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At least 811 records · Page 45Linked to original sources
PubMed1996

Open versus laparoscopic surgery: a comparison of natural antitumoral cellular immunity in a small animal model.

The scope of laparoscopic surgery has extended to the treatment of cancer. The immunological impact of laparoscopic surgery as compared with open surgery has not been well characterized. A paucity of information is available about differences or similarities of these two methods regarding natural antitumoral cellular immunity, namely, natural killer cell cytotoxicity. This study compared the activity of natural killer cells in rats subjected to pneumoperitoneum, open dissection of the retroperitoneum, and laparoscopic dissection of the retroperitoneum. When compared to control animals, rats subjected to pneumoperitoneum did not show any change in natural killer cell activity. Conversely, the groups of open surgery and laparoscopic surgery revealed significantly decreased natural killer cell cytotoxicity compared with controls (P < 0.0167). When the laparoscopic and the open surgical groups were compared to each other, no difference was found. In this study, both open and laparoscopic surgery had a suppressive effect upon the natural antitumoral cellular immunity. Pneumoperitoneum did not have an immune suppressive effect on natural killer cell activity. In this model, the advantages of laparoscopic surgery do not apply to natural antitumoral cellular immunity.

Animals↗
PubMed1997

In vitro effects of MOCA and dapsone on rat hepatic and splenic immune cells.

The industrial curing agent 4,4'-methylene-bis(2-chloroaniline) (MOCA) and the structurally related medicinal agent 4,4'-sulphonyldianiline (dapsone), are two commonly used aromatic amine compounds and documented animal carcinogens. In this study the effects of in vitro exposure to MOCA and dapsone (over a dose range of 1-200 microM on spleen and liver immune cell functions were investigated. MOCA exposure caused a dose-dependent inhibition of natural immune activities (i.e. natural killer, NK and natural P815 killer, NPK) and mitogen-stimulated proliferation of T- and B-lymphocytes, with 50% inhibition (IC50) of splenic-cell activities occurring at 145, 85, 21 and 31 microM, respectively. Liver NK and NPK activities were less sensitive to MOCA exposure and exhibited higher IC50's of 165 and 160 microM, respectively. Dapsone exposure slightly enhanced both T- and B-cell mitogenesis at low doses (1 microM) but decreased B-cell mitogenesis at high doses (IC50 = 130 microM). Natural tumouricidal activities were generally unaffected by dapsone, whilst natural cytotoxic (NC) activity was unaffected by both compounds. These results indicate that MOCA is generally immunotoxic in vitro, and may have the potential to enhance the carcinogenic effects of its genotoxic metabolite by inhibiting the tumour surveillance activities of the immune system. The relationship between immune effects and the carcinogenicity of dapsone remains unclear.

Animals↗
PubMed1984

Monocyte lysosomal enzyme release in response to naturally occurring circulating immune complexes.

To investigate the influence of naturally occurring immune complexes (ICs) on monocyte lysosomal enzyme release, blood monocytes have been isolated from normal human volunteers, purified, and maintained in culture for 5 days. These cells have been exposed in vitro to sera containing ICs and to the same sera depleted of ICs with 2% polyethylene glycol (PEG). IC-containing sera have been shown to result in increased lysosomal enzyme release (N-acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase) sustained for up to 5 days even after brief (24-h) exposure (NAG activity at 120 h, nmol substrate hydrolysed ml-1 culture supernatant: control, 98 +/- 27; 2% PEG control, 70 +/- 10; IC serum exposure for 120 h, 305 +/- 73; IC serum exposure for 24 h, 330 +/- 95; exposure to IC-depleted sera 120 h, 158 +/- 93). Further analysis showed no relationship between the total IC concentration and enzyme release, nor was there any relationship between the complement component (C3) composition of the complexes and degree of enzyme release. These results confirm the potential importance of circulating IC on monocyte activation in man and indicate that this could result in changes in macrophage activity at the sites of inflammation.

Acetylglucosaminidase↗
PubMed2004

Recognition of infected cells by natural killer cells.

Under the influence of cytokines associated with innate immunity, natural killer (NK) cells rapidly become activated and migrate to sites of infection. Upon contact with infected parenchyma they proliferate, release cytokines and/or kill cells harboring pathogens. Multiple stimulatory and inhibitory receptors can provide the integrated signals that trigger this contact-mediated NK-cell function. Recent work has begun to define the ligands for these receptors in the context of infection by certain well-studied viruses. These results, in addition to future work involving other pathogens, will provide an understanding of the molecules present on parasitized cells that mark them as targets of innate immunity.

Cytotoxicity, Immunologic↗
PubMed1996

Natural and cellular immune responses in Flinders sensitive and resistant line rats.

Major depression is associated with impairments in natural and cellular immune responses. This study characterized baseline natural and cellular immune function in the Flinders Sensitive Line (FSL) genetic animal model of depression and in Flinders Resistant Line (FRL) controls. Splenic natural cytotoxicity per natural killer (NK) cell was significantly lower in the FSL rats, suggesting that NK cells are less activated at rest in the FSL rats than in the FRL controls. Neither lymphocyte proliferative responses nor interleukin-2 production differed between the two strains. Resting baseline concentrations of plasma adrenocorticotropic hormone and corticosterone were similar between the FSL and FRL rats, indicating that hypothalamo-pituitary adrenal axis activation did not mediate immunological differences. FSL rats show abnormalities in natural immunity similar to those found in clinically depressed human beings, indicating that this animal model may be useful in understanding the neural and neuroendocrine mechanisms associated with immune alterations in depression.

Animals↗
PubMed1994

9-(2-Phosphonylmethoxyethyl) adenine increases the survival of influenza virus-infected mice by an enhancement of the immune system.

PMEA (9-(2-phosphonylmethoxyethyl)adenine) is a potent inhibitor of DNA viruses and retroviruses able to enhance natural immune functions such as natural killer cell activity and interferon production. The results reported in this paper show that the treatment with PMEA significatively decreased the mortality of mice challenged with influenza A/PR8 virus (an RNA virus, non sensitive to the antiviral effect of PMEA) compared to untreated, infected controls (median survival 8.64 days and 7.61 days, respectively), and reduced lung weight and consolidation (two surrogate markers of virus infection). Furthermore, virus titer obtained from lung homogenates was substantially decreased in PMEA-treated mice compared to controls. Finally, enhancement of natural killer cell activity was achieved in PMEA-treated A/PR8-infected mice compared to A/PR8-infected controls. Overall, results suggest that PMEA decreases the influenza virus-related mortality and morbidity through the enhancement of some immune functions, and that this effect might be additive or even synergystic with the direct inhibitory effect of DNA viruses or retroviruses induced by PMEA itself. This supports the importance of evaluating this drug in patients with diseases related to herpesviruses or to human immunodeficiency virus.

Adenine↗
PubMed1996

Th1 and Th2 in human diseases.

A large body of evidence suggests the existence of functionally polarized human T cell responses based on their profile of cytokine secretion in both the CD4+ T helper (Th) and the CD8+ T cytotoxic (Tc) cell subset. Human Th1 and Th2 cells not only produce a different set of cytokines but also exhibit distinct functional properties and the preferential expression of some activation markers, such as LAG-3 and CD30, respectively. Several factors may influence Th cell differentiation into the polarized Th1 or Th2 pathway. They include the cytokine profile of "natural immunity" evoked by different offending agents, the nature of the peptide ligand, as well as the activity of some costimulatory molecules and microenvironmentally secreted hormones, in the context of different host genetic backgrounds. Strongly polarized human Th1-type and Th2-type responses not only play different roles in protection, Th1 being effective in the defense against intracellular pathogens and Th2 against intestinal nematodes, but are also responsible for different types of immunopathological reactions. Th1-dominated responses may be involved in the pathogenesis of organ-specific autoimmune disorders, acute allograft rejection, unexplained recurrent abortions, contact dermatitis, and some chronic inflammatory disorders of unknown etiology. In contrast, Th2-type responses are responsible for Omenn's syndrome, reduced protection against some intracellular pathogens, transplantation tolerance, chronic GVDH, atopic disorders, and some systemic autoimmune diseases.

Humans↗
PubMed1994

Exercise and the immune system: a model of the stress response?

Exercise influences natural immunity, T- and B-cell functions, and cytokine responses, through circulatory (hemodynamic) changes and by endocrine hormones secreted in response to physical stress. The magnitude of the effects on the immune system reflects the intensity, duration and chronicity of the exercise. In this review, Laurie Hoffman-Goetz and Bente Klarlund Pedersen suggest that exercise-immune interactions can be viewed as a subset of stress immunology.

B-Lymphocytes↗
PubMed2003

Immunogenic measles antigens expressed in plants: role as an edible vaccine for adults.

Vaccine-induced immunity against measles is less robust than natural immunity. Waning of immunity in vaccines may eventually require a revaccination of adults. Measles antigens expressed in plants have been shown to be antigenic and immunogenic both after invasive and oral vaccination. Strategies for the vaccination of adults, the potential of an oral measles vaccine produced in edible plants and the design of suitable antigens are discussed.

Administration, Oral↗
PubMed2002

Polyspecific malaria antibodies present at the time of infection inhibit the development of immunity to malaria but antibodies specific for the malaria merozoite surface protein, MSP1, facilitate immunity.

Serum taken from mice immune to malaria as a result of infection and drug cure, or from mice immunized with a recombinant form of the merozoite surface protein, MSP1, can provide passive protection of recipient mice against the lethal parasite, Plasmodium yoelii YM. However, recipients of MSP1-immune serum go on to develop long-term immunity, whereas recipients of serum from mice naturally immune to malaria rapidly lose their resistance to infection. We demonstrate that 'infection/cure' serum suppresses the development of both antibody and cell-mediated parasite-specific responses in recipients, whereas these develop in recipients of MSP1-specific antibodies. These data have profound implications for our understanding of the development of malaria immunity in babies who passively acquire antibodies from their mothers.

Animals↗
PubMedDate not supplied

The Paul Kallos Memorial Lecture. The mast cell: a versatile effector cell for a challenging world.

Mast cells are phenotypically and functionally versatile effector cells. When activated by IgE-dependent or other mechanisms, mast cells can produce a diverse array of mediators including TNF-alpha and many other cytokines. Moreover, mast cells can express increased numbers of high-affinity surface receptors for IgE (Fc epsilonRI) and enhanced levels of IgE-dependent mediator secretion in response to elevations in concentrations of IgE. These characteristics (and others) have suggested diverse potential roles for mast cells in health and disease. To test specific hypotheses about mast cell function in allergic reactions and other biological responses in vivo, one can employ genetically mast-cell-deficient Kit(W)/Kit(W-v) mice which do or do not contain adoptively transferred mast cell populations derived from genetically compatible wild-type mice or mice with mutations that influence mast cell biology. Such work has already indicated that mast cells (and, in some cases, mast-cell-derived cytokines) can have a critical role in the expression of the acute, late-phase and chronic components of IgE-dependent allergic inflammation and can influence the development of an important functional consequence of such reactions: airways hyperresponsiveness. However, mast cells can also perform important beneficial roles in host defense, both in IgE-dependent immune responses to certain parasites and in natural immunity to bacterial infection.

Animals↗
PubMedDate not supplied

An update on human Th1 and Th2 cells.

The existence of functionally polarized human T cell responses based on their profile of cytokine secretion in both the CD4+ T helper (Th) and the CD8+ T cytotoxic cell subset has been established. Human Th1 and Th2 cells not only produce a different set of cytokines but also exhibit distinct functional properties and preferential expression of some activation markers, such as LAG-3 and CD30, respectively. Several factors are involved in the Th cell differentiation into the polarized Th1 or Th2 pathway. They include the cytokine profile of 'natural immunity' evoked by different offending agents, the nature of the peptide ligand, as well as the activity of some costimulatory molecules and microenvironmentally secreted hormones, in the context of different host genetic backgrounds. Polarized Th1-type and Th2-type responses play different roles in protection, Th1 being effective in the defense against intracellular pathogens and Th2 against intestinal nematodes. Moreover, they are responsible for different types of immunopathological reactions. Th1 responses predominate in organ-specific autoimmune disorders, acute allograft rejection, unexplained recurrent abortions, and in some chronic inflammatory disorders of unknown etiology. In contrast, Th2 responses predominate in Omenn's syndrome, transplantation tolerance, chronic graft versus host disease, systemic sclerosis; moreover allergen-reactive Th2 cells are involved in the triggering of atopic disorders.

Autoimmune Diseases↗
PubMed2002

Redirecting cytotoxic T lymphocyte responses with T-cell receptor transgenes.

In cancer and viral diseases, a great deal of research has focused on generating T-cell responses that might prove therapeutic. These efforts stem from our understanding of the immune system. It is known that the natural immune response can protect or suppress some viral infections and it is hoped that a potent T-cell mediated immune response might also be harnessed to fight cancer. Immunotherapy is a particularly attractive candidate therapy for the treatment of metastatic cancer because of the immune systems capacity for body wide surveillance. Since the generation of T cell clones is a laborious task and it is often impossible to derive T cell clones of the desired specificity and function from many individuals, especially in a timely fashion required for therapeutic interventions, T-cell receptor (TCR) gene transfer has a lot of appeal. TCR gene transfer seeks to transfer the antigen specificity of a T cell clone to other T cells. This article will review the last 15 years of research in TCR gene transfer since the first successful TCR gene transfer experiment, and seeks to give an insight into the areas of investigation currently being pursued to improve on current results and move TCR gene transfer into the clinic.

Animals↗
PubMed2024

A comprehensive meta-analysis of tissue resident memory T cells and their roles in shaping immune microenvironment and patient prognosis in non-small cell lung cancer.

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.

Humans↗
PubMed1984

[Clinico-immunologic evaluation of the sequelae of closed craniocerebral injuries].

Sixty-four patients were examined clinically and immunologically at a long-term period following craniocerebral trauma. In patients with a history of head trauma impaired adaptation mechanisms were shown to underlie the neurologic disorders, which was reflected in changes in the natural immunity system. The severity and duration of natural resistance impairments were correlated with the gravity of clinical manifestations. The study of the time-course of natural resistance parameters allows the objective evaluation of the degree of central nervous system recovery following closed craniocerebral trauma.

Acute Disease↗
PubMed1982

Rubella immunization of teenage girls in Iceland and follow-up after a severe rubella epidemic.

Of 730 Icelandic schoolgirls, 12 years of age, screened for rubella antibodies by the haemagglutination-inhibition (HI) technique, 372 (50.9%) were found to be seronegative. Rubella vaccine was administered to 355 members of this group, and to 12 girls with an HI titre of 20. Blood samples were taken 6 weeks and 1 year after immunization from 336 previously seronegative girls and from the 12 low-positive vaccinees, and tested for HI antibodies. The seroconversion rate was 99.15%. One year after immunization, 94.8% of the girls tested had an HI antibody titre of 40 or more. The geometric mean titre (GMT) of the previously seronegative girls was 62.07 at 6 weeks and 61.69 at one year after vaccination. Of the girls with an initially low positive titre, only 3 (25%) showed a significant rise. The GMT was 40 at 6 weeks, but fell to 25.2 after 1 year. Re-immunization had no effect on antibody levels in either group.A severe rubella epidemic occurred 2 years after immunization, following which 345 vaccinees and 193 naturally immune controls were studied. All subjects had been exposed to wild rubella virus at school, and rubella cases had occurred in the homes of 116 vaccinees (33.6%) and 41 control subjects (21.2%). Only 5 (1.5%) primarily seronegative vaccinees and 2 unimmunized controls (1%) showed serological evidence of infection during the epidemic.

Adolescent↗
PubMed2006

Natural IgM antibodies: from parias to parvenus.

Over the years, natural IgM antibodies were considered as the parias among the immune competent molecules. Their characteristic properties, like low affinity, cross-reactivity and pentameric structure, were assessed as difficult and nebulous. Today, mainly based on the persistent work of a few researchers and the key discoveries on innate immunity, natural IgM antibodies are "back on stage". Their important role in the immune response against invasive particles, modified self-components and altered cells is accepted. All the so far negatively judged features have to be seen in a different light, e.g. low affinity seems to be good for function and does not exclude specificity, cross-reactivity is no longer judged as unspecific, but instead as a very economic way of immune recognition and the pentameric structure is important for binding capacity and functional activities. In addition, with the use of natural IgM antibodies, a new field of tumour-specific targets has been encountered, the carbo-neo-epitopes, which are commonly found on post-transscriptionally modified membrane receptors. Having understood the typical features of natural IgM antibodies, their renaissance opens a new area of cancer therapeutics and diagnostics.

Antibodies↗