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At least 163 records · Page 9Linked to original sources
PubMed2003

Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity.

Animals↗
PubMed1978

Use of the integrated steady state rate equation to investigate product inhibition of human red cell adenosine deaminase and its relevance to immune dysfunction.

The analysis of progress curves using the integrated rate equation was applied to the adenosine deaminase-catalyzed conversion of adenosine to inosine. Adenosine deaminase was purified from human red blood cells of phenotypes ADA 1, ADA 2, and ADA 2-1. For all three types, no measurable product inhibition by inosine was observed. These results do not confirm the hypothesis that inosine accumulation in purine nucleoside phosphorylase deficiency causes adenosine deaminase inhibition, resulting in a common mechanism for the immune defects related to these two enzyme deficiencies.

Adenosine Deaminase↗
PubMed1982

Epidermodysplasia verruciformis induced by a new human papillomavirus (HPV-8). Report of a case without immune dysfunction. Effect of treatment with an aromatic retinoid.

A new case of epidermodysplasia verruciformis (EV) is reported in a 35-year-old man characterized by multiple common warts, flat warts, psoriasis-form lesions, and pityriasis-versicolor-(PV) like lesions. There was no familial history, no mental retardation, and no malignant changes. Human papilloma virus type 8 was identified in PV-like lesions. Immunologic studies detected no abnormalities: Delayed skin tests, DNCB sensitization, levels of immunoglobulins, complement components, circulating immune complexes, number of circulating lymphocytes, lymphocyte membrane markers, proliferative responses to mitogens, Ts activity, and Ts subpopulations as detected by monoclonal antibodies were considered to be within normal limits. A treatment with a retinoid aromatic (RO 10-9359) improved the clinical status of the patient and did not modify the immune parameters.

Adult↗
PubMed1992

Role of nutrition in the management of malnutrition and immune dysfunction of trauma.

Current nutrition support improves patient outcome in trauma patients. It appears to do so by limiting the adverse effects of specific nutrient or generalized nutrient deficiencies. Immunosuppression, however, continues as a significant clinical problem. This immunosuppression appears to be part of the inflammatory response that accompanies trauma, and in part, to represent the need for conditional nutrients in this setting. Three nutrients that are being evaluated include arginine, uracil as ribonucleic acid and omega-3 polyunsaturated fatty acids. Animal studies report improved immune function. Early clinical trials are reporting improved immune function and patient outcomes.

Animals↗
PubMed1977

Metabolic correlates of immune dysfunction in malnourished children.

Mononuclear cells of malnourished children contain diminished activity of phosphoglycerate kinase and pyruvate kinase (PK). The PK activity of these cells correlates well with the percentage of circulating thymus-derived lymphocytes (T-cells). Phytohemagglutinin causes an immediate increase in PK activity of mononuclear cells of malnourished patients. The correlation of PK activity with T-cells and the response of PK activity to phytohemagglutinin are in distinct contrast to observed perturbations of neonatal mononuclear cell metabolism. The relationship of the metabolic alterations to the pathophysiology of the immune system in malnutrition has not yet been defined.

Adolescent↗
PubMed1987

Immunity, viral pathology and assessment of immune dysfunction in virology and toxicology.

General patterns of tissue injury are recognized as characteristic for certain groups of viruses and certain types of host/virus interactions. Acute viral infections, limited in time and space, tend to be accompanied by florid but brief virus replication cycles in tissues and lesions or signs of disease are largely attributable to the cytolytic effects of the virus on host cells. Chronic or persistent viral diseases tend to have low (or difficult to detect) levels of infectious virus on tissues and the lesions tend to be dominated by inflammation, antiviral immune responses and/or host tissue proliferation. At the cellular level, 3 general categories of response to viral infection are recognized: acute cellular swelling with eventual cytolysis, persistent infection, and transformation (neoplastic) infection. Acute cellular swelling may be accompanied by syncytial giant cell formation and/or viral inclusion bodies. Cells persistently infected with viruses though morphologically normal, are increasingly recognized as functionally deficient and may eventually display degenerative change. Transformation to neoplastic growth can be both benign or malignant in cellular expression. In vivo, the initial neutrophilic inflammatory response to virus-induced cellular necrosis is transient and is rapidly superseded by virus-specific inflammation mediated by both humoral and cellular factors and supplemented by the numerous inflammation amplification pathways. Vasculitis, a common but frequently unappreciated event, may produce nonspecific tissue damage via hemorrhage and ischemia in addition to providing a mechanism for egress of inflammatory factors into the areas of virus-induced cellular damage. During the healing phase, repair by substitution (e.g., fibrosis and scarring) or by proliferation of uninfected replacement cells may dominate sites of viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Stress and immune dysfunction in Gulf War veterans.

The role of stress and immunological abnormalities, as well as the neuroendocrine regulation of these two variables, in illnesses in Gulf War veterans (GWVs) is unknown. Many GWV patients complain of skin and joint problems, that is, disorders that may have a common immunological basis. Post-traumatic stress disorder (PTSD), an anxiety disorder associated with chronic stress, is diagnosed in approximately 10% of the Alabama GWVs. Chronic stress can lead to a reduced capacity to resist disease. Recent work suggests that a dysregulated balance of cytokines produced by T helper cells of the immune system can play a significant role in stress-related illnesses. Indeed, a balanced immune response (cell-mediated and humoral immunity) is an important defense mechanism, and cytokines can regulate this balance. It is therefore plausible that stress-induced changes in hormones (such as cortisol and catecholamines) and cytokines, both of which have been implicated in altering levels of cellular or humoral immunity, may play a role in GWV illnesses.

Humans↗
PubMed2025

Spike protein-induced VSIR-ISX signaling disrupts metabolic homeostasis and promotes COVID-19-related immune dysfunction.

COVID-19 has caused millions of deaths worldwide since 2019. Vaccination has reduced both transmission and disease severity. However, emerging viral variants have weakened vaccine effectiveness, highlighting the need for new antiviral therapies. This study examines how the SARS-CoV-2-Spike protein (SARS-2-S) induces the VSIR-ISX signaling pathway, leading to metabolic disturbances that may worsen disease progression. Using RNA sequencing, we found that SARS-2-S expression in pulmonary cells activates genes involved in tryptophan and arachidonic acid (AA) metabolism, altering bioactive mediators like kynurenine and prostanoids, which are crucial for inflammation and immune responses. Mechanistically, the ACE2-MYD88 pathway, activated by SARS-2-S, enhances the VSIR-ISX axis through NF-κB signaling, driving these metabolic disruptions. Chromatin immunoprecipitation and genome sequencing revealed that ISX, activated via VSIR-MAPK signaling, upregulates enzymes involved in AA metabolism by binding directly to their gene promoters. Notably, disrupting the VSIR-ISX axis using shRNA interference or NF-κB inhibitors effectively mitigated these metabolic disturbances. Our findings suggest that the VSIR-ISX pathway could be a promising therapeutic target for treating COVID-19 by addressing virus-induced metabolic disruptions.

Humans↗
PubMed1990

Determinants of the ability of malignant fibroma virus to induce immune dysfunction and tumor dissemination in vivo.

The relationship of virus-induced immunological dysfunction and tumor dissemination was studied using two related tumor-causing leporipoxviruses: malignant fibroma virus (MV) and Shope fibroma virus (SFV). Recombinant viruses, produced by transferring MV's 10.7 kb BamHI C fragment to SFV, replicate in lymphocytes and suppress lymphocyte function in vitro. Those recombinants that replicate in lymphocytes and suppress lymphocyte function in vitro share about 3.5 kb from MV's C fragment. Some recombinants mimic MV in producing immune suppression and disseminated virus infection in vivo. Other recombinants, even some that are highly immunosuppressive in vitro (e.g. R71), only variably induce immune suppression in vivo, and do not cause disseminated disease. A segment of DNA from MV that transfers to Shope fibroma virus almost all of MV's virulence in vivo was identified.

Animals↗
PubMed1991

Accumulation of hyporesponsive, calcium extruding memory T cells as a key feature of age-dependent immune dysfunction.

In this review I propose a hypothesis with a number of testable predictions: that the age-dependent decline in T lymphocyte function is largely the result of the accumulation of memory T lymphocytes with over-active plasma membrane calcium pumps. This idea is consistent with much, though not all, of the currently available data. I will start by presenting the evidence that suggested and most clearly supports this idea, then discuss apparently contrary data (some of it still difficult to reconcile with the model), and lastly consider the implications of the model for our understanding of late life development of the T cell immune system.

Aging↗
PubMedDate not supplied

Sinus histiocytosis with massive lymphadenopathy: a spectrum of disease associated with immune dysfunction.

A detailed immunologic study of three cases of sinus histiocytosis with massive lymphadenopathy (SHML) was performed to better characterize this rare disorder. One patient had prominent cervical lymphadenopathy that regressed spontaneously, whereas the other two patients had persistent cervical lymphadenopathy and recurrent infections. The first patient was otherwise healthy and had normal immunologic studies. One of the latter patients had a relative increase in blood B cells, a decreased level of serum immunoglobulin A (IgA), decreased blood lymphocyte mitogenic responses to multiple mitogens (37-42% of controls), and cutaneous anergy. The other patient with persistent disease also had a relative increase in blood B cells, polyclonal hypergammaglobulinemia, and circulating immune complexes, as well as decreased blood T cells and markedly decreased blood lymphocyte responses to mitogens (12-37% of controls). Immunohistochemical stains of the lymph nodes of the three patients revealed a characteristic phenotype for the sinus histiocytes: S-100 protein, 3/3; CD14 (Leu M3) 3/3; CD11c (Leu M5), 1/1; CD71 (OKT9), 3/3; CD4 (Leu 3a), 2/3; CD1a (OKT6), 1/3; alpha-1-antitrypsin, 3/3; alpha-1-antichymotrypsin, 3/3; CD35 (C3b), 1/1; CD11b (Mo1), 0/3; CD15 (Leu M1), 0/3; HLA-DR, 0/3; and lysozyme, 0/3. This phenotype suggests that the cells of SHML have features of both the Langerhans/interdigitating cell and mononuclear phagocyte lineages. Emperipolesis by the histiocytes of B cells, T cells, and natural killer cells was demonstrated by a double-staining technique. Our findings indicate that patients with SHML may have a variably expressed immunodeficiency that predisposes them to recurrent infections.

Child↗
PubMed1997

Immune dysfunction in uremia.

Among uremic patients on hemodialysis and continuous ambulatory peritoneal dialysis treatment infectious complications leading to a high incidence of morbidity and mortality are a well documented problem. Polymorphonuclear leukocytes (PMNLs) are the main cells of the unspecific defence system during bacterial infections. There is a number of partly interdependent factors responsible for the diminished PMNL functions (chemotaxis, phagocytosis, intracellular killing by proteolytic enzymes and toxic oxygen radicals) found in uremia: iron overload, elevated levels of intracellular calcium and hemodialysis treatment per se has been shown to be involved in altered PMNL functions. Uremic toxins are circulating plasma factors accumulating in the serum of uremic patients. They are thought to play a crucial role in inhibiting the unspecific immune defence. A number of uremic toxins has already been purified and characterized. In our laboratory, a granulocyte inhibiting protein (GIP) with homology to immunoglobulin light chains has been isolated. We could show that free immunoglobulin light chains per se are able to interfere with essential PMNL functions. A GIP with homology to beta 2-microglobulin was also isolated from dialysis patients. Angiogenin was purified from uremic patients as a PMNL degranulation inhibiting protein and complement factor D was shown to adversely affect PMNL functions. A modified form of ubiquitin isolated from peritoneal dialysis patients interferes with PMNL chemotaxis. Furthermore, p-cresol was identified as a uremic solute that impairs the respiratory burst activity of PMNL. There is also increased clinical evidence for profound defects in the specific immune defence in uremia, such as the high susceptibility to viral infections in uremic patients, the deficient responses of their T lymphocytes, and the significantly depressed specific antibody responses.

B-Lymphocytes↗
PubMed1988

The development of immunotoxins for the therapy of cancer, AIDS, and immune dysfunctions.

Immunotoxins (ITs) consist of cell-reactive ligands coupled to toxins or their toxic subunits. The ligands are usually antibodies, hormones, or growth factors and the toxins are of bacterial or plant origin. In the case of the plant toxin, ricin, its structure consists of a ribosome-inactivating A chain of 32 Kd linked by a disulfide bond to a galactose-specific lectin (B chain) of approximately 30 Kd. The A and B chains of ricin can be separated following reduction and the A chain can then be purified and chemically linked to different ligands to generate a cell-reactive conjugate. Studies using A chain-containing ITs to specifically delete tumor cells, or regulatory cells of the immune system began a decade ago. Initial in vitro experiments were successful and led to further experiments in vivo. However, in vivo studies carried out over the past five years in both animals and humans have demonstrated that the efficacy of ITs or conjugates in vivo is often poor due to problems involving instability of the conjugate, inferior potency, inaccessibility of tumor cells, nonspecific binding to cells other than the target cells, and the survival of antigen-negative mutants. In addition, immune responses against both the ligand and the A chain are usually elicited, precluding repeated therapy. During the past several years, there have been attempts to solve these problems and thereby develop more effective ITs. By analogy with conventional chemotherapeutic agents, it could be predicted that immunotoxins will require many years of study to optimize their construction and therapeutic regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed2002

Severe immune dysfunction after lethal neutron irradiation in a JCO nuclear facility accident victim.

The optimal treatment for the hematological toxicity of acute radiation syndrome (ARS) is not fully established, especially in cases of high-dose nonuniform irradiation by mixed neutrons and gamma-rays, because estimation of the irradiation dose (dosimetry) and prediction of autologous hematological recovery are complicated. For the treatment of ARS, we performed HLA-DRB1-mismatched unrelated umbilical cord blood transplantation (CBT) for a nuclear accident victim who received 8 to 10 GyEq mixed neutron and gamma-ray irradiation at the JCO Co. Ltd. nuclear processing facility in Tokaimura, Japan. Donor/ recipient mixed chimerism was attained; thereafter rapid autologous hematopoietic recovery was achieved in concordance with the termination of immunosuppressants. Immune function examined in vitro showed recovery of the autologous immune system was severely impaired. Although the naive T-cell fraction and the helper T-cell subtype 1 fraction were increased, the mitogenic responses of T-cells and the allogeneic mixed leukocyte reaction were severely suppressed. Endogenous immunoglobulin production was also suppressed until 120 days after the accident. Although skin transplantation for ARS was successful, the patient died of infectious complications and subsequent acute respiratory distress syndrome 210 days after the accident. These results suggest that fast neutrons in doses higher than 8 to 10 Gy cause complete abrogation of the human immune system, which may lead to fatal outcome even if autologous hematopoiesis recovers. The roles of transplantation, autologous hematopoietic recovery, chimerism, immune suppression, and immune function are discussed.

Cord Blood Stem Cell Transplantation↗
PubMed1989

Common epitope in human immunodeficiency virus (HIV) I-GP41 and HLA class II elicits immunosuppressive autoantibodies capable of contributing to immune dysfunction in HIV I-infected individuals.

We previously reported the identification of highly conserved homologous regions located in the carboxy terminus of the HIV I gp41-envelope (aa 837-844), and the amino-terminal of the beta chain of all human HLA class II antigens (aa 19-25). Murine monoclonal antibodies, raised against synthetic peptides from these homologous regions, bound not only to the isolated peptides, but also to the native gp160 and class II molecules. In this study one-third of sera from HIV I-infected individuals, at different disease stages, were found to react with both the gp41 and class II-derived peptides. These sera also reacted with "native" HLA class II molecules. The potential affects of such autoantibodies on normal immune functions were examined. It was found that in the presence of class II-cross-reactive (but not control) sera, the proliferative responses of normal CD4+ T cells to tetanus toxoid and allogeneic stimuli were markedly decreased. In addition, these sera could eliminate class II-bearing cells by antibody dependent cellular cytotoxicity. Similar affects were seen with affinity-purified IgG antibodies from patients' sera. Thus, the "molecular mimicry" between HIV I and HLA class II antigens, may lead to the generation of autoantibodies in HIV I-infected individuals that may contribute to the early functional impairment of CD4+ T cell observed in many HIV I-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes].

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed. Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19). In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R). The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease. Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Malnutrition and immune dysfunction in patients infected with human immunodeficiency virus.

STUDY OBJECTIVE: To determine forms of malnutrition and basal metabolism at different stages of immunological impairment in clinically stable patients infected with Human Immunodeficiency Virus (HIV). DESIGN: Cross sectional study. SETTING: 53 outpatients with HIV-infection classified according to the Walter Reed staging system (WR1 to WR6). MEASUREMENTS AND MAIN RESULTS: 87% of the patients showed some evidence of malnutrition. Reduced body weight was found in 53%, 68% and 25% had decreases in fat and body cell mass, 17% had visceral protein deficiency, whereas extracellular mass and serum triglyceride concentrations were increased in 58% and 30%, respectively. Reduced serum albumin and transferrin closely paralleled immunological depression, whereas alterations in body composition were manifest early during HIV-infection (WR3) and remained unchanged during the transition to the Acquired Immune Deficiency Syndrome itself. Resting metabolic rate increased from WR1 to WR3; it remained within the expected range during later stages (WR4-WR6), but was not appropriately reduced in response to the loss in body cell mass. CONCLUSIONS: HIV-infected patients display both, calorie and protein malnutrition. Immunological depression was independent of loss of body mass, but was closely associated to decreases in serum albumin values. Nutritional assessment and intervention should therefore be performed at an early stage of HIV-infection.

Adult↗