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At least 181 records · Page 10Linked to original sources
PubMed1999

A monoclonal antibody directed against the murine macrophage surface molecule F4/80 modulates natural immune response to Listeria monocytogenes.

Whole spleen cell cultures from SCID mice release high levels of IFN-gamma when exposed to heat-killed Listeria monocytogenes (HKL). This microbe-induced and T cell-independent response depends on both macrophages (MPhi) and NK cells: HKL-stimulated MPhi release TNF-alpha and IL-12, which together activate NK cells for IFN-gamma release. We show here that this cytokine-mediated activation cascade can be modulated by a mAb against the MPhi surface glycoprotein F4/80. HKL-induced IL-12, TNF-alpha, and IFN-gamma in SCID whole spleen cell cultures was inhibited by coincubation with anti-F4/80 mAb whereas IL-1 and IL-10 were enhanced. Both effects were apparent at mRNA and protein release levels. Whereas inhibitory activities were F4/80 Ag specific, stimulatory effects were Fc dependent and nonspecific. Furthermore, cytokine inhibition by anti-F4/80 was only apparent when MPhi and NK cells were present simultaneously and in close vicinity, indicating that direct cell-to-cell contact is a prerequisite. These data suggest a novel pathway for microbe-induced MPhi/NK cell interaction involving direct cell-to-cell signaling and give the first evidence for a functional role of the MPhi surface glycoprotein F4/80.

Adjuvants, Immunologic↗
PubMed1994

Different effects of breast cancer, HIV-1 infection and chemotherapy on inducible natural immunity.

Breast cancer chemotherapy and HIV-1 viral infection (AIDS) can result in respective transient or irreversible losses of up to 40-50% of circulating lymphocytes. The relationship of lymphopenia on tumor immunosurveillance and the control of opportunistic infections has yet to be established. The objective of this study was to characterize the changes in natural killer (NK) and lymphokine activated killer (LAK) cell function associated with cytotoxic drug therapy, breast cancer and HIV-1 infection. NK and LAK activities were measured at multiple effector to target ratios. Exponential regression analysis of target cell lysis determined the maximal % target kill and the lytic potential of effector cells. Flow cytometric analysis of lymphocyte subsets in seropositive populations was performed to determine the % of NK(CD56+) cells. Taken together, our findings indicate that cytotoxic NK pool sizes increased in breast cancer patients, diminish consequent to chemotherapy. The functional capacity of individual NK and LAK cells remains intact. In contrast, the diminution of NK and LAK functional responses in HIV-1 seropositive individuals is associated with reductions in cytotoxic NK and LAK pool sizes, as well as marked reductions in cytolytic function of individual cells. Zidovudine (AZT) treatment did not affect LAK activity in HIV+ subgroups. Our findings indicate that NK and activated LAK functions are affected both by chemotherapy and disease etiology.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Status of natural immunity and the ways of its enhancement in patients with goiter].

Disease caused by goiter is marked by changes in cellular and humoral unspecific resistance before and after operation, which at times is of decisive importance in the course of the postoperative period. Natural resistance is inhibited, to a greater measure, in patients with a long history of the disease and in those with diffuse toxic goiter. The work deals with the study of natural resistance in 98 patients with goiter before and after the operation in dynamics. The immunostimulator lysozyme was used for a more favourable course of the postoperative period. This promoted increase of the organism's natural resistance. which had a favourable effect on the course of the postoperative period.

Adjuvants, Immunologic↗
PubMed1976

Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems.

Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.

Animals↗
PubMed1983

Vitamin C and immunity: natural killer (NK) cell factor.

The influence of a vitamin C regimen, 250 mg% in the drinking water, on natural killer (NK) cell activity was investigated in three highly inbred strains of mice. Spleen effector cells from these donors, both tap water control and experimental after 4-5 weeks, were tested against YAC-1 murine lymphoma target cells in a 4-hour 51Cr release assay. Ascorbate treatment was observed to be without effect on NK activity in the autoimmune- and lymphoma-prone NZB strain as well as in the normal and low cancer-incidence BALB/c and DBA/2. The relative levels of hemopoietic stem cells, purported to be decisive in determining NK levels, were of a similar order in these three strains as their relative NK activities. It appears that the established association of vitamin C with modulation of the immune response, as observed in activation of T cell-mediated immunity and the enhancement of interferon production, would not include alterations in natural cytotoxic reactivity.

Animals↗
PubMedDate not supplied

Acquisition of human cytomegalovirus infection in infants via breast milk: natural immunization or cause for concern?

Since the recognition in the 1960s that human cytomegalovirus (HCMV) infections could be transmitted by breast milk, there has been relatively little attention paid to the potential medical consequences of such infections. Indeed, since HCMV infections acquired by healthy newborn infants appear to be largely asymptomatic in nature, there has been no real incentive to develop or implement strategies to prevent transmission by this route. However, recent studies have identified a significant risk for low-birth weight, premature infants for the development of HCMV disease following acquisition of infection via breast milk. Such infections may cause considerable short-term morbidity and, in some cases, severe, life-threatening illness. There is little consensus amongst neonatologists on the approach to prevention and management of such infections. This review summarises the epidemiology and natural history of HCMV infections acquired via breast milk, and outlines available strategies for prevention and management of such infections, as well as opportunities for future clinical research on this understudied topic.

Breast Feeding↗
PubMed1998

Natural immunity and bone and muscle remodelling hormones in the elderly.

Increasing evidence has demonstrated that the immune system is closely integrated with two other physiological systems: endocrine and nervous. They communicate through circulating humoral factors such as cytokines, hormones and neurotransmitters. We undertook a cross-sectional analysis in a group of elderly subjects over 90 years to demonstrate that a functional relationship exists among the number and cytolytic activities of NK cells, bone and muscle remodelling hormones, anthropometric parameters and physical ability. Peripheral blood samples collected from 62, 90-106 years-old subjects underwent biochemical (bone and muscle remodelling hormone levels) and immunological determinations (Natural Killer cell distribution and activity), anthropometric and functional assessment. Significant associations were found among NK cell number and cytolytic activity and serum concentrations of vitamin D, anthropometric parameters, while functional independence in daily activity was only associated with NK cell number. In general a high level of physical ability was correlated with preserved body stores and vitamin D levels. In conclusion, our results stress the importance of nutritional evaluation in the clinical assessment of elderly people. The magnitude of the NK immune response, which constitutes the first line of defence against infected and neoplastic cells, is best preserved in oldest-old people with the best hormonal parameters and nutritional measures.

Aged↗
PubMedDate not supplied

[Dynamics of various indicators of natural immunity in diabetes mellitus].

Patients with diabetes mellitus displayed a suppression of humoral and cellular mechanisms of nonspecific factors of immunity protection: of bacteridical serum activity, of phagocytic neutrophil activity, and a sharp disturbance of profound skin autoflora. The amount of serum lysozyme diminished only in young patients with severe form of diabetes mellitus. In other patients the muramidase content was increased. Compensation of the disease led to an even greater elevation of this enzyme, and produced no significant influence on other natural resistance parameters.

Adolescent↗
PubMed2001

Analysis of a natural immune response against tumor antigens in a melanoma survivor: lessons applicable to clinical trial evaluations.

The long-term survival of some patients with metastatic melanoma may be attributable in part to cellular immune responses to melanoma antigens. However, little is known about the level of CTL reactivity in vivo that is required for immunological control of tumor progression. In the present report, T-cell responses were evaluated with lymphocytes obtained from tumor-involved nodes and peripheral blood of a long-term melanoma survivor. Using an ELISPOT assay, naturally occurring functional T cells, which recognize the peptide ALLAVGATK (gp100(17-25)) plus two other HLA-A3 restricted peptides, were detected in a tumor-involved lymph node. The ALLAVGATK-reactive T cells were also evaluated by MHC-tetramers staining and were found to be CD8+ CD45RO+ L-selectin(-) CD11a+, suggesting that they are antigen experienced and have a memory phenotype. Unstimulated peripheral blood lymphocytes from the same patient demonstrated no detectable T-cell responses; however, a single stimulation with ALLAVGATK peptide in vitro resulted in a dramatic expansion of peptide-reactive CTLs. This patient, with evidence of tumor-reactive CTLs targeted to several tumor antigens in a tumor-involved lymph node and with evidence of a circulating memory T-cell response, has remained disease-free for 6 years, despite prior bulky nodal metastasis. In contrast, three HLA-A3+ patients with rapidly progressive metastatic melanoma had no detectable T-cell response in tumor-involved nodes or peripheral blood lymphocytes, even after peptide stimulation ex vivo. The presented data are consistent with a systemic polyvalent immune response against tumor in this long-term survivor. These data provide an estimate of the level of CTL response that may be associated with protection from tumor recurrence.

Antigens, Neoplasm↗
PubMed2000

Effects of nickel sulfate on pulmonary natural immunity in Wistar rats.

This study was designed to investigate the in vivo effect of nickel sulfate on the pulmonary non-specific immune defences. Groups of four male Wistar rats were treated with a single intratracheal instillation of NiSO(4) at different doses: 1, 2, 4 and 8 micromol of NiSO(4) per rat. Control rats received a corresponding instillation of the saline vehicle. The effect of NiSO(4) on the cytotoxic activity of the pulmonary natural killer (NK) cells and alveolar macrophages (AM), as well as the pulmonary production of cytokines such as alpha-tumor necrosis factor (TNF-alpha) and gamma-interferon (IFN-gamma), were examined 1, 2 and 7 days later. Spontaneous NK-cytotoxicity towards mouse-derived tumor cell line, Yac-1 was suppressed 1 day after treatment at doses of 2 micromol/rat and above with only one result significant (P<0.05); 2 days after treatment the suppression was increased with all results significant at the same doses; 1 week after treatment NK activity restoration was observed except for the highest dose, 8 micromol/rat. AM-mediated cytotoxicity towards mouse-derived tumor cell line, 3T12, did not show any significant difference in treated and untreated animals. In contrast, whereas moderate levels of TNF-alpha were detected in the broncho-alveolar lavage (BAL) fluid supernatants of controls, the NiSO(4) treatment highly suppressed TNF-alpha production with a maximum observed after 2 days. TNF-alpha suppression was found to be transient, at least with the lowest NiSO(4) dose, with levels returning to normal after 7 days. A non-significant increase in IFN-gamma was observed in the BAL fluids of treated animals at each time of examination. Taken together, these results indicate that NK cell activity and TNF-alpha secretion are sensitive targets for instilled NiSO(4) in Wistar rats.

Animals↗
PubMed1983

Natural immunity to murine gonococcal bacteremia: roles of complement, leucocytes, and sex.

The roles of the serum bactericidal system, inflammatory cells, and sex in resisting gonococcal infection were studied in a murine model of gonococcal bacteremia. The role of serum killing in defense was investigated with complement component 5 deficient (C5-deficient) (B1O.D2/OSN) and normal (B1O.D2/NSN) mice. No significant differences were found between LD50's with either murine serum-sensitive or serum-resistant gonococci in those two mouse strains. However, in vitro experiments revealed a heat-stable factor in mouse serum which killed gonococci. Thus it appeared that the C5-deficient mouse is not a good model for the study of the role of C-mediated killing in resistance to gonococcal infection. Mice with Chediak-Higashi disease were used to study the role of phagocytes and natural killer cells. The difference in LD50's between affected mice (C57B1/6J beige J) and controls (C57B1/6J) was significant. The CBA/N mice, which have a B-cell maturation defect, were no more resistant to infection than control mice, which was taken as further evidence that B cells were less important than other leucocytes in innate immunity to gonococcal infection. Finally, male mice were significantly more resistant than female mice to gonococcal bacteremia. Thus, in this study the two most important determinants of resistance to gonococcal infection were inflammatory cells and sex.

Animals↗
PubMed2000

Clearance of anti-double-stranded DNA antibodies: the natural immune complex clearance mechanism.

OBJECTIVE: To develop an in vitro model for investigating the mechanism by which autoantibodies in immune complexes (ICs) that are bound to primate erythrocytes via antigen-based heteropolymers (AHPs) are cleared from the circulation and localized to the liver. METHODS: IgG anti-double-stranded DNA (anti-dsDNA) antibodies in ICs with dsDNA were bound to human erythrocytes via complement receptor 1 (CR1) either by opsonization with normal human serum as a complement source or through the use of an AHP, which consists of an anti-CR1 monoclonal antibody (mAb) that is chemically crosslinked with dsDNA. We performed parallel investigations of the mechanism of transfer of both types of erythrocyte-bound ICs to a monocytic cell line (U937). Erythrocytes with CR1-bound ICs were incubated with U937 cells under a variety of conditions, and subsequently, the levels of IgG anti-dsDNA, CR1, AHP, or C3b on both erythrocytes and U937 cells were measured by flow cytometry with appropriate fluorescently labeled probes. RESULTS: In the presence of U937 cells, both the AHP-anti-dsDNA and C3b-opsonized ICs were rapidly removed from the erythrocytes; at 37 degrees C, more than half of the complexes were removed in 2 minutes. Monomeric mouse IgG2a mAb blocked the transfer of both types of complexes by 75%, suggesting that Fcgamma receptor type I (FcgammaRI) is the main phagocyte receptor responsible for the removal of ICs from erythrocytes. Levels of CR1 on the erythrocyte surface were reduced during transfer of the AHP-anti-dsDNA ICs, suggesting that transfer involves a concomitant removal of CR1, presumably by proteolysis. CONCLUSION: Transfer of AHP-anti-dsDNA ICs from erythrocyte CR1 to model phagocytes occurs by a mechanism that is similar to the natural mechanism of IC clearance, involving recognition by FcgammaRI and removal of erythrocyte CR1 as key steps.

Animals↗
PubMed2000

Natural immune response involving anti-endothelial cell antibodies in normal and lupus pregnancy.

OBJECTIVE: To determine whether immunoglobulins with affinity for the vascular endothelium displayed any distinguishing behavior during normal and systemic lupus erythematosus (SLE) pregnancy. We also attempted to verify whether isotype expression of anti-endothelial cell antibodies (AECA) would have any predictive value for pregnancy outcome. METHODS: Sera from 38 pregnant patients with SLE, 68 normal pregnant women, and 84 nonpregnant healthy controls were studied. IgM- and IgG-AECA were determined by cellular enzyme-linked immunosorbent assay using fixed cultured human umbilical vein endothelial cells. RESULTS: A significantly higher level of IgM-AECA was found during normal pregnancy compared with that in healthy nonpregnant controls (mean +/- SD 39 +/- 12% versus 21 +/- 12%; P < 0.0001). Most pregnant patients with SLE did not have increased titers of IgM-AECA, but instead had levels similar to those found in healthy nonpregnant controls (23 +/- 12%; P not significant). The lowest levels of IgM-AECA in lupus pregnancy were associated with preeclampsia (odds ratio 16, P < 0.005). Conversely, IgG-AECA levels were significantly higher in the serum of normal pregnant women and pregnant SLE patients than in the serum of healthy nonpregnant controls (24 +/- 7% and 24 +/- 14% versus 9 +/- 7%; P < 0.0001). CONCLUSION: Our results indicate that an active immune response occurs during pregnancy. This response involves increased activity of AECA, suggesting a role of autoantibodies as a possible contributing factor toward fetal tolerance. Our observations further indicate that impaired immune regulation, such as diminished levels of serum IgM-AECA detected in SLE patients, might contribute to the impaired reproductive function commonly found in SLE.

Adult↗