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At least 109 records · Page 6Linked to original sources

Augmentation of natural immunity and correlation with tumor response in melanoma patients treated with human lymphoblastoid interferon.

Thirty-two melanoma patients treated with lymphoblastoid alpha interferon (Wellferon) were studied for augmentation of five putative parameters of natural immunity including natural killing (NK), antibody-dependent cellular cytotoxicity (ADCC), cell-mediated inhibition of growth in culture of a murine tumor (GIA), and the size of the OKTIO+ and Leu 7+ subpopulations of peripheral blood mononuclear cells (OKTIO and Leu7). This study confirms and extends our previous conclusions that interferon increases GIA and OKTIO. The increases occurred at 24 hr after interferon, both early and late in the course of treatment, and were dose dependent. NK, ADCC, and Leu7 were activated in many patients individually and mean values for NK and Leu7 were increased in the population as a whole. Two patients with complete remission showed dramatically increased natural immunity by the parameters studied, but the pattern of increase was very different for each patient. The current study of lymphoblastoid alpha interferon demonstrates the immunomodulatory potential of interferon given to melanoma patients, but it fails to support the hypothesis that augmentation of these parameters of natural immunity by interferon may result in tumor responses.

Antibody-Dependent Cell Cytotoxicity↗

Acute immune polyneuropathies: correlations of serum antibodies to Campylobacter jejuni and Helicobacter pylori with anti-GM1 antibodies and clinical patterns of disease.

Antecedent Campylobacter jejuni infection, detected by serologic tests, has been implicated in some acute immune polyneuropathies (AIP). Antibodies to Helicobacter pylori, C. jejuni, and GM1 ganglioside were measured in sera from 35 Chinese patients with AIP. Anti-GM1 antibodies were found in 54% of C. jejuni-seropositive, H. pylori-seronegative patients. In contrast, anti-GM1 antibodies were rare in sera that were either seropositive for both C. jejuni and H. pylori (P = .04) or seronegative for C. jejuni (P = .01). Motor axonal AIP was more common in the C. jejuni-seropositive, H. pylori-seronegative patients (82%) than in the bacterial antibody-negative group (38%). It was concluded that in AIP patients, C. jejuni-positive sera may be polyreactive, in that it may also react with H. pylori. In this situation, the specificity for either infection requires further validation. In contrast, sera with specific C. jejuni seropositivity are associated with both motor axonal AIP and selective serum IgG anti-GM1 antibodies.

Antibodies, Bacterial↗

Humoral immunity and correlation between ELISA, hemagglutination inhibition, and neutralization tests after vaccination against tick-borne encephalitis virus in children.

Vaccination against tick-borne encephalitis (TBE) virus is the measure of choice for disease control in endemic areas, as no treatment is available. In Italy, the province of Belluno is one of the most active TBE virus infection foci. In this study sera were examined from vaccinated children living in areas around Belluno in order to monitor the immune response after anti-TBE vaccination. For the assessment of neutralizing antibodies, a plaque reduction neutralization test (PRNT) was optimized and the correlation between enzyme-linked immunosorbent assay (ELISA), hemaglutination inhibition (HI), and neutralizing antibodies titers was evaluated. All children had high serum levels of TBE IgG in ELISA test after the vaccination, in agreement with previous studies. HI and PRNT titers ranged between very low and high levels. A good correlation between HI and PRNT titers, and with IgG ELISA titers, was observed. PRNT is an useful assay for monitoring protective immunity after the completion of anti-TBE vaccination. This type-specific assay is an important tool for differential diagnosis in cases where the presence of cross-reactive antibodies due to other flavivirus infections or vaccinations cannot be excluded.

Antibodies, Viral↗

Correlation of immune defects in hemophilia with HTLV-III antibody titers.

Of 170 hemophilia patients, 22% had high-titer, 29% had low-titer, and 49% had no antibodies against HTLV-III. The strength of HTLV-III antibodies was correlated significantly with a decreased OKT4/T8 ratio (p less than 0.0005), decreased in vitro response to pokeweed mitogen (p less than 0.025), and elevated serum neopterin (p less than 0.05) and serum IgG (p less than 0.0005). The fraction of patients with abnormal immunological findings was consistently greater among patients with high-titer than among patients with low-titer HTLV-III antibodies. Testing these immunological parameters may be useful for monitoring the breakdown of immune functions leading to AIDS.

Acquired Immunodeficiency Syndrome↗

Apoptosis correlates with immune activation in intestinal lymphoid tissue from macaques acutely infected by a highly enteropathic simian immunodeficiency virus, SIVsmmPBj14.

The PBj14 isolate of simian immunodeficiency virus, SIVsmmPBj14, induces an acutely lethal disease in experimentally inoculated pigtailed macaques, that is characterized by severe enteropathy and extensive immune activation, particularly within gut-associated lymphoid tissue (GALT). Experiments were conducted to determine whether virally induced immune activation might promote the induction of apoptosis in GALT during acute SIVsmmPBj14 infection. In situ labeling studies revealed a significant increase in the number of apoptotic cells within GALT from macaques with acute SIVsmmPBj14 infection, compared to (i) other tissues from the same animals, (ii) GALT from virus-negative animals, or (iii) GALT from macaques that were sacrificed soon after infection with SIVmac239, which does not cause acutely lethal enteropathy. These findings were confirmed by biochemical assays of DNA fragmentation, using DNA laddering and ELISA techniques. Immunostaining experiments revealed a strong positive correlation between the extent of apoptosis and the degree of immune activation, as assessed either by the number of cells which contained nuclear (activated) RelA or by the number of cells immunoreactive for CD25, a T-cell activation marker. Additional analyses of SIV antigen expression revealed that the majority of the apoptotic cells were not productively infected by SIV (i.e., that they were bystander cells). Taken together, these findings support the hypothesis that SIVsmmPBj14 efficiently induces immune activation and that this results in extensive apoptosis within gut-associated lymphoid tissue during acute viral infection.

Animals↗

[A study on the correlation between immune responses and histopathological changes of primary lesion in patients with cervical cancer following radiation therapy (author's transl)].

From an immunological viewpoint, histological changes of stromal cell reactions and regional lymph nodes were observed in uterine cervical cancer patients who received test irradiation. Delayed cutaneous hypersensitivity reaction, peripheral lymphocyte blastoid transformation, and peripheral lymphocyte subpopulations were also studied. 1) The variation of stromal reaction after test irradiation was analogous to that of delayed cutaneous hypersensitivity. 2) There was a significant correlation between the degree of stromal reaction and skin reactivity to PPD and PHA. Stromal reaction increased in proportion to PPD skin reactivity after test irradiation. 3) The degree of stromal reaction was not correlated with the ability of lymphocyte blastoid transformation and peripheral T-lymphocyte counts. 4) The prognosis was good in the cases that showed marked stromal reaction and greater enlargement of the regional lymph nodes. 5) The radiosensitivity score was correlated to PPD skin reactivity. From these observations, it was presumed that the host immunity had an effect on the curative course of uterine cervical cancer and stromal reaction was one of the histological parameters that demonstrated immune reactions.

Cervix Uteri↗

Immunopathological aspects of experimental Trypanosoma cruzi infection: correlation of immune complexes and other serological features with muscle lesions during the infection.

The pathogenesis of the tissue lesions observed in American trypanosomiasis (Chagas' disease) seems to depend on a variety of mechanisms. The present study was dedicated to the investigation of the evolution of muscle lesions and its relationship with immunological and parasitological parameters. Mice were infected i.p. with 10(5) blood forms of Trypanosoma cruzi (Columbian strain). A progressive increase in parasitaemia was observed which correlated with an increase in serum levels of IgG and IgM Trypanosoma-specific antibodies. Immune complex like material was detected in the serum (125I-C1q binding assay) on day 8 and reached maximum level between day 21 and 28. A concomitant fall in C3 levels was also observed. Inflammatory lesions and parasites were first observed in the striated muscle 2 weeks after infection. The cellular infiltrates involved macrophages and lymphoid cells; later on (week 3 onwards), intense necrosis appears and at the same time immunoglobulin and complement deposition were observed. These observations may indicate that, in addition to the cellular immune response, humoral mechanisms could contribute to the worsening of tissue lesions.

Animals↗

JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy.

Most immunosuppressed individuals who develop progressive multifocal leukoencephalopathy (PML) have a rapid fatal outcome, whereas some become long-term survivors. We explored the impact of the cellular immune response against JC virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals with PML. Of the 4 HIV+/PML survivors, all had detectable cytotoxic T lymphocytes (CTL) specific for JCV T or VP 1 proteins compared to none of the 3 HIV+/PML progressors tested. Of the 3 HIV-/PML patients, 1 was recently diagnosed with PML and showed evidence of neurologic improvement without any treatment. This patient had CTL specific for the VP1 protein of JCV. The other 2 HIV-/PML survivors were stable 3-8 years after the diagnosis of PML. They did not have any detectable CTL against JCV. These findings suggest that JCV-specific immune response is associated with favorable outcome in HIV+ individuals with PML. The lack of detectable JCV-specific CTL in 2 HIV-/PML survivors might indicate a burnt-out disease without sufficient antigenic stimulation to maintain the cellular immune response. The detection of JCV-specific CTL in an HIV- patient recently diagnosed with PML, who was showing evidence of neurological improvement without any treatment, indicates that this finding may be used as a favorable prognostic marker of disease evolution in the clinical management of patients with PML. As the quest for an effective treatment of PML continues, JCV-specific cellular immune response deserves further attention because it appears to play a crucial role in the prevention of disease progression.

AIDS-Related Opportunistic Infections↗

Durable human memory T cells quantifiable by cultured enzyme-linked immunospot assays are induced by heterologous prime boost immunization and correlate with protection against malaria.

Immunological memory is a required component of protective antimalarial responses raised by T cell-inducing vaccines. The magnitude of ex vivo IFN-gamma T cell responses is widely used to identify immunogenic vaccines although this response usually wanes and may disappear within weeks. However, protection in the field is likely to depend on durable central memory T cells that are not detected by this assay. To identify longer-lived memory T cells, PBMC from malaria-naive vaccinated volunteers who had received prime boost vaccinations with a combination of DNA and/or viral vectors encoding the multiepitope string-thrombospondin-related adhesion protein Ag were cultured in vitro with Ag for 10 days before the ELISPOT assay. Ex vivo T cell responses peaked at 7 days after the final immunization and declined substantially over 6 mo, but responses identified after T cell culture increased over the 6-mo period after the final immunization. Moreover, individual cultured ELISPOT responses at the day of challenge time point correlated significantly with degree of protection against malaria sporozoite challenge, whereas ex vivo responses did not, despite a correlation between the peak ex vivo response and magnitude of memory responses 6 mo later. This cultured assay identifies long-lasting protective T cell responses and therefore offers an attractive option for assessments of vaccine immunogenicity.

Cells, Cultured↗

Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know.

The field of vaccinology began in ignorance of how protection was instilled in vaccine recipients. Today, a greater knowledge of immunology allows us to better understand what is being stimulated by various vaccines that leads to their protective effects: that is, their correlates of protection. Here we describe what is known about the correlates of protection for existing vaccines against a range of different viral diseases and discuss the correlates of protection against disease during natural infection with HIV-1. We will also discuss why it is important to design phase 3 clinical trials of HIV vaccines to determine the correlates of protection for each individual vaccine.

AIDS Vaccines↗

RECQL correlates with immune infiltration and serves as a prognostic biomarker and therapeutic predictor in gastric cancer.

BACKGROUND: RecQ-like helicase (RECQL), a member of the RecQ-like DNA helicase family, plays a crucial role in maintaining genomic stability. However, its relevance in gastric cancer (GC) has not been fully investigated. This study aimed to explore the clinical significance, biological functions, and potential role of RECQL in the tumor immune microenvironment of GC through comprehensive bioinformatics analyses and in vitro experiments. METHODS: Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) regression were performed using public datasets [The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE150290] to identify key genes associated with GC progression. Subsequently, key pathways were identified through functional enrichment analysis, while immune infiltration and spatial transcriptomic analyses were conducted to characterize RECQL expression and its association with the tumor immune microenvironment. Finally, the effects of RECQL knockdown on the biological function of GC cells were assessed through Cell Counting Kit-8 (CCK-8), colony formation, scratch, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: RECQL was significantly upregulated in GC tissues and correlated with advanced clinical stage and poor prognosis. Gene set enrichment analysis (GSEA) revealed a strong association between high RECQL expression and DNA repair pathway. Immune infiltration analysis indicated significant enrichment of M2 macrophages in the high-RECQL group, along with upregulation of immune checkpoint molecules including PDCD1, CTLA4, and CD274. Spatial transcriptomics further demonstrated co-localization of RECQL with myeloid cell-enriched regions in tumor parenchymal areas. Furthermore, in vitro experimental results indicated that RECQL was highly expressed in GC cell lines, and its knockdown effectively inhibited the viability, proliferation, and migration capabilities of HGC-27 cells, while enhancing their apoptosis. CONCLUSIONS: RECQL serves as a promising biomarker and potential therapeutic target in GC.

DNA repair↗

Lessons learned from HIV treatment interruption: safety, correlates of immune control, and drug sparing.

Therapeutic approaches seeking to limit the exposure to antiretroviral drugs while retaining the benefits of continuous therapy have become an active area of investigation in HIV therapy research. Although early attempts to use interruptions of therapy as auto-vaccination strategies have shown little success, much has been discovered in regards to immunological correlates of viral control in acute and chronic infection, viral evolution, and the safety of single or multiple therapy interruptions in different patient sub-groups (acutely infected, chronically infected, and multi-drug resistant). Here we review safety data and candidate factors that may contribute to the striking differences observed between patients that undergo similar treatment interruption strategies but achieve different outcomes in controlling HIV replication. Differences between acute and chronic infection in the viral component (e.g. diversity of the viral pool) and the host immune system (e.g. low avidity CTL memory response), which may not be reversed by ART, may determine the potential for suppressive immune response upon therapy interruption. Consistent with goals of limiting toxicity and cost of antiretroviral drug regimens, safety outcomes to date indicate that intermittent therapy strategies may safely continue to be investigated in early and chronically infected patients. Based on ongoing research, we identify the topics to be targeted in future studies.

Anti-HIV Agents↗

The severity of immune neutropenia correlates with the maturational specificity of antineutrophil antibodies.

Sera from 15 patients with antineutrophil antibodies against peripheral blood neutrophils were incubated with normal bone marrow, and the reaction with marrow precursors was determined. Serum from controls did not deposit IgG on either peripheral blood or marrow myeloid cells. Serum from patients with moderate immune neutropenia with myeloid hyperplasia deposited IgG on neutrophils, bands and metamyelocytes, but not on earlier precursors. Serum from one patient with severe neutropenia and myeloid hypoplasia deposited IgG on myelocytes and promyelocytes as well as more mature cells. Serum from a patient with antineutrophil antibodies which impaired chemotaxis but who did not have neutropenia deposited IgG only on neutrophils and occasional bands. Immune neutropenia may become increasingly severe as antibodies become directed against earlier precursors.

Agranulocytosis↗

Correlation of Immune Responses Mediated by T Helper 1 and 2 in Children with Viral Encephalitises.

This work deals with the problem concerning the mechanisms of triggering the demyelinating process by viruses as the consequence of molecular mimicry between viral antigens and the immunodominant region of the myelin basic protein with the subsequent involvement of reactions, mediated by T helper cells 1 and 2. Special emphasis is made on the new data indicating that reagin mechanisms play an active role in the development of neuropathology, corresponding to the results obtained by the authors in the study of humoral response in multiple sclerosis patients. Thus, the presence of pronounced total and specific IgE response was established to myelin basic protein, correlating with more severe clinical manifestations of the disease. Taking into account the viral nature of the demyelinization, the authors studied a number of humoral characteristics of immune response, indicating the degree of the involvement of T helper cells 1 and 2 into the pathogenesis of acute viral encephalitises. The determination of these characteristics was carried out with the use of original methods developed by the authors. The analysis of the results obtained in this study revealed the obvious presence of relationship between the involvement of autoimmune and atopic response in children with acute viral encephalitises and the manifestation of molecular mimicry of corresponding viruses with the immunodominant region of myelin basic protein. The most prognostically unfavorable group was the group of children having rubella, adenovirus and herpetic encephalitises.

Journal Article↗

The phenotype of alveolar macrophages and its correlation with immune cells in bronchoalveolar lavage.

The phenotype of alveolar macrophages (AMs) is known to be modulated during pathological immune reactions in the lung. In this study, we wanted to determine the relationship between the AM phenotype and changes in the proportions of the various immune cells in bronchoalveolar lavage (BAL). BAL was performed in 76 consecutive patients, including 32 with sarcoidosis, 8 with idiopathic pulmonary fibrosis, 9 with pneumoconiosis, 13 with other respiratory disorders, and 14 controls without evidence of interstitial lung disease. The phenotype of AMs was studied by a panel of 15 monoclonal antibodies against various myeloid antigens, and was correlated with the proportions of cells obtained by BAL. The percentage of BAL lymphocytes showed a relationship with the expression of macrophage antigens in 11 out of 15 antigens studied (all except adhesive molecules CD11a, CD11c, CD18 and the antigen 25F9 present on mature macrophages). Furthermore, the CD4/CD8 ratio of BAL T-lymphocytes correlated with the AM expression of CD54 (intercellular adhesion molecule-1 (ICAM-1)), RFD1 (marker of dendritic cells), and CD71 (transferrin receptor). In samples with an increased number of bronchoalveolar neutrophils, the subpopulation of 27E10 positive AMs (inflammatory acute phase macrophages) was increased. Eosinophils in BAL were not associated with a significant increase in AM membrane antigen expression. Prominent changes of the AM phenotype were found in active sarcoidosis showing lymphocytic alveolitis, with more frequent expression of CD54, KiM2, CD71, CD11b and RFD9. In conclusion, this study shows that the phenotype of AMs is related to the type and intensity of the immunopathological reaction in the lung, and correlates with the proportions of bronchoalveolar cells.

Antigen Presentation↗

Tryptophan degradation in patients with gynecological cancer correlates with immune activation.

Tryptophan degradation by the enzyme indoleamine-(2,3)-dioxy genase (IDO) and neopterin production are induced within cellular immune activation by stimulation of monocyte-derived macrophages and dendritic cells with cytokine interferon-gamma. Deprivation of tryptophan represents an important antimicrobial and antitumoral immune defence mechanism but it also suppresses T-cell proliferation. Recently tryptophan degradation by tumor cells was proposed as strategy to escape immune response. In this study the relationship between tryptophan degradation and immune activation was examined in 20 patients with gynecological cancer. Concentrations of tryptophan and kynurenine were measured by HPLC in sera of patients, and to estimate IDO activity, the kynurenine to tryptophan ratio was calculated. In parallel, neopterin concentrations were measured by ELISA. Tryptophan concentrations (median, interquartile range: 43.5, 31.2-56.3 microM) were lower in patients with gynecological cancer compared to healthy individuals of similar age (53.5, 47.0-64.2 microM; P<0.05). Kynurenine concentrations (median: 1.91 vs. 1.73 microM in controls) and kyn/trp (median: 41 vs. 35 micromol/mmol in controls) were slightly higher in patients, but not significantly different. Neopterin concentrations were significantly higher in patients (median: 10.8 vs. 7.0 nM in controls; P<0.05) and correlated with the kynurenine per tryptophan ratio (r(s)=0.555; P<0.02). In conclusion, tryptophan degradation is detectable in patients with gynecological cancer. The relationship between kyn/trp and neopterin concentrations indicates that cellular immune activation rather than tumor-mediated IDO-activity is responsible (228 words).

Adult↗

Correlation of immune complexes in disseminated neuroblastoma with serum antibody to bovine serum albumin.

To evaluate the relationship between tumor burden and circulating immune complexes (IC) in children with neuroblastoma (NBL), we studied sera collected at intervals from patients with disseminated (Stage III or IV) NBL. Sera from 10 of 12 patients contained IC by the Raji cell assay at some time during the first 9 to 11 months of the study. Higher IC levels were observed in sera of female patients. Fluid-phase C1q binding tests detected IC in only 16% of sera. IC measurements by either assay did not correlate with tumor burden. However, serum IC levels, as measured by the Raji cell assay, correlated significantly with serum antibody to bovine serum albumin (BSA) (rs = 0.54; p less than 0.001, rs = r as determined by Spearman rank correlation test). Measurement of anti-BSA antibodies in sera from the 12 patients, tested serially for circulating IC, and from five additional patients revealed that these had significantly higher anti-BSA activity than was found in sera from 13 age-matched controls. Sera from females also had relatively high levels of anti-BSA. Levels of antibody to bovine gamma-globulin and casein were not abnormal. Three sera with high IC levels (greater than 800 micrograms equivalents of heat-aggregated IgG) and relatively low anti-BSA activity appeared to contain "hidden" antibodies to BSA. These were demonstrated by measuring the increase in the ability of sera to bind 125I-BSA after they had been briefly acidified and then neutralized in the presence of the labeled BSA. The possible relevance of these results to the pathophysiology of NBL is discussed in light of earlier work that reported that serum IC levels correlate with the stage of the disease in NBL.

Animals↗