[Immune dysfunctions in patients with immunoproliferative disease].
Explore the source record for details and available documents.
B-Lymphocytes↗
SEARCH · Search PubMed
Results for “Immune dysfunction”
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.
Too little oxygen, too little interleukin-2: a link between hypoxemia and cellular immune dysfunction.
Explore the source record for details and available documents.
Animals↗
Intrinsic defects in macrophage IL-12 production associated with immune dysfunction in the MRL/++ and New Zealand Black/White F1 lupus-prone mice and the Leishmania major-susceptible BALB/c strain.
We have demonstrated that macrophages (Mphi) from young, prediseased, lupus-prone MRL/++ and New Zealand Black/White F1 mice display defective production of TNF-alpha, IL-1, and IL-6, but normal production of IL-10. In an attempt to determine the potential functional implications of this phenotype for autoimmunity, we demonstrate here that endotoxin-activated Mphi from these lupus-prone mice showed dramatically reduced expression of IL-12, a cytokine essential for Th1 responses that may be defective during lupus. IL-12 production was also reduced by Mphi from the control BALB/c strain, compatible with the concept that a genetically programmed deficit in IL-12 levels may underlie the IL-4-dominated BALB/c response to infection by the parasite Leishmania major. Although both IL-12 and TNF-alpha expression defects by Mphi from lupus-prone strains are expressed rapidly after activation, treatment with each cytokine demonstrated that only TNF-alpha contributes to the subsequent dysregulation of Mphi IL-1 and IL-6 expression in these strains, and that the reduced autocrine activity of defective IL-12 or TNF-alpha levels was not causal to each other. Although the intrinsic defect in IL-12 expression by lupus-prone and BALB/c Mphi may lead to defective Th1 responses, these Mphi responded to the Th1-derived cytokine, IFN-gamma, in a normal fashion suggesting a defective role in the induction, rather than the propagation, of Th1 responses in these mice. Our finding of a conserved intrinsic defect in IL-12 production by Mphi from the two principal mouse models of multigenic lupus provides insight into how excessive humoral responses may develop, and perhaps be prevented, in systemic autoimmune disease.
Animals↗
Detection of endogenous lithium in neuropsychiatric disorders--a model for biological transmutation.
The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na(+)-K(+) ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na(+)-K(+) ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg(++). The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na(+)-K(+) ATPase inhibition. The role of membrane Na(+)-K(+) ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na(+)-K(+) ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis.
Adult↗
Heavy load exercise induced dysfunction of immunity and neuroendocrine responses in rats.
To determine whether immunity and neuroendocrine system is altered by different loads of exercise training in rats, eight-week-old male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) cage control group (CCG); 2) moderate load training (MLT) (swimming at the intensity of 1.4 m/sec water flowing for 60 min per day); 3) heavy load training (HLT) (swimming at the intensity of 1.8 m/sec water flowing for 120 min per day). MLT and HLT rats were assigned to swim for 6 days per week for total of 6 weeks. All rats were sacrificed 36 h after their last training session. Splenocytes were pooled for assay of cell proliferation and neuropeptide contents in the hypothalamus, hypophysis and plasma were determined by radioimmunoassay while glucocorticoid specific binding in intact thymus was measured by radioligand binding assay. All rats were weighed weekly. The results showed that after 6-week training, rat splenocyte proliferation in response to Con A and LPS decreased in HLT rats compared with MLT and CCG rats. In addition, the contents of beta-endorphin, dynorphin A, arginine vasopressin and oxytocin in the hypothalamus, hypophysis and plasma were altered by HLT, as shown by increased plasma concentration of glucocorticoids and decreased glucocorticoids specific binding in intact thymus compared with MLT and CCG. Furthermore, a decreased body mass in HLT rats has been observed. The body mass of HLT rats was significantly lower than that in CCG and MLT rats at the end of the swimming training period. These data suggest that 6-week heavy load training induces the dysfunction of immunity and neuroendocrine responses, which might be one of the underlying mechanisms of immune dysfunction in overtraining.
Animals↗
AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency.
Acquired immune deficiency syndrome (AIDS) is a disease caused by the human immunodeficiency virus (HIV) in which cellular immune functions are severely impaired. Acute infection and subsequent destruction of helper T cells, although occurring readily in cell cultures, do not appear to be the only mechanisms mediating helper T cell loss. Other mechanisms that may account for the loss of helper T cells include: T cell syncytia formation, decreased T cell production, and autoimmune-related destruction of helper T cells. Immune abnormalities seen early in the course of HIV infection include immune hyperactivation and autoimmune phenomena suggestive of immune dysregulation rather than immune deficiency. Many changes in immune function are, in fact, seen in HIV-seropositive patients who possess a normal number of helper T cells. Mechanisms (other than the loss of helper T cells) that may contribute to the immune abnormalities seen in these patients include noninfectious effects of HIV and HIV proteins, effects of HIV on non-T cells, autoimmune-related manifestations of HIV infection, and HIV-induced activation of normal immunosuppressive circuits.
Acquired Immunodeficiency Syndrome↗
Immune system dysfunction during exposure to poult enteritis and mortality syndrome agents.
Poult Enteritis and Mortality Syndrome (PEMS) is a condition of yet undefined etiology. Affected flocks may exhibit 100% morbidity with mortality up to 50% or more between 2 to 4 wk of age. The current study reports the immune status of poults experimentally infected with PEMS agent(s) in various trials. When compared with the unchallenged controls, PEMS-infected poults had significant atrophy of the bursa (up to 2-fold), thymus (up to 11-fold), and spleen (up to 2-fold) (P < or = 0.05). When challenged with SRBC, PEMS-infected poults had 1 to 2 log2 lower anti-SRBC antibody titers than the controls (P < or = 0.05). Responsiveness to a mitogenic lectin, phytohemagglutinin-P, was reduced significantly in PEMS poults (P < or = 0.05). These data show that the immune system of the poults is compromised significantly during PEMS infection in terms of lymphoid organ integrity and humoral and cell-mediated immunity. These findings imply, therefore, that immune dysfunction may contribute to the mortality observed during PEMS outbreaks.
Aging↗
Trauma-induced suppression of antigen presentation and expression of major histocompatibility class II antigen complex in leukocytes.
The immune response to trauma, shock, and/or sepsis appears to exhibit a bimodal response, in which there is an early exaggerated inflammatory response, giving way over time to a state of hyporesponsiveness or immune dysfunction. This state of immune dysfunction is frequently associated with increased infectious complications and/or mortality, seen following shock or trauma. In this article, we present an overview of some of those changes that have been seen with respect to the process of major histocompatibility class II (MHC class II) antigen presentation by macrophage, a key component of the overall host immune response to foreign bacterial and/or fungal pathogens encountered following shock/trauma (with a particular emphasis on hemorrhagic shock as a component of traumatic shock). With respect to the overall process of antigen presentation, defects (dysfunction) are evident not only in models of shock and sepsis, but also in traumatized patients. Studies of the capacity of a monocyte's/macrophage's ability to present antigen indicate that defects can be detected, not only in those steps involved in antigenic processing, but also in MHC class II molecule expression and accessory molecule function (or its inhibition) following shock. Those changes in the macrophage's capacity to process antigen seen during the first 24 h after hemorrhagic shock appear to be associated with the cell's metabolic response to regional hypoxia and/or the shift to proinflammatory mediator release (tumor necrosis factor, interleukin [IL]-1, IL-6, etc.). This initial acute response to shock appears to act as the nidus for chronic anti-inflammatory mediator release (prostaglandin E2, transforming growth factor-beta, IL-10, IL-4, nitric oxide, etc.), which may mediate the sustained depression of the antigen-presenting cell's function.
Animals↗
Hypothalamic digoxin, geomagnetic fields and human disease--a hypothesis.
The human hypothalamus synthesis an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin-mediated model for quantal perception of geomagnetic fields is proposed. External geomagnetic fields can produce membrane Na(+)-K(+) ATPase inhibition. The inhibition of Na(+)-K(+) ATPase can contribute to increase in intracellular calcium and decrease in magnesium, which can result in (1) defective neurotransmitter transport mechanism, (2) neuronal degeneration and apoptosis, (3) mitochondrial dysfunction, (4) defective golgi body function and protein processing dysfunction, (5) immune dysfunction and oncogenesis. Geomagnetic fields can thus regulate cellular function and contributing to the pathogenesis of disease.
Apoptosis↗
Myeloid progenitor cells mediate immune suppression in patients with head and neck cancers.
Patients with squamous cell carcinomas of the head and neck (HNSCC) have profound defects in their immune defenses. We have shown that among the mechanisms that contribute to this immune dysfunction are immune inhibitory CD34+ progenitor cells, whose levels become elevated in the peripheral blood and within the tumor tissue. One goal of our studies is to overcome the immune inhibitory activities of tumor-induced CD34+ progenitor cells by stimulating their differentiation into cells, such as dendritic or monocytic cells, that can stimulate immune reactivity to autologous cancer. Results of in vitro analyses with CD34+ suppressor cells of HNSCC patients and of in vivo studies in animal tumor models have shown the capacity of tumor-induced CD34+ cells to differentiate into cells that phenotypically resemble monocytic or dendritic cells. Whether these cells can differentiate into dendritic cells in HNSCC patients is currently being tested. Less clear is whether the pathway by which the tumor-induced CD34+ cells differentiate will result in cells having the full capacity to function as potent stimulators of immune reactivity to autologous tumor.
Animals↗
Deficient type I protein kinase A isozyme activity in systemic lupus erythematosus T lymphocytes.
Systemic lupus erythematosus (SLE) is an autoimmune disorder of indeterminate etiology characterized by a dysfunctional cellular immune response. We have previously identified a metabolic disorder of the adenylate cyclase/cAMP/protein kinase A (AC/cAMP/PKA) pathway characterized by impaired cAMP-inducible, PKA-catalyzed protein phosphorylation in intact T lymphocytes from subjects with severe SLE disease activity. Because this metabolic disorder may contribute to abnormal T cell immune effector functions, we tested the hypothesis that impaired PKA-dependent protein phosphorylation is the result of a PKA isozyme deficiency in SLE T lymphocytes. Compared with healthy and rheumatoid arthritis (RA) controls, subjects with severe SLE activity exhibited reduced PKA-catalyzed phosphorylation of proteins in the T lymphocyte plasma membrane where the type I isozyme of PKA (PKA-I) is predominantly localized. Both silver staining and biosynthetic labeling of membrane-associated proteins with [35S]methionine demonstrated that reduced protein phosphorylation was not due to either an altered distribution of or absence of proteins. Moreover, phosphorylation of SLE membrane-associated proteins with the PKA catalytic (C) subunit showed a similar distribution and extent of phosphorylation compared with membrane proteins from healthy T cells, suggesting that SLE T cell membrane proteins could be phosphorylated. Sequential column chromatography of the type I and type II isozymes of PKA (PKA-I, PKA-II) demonstrated a deficiency of PKA-I isozyme activity. Compared with a ratio of PKA-I to PKA-II activity of 4.2:1 in healthy T cells, the activity ratio in T cells from subjects with severe SLE disease activity was 0.99:1 (P = 0.01, SLE versus healthy controls for PKA-I). The deficient PKA-I activity was associated with a significant increase of free C-subunit activity (P = 0.04, SLE versus healthy controls for C-subunit). T cells from subjects with mild/moderate SLE disease activity also exhibited diminished PKA-I activity, yielding a ratio of PKA-I to PKA-II activity of 2.4:1. By contrast, T cells from RA controls possessed increased PKA-I, PKA-II, and free C-subunit activities compared with healthy controls, resulting in a ratio of PKA-I to PKA-II activity of 3.6:1. We conclude that the reduced PKA-catalyzed protein phosphorylation in the plasma membrane of SLE T cells is the result of deficient PKA-I isozyme activity. This is the first identification of a deficiency of PKA activity in SLE T lymphocytes; the deficiency, resulting in diminished protein phosphorylation, may alter cellular homeostasis, contributing to the cellular immune dysfunctions observed in SLE.
Adult↗
Inhibition of membrane Na+-K+ ATPase activity: a common pathway in central nervous system disorders.
OBJECTIVES: The study was conducted to assess the role of hypothalamic digoxin in neuropsychiatric and systemic disorders. A hypothesis regarding the central role of hypothalamic digoxin in neuroimmunoendocrine integration is proposed. METHODOLOGY: Blood samples from patients of CNS glioma, multiple sclerosis, systemic lupus erythematosis, subacute sclerosing panencephalitis, primary generalized epilepsy, Parkinson's disease, Down syndrome, AIDS dementia with neuropsychiatric features, syndrome X with multiple lacunar state, senile dementia, familial group (a family with familial coexistence of schizophrenia, Parkinson's disease, primary generalized epilepsy, malignant neoplasia, rheumatoid arthritis and syndrome X over three generations), schizophrenia and manic depressive psychosis were analysed for RBC membrane Na+-K+ ATPase, levels of digoxin and Mg++. RESULTS: Inhibition of RBC membrane Na+-K+ ATPase activity was observed in most cases along with increase in the levels of serum digoxin and decrease in the level of serum Mg++. CONCLUSION: The decreased Na+-K+ ATPase activity can be due to increased digoxin, which is a potent inhibitor of this enzyme. The inhibition of Na+-K+ ATPase can contribute to increase in intracellular calcium and decrease in magnesium, which can result in 1) defective neurotransmitter transport mechanism, 2) neuronal degeneration and apoptosis, 3) mitochondrial dysfunction, 4) defective golgi body function and protein processing dysfunction, 5) immune dysfunction and oncogenesis. The mechanism of how increased intracellular calcium and decreased magnesium can contribute to the above effects is discussed.
Adult↗
[Serum cytokines and cytokine receptors in children after small or larger surgical interventions with halothane anesthesia].
Immune dysfunction or immune defect syndrome can result postoperatively. It is not yet clear what part is played by the operative trauma itself or by narcotics. To answer this question, 54 patients (ASA 1) aged between 4 and 16 were examined. In group I there were 28 patients with minor operations and in group II 26 patients with moderate ones. We chose halothan, N2O and O2 for inhalational anaesthesia for all patients, IL-6. TNF alpha, IL-IRA, IL-2R and sTNF-RII measuring times were preoperative directly postoperative and on the first and third postoperative days. In contrast to TNF-alpha, IL-6 showed itself in both groups to be an "early" immune parameter with trauma-related kinetics. IL-IRA increased in both groups with significant values on the first postoperative day. Trauma-related differences between the groups were apparent. sIL-2R was less pronounced, IL-6 and IL-IRA parameters proved to be sensitive indicators of operative trauma intensity. The differing IL-IRA kinetic after minor or moderate trauma indicates that narcotic effects may be manifested at cytokine receptor level. Monitoring of the presented parameters on the first and third postoperative days together with base data appears to be appropriate for determining perioperative immune reaction.
Adolescent↗
A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction.
Immune function in normal pregnancy and the postpartum period remains poorly defined. We hypothesized that a comparative study between pregnant women with normal and abnormal immune function would further our understanding of the immune mechanisms of pregnancy. We chose to study a cohort of pregnant women at risk for the development of postpartum thyroid dysfunction (PPTD) as well as a group of normal controls. We chose PPTD as the model for abnormal immune function because of the relative ease of monitoring disease development and the relatively high prevalence for PPTD reported in earlier studies. Five hundred and fifty-two women were screened for the presence of thyroid autoantibodies in the first trimester of pregnancy. Thirty-three thyroid autoantibody-positive women and 28 thyroid autoantibody-negative women were followed prospectively throughout pregnancy and 6 months into the postpartum period. Lymphocyte subset analyses, thyroid function tests, and thyroid autoantibodies (antihuman thyroglobulin and antithyroid peroxidase) were performed at defined intervals. All patients were HLA serotyped. Normal pregnancy was principally characterized by decreased CD4+ T-cells and increasing CD8+ T-cells, causing a significant fall in the CD4+/CD8+ ratio in late pregnancy and into the postpartum period. Women who developed PPTD had 1) a higher CD4+/CD8+ ratio (P = 0.04), 2) activation of T-cells in the postpartum period (P = 0.02), and 3) significantly higher thyroid autoantibody titers (antihuman thyroglobulin, P = 0.02; antithyroid peroxidase, P = 0.0018). We found an overall incidence for PPTD of 8.8%. These data demonstrated that women who were thyroid autoantibody positive in the first trimester of pregnancy had a one in three chance of developing PPTD. We observed a significant fall in the T-cell helper/suppressor ratio in normal pregnant women, which was associated with distinct T-cell subset changes. This pregnancy-initiated T-cell regulation reflected an overall suppression of immune function. The development of PPTD was a frequent postpartum event in our population and was associated with a triad of immune markers: a reduction in the normal immune suppression of pregnancy (as indicated by higher T-cell helper/suppressor ratios), enhanced postpartum T-cell activation, and elevated thyroid autoantibodies. The reduction in the degree of immune suppression was, therefore, a major factor in the development of PPTD. Our results define immunological changes that occur in normal pregnancy and distinct immunological abnormalities necessary for the development of PPTD.
Autoantibodies↗
Immunotoxicology today.
Immunotoxicology is a science which deals with the effects of physical and chemical agents and other toxic substances on the immune system. The discipline includes study of the detection, occurrence, adverse effects, and mechanisms of chemically-induced immune dysfunction. Many drugs and chemicals are known to compromise the immune response of a host which is extremely vulnerable and sensitive to perturbation by these agents. The consequences of immune dysfunction may be expressed in reduced resistance to infectious and neoplastic diseases, or enhanced hypersensitivity and autoimmunity. The immunomodulating profiles of xenobiotics may be diverse, involving several components of the immune system, or they may selectively compromise an individual compartment of the immune response. Many drugs and chemicals are known to result in immune disregulation in animals, but a paucity of information is available to indicate the effects of xenobiotics on systemic immunity in humans. Epidemiological studies and research designed to assess chemical immunomodulation in man are necessary to confirm animal data. Further, a definitive diagnosis for chemically-induced immune dysfunction must include several etiologies and body organ systems, since a triad of reciprocal interactions exists between the immune, endocrine, and central nervous systems.
Animals↗
Vaccinology, immunology, and comparative pathogenesis of measles in the quest for a preventative against AIDS.
Current approaches to the prevention and control of AIDS by vaccines and by chemotherapy have failed to provide satisfactory solutions to this important medical problem and have failed, in addition, to provide definitive guidelines for future research endeavor. Vaccine research must and will continue but it is possible that a safe and effective vaccine may never be developed and it may be timely to explore, in addition, alternative means for immunological intervention in AIDS. Both immunoprophylactic and immunotherapeutic efforts might be assisted by manipulating the T helper 1 (Th1) and T helper 2 (Th2) subsets of CD4+ T helper cells, which is therefore worthy of exploration. Selective control of immune response by the two T helper subsets is by release of different cytokines that promote either cellular or humoral immunity, the latter of which may be associated with inappropriate immune responses and with immune dysfunction. Discovery of the Th1 and Th2 subsets and definition of the cytokines they release provide a new avenue toward possible development of a safe and effective vaccine and an approach, in addition, to correction of immune dysfunction by selective cytokine administration or by cytokine ablation by antagonists or antibodies. AIDS pathogenesis and immune dysfunction are complex and understanding them may be overwhelmed by an excess of possibilities. Simplification of the endeavor might benefit from comparative studies of the pathogenesis of measles, in which there also is immune deficiency but usually with spontaneous viral clearance, reversal of immune dysfunction, and total recovery. In addition, measles presents as a single disease and is caused by antigenically stable virus. Identification of the process whereby measles immunodeficiency is spontaneously reversed might be of importance in attempting to devise means for similar reversal in AIDS.
AIDS Vaccines↗
[Respective indications of enteral or parenteral nutrition during pre- and post-operative periods].
Denutrition is often associated with poor postoperative outcome. However, a large body of evidence, from studies comparing perioperative parenteral (PN) or enteral (EN) nutrition to the absence of perioperative nutrition, suggests that perioperative nutritional support provides significant improvements in both nutritional status and postoperative clinical outcome in selected patients who are or will become malnourished. The aim of this study was to select and review all relevant articles comparing perioperative parenteral and enteral nutritional support, either in terms of clinical outcome, or risks and costs, or in pathophysiological terms. Twelve clinical reports were reviewed. All contained methodological flaws, mainly type II statistical error due to an insufficient number of patients, inaccurate primary diagnosis, absence of blinding, and lack of objective criteria of judgement. These concerns warrant caution in interpreting the results. Moderately strong (grade B) recommendations can only be drawn from these studies: PN (compared to early EN) is associated with a higher rate of sepsis in patients following abdominal trauma; EN is as efficient as PN in patients following surgery; EN is safe and cheaper than PN. PN formulae lack many important nutrients (glutamine, arginine, cysteine, peptides, fibers, n-3 polyunsaturated fatty acids, and nucleotides). Many experimental (animal) and some clinical (in non surgical patients) studies showed that PN (compared to EN) induces gut mucosal atrophy, liver dysfunction, gut bacterial translocation and immune dysfunction. The final aim of PN and EN would therefore strikingly differ. The qualitatively imperfect PN would only supply the fasting patient with quantitative amounts of calories and proteins. Due to initially limited digestive tolerance, EN provides less nutrition than PN does, but would finally lead to the same or even better outcome, due to its ability to counteract stress induced gut and immune dysfunction. Current evidence therefore suggests that early EN is superior to PN in trauma patients, and not different from but cheaper (and therefore more cost-effective) than PN in surgical patients. Further controlled, randomised, and blinded studies including sufficient sizes of groups are required, especially in the surgical setting, to address a large number of still unanswered questions.
Enteral Nutrition↗
Necrotizing herpetic retinopathies. A spectrum of herpes virus-induced diseases determined by the immune state of the host.
PURPOSE: Necrotizing herpetic retinopathies (NHR), a new spectrum of diseases induced by viruses of the herpes family (herpes simplex virus, varicella-zoster virus and cytomegalovirus), includes acute retinal necrosis (ARN) occurring in apparently immunocompetent patients and progressive outer retinal necrosis (PORN) described in severely immuno-compromised patients. Signs of impaired cellular immunity were seen in 16% of ARN patients in a review of 216 reported cases, indicating that immune dysfunction is not only at the origin of PORN but might also be at the origin of ARN. The aim of this study was to correlate clinical findings in NHR patients with their immunologic parameters. METHODS: Charts from patients with the diagnosis of ARN or PORN seen from 1990 to 1995 were reviewed. Clinical characteristics and disease patterns were correlated with immunological parameters taking into account CD4 lymphocyte rate in AIDS patients and blood-lymphocyte subpopulation determination by flow cytometry, cutaneous delayed type hypersensitivity testing and lymphocytic proliferation rate to seven antigens in HIV-negative patients. RESULTS: During the period considered, 11 patients and 7 patients fulfilled the criteria of ARN and PORN respectively. Immune dysfunctions were identified in most patients. Mild type of ARN and classical ARN were associated with discrete immune dysfunctions, ARN with features of PORN was seen in more immunodepressed patients and classical PORN was always seen in severely immunodepressed HIV patients. CONCLUSION: Our findings suggest that NHR is a continuous spectrum of diseases induced by herpes viruses, whose clinical expression depends on the immune state of the host going from mild or classical ARN at one end in patients with non-detectable or slight immune dysfunction to PORN in severely immunodepressed patients at the other end and with intermediary forms between these extremes.
AIDS-Related Opportunistic Infections↗