Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “immune profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2000

A new approach for rapid detection and typing of serum monoclonal components.

When used independently, none of the routine methods to explore serum monoclonal components (MC), including: serum protein electrophoresis (SPE), immunoelectrophoresis (IEP), kappa to lambda ratio (KLR) and immunofixation (IFE), provides a comprehensive quantitative and qualitative identification of the MC. In the past few years the concept of 'protein profile', based on immunonephelometric quantifications of serum proteins, has become widely used. It consists of a qualitative and quantitative graphic representation of numerous serum proteins including immunoglobulins. Aim of study was to develop a multidimensional model based exclusively on protein profiles labeled the protein profile prediction method (PPPM) to improve routine MC detection and typing. Serum samples from 127 hospitalized patients and 99 healthy blood donors were submitted to all of the following: SPE, IFE, KLR and a protein profile (which included IgM, IgA, IgG, kappa and lambda chain detections and quantification). The presence of a MC using IFE was chosen as the gold standard. Healthy donors and patients were randomly divided into two groups defined as testing and validation groups. A logistic model was designed based on the protein profiles of the testing group leading to the determination of a threshold value (called Z(r)) for MC detection. It was then tested to detect MC in the validation group. Using IFE, 73 MC were found in the 127 hospitalized patients. Using the threshold value for MC detection of Z(r)=1.86, the PPPM showed greater sensitivity (94.6%) in detecting a MC compared to either SPE (64.8%) or KLR (89.2%). This result was obtained without diminished specificity (80.8%). The association of SPE or KLR to PPPM did not significantly increase the sensitivity of the PPPM. In the validation group, for samples which had a high predictive probability of a MC using PPPM, the correct MC typing was identified in up to 77% of sera using PPPM only. These results may be interesting in helping to determine when supplementary IFE analysis is required to qualitatively analyze a MC. PPPM allows MC detection with great sensitivity. The immune protein profile dramatically increases the sensitivity of either SPE and/or KLR in detecting MC and may also allow heavy and light chain typing.

Antibodies, Monoclonal↗
PubMed1999

Cervical lymph nodes play the role of regional lymph nodes in brain tumour immunity in rats.

Recent physiological and anatomical studies have demonstrated that a major fraction of brain interstitial and cerebrospinal fluid drains into cervical lymph nodes (CLN) in a number of experimental animals. To investigate the role of CLN in brain tumour immunity, temporal profiles of MHC class II molecule expression and T lymphocyte subsets in brain tumours, CLN and other lymphoid tissues were analysed by immunocytochemistry. A total of 64 Wistar rats weighing 250 g were used. Two weeks after the transplantation of C6 glioma cells (10(6) cells/1 microl) into a rat brain, expression of MHC class II molecules was induced in the brain and all systemic lymphoid tissues examined. However, the subsequent appearance of CD4 or CD8 positive cells was strictly confined to CLN, and coincided with the infiltration of such cells into the brain tumour 2 weeks after transplantation. In the group of animals in which cervical lymphadenectomy was followed by intracerebral transplantation of C6 glioma cells, infiltration of CD4 or CD8 positive cells into the brain tumour was delayed until 3 weeks after the transplantation, and the production of such cells was by the spleen. These results suggest that CLN act as regional lymph nodes in brain tumour immunity.

Animals↗
PubMed2025

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age.

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan.

Humans↗
PubMed2006

Functional gene analysis of individual response to challenge of SIVmac239 in M. mulatta PBMC culture.

It has previously been shown in macaques that individual animals exhibit varying responses to challenge with the same strain of SIV. We attempted to elucidate these differences using functional genomics and correlate them to biological response. Unfractionated PBMC from three rhesus macaques were isolated, activated, and infected with SIVmac239. Interestingly, one of the three animals used for these experiments exhibited a completely unique response to infection relative to the other two. After repeated attempts to infect the PBMC from this animal, little or no infectivity was seen across the time points considered, and corresponding to this apparent lack of infection, few genes were seen to be differentially expressed when compared to mock-infected cells. For the remaining two animals, gene expression analysis showed that while they exhibited responses for the same groups of pathways, these responses included differences specific to the individual animal at the gene level. In instances where the patterns of differential gene expression differed between these animals, the genes being differentially expressed were associated with the same categories of biological process, mainly immune response and cell signaling. At the pathway level, these animals again exhibited similar responses that could be predicted based on the experimental conditions. Even in these expected results, the degree of response and the specific genes being regulated differed greatly from animal to animal. The differences in gene expression on an individual level have the potential to be used as markers in identification of animals suitable for lentiviral infection experiments. Our results highlight the importance of individual variation in response to viral challenge.

Animals↗
PubMed2006

Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.

While it is well established that infection with the rodent hookworm Nippostrongylus brasiliensis induces a strongly polarized Th2 immune response, little is known about the innate host-parasite interactions that lead to the development of this robust Th2 immunity. We exploited the transient pulmonary phase of N. brasiliensis development to study the innate immune responses induced by this helminth parasite in wild-type (WT) and severe-combined immune deficient (SCID) BALB/c mice. Histological analysis demonstrated that the cellular infiltrates caused by N. brasiliensis transit through the lungs were quickly resolved in WT mice but not in SCID mice. Microarray-based gene expression analysis demonstrated that there was a rapid induction of genes encoding molecules that participate in innate immunity and in repair/remodeling during days 2 to 4 postinfection in the lungs of WT and SCID mice. Of particular note was the rapid upregulation in both WT and SCID mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role for alternatively activated macrophages (AAMs) in pulmonary innate immunity. Immunohistochemistry revealed that nearly all alveolar macrophages became YM1-producing AAMs as early as day 2 postinfection. While the innate responses induced during the lung phase of N. brasiliensis infection were similar in complexity and magnitude in WT and SCID mice, only mice with functional T cells were capable of maintaining elevated levels of gene expression beyond the innate window of reactivity. The induction of alternatively activated alveolar macrophages could be important for dampening the level of inflammation in the lungs and contribute to the long-term decrease in pulmonary inflammation that has been associated with helminth infections.

Animals↗
PubMed2006

Innate immune responses in NF-kappaB-repressing factor-deficient mice.

NF-kappaB-repressing factor (NRF) is a transcriptional silencer protein that specifically counteracts the basal activity of several NF-kappaB-dependent promoters by direct binding to specific neighboring DNA sequences. In cell culture experiments, the reduction of NRF mRNA leads to a derepression of beta interferon, interleukin-8, and inducible nitric oxide synthase transcription. The X chromosome-located single-copy NRF gene is ubiquitously expressed and encodes a protein of 690 amino acids. The N-terminal part contains a nuclear localization signal, the DNA-binding domain, and the NF-kappaB-repressing domain, while the C-terminal part is responsible for double-stranded RNA binding and nucleolar localization. To study the function of NRF in a systemic context, transgenic mice lacking the NRF gene were created. Against predictions from in vitro experiments, mice with a deletion of the NRF gene are viable and have a phenotype that is indistinguishable from wild-type mice, even after challenge with different pathogens. The data hint towards an unexpected functional redundancy of NRF.

Animals↗
PubMed2005

Differential expression of rat beta-defensins.

The innate immunity, utilizes a battery of broad-spectrum antibacterial cationic polypeptides (3-5 kDa) named alpha- and beta-defensins. Several beta-defensins have been isolated and shown to play a role in the defense of various tissues. Herein, we report the expression pattern of two rat beta-defensins, rBD-1 and rBD-2, in liver, kidney, lung, spleen, and brain using RT-PCR. To study polymorphism and verify gene identity, all cDNA products were sequenced. rBD-1 was expressed in the kidney, lung, brain, but not in spleen or liver, whereas rBD-2 was expressed in the lung, but not in the kidney or spleen. In addition, rBD-2 was expressed in the brain and liver. No polymorphism was found in the genes encoding rat beta-defensins. These findings demonstrate a different expression pattern for rBD-2 than what has been reported. We conclude that the rat may be a useful model to investigate the function and contribution of beta-defensins to host defense.

Animals↗
PubMed2001

Ozone-induced modulation of cell-mediated immune responses in the lungs.

Most pulmonary immunotoxicology studies of ambient pollutants have been broadly designed to discern if overall humoral or cell-mediated immunity (CMI) was altered; few have assessed effects on particular aspects of immune function. We hypothesized that effects from ozone (O3) exposure on pulmonary CMI are linked in part to changes in local immune cell capacities to form and/or to interact with immunoregulatory cytokines. Rats exposed to 0.1 or 0.3 ppm O3 4 h/day 5 days/week, for 1 or 3 weeks were assessed for resistance to, and pulmonary clearance of, a subsequent Listeria monocytogenes challenge. In situ cytokine release and immune cell profiles were also analyzed at different stages of the antilisterial response. Although O3 exposure modulated CMI, effects were not consistently concentration- or duration-dependent. Exposure did not effect cumulative mortality from infection, but induced concentration-related effects upon morbidity onset and persistence. All 1-week exposed rats had listeric burdens trending higher than controls; 0.3 ppm rats displayed continual burden increases rather than any onset of resolution. Rats exposed for 3 weeks had no O3-related changes in clearance. No exposure-related effect on neutrophil or pulmonary macrophage (PAM) numbers or percentages was noted. Bacterial burden analyses with respect to cell type showed that Listeria:PAM ratios in 0.3 ppm rats ultimately became greatest compared to all other rats. In situ IL-1alpha and TNFalpha levels were consistently higher in O3-exposed rats. All rats displayed increasing in situ IFNgamma levels as infection progressed, but no constant relationship was evident between IFNgamma and initial IL-1alpha/TNFalpha levels in O3-exposed hosts. It seems that short-term (i.e., 1 week) repeated O3 exposures imparted more effects upon CMI than a more prolonged (i.e., 3 week) regimen, with effects manifesting at the level of the PAM and in the cytokine network responsible for immunoactivation.

Animals↗
PubMed2000

Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.

Groups of sooty mangabey monkeys (SMM) were vaccinated and boosted with Mycobacterium bovis bacillus Calmette-Guerin (BCG), or BCG + low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M. leprae (ML) challenge, these and unvaccinated, unchallenged control monkeys were immunologically observed longitudinally for approximately 3 years. SMM [multibacillary (MB) leprosy-prone as a species] were not protected clinically by BCG or BCG + HKML, although the disease progress was slowed by vaccination with BCG alone. The longitudinal immune response profiles to BCG or BCG + HKML in SMM showed that: 1) vaccination with BCG or BCG + HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to ML antigens, which returned to baseline post-boosting and post-live ML challenge; 2) BCG + LD HKML-vaccinated groups gave the largest blastongenic response (SI = 23) followed by the BCG + HD HKML group (SI = 14.5) and by the BCG-only vaccinated group (SI = 3.6); 3) significantly diminished numbers of blood CD4+ (helper) and CD4+CD29+ (helper-inducer) T-cell subsets were observed longitudinally in all ML-challenged groups compared to controls regardless of whether they had been vaccinated or not; 4) CD8+ (suppressor) T-cell numbers remained longitudinally constant, on average, in all ML-challenged groups (vaccinated or not) compared to controls; 5) there was a significant decrease in the CD4+:CD8+ ratio over time in all ML-challenged groups (vaccinated or not); 6) vaccination with BCG or BCG + LD or HD HKML resulted in significantly increased numbers of CD4+CD45RA+ (suppressor-inducer) T cells longitudinally compared to the unvaccinated, ML-challenged control group; and 7) over time, vaccination with BCG + HKML followed by live ML-challenge produced higher IGM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody response ratios than BCG-only vaccinated, ML-challenged monkeys or unvaccinated, ML-challenged SMM, consistent with prior observations that IgG anti-PGL-I responses correlate with resistance to and protection from clinical leprosy and IgM anti-PGL-I responses correlate with increased susceptibility.

Animals↗
PubMed1986

Monocyte migration explains the changes in macrophage arachidonate metabolism during the immune response.

The profile of arachidonic acid metabolites in resident peritoneal macrophages is distinctly different from the profile of macrophages isolated after an acute bacterial infection. The latter produce decreased prostaglandins E2 and I2 and leukotriene C4 while conserving the synthesis of thromboxane A2. We show here that the initial changes in peritoneal macrophage arachidonate metabolism during the immune response appear to be the result of the large influx of blood monocytes, which have a characteristic metabolism distinct from resident macrophages. We demonstrate that the initial decrease in peritoneal macrophage arachidonate metabolism and the increase in macrophage numbers occur simultaneously after infection with Listeria monocytogenes. Also the macrophage arachidonate metabolism seen at the height of the peritoneal cellular influx is the same as that of purified blood monocytes. Both Listeria peritoneal macrophages and blood monocytes produce equal or greater quantities of thromboxane A2 relative to prostaglandins I2 and E2 or leukotriene C4 whereas resident cells produce 1/10 to 1/25 as much thromboxane A2 compared to the other products. Furthermore, the changes in peritoneal macrophage arachidonate metabolism in response to Listeria infection do not occur if the influx of blood monocytes is stopped by irradiating the mice prior to infection implying that the cellular influx is necessary to see the changes in arachidonate metabolism. Finally, activation of peritoneal macrophages, measured as an increase in Ia expression, occurs 36 hr after the influx of monocytes from the blood and the resultant shift in arachidonate metabolism during Listeria infection.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Social economics of childhood glucocorticoid stress response and health.

This study examines socioeconomic conditions, psychosocial stress, and health among 264 infants, children, adolescents, and young adults aged 2 months to 18 years residing in a rural Caribbean village. Fieldwork was conducted over a 9 year period (1988-1996). Research methods and techniques include salivary cortisol radioimmunoassay (N = 22,438), systematic behavioral observations, psychological questionnaires, health evaluations, medical records, informal interviews, and participant observation. Analyses of data indicate complex relations among socioeconomic conditions, stress, and health. Household income, land ownership, parental education, and other socioeconomic measures are weakly associated with child illness. There is no evidence that apparent material benefits of high socioeconomic status--such as improved housing, diet, work loads, and access to private healthcare--have important direct effects on child health in this population. However, social relationships, especially family environment, may have important effects on childhood psychosocial stress and illness. Abnormal glucocorticoid response profiles, diminished immunity, and frequent illness are associated with unstable mating relationships for parents/caretakers and household composition. We suggest that family relationships and concomitant stress and immunosuppression are important intermediary links between socioeconomic conditions and child health.

Adolescent↗
PubMedDate not supplied

Classification of chemical allergens according to cytokine secretion profiles of murine lymph node cells.

Characteristic cytokine secretion profiles, consistent with the selective activation of discrete functional subpopulations of T helper (Th) cells, have been demonstrated following repeated topical exposure of mice to chemical contact or respiratory allergens. Draining lymph node cells (LNC) derived from animals treated with the respiratory allergen trimellitic anhydride (TMA; 10%) expressed high levels of the Th2 cytokines interleukins 4 and 10, but little of the Th1 cell product interferon gamma. Under conditions of exposure of equivalent immunogenicity with respect to LNC proliferation, the contact allergen 2,4-dinitrochlorobenzene (DNCB) provoked the converse pattern of cytokine secretion. The purpose of the present investigations was to examine dose-response relationships with respect to cytokine production with a wider range of chemical allergens. In each case, cytokine secretion patterns were compared with those observed with LNC prepared from animals exposed concurrently to TMA or DNCB. Despite some inter-experimental variation in the absolute amounts of cytokines produced, DNCB- and TMA-activated LNC invariably expressed Th1- and Th2-type patterns, respectively. At all concentrations tested, the contact allergens isoeugenol and formaldehyde stimulated a Th1-type cytokine secretion profile, whereas a Th2-type pattern was induced following exposure to the chemical respiratory allergens cyanuric chloride and diphenylmethane diisocyanate. These data demonstrate that divergent cytokine secretion profiles characterize immune responses to different classes of chemical allergen and suggest that it may be possible, in a single integrated assay, to identify and classify chemical allergens as a function of induced cytokine production patterns.

Allergens↗
PubMed1981

Primary and secondary in situ antibody response: abnormal affinity maturation pattern in mice carrying the xid gene.

The xid gene in mice controls a recessive defect resulting in the absence of a late maturing subset of B cells. Whereas the responsiveness pattern of these mice have been clearly defined in terms of their ability or inability to make antibodies to certain classes of thymus-independent antigens, there are conflicting reports in regard to affinity maturation of the antibody response to thymus-dependent antigens. To resolve this controversial issue, the two major isotypes of the IgG response, namely IgG1 and IgG2a were examined with a highly sensitive radioimmunoassay that measures both the magnitude and affinity of the anti-2,4-dinitrophenyl antibody of each isotype in individual serum samples. It was found that the xid gene reduced the amount but not affinity of the IgG1 antibody produced, whereas it impaired the whole IgG2a responses severely. In fact, mice carrying the defective gene were unable to mount a secondary IgG2a response, measured either quantitatively or qualitatively in terms of increased affinity. To test the possibility that Lyb3, an isogenic B cell-triggering receptor lacking in xid-mutant mice, plays a direct role in the maturation of the immune response, the antibody profile in normal mice immunized eigher with antigen alone or in combination with anti-Lyb3 receptor substantially elevated and accelerated the primary IgG2a response, whereas it had little effect on the IgG1 response.

Animals↗
PubMed2006

Arthritis induced with cartilage-specific antibodiesis IL-4-dependent.

It is widely believed that IL-4 exerts its influence by profiling the immune response during priming and expansion of immune cells, and thereby modulates the outcome of chronic inflammation. In the present investigation, collagen antibody-induced arthritis (CAIA) was used to delineate the role of IL-4 in a T cell-independent inflammatory phase. Mice predisposed to Th2 cytokines (BALB/c and STAT4-deficient mice) developed a more severe arthritis than mice biased towards Th1 cytokines (C57BL/6 and STAT6-deficient mice). Reduced incidence of CAIA was observed in IL-4-deficient mice compared to control littermates. Infiltrating cells in the paws of IL-4-sufficient mice had increased osteoclast activity and tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion. Massive infiltration of granulocytes and joint and cartilage damage were present in arthritic paws. Depletion of IL-4 suppressed CAIA, which was abrogated by IFN-gamma neutralization. IL-1R- and IL-1RTNFR-deficient mice were completely resistant to CAIA. Thus, IL-4 promotes an antibody-mediated and TNF-alpha/IL-1beta-dependent inflammation in vivo.

Animals↗
PubMed1991

Adaptation and serial passage of porcine group C rotavirus in ST-cells, an established diploid swine testicular cell line.

A porcine group C rotavirus (strain Cowden-AmC-1) was adapted and serially passaged in an established diploid swine testicular cell line (ST cells). Growth of group C rotavirus in ST cells, which in maintenance medium required trypsin, but not pancreatin resulted in cytopathic effect characterized by cellular stranding and subsequent cell lysis. Active replication and assembly were confirmed by RNA profile analysis, immune electron microscopy and immunofluorescence. Adaptation of non-group A rotavirus to a continuous cell line has not previously been reported and should facilitate progress in diagnostic procedures and vaccine development.

Adaptation, Physiological↗
PubMed2026

Integrative analysis and experiment validation of SLC12A8 as a biomarker for the malignant transition from endometriosis to endometriosis associated ovarian cancer.

Endometriosis (EM) is a chronic inflammatory, estrogen‑dependent benign gynecological disorder. A subset of patients with EM may subsequently develop endometriosis‑associated ovarian cancer (EAOC), implying a biological continuum between these two conditions. Nevertheless, the molecular events underlying the progression from benign endometriotic lesions toward EAOC remain incompletely characterized. In this study, transcriptomic datasets retrieved from the GEO database were interrogated through differentially expressed gene screening, functional enrichment analysis, and weighted gene co‑expression network analysis (WGCNA) to identify key genes and pathways relevant to EM and EAOC. Candidate genes were further prioritized by integrating survival analysis via the Kaplan‑Meier Plotter, LASSO regression, random‑forest modeling, and CIBERSORT immune‑infiltration profiling. Loss and gain‑of‑function cellular models were established using siRNA and overexpression plasmids, and in‑vitro functional assays were performed to characterize the phenotypic effects of target genes.We identified several candidate genes associated with EM and EAOC and evaluated their discriminatory performance. Among them, SLC12A8 elevated expression across EM and EAOC tissues and exhibited moderate diagnostic capacity. Higher SLC12A8 expression was also associated with poorer prognosis in EAOC patients. In‑vitro experiments further demonstrated that SLC12A8 modulates proliferation, invasion, and migration in both EM and EAOC cell lines. Collectively, our exploratory research findings support SLC12A8 as a candidate functional mediator and potential biomarker linked to EM‑EAOC pathological progression, thereby extending the mechanistic understanding of these disorders.

Female↗
PubMed1995

Oral and parenteral vaccination against Trichinella spiralis infections in high- and low-responder mice.

Vaccination by different routes and with different adjuvants is known to influence profiles of immune responses and may be used to overcome genetically determined low-responsiveness to infection. A mouse model of infection with the intestinal nematode Trichinella spiralis was used to investigate the effect of mode of vaccination upon immune responsiveness and worm expulsion phenotype in high- (NIH) and low- (C57 BL/10) responder strains of mice. Muscle larval homogenate antigen was given subcutaneously in Freund's complete adjuvant (FCA) to induce a systemic immune response or with cholera toxin (CT) orally to stimulate mucosal immunity. Both approaches significantly protected NIH mice. Vaccination with FCA was correlated with elevated serum IgG after infection, whereas oral CT-vaccination resulted in increased levels of intestinal IgA. Neither type of vaccination successfully protected the low-responder C57 BL/10 strain and there were no effects on the low antibody levels that infection induced in this strain.

Administration, Oral↗
PubMed1991

The impact of naturally occurring DR3 microvariants, DRw17 and DRw18, on T-cell allorecognition.

The limited amino acid sequence differences between the DR3 microvariants, DRw17 and DRw18, are found in the second variable region of the DR beta chain (residues 26 and 28) as well as in framework residues 47 and 86. Using selected responder/stimulator combinations, alloproliferative T-lymphocyte clones (TLC) were generated which recognize either a supertypic DR3-related determinant(s) or only those T-cell recognition determinants created by the four amino acids which differ between DRw17 and DRw18. Results indicate that the microvariation creates potent T-cell recognition determinants while leaving the DR3-related determinant(s) unaffected. Several TLC were generated which recognize the DRw18 molecule strongly and the DRw52c molecule weakly reflecting the sequence similarity between these molecules. In addition, one TLC was generated which recognizes DRw18 and DRw14,Dw9 but not DRw14,Dw16 molecules, a result not predicted by linear amino acid sequence comparisons. The intricate and sometimes unpredictable allorecognition patterns observed demonstrate that the molecular context of a specific amino acid sequence is as important as the actual sequence in forming a T-cell recognition site and, thus, in shaping the immune response profile of a given allele.

Antibodies, Monoclonal↗