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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↗

PubMed1979

Functional activation of immune lymphocytes by antigenic stimulation in cell-mediated immunity. IV. Role of macrophage and its soluble factor in antigen-induced MIF production of immune T lymphocytes.

Histocompatibility-linked restriction of macrophage-T lymphocyte interaction in antigen-induced MIF production by sensitized lymphocytes was examined, by using combinations of inbred strain 2, strain 13, and JY-1 guinea pigs. The effective interaction of the antigen-bearing macrophages with the immune T lymphocytes was observed when the donor of the antigen-bearing macrophages and that of the immune lymphocytes shared Ia antigens of the major histocompatibility complex. Identities of B antigens and S antigens were not important for this cooperation. It was further demonstrated that the previously reported soluble factor derived from LPS-stimulated peritoneal adherent cells (macrophages) could help antigenic activation of the immune lymphocytes across the strain barrier provided a small number of macrophages (0.01%) from syngeneic strain were present. These results show that the presence of macrophages is absolutely required to present antigen to immune T lymphocytes in a genetically restricted manner and the soluble factor from macrophages appears to give a nonspecific effect on the lymphocyte activation in addition to or in collaboration with antigenic stimulation.

Animals↗

PubMed1980

Immune processes in the course of infection with dysentery bacilli. IV. Transfer of immunity by means of fractions isolated from sera of mice immunized with dysentery bacilli.

Studies in mice on the protective activity of sera fractions isolated from immune sera, showed that viable as well as killed dysentery bacilli evoke in mice immunity, which can be transferred to other mice by serum or globulin fractions isolated from the serum. It was shown that protective activity is localized in the globulin fraction of IgM and IgG class. No correlation between the titers of specific antibodies and protective activity of components of the globulin fractions was found. Moreover, it was demonstrated that the globulin fraction isolated from the serum of normal mice is capable to transfer the immunity, whereas whole serum does not exhibit any protective activity. Possible mechanism of the immunity caused by transfer of the serum fractions into lethally infected-recipients was presented in the discussion.

Animals↗

PubMed2006

An immune edited tumour versus a tumour edited immune system: Prospects for immune therapy of acute myeloid leukaemia.

Cell based therapies for acute myeloid leukaemia (AML) have made significant progress in the last decade benefiting the prognosis and survival of patients with this aggressive form of leukaemia. Due to advances in haematopoietic stem cell transplantation (HSCT) and particularly the advent of reduced intensity conditioning (RIC), the scope of transplantation has now extended to those patients previously ineligible due to age and health restrictions and has been associated with a decrease in transplant related mortality. The apparent graft versus leukaemia (GvL) effect observed following HSCT demonstrates the potential of the immune system to target and eradicate AML cells. Building on previously published pre-clinical studies by ourselves and others, we are now initiating a Phase I clinical study in which lentiviral vectors are used to genetically modify AML cells to express B7.1 (CD80) and IL-2. By combining allogeneic HSCT with immunisation, using the autologous AML cells expressing B7.1 and IL-2, we hope to stimulate immune eradication of residual AML cells in poor prognosis patients that have achieved donor chimerism. In this report we describe the background to cell therapy based approaches for AML, and discuss difficulties associated with the deployment of a chronically stimulated, hence exhausted/depleted immune system to eradicate tumour cells that have already escaped immune surveillance.

Acute Disease↗

PubMed1975

Immune plasma-dependent cytotoxicity of immune and non-immune peripheral lymphoid cells for target cells coated with bacterial outer unit membrane.

The development of a model system for use in the study of lymphoid cell cytotoxicity to bacterial membrane antigens was attempted. In this system 51 Cr-labelled chicken red blood target cells were coated with pieces of the outer unit membrane of leptospirae rather than with soluble antigens. Using the model system to study dog peripheral immune lymphoid cell cytotoxicity to coated target cells we found that both immune and non-immune lymphocytes are antibody dependent for the expression of their cytotoxicity. It was also found that the unit membrane preparation from leptospirae can serve as a good antigenic stimulant to immune dog lymphoid cells as measured by increased [3H]thymidine uptake.

Animals↗

PubMed1988

Cells involved in the immune response. XXXVI. The thymic antigen-specific suppressor cell in the immunized rabbit is a T cell with receptors for FcG and the antigen and it acts, via a secreted suppressor factor, directly on the immune splenic AFC B cell to inhibit antibody secretion.

Following i.v. immunization of the normal outbred rabbit with sheep (SRBC) or horse (HRBC) erythrocytes, antigen-specific suppressor cells are generated in the thymus capable of inhibiting the generation of haemolytic plaques by the autologous or allogeneic splenic antibody-forming cells (AFC) in the plaque-forming cell (PFC) assay. These suppressor cells secrete an antigen-specific suppressor factor in short-term (4-24 hr) culture in vitro. The suppressor cells are not detected in the thymus prior to Day 4, exhibit peak activity between Days 5 and 11 post-immunization, and decline slowly thereafter. Suppressor cells can no longer be detected in the thymus by Day 60 postimmunization. Suppressor cells are not detected in any of the other lymphoid organs of the immunized rabbit nor in any lymphoid organ in the unimmunized rabbit. The thymic suppressor cell is a T cell with surface receptors for the antigen (SRBC or HRBC) and for FcG. On the other hand, the AFC B cells generated in the spleen of the immunized rabbit possess cell-surface receptors for only the antigen and not for FcG. Both the suppressor cells and the secreted suppressor factor act directly on the AFC B lymphocytes to inhibit the generation of antigen-specific haemolytic plaques in the PFC assay.

Animals↗

PubMed1999

The induction of systemic and mucosal immune responses following the subcutaneous immunization of mature adult mice: characterization of the antibodies in mucosal secretions of animals immunized with antigen formulations containing a vitamin D3 adjuvant.

Systemic and mucosal immune responses were effectively induced following the subcutaneous administration of Haemophilus influenzae type b oligosaccharide conjugated to diphtheria toxoid vaccine in a formulation containing the active form of vitamin D3. IgA and IgG antibodies with specificity for both the protein and oligosaccharide components of the vaccine were detectable in mucosal secretions following immunization. The IgA and IgG mucosal antibodies were produced locally, and were functional as demonstrated by their diphtheria toxin neutralizing activity. Our data suggests that subcutaneous tissues can effectively serve as effective antigen presenting sites for both mucosal and systemic immune responses to antigens administered in combination with vitamin D3.

Adjuvants, Immunologic↗

PubMedDate not supplied

The immune decision toward allograft tolerance in non-human primates requires early inhibition of innate immunity and induction of immune regulation.

Brief treatment of rhesus macaques with immunotoxin plus 15-deoxyspergualin has yielded exceptional numbers (54%) of stable tolerant kidney allograft recipients, surviving over 6 years without rejection or immunosuppression. An early increase in IL-10 and reduction in IFNgamma distinguished recipients that subsequently became tolerant. Furthermore, analysis suggested that this immune switch was programmed within hours of transplantation. Administering deoxyspergualin within 5 h of surgery gave a higher incidence of tolerance (76%) compared to administration >5 h before or after surgery (11%, P<0.01). Deoxyspergualin inhibits nuclear translocation of activated NF-kappaB through heat shock proteins. Lymph node biopsies from tolerant recipients showed significant reductions in cytoplasmic expression of Hsp70 and RelB and almost complete inhibition of nuclear translocation of both. The early timing effect of deoxyspergualin suggests a crucial limitation to induction of stable tolerance is activation of Hsp-dependent innate responses to damage by ischemia-reperfusion. This was supported by studies in murine kidney reperfusion injury, where deoxyspergualin given 5 h before reperfusion protected renal function and reduced levels of IL-6 and IL-12. The narrow timing window for initiating deoxyspergualin treatment suggests the innate immune system is poised to defeat allograft tolerance induction, so effective blockade of NF-kappaB-mediated innate immunity must be in place early, to enable development of a tolerogenic environment.

Animals↗

PubMed1979

Experimental glomerular lesions induced by chronic immune complex formation. I. Formation and elimination of the immune complex (relationship between the immune status and the glomerular changes).

Chronic immune complex formation was induced in rabbits by daily administration of 12.5 g bovine serum. In good antibody producer animals immediate immune complex production and elimination from the circulation were demonstrable. This was followed within a few minutes by the appearance of free 125I in fairly large amounts in blood, as a sign of immediate phagocytosis and disintegration of the 125I-labelled immune complexes. Phagocytic activity decreased in the host animal during chronic heteroprotein administration in every case. The earliest glomerular changes were those of exudative glomerulonephritis, the extent of which depended on the antibody productivity of the animal. Persistent immunocomplexaemia induced by administration of the antigen over 60 and 100 days, respectively, resulted in mesangioproliferative glomerulonephritis in 7, in membranoproliferative glomerulonephritis in 3, and in membraneous glomerulonephritis in 1 out of 11 laboratory animals.

Animals↗

PubMed1997

Glomerular handling of immune complex in the acute phase of active in situ immune complex glomerulonephritis employing cationized ferritin in rats. Ultrastructural localization of immune complex, complements and inflammatory cells.

The ultrastructural localization of immune complex (IC) and inflammatory mediator systems in the glomerulus was investigated in active in situ IC glomerulonephritis employing cationized ferritin in rats. Glomerulonephritis was induced by unilateral renal perfusion of cationized ferritin as antigen (Ag) in preimmunized rats, and anti-ferritin antibody (Ab), C3 and the rat C5b-9 complex were localized by means of immunogold electron microscopy. Ag-Ab complexes were initially formed subendothelially, associated with C3, and attracted platelets, polymorphonuclear leucocytes (PMN) and monocytes. Then Ag-Ab complexes, without C3, passed across the glomerular basement membrane to re-aggregate subepithelially accompanied by C3 deposition after 1 day. Ag-Ab complexes without C3 accumulated in the inter-podocyte space within 1 day and were seen in the epithelial cells at 6 h. C5b-9 complexes were found in subepithelial immune deposits and in membrane vesicles of the epithelial cells, but only in very small amounts in subendothelial immune deposits. Accumulated platelets, PMN, and monocyte were in direct contact with endothelial cells or subendothelial IC. PMN and monocytes contained Ag, Ab and C3 in intracytoplasmic vacuoles. Ag-Ab complexes were also found in the mesangial matrix adjacent to the subendothelial region after 2 h and increased slightly in number, with expansion of the mesangial area thereafter. Most ICs formed in the subendothelial space rapidly formed lattices of a size that activated C3 and were then translocated to the subepithelial space. The potential ability of C3 to solubilize ICs in the subendothelial region may be important in this process. Endocytosis of subendothelial ICs by PMN and/or monocytes and the movement of ICs to the mesangial matrix may also contribute to the removal of IC from the subendothelial space.

Acute-Phase Reaction↗

PubMed1999

Treatment of childhood acute immune thrombocytopenic purpura with anti-D immune globulin or pooled immune globulin.

OBJECTIVE: To evaluate the effectiveness of initial treatment of children with acute immune thrombocytopenic purpura (ITP) with anti-D immune globulin (anti-D) or pooled IgG immune globulin (IVIg). STUDY DESIGN: The medical charts of 33 children diagnosed with acute ITP from May 1995 to October 1997 were reviewed. Patient data were eligible for analysis if, for the new diagnosis of acute ITP, the patient had received either anti-D at 45 to 50 microg/kg (WinRho SD, NABI) or IVIg at 0.8 to 1 g/kg (Gammagard SD, Baxter-Highland). The platelet response time for each treatment group was compared by the Mann-Whitney U test. RESULTS: Time to achieve a platelet count >/=20 x 10(9 )/L (20,000/mm3 ) was 1.54 +/- 0.51 days in the IVIg group (n = 13) and 1.26 +/- 0.82 days in the anti-D group (n = 14) (P =.34). Time to achieve a platelet count >/=40 x 10(9 )/L (40,000/mm3 ) was 1.77 +/- 0.74 and 1.49 +/- 1.01 days for the IVIg and anti-D groups, respectively (P =.32). Children given IVIg were hospitalized for 2.1 +/- 0.87 days, whereas those given anti-D were hospitalized for 1.94 +/- 1.08 days. A net decrease in hemoglobin concentration was observed after receipt of IVIg (9.1 +/- 7.3 g/L [0.91 +/- 0.73 g/dL]) and after anti-D therapy (4.5 +/- 10.3 g/L [0.45 +/- 1.03 g/dL], P =.23). No patient required intervention for hemolysis. CONCLUSIONS: In this retrospective analysis anti-D was as effective as IVIg for the treatment of acute ITP in children. However, randomized, controlled trials are needed to establish the role of anti-D in the treatment of acute ITP in children.

Adolescent↗

PubMed1991

Obstacles to achieving immunization for all 2000: missed immunization opportunities and inappropriately timed immunization.

Missed opportunities and inappropriately time immunization substantially reduced the coverage achieved in Mozambique and Guinea Conakry. During coverage surveys in Mozambique, we noted dates of attendance at a health facility for growth monitoring or vaccination, and in Conakry we also abstracted dates of curative care visits from home-based documents. In Mozambique, an average of 84 per cent of children aged 12-23 months had documents, and an average of 53 per cent of children were fully and correctly vaccinated. Among children with cards, 11 per cent had received all vaccines, but at least one dose was applied before the recommended age or with too short an interval between doses (inappropriately timed vaccinations). A further 8 per cent of children had sufficient documented contacts with preventive services to be fully vaccinated, but immunization opportunities had been missed. In Conakry, 54 per cent of 12-23 month-old children had immunization cards, and only 19 per cent were fully and correctly vaccinated. Among children with cards, 9 per cent had received all vaccines, but some were inappropriately timed, and 19 per cent had enough contacts with curative or preventative services to be fully vaccinated, but opportunities had been missed. We recommend that home-based records document all health centre visits, including those for curative care, and that missed opportunities and vaccination timing be routinely evaluated during vaccine coverage surveys.

Guinea↗

PubMed1999

Intranasal immunization of mice with influenza vaccine in combination with the adjuvant LT-R72 induces potent mucosal and serum immunity which is stronger than that with traditional intramuscular immunization.

Immunization of mice by the intranasal route with influenza virus hemagglutinin in combination with the mutant Escherichia coli heat-labile enterotoxin R72 (LT-R72) induced significantly enhanced serum and mucosal antibodies, surpassing, in most cases, responses achieved by traditional intramuscular immunization using inactivated split influenza vaccine. Furthermore, intranasal immunization with LT-R72 induced a potent serum immunoglobulin G2a response, indicating that this adjuvant has Th1 character.

Administration, Intranasal↗

PubMed1987

[Genetics of the immune response of Karakul sheep immunized with E. coli and Salmonella vaccines. An analysis of the intensity of the immune response in 2d-generation and reverse-cross hybrids].

For the genetic analysis of the character of inheriting the immune response and the study of the possibility of immunoselection in astrakhan sheep, the test crossing of the previously selected and raised animals in different genetic combinations has been made. Regularities in inheriting the intensity of immune response in hybrids F2 and BC1 of astrakhan sheep, highly responsive to E. coli and Salmonella vaccines, confirm the dominant character of the capacity for intensive immune response. The second-generation hybrids obtained by the crossing of the animals, either highly responsive or weakly responsive to E. coli or Salmonella vaccine, show a high degree of concordance in their capacity for response to this antigen. This confirms the possibility for the immunoselection of sheep by their capacity for response to a given vaccine.

Animals↗

PubMed1982

[Genetics of the immune response of Karakul sheep immunized with E. coli and Salmonella vaccines. I. Individual differences in the immune response].

The capacity for immune response after immunization with E. coli and Salmonella vaccines has been analyzed in a population of astrakhan sheep, depending on their genotype. Sharply defined individual differences in immune response to the same antigen have been shown, and oppositely reacting animals have been selected. Among the animals showing highly pronounced reaction to one antigen (E. coli) the presence of the animals with a low level of reaction to the other antigen (Salmonella), and vice versa, has been established.

Agglutinins↗

PubMed1978

Immune response to immunization via the anterior chamber of the eye. II. An analysis of F1 lymphocyte-induced immune deviation.

Exposure to alloantigen via the anterior chamber of the eye elicits a transient suppression of cellular immunity, whereas humoral immunity is preserved--i.e. F1 LI-ID. The majority of lymphoid cells inoculated into the anterior chamber are retained within the posterior segment of the eye. The latter serves as a depot of alloantigen, allowing the chronic egress of small numbers of cells into the vascular tree. The persistence of this antigen depot is essential to the development of F1 LI-ID. Since there is a preferential distribution of cells that migrate from the eye to the spleen, the functional integrity of the latter is also necessary to elicit F1 LI-ID. It is concluded that an anatomically intact spleen, i.v. presentation of antigen, and persistence of antigen within the eye are all important to the elicitation of this phenomenon.

Animals↗

PubMed2000

The cost of treating immune thrombocytopenic purpura using intravenous Rh immune globulin versus intravenous immune globulin.

Multiple factors, including efficacy, toxicity and cost, may influence the decision to treat immune thrombocytopenic purpura (ITP) with intravenous immune globulin (IVIG) or intravenous Rho (D) immune globulin (IV RhIG). We conducted a survey of 50 hospitals in 31 states to determine the costs for treating ITP using conventional doses for IVIG or IV RhIG, based on package insert recommendations. The average cost for a dose of IVIG ($2,771) was 71.7% ($1,157) more than that for a dose of IV RhIG ($1,614). In the absence of clearly defined differences in clinical outcomes when treating ITP with IVIG or IV RhIG, the difference in cost may be an important factor in selecting the treatment.

Data Collection↗