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Results for “Immune dysfunction”

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At least 559 records · Page 31Linked to original sources
PubMed1991

A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest.

A major feature of human immunodeficiency virus (HIV) infection is disordered B-cell function, which paradoxically includes both pathologic overactivity (elevated serum antibodies, lymphadenopathy, and increased risk for lymphoma) and underactivity (impaired antibody immunity, particularly to bacterial polysaccharide antigens). B-cell immune dysfunction contributes significantly to HIV-related morbidity and also represents an obstacle to eventual definitive treatment by anti-HIV immunization. Our laboratory has recently identified in normal B-cell populations certain VH gene subfamilies with a developmentally regulated pattern of utilization. In particular, B cells bearing rearranged VH3L were rare in the germinal center but uniformly abundant in the blood and lymphoid mantle zone. We used this index gene subfamily as a clonal criterion for the pattern of B-cell development in lymphocytes of HIV-positive individuals. In a series of 19 HIV-positive subjects, a striking deficit of VH3L B cells was observed; in contrast, none of the 16 normal subjects showed this abnormality. Other VH subfamilies (VH1N, VH4/6, and VH5N) were unaffected in the HIV-positive patients. This VH3L clonal deficit and other recent phenotype and histopathologic findings suggest that the general B-cell dysfunction in HIV is due to a discreet maturational arrest at the germinal center stage.

B-Lymphocytes↗
PubMed2004

The SAP family of adaptors in immune regulation.

SAP and EAT-2 define a new class of adaptor proteins composed almost exclusively of a Src homology 2 (SH2) domain. By way of their SH2 domain, SAP-like adaptors interact with tyrosine-based motifs in the cytoplasmic region of SLAM-related receptors, a family of immune cell-specific molecules involved in immunoregulation. Recent findings indicate that SAP is required for the functions of SLAM family receptors, as a consequence of its ability to promote recruitment of Src-related protein tyrosine kinase FynT and allow SLAM-related receptors to transduce tyrosine phosphorylation signals. SAP is mutated in X-linked lymphoproliferative (XLP) syndrome, a rare inherited human disease characterized by an deregulated immune response to Epstein-Barr virus infection. Several lines of evidence indicate that defects in the activities of SLAM-related receptors caused by SAP deficiency account for the immune dysfunctions associated with XLP.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Cellular immune activation in Gulf War veterans.

The etiology and pathology of illnesses related to the first Persian Gulf War are unclear. Among the constellation of symptoms noted in sick veterans, some, such as skin rashes, musculoskeletal pains, and neuropsychiatric problems, have been proposed to reflect an underlying immune dysfunction. In this study we explored the hypothesis that sickness following deployment to the Gulf in 1991 is associated with altered immune function, and we examine possible associated exposures. In particular, we focused on peripheral blood Th1/Th2 balance by measuring intracellular production of IFN-gamma, IL-2 (Th1), IL-4 (Th2), and IL-10 by CD4 T cells, using a nested case control study design within a large epidemiological survey. We compared symptomatic Gulf War veterans (sGWV) with well GWVs (wGWV), and a second control group of symptomatic veterans who served in Bosnia or were nondeployed military personnel of the same era. We found evidence for an altered immune status in sGWV in comparison to the other study groups. In particular, ongoing Th1-type immune activation was associated with multisymptom illness in GWVs, with sick veterans having significantly elevated levels of IFN-gamma and IL-2 producing CD4+ cells in the absence of in vitro stimulation compared with wGWVs (P = 0.01 and P =0.001). In vitro polyclonal activation revealed significantly elevated levels of IL-10 producing memory CD4 cells in sGWVs (P <0.001), but other cytokines were normal. In terms of possible exposures that might influence immune function, we found a trend for reduced levels of IFN-gamma producing cells after polyclonal activation with increasing numbers of vaccines administered (P <0.05) but no changes in other cytokines. These data show that multisymptom illness in Gulf War veterans is characterized by ongoing Th1-type immune activation and a biased generation of memory cells secreting the suppressor cytokine, IL-10.

Bosnia and Herzegovina↗
PubMed2004

Exercise, nutrition and immune function.

Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function. Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune function and have other adverse effects on health. Immune system depression has also been associated with an excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. Conversely, consuming 30-60 g carbohydrate x h(-1) during sustained intensive exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence that so-called 'immune-boosting' supplements, including high doses of antioxidant vitamins, glutamine, zinc, probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking.

Exercise↗
PubMed2004

Oral opportunistic infections in HIV-positive individuals: review and role of mucosal immunity.

Oral opportunistic infections in the HIV-positive individual have been documented since the first reports of the epidemic, with many lesions associated with reduced CD4(+) T lymphocyte cell count. The most common oral lesions seen in HIV disease prior to the advent of highly active antiretroviral therapy (HAART) were oropharyngeal candidiasis and oral hairy leukoplakia. However, since the advent of HAART while many oral lesions have decreased significantly the incidence of oral warts has surprisingly increased. Despite the correlation of diminished CD4(+) T lymphocyte count to the occurrence of these lesions, it is rare for the lesions to occur concurrently suggesting that each pathologic lesion type is associated with distinct host immune dysfunctions. To date, the oral opportunistic infection most frequently investigated is oropharyngeal candidiasis, where data suggests that both systemic and local immunity is important for protection against infection. In contrast, recent investigations into the host responses associated with oral hairy leukoplakia and oral warts show little to no evidence of systemic or mucosal immune responsiveness despite the presumed competence of several types of leukocytes other than CD4(+) T cells. Together these data are suggesting that susceptibility to oropharyngeal candidasis in HIV-positive persons is predominantly immune-based, whereas protection or susceptibility to oral hairy leukoplakia and oral warts may be more associated with factors other than mucosal immune function.

AIDS-Related Opportunistic Infections↗
PubMed1990

[The frequency of miscarriages in the users of oral contraception].

Overuse of oral contraceptives (OC) is currently raising medical problems due to this medication's side effects on the immune system of future mothers. The high rate of miscarriages recorded among OC users is only one facet of the immune disorders often found in these women. This article emphasizes the precautions that should be taken with such medications in teen-agers. If the pregnancy is accompanied with an immune dysfunction exposing the future mother to subsequent infections, this will occur in patients weakened by OC, and will result in troublesome immune disorders. Therefore the notion of OC and miscarriage in pregnant women must lead to consider these as high at risk patients.

Abortion, Induced↗
PubMed1993

[Opportunistic infections in patients with disordered immune status].

Dysfunction of the immune system can result in opportunistic infections, which are frequently responsible for high morbidity and mortality. With regard to surgery, opportunistic infections are found in specific risk groups, including individuals with tumors, AIDS, thermic or mechanical trauma and organ transplantation. These infections can be caused by bacteria, fungi, viruses and protozoa. If there are indications of a possible opportunistic infection, a rapid diagnosis is required, followed by immediate therapeutic intervention.

AIDS-Related Opportunistic Infections↗
PubMed1993

Effect of the HELLP syndrome on maternal immune function.

The HELLP syndrome occurs in less than 1% of gravidas and is characterized by hemolysis, elevated liver enzymes and low platelet count. The status of immune function in these high-risk patients is not known but may be of great importance in better understanding the basis, if any, of immune dysfunction in pregnancy-associated hypertensive disorders and from the potential compounding effect of infection upon an already debilitated patient. We assessed maternal immune status in patients with the HELLP syndrome using conventional in vitro techniques. The results of these studies clearly show a depression of both T and B cell potential and impaired monocyte handling of intracellular pathogens (up to 33%, 11% and 17% of control values, respectively). The onset of this immunosuppression occurred before the clinical diagnosis of HELLP syndrome was made and persisted for at least 14 days after clinical resolution. Results of cell admixture studies suggest that these effects are mediated by accessory cells or their products and do not represent true lymphocyte dysfunction. The risk of opportunistic infections may therefore be increased in the patient with the HELLP syndrome because of this generalized immunosuppression and profound decrease in monocyte phagocytic and bactericidal activity.

Adult↗
PubMed1995

Urticarial vasculitis: an autoimmune disorder following therapy for Hodgkin's disease.

Immunological abnormalities have been described in patients with Hodgkin's disease, both associated with the malignancy itself and occurring secondary to therapy. These abnormalities often manifest as an immunodeficiency state, but can also present as immune dysregulation and autoimmune disease. We report two young patients with Hodgkin's disease who, following successful therapy, developed urticarial vasculitis (UV), a form of cutaneous autoimmune vasculitis. Both patients also had systemic symptoms including fever, an elevated erythrocyte sedimentation rate and serum copper, and abnormal in vitro studies of lymphocyte enumeration and proliferation. Distinguishing UV from recurrent Hodgkin's disease was especially difficult in one patient, and was possible only by lymph node biopsy. One patient has responded well to immunosuppressive therapy, while the other, who has more profound immune dysfunction, has developed a chronic autoimmune disorder. UV may thus occur in patients after therapy for Hodgkin's disease; we hypothesize that immune dysregulation, either associated with the malignancy or resulting from therapy, is important in the pathogenesis of this autoimmune process.

Adolescent↗
PubMed1976

Chronic cytomegalovirus infection, immunodeficiency, and monoclonal gammopathy-antigen-driven malignancy?

An infant with severe combined immunodeficiency had normal numbers of lymphocytes which bore E rosette and surface Ig markers in an appropriate distribution. However, only minimal responsivity to in vitro stimulation by mitogens and allogenic cells, and none to antigens could be elicited; functional antibody responses were also nil, except to cytomegalovirus. Intrauterine-acquired cytomegalovirus may have caused his immune dysfunction, although the possibility of a postnatal infection cannot be excluded. Therapy with transfer factor and thymus transplantation was unsucessful in restoring immunity and may have aggravated a pre-existing monoclonal gammopathy. It is possible that the monoclonal protein was derived from B-cells transplacentally received from the patients mother.

Antibody Formation↗
PubMed1991

RRR-alpha-tocopheryl succinate enhances T cell mitogen-induced proliferation and reduces suppressor activity in spleen cells derived from AEV-infected chickens.

RRR-alpha-tocopheryl succinate was demonstrated to be a potent in vitro modulator of retrovirus-induced immune abnormalities. Spleen cells from avian erythroblastosis virus (AEV)-infected chickens exhibit suppressed T cell mitogen-induced proliferative responses and elevated levels of suppressor T cell activity. In vitro addition of RRR-alpha-tocopheryl succinate resulted in amelioration of these abnormalities. Antioxidants including Trolox (a water-soluble analogue of RRR-alpha-tocopherol with antioxidant properties) and a combination of butylated hydroxyanisole and butylated hydroxytoluene were able to restore immune functions to levels similar to those achieved with RRR-alpha-tocopheryl succinate treatment. Aspirin, an irreversible inhibitor of cyclooxygenase activity, was capable of ameliorating some of the AEV-induced immune dysfunctions. These studies suggest a role for the antioxidant functions of RRR-alpha-tocopheryl succinate in modulation of retrovirus-induced immune abnormalities.

Alpharetrovirus↗
PubMed2003

Interaction between the innate and adaptive immune systems is required to survive sepsis and control inflammation after injury.

Substantial clinical and laboratory research has revealed that major injury causes abnormalities in both the innate and adaptive immune systems. However, the relative importance of each of these systems in the immune dysfunction after injury is poorly understood and difficult to establish by clinical studies alone. Rag1 (-/-) C57BL/6 mice (Rag1), which lack an adoptive immune system, and immune-sufficient wild-type (WT) C57BL/6 mice underwent 25% total body surface area burn injury or sham injury under anesthesia and were subjected to cecal ligation and puncture (CLP) at day 10 postinjury, a time of high CLP mortality in this model. To test the effect of adaptive immune deficiency on inflammatory cytokine production after injury, adaptive cell-depleted splenocytes from sham and burn WT and Rag1 mice were stimulated with LPS, and TNF-alpha and IL-6 production were assayed at days 1 and 7 postinjury. Intracellular expression of TNFalpha and IL-6 by F4/80 macrophages was also assessed on day 7 by intracellular cytokine staining. Finally, Rag1 animals were reconstituted with WT splenocytes, and the effect of such reconstitution on CLP survival and cytokine production was determined. Survival of sham WT animals after CLP was significantly higher (P < 0.01) than survival of burn WT and Rag1 sham and burn animals, all of which had equivalently low survival. Reconstitution of Rag1 animals with WT splenocytes restored CLP survival to WT sham levels. Splenocytes from Rag1 burn mice showed significantly augmented cytokine production when compared with WT burn mice on day 7 (P < 0.05). Reconstitution of Rag1 mice with WT splenocytes at the time of injury returned cytokine production to WT levels. Intracellular cytokine expression in F4/80 macrophages was increased to a similar degree after burn, but not sham burn injury in Rag1, reconstituted Rag1 and WT animals. These studies demonstrate that the adaptive immune system is necessary for protection from polymicrobial sepsis and plays a significant role in regulating the inflammatory response to injury.

Animals↗
PubMed1998

Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice.

Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Animals↗
PubMed1991

Immunobiologic aspects of head and neck cancer. Clinical and laboratory correlates.

The role of the immune system in the pathogenesis and treatment of cancer remains to be determined. Impairment of humoral and cellular immunity has been associated with various factors implicated in head and neck cancer--tobacco, alcohol, and malnutrition. Whether these immune dysfunctions are causative or a secondary effect is not known. Patients with head and neck cancer have well-documented defects in immune function. In general, depression in cellular immunity has been noted, which can be correlated with stage of disease and prognosis. Conversely, increased humoral immune responses are seen, especially salivary IgA and circulating immune complexes. It may be that IgA or immune complexes are capable of suppressing the cellular immune response. Clinical trials utilizing biologic response modifiers in head and neck cancer have begun. Preliminary studies with heavily pretreated patients have demonstrated antitumor activity, suggesting that immunotherapy may provide a treatment alternative. In conclusion, the weight of evidence suggests that the immune response to head and neck cancer does play a role in the pathogenesis of the disease. A better understanding of the host-tumor interaction will allow for improved utilization of biologic response modifiers in the treatment of head and neck cancer.

Antibody Formation↗
PubMed2026

Proteins as Regulators of Metabolic Changes in Sepsis: Alterations in Body Fluids, Immune Cells, and Organs through the Eyes of Proteomics.

Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection and profound metabolic alterations that contribute to immune dysfunction and organ failure. This Review synthesizes proteomic evidence on sepsis-associated alterations in proteins involved in metabolic pathways across circulating biofluids, immune cells, and organs. Across plasma and urine, proteomic studies identify disturbances in lipoprotein-associated pathways, redox homeostasis, mitochondrial function, and substrate metabolism, indicating that protein signatures of metabolic dysregulation are systemic and detectable across biofluids. In immune cells, monocytes and neutrophils, proteomic analyses reveal a shift toward glycolysis with concurrent impairment of mitochondrial pathways alongside phenotype-dependent differences in lipid and redox-related programs. Organ-level studies further show that metabolic responses are heterogeneous, with distinct trajectories in the kidney, heart, liver, lung, skeletal muscle, and brain. These observations support the concept that sepsis involves compartment-specific remodeling of metabolism-associated protein networks rather than a single convergent metabolic state. Proteomics also highlights potential translational opportunities by identifying metabolism-associated proteins linked to disease severity, clinical phenotypes, and biologically distinct patient subgroups, although the current evidence remains largely exploratory and context-dependent. Overall, proteomics provides a complementary framework for understanding the molecular regulation of sepsis-associated metabolic dysfunction and may refine biological stratification and therapeutic targeting, particularly when integrated with longitudinal sampling and multiomic data.

Humans↗
PubMed1980

Analysis of normal and mutant forms of human adenosine deaminase - a review.

A deficiency of the enzyme adenosine deaminase is associated with an autosomal recessive form of severe combined immunodeficiency disease in man. The molecular forms of the normal human enzyme have now been well characterized in an effort to better understand the nature of the enzyme defect in affected patients. In some human tissues adenosine deaminase exists predominantly as a small molecular form while in other tissues a large form composed of adenosine deaminase (small form) and an adenosine deaminase-binding protein predominates. The small form of the enzyme purified to homogeneity by antibody affinity chromatography is a monomer of native molecular weight of 37,600. The adenosine deaminase-binding protein, purified by adenosine deaminase affinity chromatography, appears to be a dimer of native molecular weight 213,000 and contains carbohydrate. Based on direct binding measurements, chemical cross-linking studies and sedimentation equilibrium analyses, small form adenosine deaminase has been shown to combine with purified binding protein in a molar ratio of 2:1 respectively to produce the large form adenosine deaminase. Reduced, but widely ranging levels of adenosine deaminating activity, have been reported in various tissues of adenosine deaminase deficient patients. Further, the characteristics of this residual enzyme activity have been analyzed immunochemically to substantiate genetic heterogeneity in this disorder. While many types of immunodeficiency are currently recognized in man, in most cases the molecular defect is unknown. The discovery of a deficiency of the enzyme, adenosine deaminase, ADA, (EC 3.5.4.4), in some patients with severe combined immunodeficiency disease represented an early clue to the pathogenesis of immune dysfunction at the molecular level 1-4. Affected patients with markedly reduced levels of ADA exhibit a defect of both cellular and humoral immunity characterized clinically by severe recurrent infections with a fatal outcome if untreated. Attempts to elucidate the nature of the genetic mutation(s) leading to the reduction of ADA activity in these immunodeficient patients have been complicated in part by an incomplete understanding of the nature of ADA in normal tissues. In this review we will consider the structural characteristics of the normal and mutant forms of ADA as they are currently understood.

Adenosine Deaminase↗
PubMed2005

Cellular immune responses against hepatitis C virus.

Cellular immune responses are typically important in recovery from acute infections, and studies of acute hepatitis C confirm that broadly directed CD4+ and CD8+ T cell responses are associated with spontaneous clearance of infection. However, a major unanswered question is what role the cellular immune response plays in progression of liver disease during chronic infection. Classic models of hepatitis C suggest that cellular immune responses promote liver injury, either by causing direct cytolysis of infected cells or by promoting inflammation. However, clinical evidence suggests that persons with cellular immune dysfunction, such as that due to with human immunodeficiency virus (HIV) infection, have more-rapid disease progression. Recent data suggest that cellular immune responses do serve to limit the progression of liver disease, even if they are ineffective at clearance of virus. There is limited information on the effect of HIV coinfection on the cellular immune response to hepatitis C virus, but further study of this issue might shed light on the pathogenesis of liver disease in both immunocompromised and nonimmunocompromised hosts.

Animals↗
PubMed1995

Interleukin-1 and interleukin-1 receptor antagonist production during haemodialysis: which cytokine is a surrogate marker for dialysis-related complications?

Studies have shown differences between host defence dysfunctions in patients with end-stage renal disease (ESRD), patients treated with continuous ambulatory peritoneal dialysis (CAPD) and those undergoing chronic haemodialysis. Immune dysfunction is well documented in haemodialysis patients, particularly after a few years of dialysis treatment. The unresolved question is whether there is a surrogate marker(s) for dialysis-related changes which can be monitored easily and which prospectively predicts deteriorating health, dialysis-related complications and/or mortality. The issue is one of finding a marker for host perturbation solely related to haemodialysis. The criteria for such a marker(s) worthy of being investigated are: (1) does it change with alterations made to the membrane or the quality of the dialysate; (2) is the marker independent of the patient's intrinsic renal disease; (3) does the marker reflect the pathophysiology of 'bioincompatibility'? In this overview, the effects of chronic haemodialysis on interleukin-1 (IL-1) and IL-1 receptor antagonist (IL-1Ra) production by peripheral blood mononuclear cells will be discussed. Recent data suggest the IL-1Ra rather than IL-1 itself is a marker for chronic monocyte activation and bioincompatibility.

Biomarkers↗