Primary Immune Response In Mice Research Articles

The mechanism of thymus-dependent antibody formation in bone marrow.

During the primary immune response of mice to i.v. administered thymus-dependent antigens the spleen is the major site of localization of antibody-producing plaque-forming cells (PFC). During the secondary response, on the other hand, large numbers of PFC not only appear in the spleen, but also in the bone marrow. By inducing B memory cells with a DNP-carrier complex and activating the DNP-specific B memory cells with the same hapten conjugated to a heterologous carrier, we show in this paper that B memory cells, but not necessarily T memory cells, must be present before booster immunization for PFC to appear in the bone marrow. The origin of the PFC that appear in the bone marrow during secondary type immune response was studied in parabiotic mice consisting of members congenic for the Igh-1 locus. From analysis of the allotype of antibodies produced by PFC in the marrow of such pairs of parabionts it appeared that antibody formation in bone marrow is dependent on the immigration into the marrow of B memory cells activated in peripheral lymphoid organs. Consistent with such a migration of activated cells, radioautographic studies in guinea pigs demonstrated an influx of newly formed mononuclear cells into the bone marrow via the blood stream during the first 3 days after intravascular antigen administration.

“In vivo” effects of acetylsalicylic acid and two ether derived compounds on primary immune response and lymphoblastic transformation

A comparison was performed of acetylsalicylic acid and two ether derivatives (Benorilate and Eterilate) and indomethacin in order to ascertain the in vivo effects on the lymphoblastic transformation and the primary immune response in mice. The humoral response in Benorilate- and Eterilate-treated mice was 40–50% lower than that of the controls, whereas in acetylsalicylic acid-treated mice the response was only 25% inhibited. The number of immunoglobulin synthesizing cells was neither reduced by acetylsalicylic acid nor by its derivatives, although indomethacin treatments (used for comparative purposes) inhibited by 40% the number of direct plaque-forming cells on the days tested. Mitogen-induced proliferation of spleen lymphocytes was also inhibited in the treated mice; these inhibitions were negligible in the case of cells from acetylsalicylic acid-treated mice activatged by concanavalin A and slight in cells from Benorilate-treated mice activated by bacterial lipopolysaccharide. When lymphocytes from drug-treated animals were further cultured in the presence of the same drug, a variable inhibition of mitogen-induced proliferation was observed. These different in vivo effects of acetylsalicylic acid and the two ether derivatives and indomethacin may be due to a distinct action on diverse lymphocyte subpopulations altering their cellular collaborative interactions or modifying the prostaglandin availability.

Effect of chronic administration of morphine on primary immune response in mice.

The effect of 3 different doses of chronically-administered morphine on the primary immune response was studied in mice by estimating spleen/body weight ratio and serum hemolysin production against sheep red blood cells (SRBC). It was observed that morphine exerted a dose-dependent inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. The findings suggest that the inhibitory effect of morphine is specific.

Primary Immune Response of Mice to Sheep Erythrocytes During the Course of Infection with Listeria monocytogenes

The influence of an infection with a sublethal dose of viable Listeria monocytogenes on the primary antibody-forming potential of mice against sheep erythrocytes (SE) was monitored by means of counting plaque-forming cells (PFC) in the spleen and measuring circulating antibodies against SE. Additionally, the course of infection was followed by determination of viable bacteria in the spleen. As against the injection of killed L. monocytogenes, infection with viable bacteria did not display any significant influence on the immune response against SE when the immunogenic stimulus was given either stimultaneously with the bacteria or on day 4 or 13 of infection, respectively. Vice versa, the immunization with the particulate antigen had no measurable influence on either course of outcome of infection with the parasite.

The mechanism of immune suppression in BALB/c mice bearing the plasmacytoma TEPC-183

Mice bearing transplantable plasmacytomas have an immune defect closely resembling the defect of patients with multiple myeloma. They have a severe impairment of the primary immune response to both T-dependent and T-independent antigens, yet their secondary immune response is much less impaired. The aim of this series of experiments was to document the primary immune response of mice bearing the plasmacytoma TEPC-183. Healthy mice and mice bearing the reported non-immunosuppressive tumour MOPC-104E were used as controls. The response to chicken red blood cells (CRBC) was documented by a complement dependent cytotoxicity assay for IgM and an antibody dependent cellular cytotoxicity assay for IgG. The defect was shown to affect both the primary IgM and IgG responses to CRBC but could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Immunological memory was also impaired in TEPC-183-bearing mice. In a second series of experiments the primary immune responses of immunologically deprived syngeneic mice were measured after they had been reconstituted with cells from normal or tumour-bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950 R. Lymphoid preparations from TEPC-183-bearing mice were as effective as those from healthy controls in reconstituting primary immune responses. When mice were deprived of macrophage function using large doses of horse red blood cells, macrophage preparations from normal mice were able to restore primary immune responsiveness partially. However, macrophages from TEPC-183-bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183 is due to a macrophage rather than lymphocyte abnormality.

Non-H-2 antigens serving as carrier determinants in a primary anti-Thy-1 response in mice.

The primary immune response of mice to the Thy-1 antigens was elicited by intravenous injection of thymocytes from H-2 compatible donors. The magnitude of the ensuing response judged by the number of plaque forming cells producing antibodies lytic for the Thy-1 bearing cells was influenced by some non-H-2 antigens present on the immunizing thymocytes. Absence of non-H-2 incompatibility resulted in a poor response whereas the presence of such an incompatibility allowed a good response. Genetic analysis revealed that the non-H-2 incompatibility affecting the anti-Thy-1 response is controlled by 1-3 independently segregating genes presumably determing molecules acting as carrier determinants for otherwise poorly immunogenic Thy-1 antigens. The carrier effect appeared to be influenced by the gene dosage of the carrier molecules on the immunizing cells. The data presented are discussed in the context of the current concepts of the mechanisms controlling various immune responses.

Immune suppression in BALB/c mice bearing the plasmacytoma TEPC‐183: Evidence for normal lymphocyte but defective macrophage function

This paper analyses impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183. Healthy animals and mice bearing the reported non-immunosuppressive tumour MOPC-104E were used as controls. The defect was shown to affect both primary IgG and IgM responses to chicken cells (CRBC) and to be related to tumour size. However, the primary immune depression could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Secondary responses were also depressed. This depression was more pronounced if the animals was primed after, rather than before, tumour implantation. Further studies involved the measurement of primary immune responses of immunologically deprived syngeneic mice, after they had been reconstituted with cells from normal or tumour-bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950R. Various lymphoid preparations from TEPC-183-bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC-183 is due to a macrophage, rather than a lymphocyte, abnormality. However, none of these transfer studies suggested that positive suppression of primary immune responses was being mediated by cells from TEPC-183-bearing mice.

Comparative study of immunobiological activities ofPseudomonas aeruginosa andBrucella melitensis lipopolysaccharides

The toxic activity ofBrucella melitensis andPseudomonas aeruginosa lipopolysaccharides as well as their behavior as immunogens, mitogens, and interferon inducers have been studied. Although their toxicities were very similar, the former molecule was incapable of eliciting a primary immune response in mice. Rabbit hyperimmunization gave titers half of those obtained withP. aeruginosa lipopolysaccharide. Optimal mitogenic responses of spleen cell cultures were obtained using 10–50 μg/ml and 50–100 μg/ml ofPseudomonas andBrucella lipopolysaccharide, respectively, giving the latter a lower stimulation of3H-thymidine uptake. Interferon titers induced in chickens byBrucella lipopolysaccharide were three times lower than those obtained withPseudomonas lipopolysaccharide.

Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen. VII. The conveyer hypothesis and its mathematical expression.

The conveyer hypothesis is based on the fact that because of clone predetermination, antibody production takes place in an organism without the presence of antigen as a result of natural cell differentiation. Soluble antigen is an analogue of a specific mitogen which gives rise to reproduction mainly of cells carrying on their surface the immunoglobulin receptors to the given antigen. The mathematical model of the conveyer hypothesis takes into account the initial conditions, among them the background level of antibody-producing cells before injection of a soluble antigen, migration of precursor cells in the draining lymphoid organ, and the rate of precursor differentiation, including the rate of the change of the immunoglobulin receptor number on the cell surface. Changes of antigen concentration in blood determine the intensity of precursor proliferation. Comparison of real experiments (intraperitoneal injections of capsular antigen of Pasteurella pestis into inbred mice) with calculations done on the basis of the developed mathematical model shows a definite qualitative resemblance with the kinetics of antibody-producing cells and free antibodies as well as with the decrease of free antigen concentration in blood. In spite of some differences between model experiments and real experiments the conveyer hypothesis and its mathematical model appear suitable for describing the primary immune response of mice immunized with low doses of capsular antigen of Pasteurella pestis.

Aggregated immunoglobulins on the surface of rapidly dividing antigen-binding lymphocytes

In the primary immune response of mice to sheep's red cells rosette-forming cells with aggregated immunoglobulins on their surface appear in the fraction of small lymphocytes in the spleen. These cells effectively incorporate thymidine and can be eliminated in vivo by injecting the mice with large doses of the tritiated base. It can be concluded from the results that rapidly dividing lymphocytes, specifically binding antigen, characteristically have aggregated immunoglobulins on their surface.

Adjuvant and Suppressor Activity of the Polycation Protamine Hydrochloride in the Primary Immune Response of Mice

The effect of protamine hydrochloride (PH), a polycation, on the primary immune response of mice to sheep red blood cells (SRBC) was studied.Like other adjuvants, PH enhances or depresses the immune response depending on the time of injection of PH in relation to the antigenic challenge.The suppressive effect of PH correlated with the appearance of « activated » macrophages in the peritoneal cavity.A second injection of PH together with antigen abolished this suppressive effect.Transfer of « activated » macrophages resulted in an enhanced immune response when antigen was administered at the time of transfer, and in a depressed response when the antigen was given 1 or 2 days after transfer.It is concluded that the duration of the influence of «activated» macrophages on T or B cells determines the subsequent immune reactivity.It is discussed that the basic mechanism of action of PH is its ability to release lysosomal enzymes from macrophages.The mechanism by which these enzymes amplify the immune response remains to be clarified.

Effect of extracts of the spleen on the primary immune response in mice

The possibility of enhancing the primary immune response in sexually mature mice by means of splenic extracts was demonstrated by Jerne's direct test in experiments on mice. The importance of the dose of the extracts and the time of their administration for the manifestation of their stimulating action was studied.

Restoration of the immune response by macrophages in mice after administration of immunodepressants

The possibility of restoring the primary immune response in mice immunized with bacteriophage T2 after administration of various immunodepressants (actinomycin D, olivomycin, rifampicin, chloramphenicol, chloroquine, histone F2a, and bacterial lipopolysaccharide) was studied. For this purpose peritoneal macrophages from intact syngeneic donors were transferred simultaneously with injection of the antigen into the recipients following administration of the immunodepressants. The immunodepressive effects of most of the substances studied could be completely compensated in this way. Macrophages can thus be regarded as one of the sites of action of the immunodepressants studied. The results also indicate a role of the macrophages in the induction of the primary immune response to bacteriophage T2 (synthesis of phage-neutralizing antibodies).

Injectable selenium: effect on the primary response of mice (38472).

Sodium selenite administered to mice ip (ca.5 mug Se) enhances the primary immune response to the sheep red blood cell angigen. Enhancement of the primary immune response is greatest when Se is administered prior to or simultaneously with the sheep red blood cell antigen.

Development of Alterations in the Primary Immune Response of Mice by Exposure to Fresh Cigarette Smoke

Mice were exposed daily to fresh cigarette smoke for varying periods up to 294 days. The plaque-forming cell response present in the lung, mediastinal and cervical lymph nodes, blood and spleen of exposed animals was measured 7 days after intratracheal inoculation with sheep erythrocytes. This was compared to the response in age-matched controls. The response in all organs showed progressive impairment over the exposure period. The response of the lymph nodes was initially enhanced by the smoking, but after continued exposure became severely depressed.

Immunologic responses of mice fed diets supplemented with selenite selenium.

SummaryThese experiments indicate that dietary Se at levels above that generally accepted as nutritionally adequate (0.1 ppm) enhances the primary immune response in mice as measured by the PFC test and by hemagglutination.

A Predictive Equation for the Primary Immune Response of Mice to Adsorbed Tetanus Toxoid As a Function of Dose of Antigen and Dose of Adjuvant

Abstract Of all the adjuvants used in experimental immunology, the insoluble aluminum compounds comprise the only type permitted in human immunization. They confer a 3- to 10-fold higher primary immune response to the usual protein antigens over that available from the plain fluid state, and such priming enhances the secondary response 20- to 40-fold. Immunologists have long been interested in this more complex dose-response relationship with two independent variables, dose of antigen interacting with dose of adjuvant. Applying the data of a human field trial by using four preparations of AIPO4-adsorbed tetanus toxoid with different antigen-adjuvant ratios, the author previously derived an equation that predicted the mean primary serum antitoxin response of subject groups from the dose of antigen and adjuvant injected. The present paper demonstrates the fit of this equation, with the constant terms changed, to the published data of another investigator who used mice to test 14 adsorbed tetanus toxoid preparations differing in antigen-adjuvant ratio. The probit-survival primary responses of the mice were predicted with reasonable accuracy for all 14 preparations by entering the dose of antigen and of adjuvant of each into the equation. The implications for biologic standardization and for the mechanism of the primary immune response are discussed.

The primary immune response in mice. 3. Retention of sheep red blood cell immunogens by the spleen and liver.

The antibody-inducing activities of foreign red blood cell immunogens sequestered in the spleens and livers of mice injected with sheep erythrocytes were evaluated during the early periods of the immune response. Estimates of immunogenicity, obtained from the magnitudes of anti-sheep red blood cell hemolysin responses evoked in sensitized recipient mice by subcellular tissue fractions prepared from these phagocytic organs, showed that the liver and spleen differ greatly in their handling of this particulate antigen. The liver, functioning primarily as a scavenger organ, destroys completely the immunogenicity of the heterologous erythrocytes in 12 hr. In contrast, the spleen handles foreign erythrocyte immunogens in at least two different ways: approximately 90% of the initially sequestered activity is rapidly destroyed by the spleen in 6 hr, but the remaining activity, associated chiefly with a tissue fraction possessing the sedimentation properties of "light mitochondria," is retained at a significant level for 3 days, and then progressively decreases to a low level until the 7th day. A correlation of the observed changes in the properties of the immunogenic tissue fraction with known cellular events in the spleen stimulated by antigens indicates that the retention of the degradable erythrocyte immunogen is essential for stimulating and maintaining immune reactions in this antibody-producing organ.

Response of mouse T and B lymphocytes to sheep erythrocytes.

THE primary immune response of mice to sheep red blood cells (SRBC) involves two types of lymphocytes: the antibody-forming cell series, whose precursors are found in bone marrow (B cells) and cooperating or “helper” cells of uncertain function whose precursors are found in the thymus (T cells)1. Within 24 h of an intravenous injection of SRBC, an increase of haemolytic antibody plaque-forming cells (p.f.c.) occurs in the spleen, reaching a peak 5 days later. Part, but not all, of this increase is due to division among the B cells2. T cells in the spleen also undergo a wave of mitosis, detectable from the second to the fifth day3.

Stimulation of humoral antibody formation by polyanions. I. The effect of polyacrylic acid on the primary immune response in mice immunized with sheep red blood cells.

AbstractThe effect of a polyanion, polyacrylic acid, on the primary immune response in mice inoculated with sheep red blood cells was investigated. Polyacrylic acid caused early appearence and enhancement of 19 S and 7 S plaque‐forming cell response in mice from 48 h to 10 days after antigen inoculation. Hemolytic antibody titers confirm these results. The degree of the stimulation of the immune response by PAAC was dependent on the antigen and PAAC doses and their routes of administration. The polyanion also increased the background of 19 S plaque‐forming cells in nonimmunized mice and the serum γ‐globulin levels. The effects of polyacrylic acid and the effects caused by natural or synthetic polynucleotides and pyrancopolymer on immune response suggest that the polyanionic structure common to these substances may be responsible for their stimulating activity.