cells were activated.

ATC derived from a given strain did not enhance the PFC responses of “bystander” spleen cells which were syngeneic with the ATC unless an appropriate target cell population was added to the culture. Supernatants were prepared which enhanced in vitro PFC responses. The supernatants came from cultures of ATC mixed with target cells.

The source and nature of the factor responsible for the enhancing activity have not yet been determined. The mechanism of the enhancement is not known, but it may be related to the observation that addition of ATC or enhancing supernatants to normal spleen cell cultures apparently stimulated cell division to the extent that the normal decline in cell number in primary cultures was eliminated and in some cases recoverable cell counts significantly increased during the 5-day period.
A New Preparative Method for Isolation of Human C3 with Affinity Chromatography
Authors: Molenaar J. L. , Müller M. , Pondman K. W.
Published: December 2022

A new preparative method for isolation of highly purified human C3 was developed by using a reversed application of affinity chromatography. Antisera against contaminations usually present in crude C3 preparations were produced. These antibodies were irreversibly coupled to Sepharose 4B and as a whole used in column form. When crude C3 preparations were applied to these columns the impurities were bound and thus eliminated. The resulting C3 preparations were pure when tested in concentrations of 5 mg/ml against anti-human serum and when tested by immunizing rabbits. C3 appeared to be homogeneous in the analytical ultracentrifuge, in polyacrylamide gel electrophoresis, and according to N-terminal amino acid analysis. The recovery from 400 ml normal human serum was about 65 mg.
Guinea Pig Lymphotoxin (LT)
Authors: Rosenberg Steven A. , Henrichon Margaret , Coyne John A. , David John R.
Published: December 2022

Lymphotoxin (LT) was found to be present in the same supernatants as antigen-stimulated guinea pig lymphocytes in which migration-inhibitory factor (MIF) was found. LT activity was determined by staining target cells with trypan blue, counting the cells present in the media and determining their viability, direct observation by time-lapse cinematography and measuring protein synthesis by surviving target cells. Like migration-inhibitory factor, the induction of LT release was antigen specific. LT was effective on a number of different target cell lines; however, young cultures of guinea pig embryo fibroblasts were resistant to it.
The Molecular Classes of Two Homocytotropic Antibodies in the Mouse
Authors: Schwartz Harvey A. , Levine Bernard B.
Published: December 2022

Heat-labile homocytotropic antibody (HCA), which persists in homologous skin sites for long periods of time, and heat-stable HCA, which persists in skin sites for short periods of time, were studied to determine their immunoglobulin classes. Absorption was done in liquid phase with monospecific antisera against mouse IgG2, IgG3, IgM and IgA, and with a Sepharose-coupled insoluble anti-IgG1. The short-latency, heat-stable HCA was completely removed with anti-IgG1 and by none of the other absorptions, i.e., it is an IgG1 antibody. The long-latency, heat-labile HCA was not removed by any of the immunoabsorptions. In addition, neither of the mouse HCA was removed from immune sera by absorption with a potent anti-human IgE antiserum, and fixation of mouse HCA to mouse skin was not blocked by human IgE Fc at 10 µ/ml concentration. The long-latency HCA is similar in many properties to human IgE and is accordingly tentatively called mouse “IgE” antibody. However, immunologic cross-reactivity between mouse and human IgE could not be demonstrated, nor could fixation of mouse IgE to mouse skin be blocked by human IgE Fc.
The Use of Column-Bound B Lymphocytes for Absorption of Antisera to T Lymphocyte Antigens
Authors: Hudson Leslie , Phillips Bernice
Published: December 2022

Antisera raised in rabbits to BALB/c brain homogenates were not specific for thymus-derived (T) lymphocytes when tested by indirect immunofluorescence. After absorption with liver cells, erythrocytes and bone marrow-derived (B) cells adsorbed to an anti-Fab immunoadsorbent column, the antisera stained all thymocytes from BALB/c and AKR mice but only a proportion of lymphocytes from spleen and lymph node. Virtually no cells were stained in nude mouse lymphocyte suspensions. Staining of lymphocytes fractioned by affinity chromatography into T and B cells provided further evidence for the specificity of the absorbed antiserum.
Characterization of an Immunosuppressive Factor Present in Mouse Serum
Authors: Veit Bruce , Michael J. Gabriel
Published: December 2022

Serum of unimmunized mice contains an inhibitor capable of suppressing the immune response of mouse spleen cell cultures to sheep erythrocytes. The concentration of this serum inhibitor increases after immunization of mice with erythrocyte antigens.

The serum inhibitor exerted its effect in the early stages of the immune response. Addition of mouse serum to spleen cells up to 48 hr after initiation of in vitro cultures was immunosuppressive. Washing or trypsinization of serum-incubated spleen cells removed the inhibitory effect. Plastic-adherent populations of spleen cells were not inactivated by the mouse serum factor whereas nonadherent cells were markedly affected.

The inhibitory factor was purified by ammonium sulfate precipitation and Sephadex chromatography. The immunosuppressive factor was found to migrate to the α-region, and its inhibitory function was not related to RNase activity.
Cooperative Effects in Antibody Formation Produced by Hapten-Specific Delayed Sensitivity
Authors: Hanna Nabil , Leskowitz Sidney
Published: December 2022

The ability of delayed sensitivity specific for the azobenzenearsonate (ABA) group to function as a carrier cooperating in the production of antibody to another determinant has been demonstrated in guinea pigs. If guinea pigs are primed with bovine serum albumin (BSA) in alum, the cooperative effect produced by a boost with ABA-BSA leads only to γ1-anti-BSA antibody. If animals are primed with BSA in incomplete Freund's adjuvant, some γ2-antibody is produced as well as γ1-antibody. Priming with BSA in complete Freund's adjuvant leads to sufficient self-helper effects so that no increased antibody production is seen as a consequence of ABA helper effects.

The ABA helper effect is seen only if animals have ABA-specific delayed sensitivity, not ABA-specific antibody. Best cooperation is achieved when ABA and BSA are covalently linked.
Genetic Control of Immune Responses to Synthetic Polypeptides in Mice: Cellular Analysis of the Phenotypic Correction of the Ir-3 Gene Defect by Polyadenylic-Polyuridylic Acid
Authors: Mozes Edna , Shearer G. M. , Sela Michael , Braun Werner
Published: December 2022

Antibody responses to the multichain synthetic polypeptide poly (L Tyr, L Glu)-poly L Pro-poly L Lys, (T, G)-Pro--L, and to the Pro-L portion of the related polymer poly (L Phe, L Glu)-poly L Pro--poly L Lys, (Phe, G)-Pro--L, are controlled by the dominant, autosomal, non-H-2-linked, Ir-3 gene. SJL/J and DBA/1 mice are the respective high and low responder strains to Pro-L. Injection of low responder DBA/1 mice with 300 µg poly(A)·poly(U) 24 hr after immunization with either of these immunogens resulted in an enhancement of DBA/1 anti-Pro--L titers which were indistinguishable from those of untreated or poly(A)·poly(U)-treated SJL/J mice. In contrast, no effect of poly(A)·poly(U) on enhancing the antibody responses to poly (L Phe, L Glu)-poly DL Ala--poly L Lys, (Phe, G)-A-L, or to the (Phe, G) immunopotent region of (Phe, G)-Pro-L (immune responses controlled by the H-2-linked Ir-1 gene) was obtained. The anti-Pro--L response was also enhanced in another low responder strain, DBA/2. Thus, the effects of poly(A)·poly(U) described here are selective for phenotypic “correction” of antibody responses controlled by the Ir-3 gene only, and confirm that the modes of action of the Ir-1 and Ir-3 genes are distinct. Enhancement of the DBA/1 anti-Pro--L response using (Phe, G)-Pro-L, which contains two immunopotent regions, occurred at the expense of the anti-(Phe, G) response.

Limiting dilution patterns of low responder spleen and marrow cells were quantitatively and qualitatively affected by administering poly(A)·poly(U) to the syngeneic hosts 24 hr after immunization with (T, G)-Pro--L. No effect of the polynucleotide was detected for dilutions of SJL/J high responder spleen cells, nor for those of DBA/1 low responder thymocytes. The lack of effect of poly(A)·poly(U) on thymocytes was verified in a two-step experimental design by exposing the thymocytes to antigen and the polynucleotide in the absence of marrow cells, followed by transferring the thymus-derived and marrow cells to irradiated test recipients. These results, as well as those (published elsewhere) for the Pro--L specific response, are compatible with the hypothesis that the immunologic effect of the Ir-3 gene is expressed at the level of cell-to-cell interaction, and that poly(A)·poly(U) immunologically “corrects” expression of this gene by making the interaction of the complementary cell types more effective.
The Immune Response Against Hapten-Autologous Protein Conjugates in the Mouse
Authors: Rubin Bent , Hiesche Klaus , Schirrmacher Volker , Wigzell Hans
Published: December 2022

The present experiments were carried out to determine whether antibody formation in response to a hapten coupled to a non-immunogenic carrier was thymus-dependent. Mouse serum albumin (MSA) was used as the nonimmunogenic carrier. The anti-hapten responses to hapten-MSA conjugates of different hapten density were compared to the anti-hapten responses to hapten coupled to heterologous carriers in the following types of mice: 1) normal mice, 2) thymectomized, irradiated, and bone marrow cell reconstituted (TXBM) mice, 3) “sham”-thymectomized mice, and 4) TXBM mice further reconstituted with thymocytes (TXBMT mice).

The anti-hapten response to hapten-MSA conjugates of medium and high density were all found to be suppressed in TXBM mice, whereas in TXBMT mice it was fully reconstituted. Thus, the antibody response to hapten-MSA conjugates in the mouse is thymus-dependent regardless of hapten density.