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Results for “Immune dysfunction”

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PubMed1988

Immune dysfunction in the critically ill infant and child.

Factors contributing to the high prevalence of immunodeficiency in the PICU population include conditions that lead to frequent requirement of intensive care, suppression of immunity secondary to an acute insult, and iatrogenic measures. The immunodeficiency observed in the critically ill correlates well with their susceptibility to infection and explains the high prevalence of nosocomial sepsis in the PICU--a major cause of morbidity and mortality in critically ill children. Dysactivation of the immune system during an acute insult, with the subsequent release of humoral mediators from activated immune cells, leads to tissue injury and may be involved in the pathogenesis of ARDS, DIC, capillary leak syndrome, and to the development of multiple organ system failure. Suggested approaches to correct the immunodeficiency in the critically ill include reconstitutional immunotherapy, mediator-inhibiting drugs, and mediator removal by plasma exchange. Intensivists should be aware of the phenomenon of immunodeficiency in the critically ill, be accordingly aggressive in diagnosing and treating infections, and avoid, as much as possible, measures that further suppress immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Reversal of immune dysfunction in osteopetrotic rats by interferon-gamma: augmentation of macrophage Ia expression and lymphocyte interleukin-2 production and proliferation.

Lymphocytes from osteopetrotic (op) rats, compared to their normal (n) littermates, exhibit defective immune functions associated with their inability to resorb bone. Among these immune defects are the failure of their spleen cells to proliferate normally to mitogens and to generate IL-2. Addition of exogenous IL-2 failed to reverse the suppressed proliferation in the op spleen cells, indicating that additional defects were involved in the suppression. Phenotypic analysis of cellular constituents of op and n spleens revealed that the percentages of T cells, macrophages, and IL-2 receptor positive cells were not different. Furthermore, there was no difference in CD4 (W3/25) and CD8 (OX8) cells. However, the Ia+ (OX3) cells in the op spleen represented less than 50% of those found in the n spleen, but the op had higher levels of transferrin receptor (OX26). On the basis of the ability of interferon-gamma (IFN-gamma) to increase Ia expression, this cytokine was added to op spleen cells (10-50 U/ml) and found to increase the number of Ia+ cells to the level found in n spleen cells. Moreover, pretreatment of op spleen cells with IFN-gamma restored their ability to proliferate to mitogens and their responsiveness to IL-2. Not only did IFN-gamma reverse the defective response to IL-2, but it also augmented the defective IL-2 production by op spleen cells. Taken together, these findings demonstrate that IFN-gamma can reverse many of the impaired immune functions characteristic of op spleen cells in vitro. Furthermore, these data suggest that IFN-gamma may provide an important avenue of treatment in these animals that may contribute to restoration of normal bone resorption.

Animals↗
PubMed1977

[Immune dysfunctions in aging (author's transl)].

The frequency of certain infectious diseases, autoimmune disorders and neoplasias reveals a correlation to age. Therefore, the potential pathogentic role of a series of humoral and cellular immune functions is discussed. The concentrations of immunoglobulins increase with age. Though the humoral immune response appears to be rather undisturbed, there is a definite and progressive reduction of delayed type hypersensitivity reactions in the elderly. Based upon own investigations the significance of cell-inherent factors on age-dependence of cell-mediated immunity is underlined, consisting of an age-correlated alteration of a T-cell subpopulation The increasing morbidity or mortality of infectious diseases, i.e. tuberculosis, salmonellosis and viral hepatitis in the older age-group, additionally, may be explained by a reduced cell-mediated immunity known to play an important role in immune defense mechanisms particulary in these diseases.

Adult↗
PubMed1991

Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors.

Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.

Aged↗
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↗
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↗
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↗
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↗
PubMed1990

Immune dysfunction expressed selectively on L3T4+ T cells in the tumor-bearing state.

Spleen cells from normal C3H/He or BALB/c mice generate cytotoxic T-lymphocyte (CTL) responses to both trinitrophenyl (TNP)-modified syngeneic cells (TNP-self) and allogeneic cells. In contrast, cells from these strains of mice bearing a syngeneic tumor failed to induce anti-TNP-self-CTL responses, although portions of the same responding cells generated comparable anti-allo-CTL responses to those induced by normal responding cells. Although anti-allo-CTL responses were inducible from only Lyt-2+ T-cell subset of responding cells from normal or tumor-bearing mice, induction of TNP-CTL responses required the participation of L3T4+ T-cell subset as well as Lyt-2+ CTL precursors. In addition, the fact that the addition of concanavalin A-stimulated culture supernatant to cultures of responding cells from tumor-bearing mice resulted in the induction of appreciable anti-TNP-self CTL responses demonstrated the defect of L3T4+ T-cell function in the tumor-bearing state. Such a functional defect was ascribed neither to the loss of L3T4+ T cells nor to the generation of suppressor cells in spleen cells of tumor-bearing mice. It was found on one hand that in vitro stimulation of antigen-presenting cell (APC)-depleted normal responding population with TNP-self prepared from cells of normal or tumor-bearing mice produced comparable anti-TNP CTL responses. On the other hand, APC-depleted responding cells from tumor-bearing mice were unable to induce anti-TNP CTL responses under conditions in which APC-depleted normal responding cells induced an effective TNP-CTL response. These results indicate that selective impairment of L3T4+ T cell-mediated immunity is induced in the tumor-bearing state and that such an impairment is ascribed to the dysfunction of L3T4+ T cells themselves, but not of APC required for the activation of L3T4+ T-cell subset.

Animals↗