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Results for “Immune dysfunction”

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At least 127 records · Page 7Linked to original sources
PubMed1988

Human retroviruses and herpes viruses: their role in immune dysfunctions and neoplasia.

Human retroviruses (HTLV-I, HTLV-II, HIV-1, and HIV-2) and some human herpes viruses (notably EBV and HHV-6 or HBLV) infect chiefly target cells of the immune system. They can alter function of these cells, leading to many side effects, including mild (HTLVs), transient (EBV, HHV-6), or profound (HIVs) immune impairment with the associated clinical consequences. The retroviruses can also cause injury to the central nervous system but the mechanisms are poorly understood. An almost opposite effect of all of these immunocytotropic viruses is their capacity to directly induce abnormal cell growth of their target cells or indirectly of other cells. In addition to their importance in human disease, studies of these viruses are helping to provide new insights into the molecular mechanisms of gene regulation, fundamental aspects of the immune system, and of the origin, cellular and molecular pathogenesis of human tumors.

Deltaretrovirus↗
PubMedDate not supplied

Invited comment: lipids and the development of immune dysfunction and infection.

Excessive W-6 PUFA metabolism due to high levels of dietary fat intake can encourage infection via prolonged inflammation, enhanced Gram negative survival, reticuloendothelial blockage, immunosuppression, and monokine depression. Lipids can influence host immunity by altering eicosanoid metabolism and membrane structure and function. Further investigations are essential to answer questions regarding the levels and properties of various essential fatty acids in TPN lipid emulsions. Combining the features of LCT in the form of W-3 PUFA (fish oil) and MCT in the form of medium-chain triglyceride in a "structured lipid" may decrease infection and may improve survival rates by producing fewer inflammatory eicosanoids of the two- and four-series, and serving as a more "efficient fuel." The introduction of W-3 polyunsaturated fatty acids into the TPN emulsions as well as into normal diets may provide an important therapeutic advance in the pathogenesis of disease. Such unique antiinflammatory properties of W-3 PUFA require intensive research.

Animals↗
PubMed2000

Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non-Hodgkin's lymphoma patients.

OBJECTIVE: In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. MATERIALS AND METHODS: We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. RESULTS: Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-gamma and tumor necrosis factor-alpha were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-gamma were decreased significantly on day 365 compared with pretransplant levels. CONCLUSIONS: The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine.

Adult↗
PubMed1997

Immune dysfunction in patients with obstructive jaundice, mediators and implications for treatments.

Patients with obstructive jaundice have an increased perioperative complication rate. Sepsis, bleeding, wound problems, renal and liver malfunction are all seen in these patients. Assessment of immune function has been an active research area in these patients. This review will examine various aspects of immune functions in obstructive jaundice, discuss the recent research results and controversies and then go on to discuss the relevant mediators of immune function and some possible implications for treatment.

Animals↗
PubMedDate not supplied

Immune dysfunction in experimental versus naturally occurring neurofibromatosis in damselfish.

Damselfish neurofibromatosis [DNF], a neoplastic disease characterized by multiple, neurofibromas and malignant schwannomas, is currently the only naturally occurring animal model of human neurofibromatosis type-1. Previous studies of immune function in DNF affected fish indicated the potential for significant immunosuppression in advanced stages of the disease. The current study compares healthy animals with fish captured in the wild bearing spontaneous tumors and with animals bearing experimental tumors transmitted in the laboratory. In order to determine the effects of tumor burden on the immune capabilities of these animals, proliferative responses to mitogens and toward allogeneic cells were tested. The data presented here indicate that animals bearing advanced tumors of experimental origin are profoundly immunocompromised. Similarly, some spontaneous tumor-bearing animals are deficient in proliferative immune responses, and splenocytes from most animals fail to respond to mitogens. However, a proportion of animals with stage 5 spontaneous tumors retain immune reactivity, and are capable of alloreactions comparable to those of normal individuals when stimulated with cells from healthy [4/10, 40%] or other tumor-bearing [4/8, 50%] animals. The contributions of tumor size, distribution and cytokine production to the differential immune impairment are discussed.

Animals↗
PubMed2001

Central role of leukemia-derived factors in the development of leukemia-associated immune dysfunction.

INTRODUCTION: The underlying mechanism of tumor-associated T-cell dysfunction has been suggested to be due to an acquired abnormality in the T-cell receptor signaling complex, however, tumor-derived inhibitory factors acting on immune effectors could also explain the observed immunosuppression. Here, in a murine acute leukemia model, responses (proliferation and IL-2 secretion) to mitogens were suppressed in the early stages of leukemic progression due to a leukemia-derived soluble factor(s). MATERIALS AND METHODS: Correlations between the development of immunosuppression and changes in expression of TCR signaling proteins (CD3-zeta, p56(lck), p59(fyn)), calcium mobilization, and total tyrosine kinase activity following TCR stimulation were examined. RESULTS: In contrast to reduced responses to mitogens seen as early as 1 week following injection of leukemic cells, signaling abnormalities were only seen in advanced disease (ie four weeks). The only significant alteration in signaling protein expression was loss of CD3-zeta for four weeks following the initiation of leukemia. Importantly, a direct role of a leukemia-derived soluble factor(s) in the loss of CD3-zeta could be shown in vitro by co-culturing splenocytes with leukemic cells separated by a transwell for seven to 10 days. Further studies demonstrated that the leukemia-derived factor(s) stimulated splenic macrophages to secrete a second soluble factor(s) that caused the loss of CD3-zeta. CONCLUSION: These data indicate that soluble leukemia-derived factor(s) have both immediate immunosuppressive actions and a later effect acting indirectly to induce intrinsic defects in T-cell signaling pathways via accessory cells. In some tumors, there is evidence that the soluble factor is Fas-ligand, which induces apoptosis in tumor-infiltrating T cells and the action of activated caspases cleave CD3-zeta. In this model, the soluble factor prevents apoptosis indicating a second mechanism is responsible for the loss of T-cell signaling proteins.

Acute Disease↗
PubMed1992

Immune dysfunction following infection with chicken anemia agent and infectious bursal disease virus. I. Kinetic alterations of avian lymphocyte subpopulations.

The potential effect of chicken anemia agent (CAA) alone or in combination with infectious bursal disease virus (IBDV) on the immune system of young chickens was determined by measuring alterations in hematocrit values, lymphoid organ-to-body weight ratios and lymphoid cell concentrations at 4, 7, 10, 14, 17, 21, 28 and 42 days post-inoculation (PI). Lymphocyte subpopulations were identified and counted by flow cytometry using cell suspensions stained with monoclonal antibodies (Mabs) for panlymphocytes (K55), cytotoxic T-cells (CTLA3), T-helper cells (CT3), Ia-expressing cells (P2M11) and macrophages (P7). Chicken anemia agent induced a substantial but transient decrease in hematocrit value, thymus-to-body weight ratio and bursa-to-body weight ratio between 7 and 21 days PI corresponding to a generalized lymphocytopenia in the thymus, bursa and spleen. However, cytotoxic T-cell, T-helper cell and Ia-expressing cell concentrations increased in the bone marrow of birds inoculated with CAA alone or in combination with IBDV during the same time period. T-helper-to-cytotoxic T-cell ratios increased in the thymus and spleen during severe lymphocytopenia, indicating a selective decrease in cytotoxic T-cells. T-helper-to-cytotoxic T-cells ratios increased in the bone marrow, indicating a selective increase in T-helper cell concentrations. The increase in Ia-expressing cells in the bone marrow may be a reflection of increased number of activated T-cells which express Ia antigen. Infectious bursal disease virus alone induced a persistent depression of Ia-expressing cells in the bursa and the spleen and no measurable change in the bone marrow lymphocyte subpopulations. Chickens inoculated simultaneously with CAA and IBDV experienced clinical signs observed in chickens inoculated with each virus separately with a prolonged acute phase prior to recovery or mortality.

Animals↗
PubMed1999

Immune dysfunction in trauma.

This article documents that all immunomodulation strategies for patients sustaining traumatic injury are still under intense investigation. Although we can speculate that combination strategies may be more beneficial than single-agent immunomodulation approaches, comprehensive clinical studies are required to determine efficacious immune therapy for trauma patients. The only strategy available to clinicians caring for trauma patients is immunonutrition, and this should be strongly considered as a rational approach to improve immune function and reduce septic complications in critically ill or injured patients.

Adjuvants, Immunologic↗
PubMed1992

[Chronic fatigue immune dysfunction syndrome].

Chronic fatigue syndrome (CFS) is characterized by unexplained, debilitating fatigue or easy fatigability lasting longer than six months. While a viral basis of infection is proposed to be the cause of CFS, other viral infections do not generally persist after several weeks. Immunological disorders, including abnormal functions and distributions of T lymphocytes, B lymphocytes, natural killer (NK) cells, and monocyte/macrophages, are described in CFS. NK cells are known to play an important role in host resistance against viral infection as well as in the regulation of the immune systems. Restoration of NK activity resulted in recovery from CFS. Taken together, immunological abnormalities, especially dysfunction of NK cells, may be involved in CFS.

B-Lymphocytes↗
PubMed1999

Immune dysfunction in patients with diabetes mellitus (DM).

Patients with diabetes mellitus (DM) have infections more often than those without DM. The course of the infections is also more complicated in this patient group. One of the possible causes of this increased prevalence of infections is defects in immunity. Besides some decreased cellular responses in vitro, no disturbances in adaptive immunity in diabetic patients have been described. Different disturbances (low complement factor 4, decreased cytokine response after stimulation) in humoral innate immunity have been described in diabetic patients. However, the clinical relevance of these findings is not clear. Concerning cellular innate immunity most studies show decreased functions (chemotaxis, phagocytosis, killing) of diabetic polymorphonuclear cells and diabetic monocytes/macrophages compared to cells of controls. In general, a better regulation of the DM leads to an improvement of these cellular functions. Furthermore, some microorganisms become more virulent in a high glucose environment. Another mechanism which can lead to the increased prevalence of infections in diabetic patients is an increased adherence of microorganisms to diabetic compared to nondiabetic cells. This has been described for Candida albicans. Possibly the carbohydrate composition of the receptor plays a role in this phenomenon.

Antibody Formation↗
PubMed2026

Malignant epithelial states drive immune dysfunction in ampulla of Vater carcinoma.

BACKGROUND: Ampulla of Vater (AoV) carcinoma is a rare malignancy arising at the junction of intestinal and pancreatobiliary epithelium. Its heterogeneous clinical behavior and histological diversity have hindered therapeutic advances, and the cellular basis of this heterogeneity remains unclear. We aimed to construct a single-cell transcriptomic atlas of AoV carcinoma, with a focus on identifying epithelial subtypes and their interactions with the tumor microenvironment (TME). METHODS: We performed single-cell RNA sequencing on eight primary AoV tumors and four matched normal tissues. Comprehensive clustering and transcriptomic analyses identified cell-type composition, epithelial heterogeneity, and tumor-immune interactions. Findings were validated using deconvolution of bulk RNA-seq data from 62 AoV carcinoma patients. Results Malignant epithelial cells were categorized into four distinct subtypes: Int-Wnt, PB-KRAS, Int-Hypoxia, and Cycling stage. PB-KRAS cells exhibited stem-like transcriptional programs and high genomic instability. Deconvolution analysis of bulk RNA-seq data from the independent AoV cohort revealed that enrichment of the PB-KRAS subtype correlated with tumor recurrence and poor survival. Our immune profiling analysis discovered a significant association between PB-KRAS subtype and GZMK+ CD8+ T cells, which are in a pre-dysfunctional state, alongside SPP1+ macrophages exhibiting immunosuppressive traits. Spatial transcriptome data further supports the immunosuppressive natures of TME around PB-KRAS subtype malignant epithelial cells in AoV carcinoma. CONCLUSIONS: Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.

Ampulla of Vater carcinoma↗
PubMed1981

An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction.

Eleven cases of community-acquired Pneumocystis carinii pneumonia occurred between 1979 and 1981 and prompted clinical and immunologic evaluation of the patients. Young men who were drug abusers (seven patients), homosexuals (six), or both (two) presented with pneumonia. Immunologic testing revealed that absolute lymphocyte counts, T-cell counts, and lymphocyte proliferation were depressed, and that humoral immunity was intact. Of the 11 patients, one was found to have Kaposi's sarcoma, and another had angioimmunoblastic lymphadenopathy. Eight patients died. In the remaining three, no diagnosis of an immunosuppressive disease was established, despite persistence of immune defects. These cases of pneumocystosis suggest the importance of cell-mediated immune function in the defense against P. carinii. The occurrence of this infection among drug abusers and homosexuals indicates that these groups may be at high risk for this infection.

Adult↗