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At least 19 recordsLinked to original sources
PubMed1992

Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis.

We have studied the capacity of a selected fraction of Mycobacterium tuberculosis extracellular proteins (EP) released into broth culture by mid-logarithmic-growth-phase organisms to induce cell-mediated immune responses and protective immunity in a guinea pig model of pulmonary tuberculosis. Guinea pigs infected with M. tuberculosis by aerosol but not uninfected control guinea pigs exhibit strong cell-mediated immune responses to EP, manifest by dose-dependent cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. Guinea pigs immunized subcutaneously with EP but not sham-immunized control guinea pigs also develop strong cell-mediated immune responses to EP, manifest by dose-dependent cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. EP is nonlethal and nontoxic to guinea pigs upon subcutaneous immunization. Guinea pigs immunized with EP and then challenged with aerosolized M. tuberculosis exhibit protective immunity. In five independent experiments, EP-immunized guinea pigs were consistently protected against clinical illness, including weight loss. Compared with EP-immunized guinea pigs, sham-immunized control guinea pigs lost 12.9 +/- 2.0% (mean +/- SE) of their total weight. EP-immunized guinea pigs also had a 10-fold reduction in viable M. tuberculosis bacilli in their lungs and spleens (P = 0.004 and 0.001, respectively) compared with sham-immunized control animals. In the two experiments in which some guinea pigs died after aerosol challenge, EP-immunized animals were protected from death. Whereas all 12 (100%) EP-immunized guinea pigs survived challenge with aerosolized M. tuberculosis, only 6 of 12 (50%) sham-immunized control guinea pigs survived challenge (P = 0.007, Fisher exact test). This study demonstrates that actively growing M. tuberculosis cells release immunoprotective molecules extracellularly, that a subunit vaccine against tuberculosis is feasible, and that extracellular molecules of M. tuberculosis are potential candidates for a subunit vaccine.

Aerosols↗
PubMed1986

Cells involved in the immune response. XXXII. Surgical extirpation of the spleen in the early memory period following primary i.v. immunization of the outbred rabbit results in a marked impairment of a subsequent immune response to the specific antigen: an immunological explanation for the overwhelming postsplenectomy syndrome.

Rabbits immunized intravenously(iv) with sheep erythrocytes(SRBC) (primary response) pass through a period which begins at about Day 35 postprimary immunization and extends to about Day 120 during which time all detectable spontaneous AFC (immediate PFC) and memory AFC(cells which generate PFC in culture) are detected only in the spleen. Prior to Day 30 postprimary iv immunization, large numbers of immediate PFC are detected in the circulation and the bone marrow as well as in the spleen. By Day 120 postprimary iv immunization, memory cells can be detected in significant numbers in the thymus and the popliteal lymph nodes (PLN) as well as in the spleen. The number of memory cells in the PLN and thymus increases over the course of the following 6 months. Rabbits splenectomized on Day 40 postprimary iv immunization and subjected to reimmunization iv with 10(9) SRBC 1, 5, or 8 months later were unable to give significant secondary immune responses. Only the thymus and PLN cells, cultured in vitro with the antigen(SRBC), 1, 5, or 8 months postprimary immunization, generated secondary immune(PFC) responses and these responses were feeble at best. The failure of the immunized rabbit to give a significant secondary immune response to SRBC if splenectomy was first carried out at a time postprimary iv immunization when all memory cells to the original antigen are sequestered only in the spleen (i.e., days 40 to 100) constitutes an animal model which provides a credible immunological explanation for the postsplenectomy syndrome which affects a minority of splenectomized individuals. These individuals, like the rabbits splenectomized on Day 40 postprimary immunization, lack the capacity to evoke a strong secondary immune response to particular infectious microorganisms and succumb in a few days with fulminant septicemia unless aggressive chemotherapy is instituted upon initial sign of infection.

Animals↗
PubMed1992

Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization.

Malaria transmission-blocking immunity has been studied in natural malarial infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while still in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection or following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent.

Animals↗
PubMed1986

Cells involved in the immune response. XXXIII. Antibody-forming cells in the popliteal lymph nodes in the immunized splenectomized rabbit following intravenous immunization and their subsequent dissemination to the thymus.

Rabbits were splenectomized (splx) and immunized intravenously (iv) with sheep erythrocytes (SRBC) 14 days later. At the height of the primary immune response on Day 8 postimmunization, significant numbers of plaque-forming cells (PFC), that is, antibody-forming cells (AFC) synthesizing and secreting antibodies, were detected in the popliteal lymph nodes (PLN) and lesser numbers were detected in the bone marrow and the circulation. No PFC were detected in any of the other lymphoid organs. Rabbits were sacrificed at 1, 2, 6, or 9 months post-primary iv immunization and cell cultures of the lymphoid organs were set up with the antigen, SRBC, to induce secondary immune responses in vitro. Only the PLN cells challenged with SRBC in vitro 1 month post-primary immunization generated PFC and only PLN and thymus cells generated PFC in vitro at the three other challenge periods, thus demonstrating the existence of memory cells in only these two lymphoid organs in the splx rabbits. Following in vivo secondary immunization iv with SRBC 2, 6, or 9 months post-primary iv immunization. PFC were consistently detected only in the PLN and the bone marrow and inconsistently in the circulation. No PFC were detected in the thymus or in any of the other lymphoid organs. Paradoxically, neither the bone marrow nor the circulating mononuclear cells of these rabbits generated PFC during in vitro culture with SRBC, whereas the thymus cells and the PLN cells generated many PFC in culture with SRBC. These results demonstrate that the thymus contains memory cells following primary immunization of the splx rabbit which are not accessible to particulate antigens injected intravenously, possibly due to a blood-thymus barrier to particulate antigen, and therefore cannot be activated in vivo into secondary antibody formation. The results also indicate that the AFC detected in the circulation and in the bone marrow following primary iv immunization, which do not generate PFC in antigen-stimulated cultures in vitro, are degenerating cells whereas the AFC in the PLN and thymus, which generate many PFC in antigen-stimulated cultures in vitro, constitute the noncirculating precursors of the long-lived memory cells in the splx rabbit. This role of the thymus and PLN as reservoirs for memory cells in the immunized splx rabbit is not influenced by nor is it a result of splx since the thymus and PLN have both been shown to be the major sources of memory cells, along with the spleen, in the immunized nonsplx rabbit.

Animals↗
PubMed1986

Effects of anti-schistosomal chemotherapy on immune responses, protection and immunity. II. Concomitant immunity and immunization with irradiated cercariae.

Resistance of mice to challenge infections of Schistosoma mansoni was evaluated before and after elimination of their primary, established S. mansoni infections with the chemotherapeutic drug praziquantel. Mice treated after either 10 or 20 weeks of primary infection were challenged 6 or 10 weeks after treatment. Mice infected for for 10 weeks prior to treatment expressed progressively less resistance 6 and 10 weeks after treatment. By 10 weeks after treatment significant levels of protection were no longer observed. Resistance waned more slowly if mice were treated 20 weeks after infection, and there was still significant expression of resistance to challenge 10 weeks after treatment. A separate set of experiments evaluated the use of highly irradiated cercariae as a vaccine in mice that had been previously infected with S. mansoni and cured with praziquantel. It was observed that effective immunizations were possible in previously infected mice. These studies demonstrate that established resistance waned after treatment and the rate of loss of protection was dependent upon the duration of infection prior to treatment. Furthermore, the irradiated cercarial vaccine studies indicate that in the murine model induction of immunological resistance was feasible following chemotherapeutic treatment of infected populations.

Animals↗
PubMed1977

Immune response to immunization via the anterior chamber of the eye. I. F. lymphocyte-induced immune deviation.

The immunizing abilities of alloantigens placed within the anterior chamber of the eye have been studied in inbred rats. Although intracameral inoculation of F1 hybrid lymphocytes into parental strain recipients elicited both cell- and antibody-mediated immunity, a delimited interval was identified postinoculation during which the systemic cell-mediated immune response was suppressed as indicated by prolonged acceptance of orthotopic skin allografts. The prompt appearance of hemagglutinating antibodies in the serum of immunized rats followed a time course which coincided with the suppression of cell-mediated immunity and suggested that the two events are casually related. Since exposure to allogeneic antigens on lymphoid cells via the anterior chamber elicits a transient suppression in cell-mediated immunity, where humoral immunity is preserved, the phenomenon resembles immune deviation.

Animals↗
PubMed1985

Prophylactic immunization against experimental leishmaniasis. IV. Subcutaneous immunization prevents the induction of protective immunity against fatal Leishmania major infection.

Durable immunity against fatal L. major infection in genetically susceptible mice can be induced by immunization with 150,000-rad irradiated or heat-killed promastigotes administered i.v. or to a lesser extent i.p. Conversely, subcutaneous (s.c.) and intramuscular (i.m.) injections are not only totally ineffective but generally increase susceptibility to and enhance the progression of the disease, leading to earlier mortality. This detrimental effect is particularly evident with lower infecting challenge doses. Disease exacerbation is apparent in mice given 4 X s.c. injections of as few as 2 X 10(4) irradiated promastigotes, but it appears most potent after doses of 2 X 10(7). When mice given 4 X s.c. injections were subsequently immunized i.v. with 2 X 10(7) irradiated promastigotes, they failed to develop any evidence of protection against infection with 2 X 10(5) promastigotes, whereas mice given i.v. immunization alone were strongly protected. Thus, s.c. injections are capable of blocking the prophylactic effect of i.v. immunization with irradiated parasites. This inhibitory effect can be achieved with a single s.c. injection, although rather less potently than with four, and is even effective against four repeated weekly i.v. immunizations. Once induced, the effect persists undiminished after 100 days. A weaker effect is also inducible by s.c. injection given after i.v. immunization. The blocking effect of s.c. injection is not dependent on continuing viability of the promastigotes, as it can be induced equally readily with heat-killed, formalin-fixed, or sonicated parasites. The phenomenon extends to mouse strains genetically resistant as well as susceptible to L. major infection and, in congenic mice of BALB background, is independent of the major histocompatibility (H-2) gene complex.

Animals↗
PubMed1975

Immune complexes in the spleen. Replacement of immune complexes trapped in spleen follicles by new immune complexes from the circulation.

The fate of intravenously injected 125I-BGG-anti-BGG in the spleen of mice was studied using autoradiography. Part of the labelled immune complexes was trapped in the follicles of the spleen as could be expected. In a first experiment it was found that injections with unlabelled immune complexes were followed by a partial release of the labelled immune complexes from the follicles. In a second experiment unlabelled immune complexes retained in spleen follicles appeared to inhibit the trapping of intravenously injected labelled immune complexes to some degree and for some time. The conclusion was drawn from these experiments that immune complexes, which normally remain in part of the lymphoid follicles for a long period, may be replaced by new immune complexes from the circulation. This seems important since trapping in lymphoid follicles of antigen complexed by antibody is the only known mechanism by which small amounts of antigen may be preserved in the body for a long time after the initiation of antibody production. The bulk of antigen and antigen-antibody complexes is removed by phagocytosis followed by destruction. It appeared also that, although all spleen follicles in the mouse spleen is able to retain the complexes for a longer time. Possible explanations for these individual differences between the follicles of one spleen are discussed.

Animals↗
PubMed1975

Immunity to Toxoplasma gondii induced in vitro in non-immune mouse macrophages with specifically immune lymphocytes.

Male and female CBA mice were used to study in vitro the mechanisms involved in the development and expression of cellular immunity to toxoplasma infection. The lag phase preceding toxoplasma division was delayed in nonimmune macrophages obtained from peritoneal cavities stimulated with thioglycollate. Specific anti-toxoplasma activity was conferred on nonimmune macrophages incubated with toxoplasma-immune spleen lymphocytes and soluble toxoplasma antigen. Treatment of immune spleen cell populations with anti-theta serum plus complement abolished completely their activity of conferring anti-toxoplasma activity on nonimmune macrophages, demonstrating that the essential cells were T lymphocytes. The mediator(s) responsible for the acquisition of immunity to toxoplasma in the nonimmune macrophages were soluble. Heat-inactivated, toxoplasm-immune macrophages of fibroblasts. The findings are related to previous investigations of induced immunity in animals and man.

Animals↗
PubMed1976

Comparison of the humoral and cellular immune response after immunization with live, UV inactivated herpes simplex virus and a subunit vaccine and efficacy of these immunizations.

Antibody and cell-mediated immune responses were measured in rabbits immunized with live, UV inactivated herpes simplex virus or with a subunit vaccine containing envelope proteins. All the types of immunization procedures induced the production of antibody as well as a specific cellular immunity. Furthermore, the subunit vaccine was as effective as the immunization with live or UV inactivated virus to prevent death upon challenge with live HSV. Live HSV induced a transient unresponsiveness of both B and T cells to in vitro stimulation with various mitogens.

Animals↗
PubMed1988

[Systemic humoral immune response to food antigens following oral immunization or immunization via the respiratory tract].

Differences and similarities of the systemic humoral immune response to cow's milk proteins were investigated after exposure of the gut or of the airways to antigen, both in children and in rabbits. Circulating antibodies were determined by radioimmunoassay (children and rabbits) and by enzyme-linked immunosorbent-assay in a small number of children. An age-dependent reference range was established, reflecting the rapid change of active antibody formation after oral immunization against bovine serum albumin in healthy, non-breastfed children up to the age of 24 months (n = 181). In contrast 16 children with recurrent aspiration due to anatomical disturbances or swallowing difficulties, all had antibody-titers well above this reference range. 7 of 9 children with cow's milk protein intolerance and with failure to thrive (oral immunization) also showed high concentrations of milk antibodies in the circulation. In adult rabbits immunized by oral or inhalational route, the vigorous immune response seen in recurrent aspiration could be mimicked. As investigated by enzyme-linked immunosorbent assay, higher titers of antibodies to bovine serum albumin, alpha-lactalbumin, beta-lactoglobulin, alpha-casein and bovine gammaglobulin could be shown in all isotypes tested (specific anti-IgG, -IgA, and -IgE) both in recurrent aspiration (n = 11) and cow's milk protein intolerance (n = 4) as compared to normal age-matched children (n = 14).

Animals↗
PubMed1986

Immune complexes, serum proteins, cell-mediated immunity, and immune regulation in patients with squamous cell carcinoma of the head and neck.

A collaborative study of the humoral and cellular immune status of patients with carcinoma of the Head and Neck (H&N) was conducted at the West Virginia University (WVU) hospital. In addition, blind-coded serum panels were supplied on H&N cancer patients being treated at the National Cancer Institute (NCI). Serum protein analysis of the WVU study groups revealed that at the pretreatment sampling, the alpha-1 acid glycoprotein (AGP), total complement, and IgA levels were significantly elevated. The AGP levels and total complement levels declined to normal levels in the post-treatment period, whereas the IgA levels remained elevated throughout the entire observation period. Levels of serum immune complexes (SIC) were measured in both the WVU and NCI H&N cancer populations using the polyethylene glycol (PEG) precipitation method. In both survey populations all cancer groups had significantly elevated levels of SIC when compared to any of the control populations. The SIC levels never returned to comparative normal values even in cases after successful treatment. A subpopulation of the WVU-H&N cancer study group underwent a short course of intravenous hyperalimentation prior to their treatment regimen. These patients demonstrated a transient decrease in their SIC levels as well as a concomitant increase in their in vitro cell-mediated immune (CMI) correlates. The analysis of in vitro CMI correlates of the WVU study group using both polyclonal mitogens and specific antigens demonstrated a significant depression in these parameters pretreatment and post-treatment. In addition, it was observed that the time course for elevation of selected serum proteins (i.e., IgA and SIC) correlated with concomitant drops in CMI activity. Investigations were also conducted into the effects of immune complex-rich serum fractions upon selected in vitro CMI correlates. Significant blockage of a normal donor leukocyte migration-inhibition assay was demonstrated. Also, a similar inhibition of the ability of normal human lymphocytes to form high affinity rosettes was accomplished with serum from H&N cancer patients.

Adult↗
PubMed1985

Studies on immunity in hybridoma-bearing mice. B. Immunity against the hybridoma. I. Studies on the immune state of mice after rejection of the hybridoma.

Anti-dinitrophenyl IgE secreting hybridoma B 53 cells may be rejected when injected subcutaneously in BALB/c mice. These mice are immune as they withstand without any ill effect the intraperitoneal injection of LD100 B 53 cells. Sera from mice which rejected the tumor have cytotoxic antibodies against the hybridoma, as shown by in vitro tests, but serum cannot transfer immunity to naive BALB/c mice against hybridoma B 53. Spleen cells from mice which have rejected the tumor might transfer immunity against B 53 hybridoma, and with Winn tests it has been shown that these spleen cells are very effective against the B 53 cells and also against the myeloma cells which were used for the fusion to construct the B 53 hybridoma. Subcutaneously injected B 53 cells not only produce anti-DNP IgE secreting tumors, but often also metastasize to spleen, and they are sometimes detected in the circulating blood. Mice with splenic metastasis or with detectable circulating B 53 cells generally die. However, we did observe one mouse with splenic metastasis which successfully rejected the tumor and became immune to B 53 cells.

Animals↗
PubMed1992

A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity.

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.

AIDS Vaccines↗
PubMedDate not supplied

The immune system and intravenous administration of immune globulin. Part I, The immune system.

Interest in the immune response has greatly increased, mostly because of the discovery of the AIDS virus. An understanding of the basic function of the normal human immune system is vital knowledge for today's nurse. Part 1 of this article describes normal immune response as well as abnormal immune system function, and correlates this information with the clinical picture of the patient.

Antibody Formation↗
PubMed1987

Macrophage activation as an immune correlate to protective immunity against schistosomiasis in mice immunized with an irradiated, cryopreserved live vaccine.

Immune responses against Schistosoma mansoni were evaluated in C57BL/6 mice injected with one of two populations of irradiated schistosomules, the larval preparations differing only in the degree of freezing-induced damage sustained upon cryopreservation. Mice injected with larvae which successfully withstood cryopreservation showed a significant reduction in worm burden following cercarial challenge. No protection was achieved in mice which received larvae damaged by a suboptimal thawing rate. Parallel comparison of several humoral and cellular responses in mice which received either inoculum revealed that induction of activated macrophages and production of macrophage-activating lymphokine activity were the strongest correlates to development of protective immunity. Protected mice also showed marginal 30-min skin test reactivity and weak but transient 24-h delayed-type hypersensitivity to a soluble adult worm preparation. In contrast, indistinguishable levels of circulating antibodies to soluble and tegumental antigens developed in the two immunization groups, and antigen-stimulated lymphocyte blastogenic responses were strong and essentially equivalent in magnitude. These studies strongly suggested that in this new model for investigating anti-schistosome effector mechanisms, responses contributing to the development of activated macrophages may be essential for induction of protective immunity.

Animals↗
PubMed1986

Studies on immunity in hybridoma-bearing mice. B. Immunity against the hybridoma. II. The phenotype and specificity of the immune cell.

When appropriate numbers of anti-dinitrophenyl (DNP) immunoglobulin (Ig) E-secreting hybridoma (B 53) cells were injected s.c. into normal BALB/c mice, some of the recipients rejected the tumors. These mice were shown to be immune to B 53 as they withstood, without any ill effect, the i.p. injection of lethal doses of B 53 cells. In previous studies, it was shown that the spleen cells of these mice protected against the growth of B 53 cells. In this study, the characteristics and specificity of the immune spleen cells were examined. The cells responsible for this immunity were shown to be T cells that express Ly-2 on their surface. These cells were shown in in vivo and in vitro assays to limit the growth of the immunizing hybridoma, as well as some but not all BALB/c plasmacytomas and hybridomas.

Animals↗