Role Of Immunological Mechanisms Research Articles

Frailty in Aging HIV-Positive Individuals: An Evolving Healthcare Landscape.

The life expectancy of people living with HIV (PLWH) has greatly increased due to advancements in combination antiretroviral treatment (cART). However, this longer life has also increased the prevalence of age-related comorbidities, such as frailty, which now manifest sooner in this group. Frailty, a term coined by the insurance industry, has been broadened to include physical, cognitive, and emotional elements and has been recognized as a critical predictor of negative health outcomes. With the median age of PLWH now in the mid-50s, treating frailty is critical given its link to chronic diseases, cognitive decline, and even death. Frailty assessment tools, such as the Frailty Phenotype (FP) and the Frailty Index (FI), are used to identify vulnerable people. Understanding the pathophysiology of frailty in PLWH indicates the role of immunological mechanisms. Frailty screening and management in this group have progressed, with specialized clinics and programs concentrating on multidisciplinary care. Potential pharmacotherapeutic solutions, as well as novel e-health programs and sensors, are in the future of frailty treatment, but it is critical to ensure that frailty evaluation is not exploited to perpetuate ageist healthcare practices. This narrative review investigates the changing healthcare environment for older people living with HIV (OPLWH), notably in high-income countries. It emphasizes the significance of identifying and managing frailty as a crucial feature of OPLWH's holistic care and well-being.

Факторы формирования неопластических процессов в шейке матки

Aim: Review the literature data on the pathogenetic aspects of the formation of squamous intraepithelial lesions and the role of immunological mechanisms in the formation of this group of cervical diseases. Key Points. Cervical cancer (CC) is a multi-stage process that is often preceded by human papillomavirus (HPV)-associated intraepithelial lesions. The establishment of causal interactions between the virus and malignancy, as well as the study of epidemiological data, leads to the formation of models of cervical carcinogenesis: infection, persistence, progression to the precancerous stage, and finally, cervical cancer. Despite the clear and obvious path of malignancy, as well as the availability of generally available diagnostic methods in the arsenal of a practicing obstetrician-gynecologist, the assessment and prediction of the further development of cervical pathologies in patients of active reproductive age remains difficult. In general, cervical cancer can be considered an excellent model for understanding the staging of malignancy processes, which will be primarily associated with the impact of human papillomavirus infection and changes in the immunological aspects of endo-and exo-cervix. Conclusion. An analysis of sources published in the Cochrane Librare, Google Scolare and PubMed systems was carried out. In recent years, the understanding of human papillomavirus-associated tumor interaction with the host immune system has improved, so the development of new approaches targeting immune checkpoints has sparked interest in the use of immunotherapy in cervical cancer. CC is curable if detected at an early stage. However, reliable diagnostic and prognostic markers related to the physiological and pathological regulation of cervical cancer are currently not available. Therefore, the approach to the treatment of cervical cancer has remained unchanged for several decades, and new diagnostic strategies are currently required, due to the interaction of the immune system and the virus. Keywords: genotyping, apoptosis, cervical neoplasia, polymerase reaction, interleukin-18, tumor necrosis factor alpha, viral load.

Impact of sterile leukocyturia on outcome of critically ill patients with severe acute kidney injury.

The role of immunological mechanisms on renal regeneration and functional recovery after an episode of Acute Kidney Injury (AKI) is still understudied. We aim to evaluate the impact of sterile leukocyturia on outcomes of critically-ill AKI patients. A retrospective analysis of critically-ill patients with stage ≥2 AKI by KDIGO was performed. Patients with urinary tract infection, previous renal replacement therapy, chronic kidney disease stage >3 and kidney, urinary tract or prostatic cancer were excluded. Sterile leukocyturia was defined as a positive leukocyte esterase value. 108 patients with stage ≥2 AKI were included, 39.8% of which had sterile leukocyturia. AKI patients with sterile leukocyturia were older, had more cardiovascular disease and a lower baseline renal function (p<0.05). They had a higher serum creatinine and leukocytosis at admission, were more frequently septic (p<0.05) and had more persistent AKI by both KDIGO criteria at multivariable analysis (OR 6.130, 95% CI 2.007-18.747). Sterile leukocyturia was associated with different patient baseline and AKI characteristics and more persistent AKI by both KDIGO criteria. Sterile leukocyturia may represent a surrogate marker of renal inflammation during AKI.

The Role of Immunological Mechanisms in Physiological Pregnancy and the Consequences of Disturbing Them during in vitro Fertilization

The Role of Immunological Mechanisms in Physiological Pregnancy and the Consequences of Disturbing Them during in vitro Fertilization

Serum exosomes of chronic gastritis patients infected with Helicobacter pylori mediate IL-1α expression via IL-6 trans-signalling in gastric epithelial cells.

Emerging evidence has linked the exosomes to many immunological disorders, including infectious diseases. However, knowledge regarding the role of exosomes in Helicobacter pylori infection is limited. Here, we show that serum exosomes from chronic gastritis patients with H. pylori infection (Hp exosomes) stimulate the expression of the soluble interleukin (IL)-6 receptor (sIL-6R), which is involved in IL-6 trans-signalling in gastric epithelial cells. Interestingly, sIL-6R up-regulates expression of the proinflammatory cytokine IL-1α, and the neutralization of sIL-6R suppresses IL-1α secretion. Thus, Hp exosomes regulate IL-1α expression via sIL-6R-mediated IL-6 trans-signaling. Altogether, this study reveals a novel perspective in which exosomes play a vital role in immunological mechanisms during H. pylori infection.

Adult-Onset Distal Renal Tubular Acidosis with Hypokalemic Quadriparesis in a Patient with Autoimmune Hypothyroidism

A 40-year-old lady, a known case of hypothyroidism, presented with 1-day history of progressive weakness in all four limbs and reported a history of similar episodes since 3 years. Clinical examination revealed grade 2 hyporeflexic quadriparesis without any bulbar involvement. Workup revealed hypokalemia, non-anion gap hyperchloremic metabolic acidosis and alkaline urine suggestive of distal renal tubular acidosis (RTA). Antiperoxidase and antithyroglobulin antibodies were positive, suggestive of an autoimmune basis for hypothyroidism. She was managed with intravenous potassium chloride, thyroid replacement and bicarbonate therapy, following which remarkable recovery was noted. One week later, she was discharged on oral thyroxine and oral sodium bicarbonate and she remained weakness-free for a follow-up period of over 1 year. RTA presenting in a setting of autoimmune hypothyroidism is a rare occurrence and the possible role of immunological mechanisms and thyroxine deficiency in the pathogenesis of acidification defect seems most likely.

Is there a Role for Immunological Mechanisms in Etiopathogenesis of Obsessive Compulsive Disorder?

Byline: Naren. Rao, M. Reddy, Janardhan. Reddy Obsessive compulsive disorder (OCD) is a common and debilitating neuropsychiatric disorder with a prevalence of approximately 2%. Though selective serotonin reuptake inhibitors (SSRI) are the mainstay of treatment, it is increasingly being recognized that serotonin abnormality may be the final common pathway and other mechanisms may also play important roles in the etiopathogenesis of OCD. Growing evidence from different lines of research in the last few years suggest possible role of immunologicalabnormalities in the pathogenesis of OCD. [sup][1] Influential studies from National Institute of Mental Health suggested higher prevalence of OCD and tics in patients with Sydenham's chorea and group A Streptococcal infection, implicating immunological mechanisms in a subtype of childhood OCD such as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). [sup][2] Following this, studies examined other markers of immune abnormality and reported higher concentration of anti-basal ganglia antibodies [sup][3] and increased prevalence of B lymphocyte marker D8/17 [sup][4] in OCD patients than in healthy controls. Neuroimaging studies supported immune hypothesis in PANDAS, reporting decreased basal ganglia volume in children with streptococcus-associated OCD [sup][5] as well as correlation between basal ganglia volume and anti-basal ganglia antibody titers. [sup][5],[6] While these results suggest a role of immunological mechanisms in the pathogenesis of OCD, one needs to be careful before drawing final conclusion because these results are preliminary and not unequivocal. [sup][7] Recent research advances in psychoneuroimmunology have implicated cytokines as mediators between brain and immune system. In addition to their role in peripheral inflammation, cytokines affect central nervous system functioning by altering the neurotransmitter systems, importantly serotonin and glutamate. Pro- and anti-inflammatory cytokines have stimulatory and inhibitory effects, respectively, on the activity of enzyme indoleamine 2,3 dioxygenase (IDO). Stimulation of IDO converts tryprophan to kynurenine, decreasing tryptophan availability for serotonin production. Kynurenine is further converted to quinolinic acid, which is a glutamate (NMDA) receptor agonist. [sup][8] Hence, cytokines are proposed to play an important role in the pathogenesis of different neuropsychiatric disorders such as depression, post-traumatic stress disorder, schizophrenia, and dementia. In the last decade, studies have examined plasma cytokines in the pathogenesis of OCD, but have reported inconclusive results. On the other hand, few studies have reported elevated cytokine levels in OCD, with majority studies reporting absence of difference between patients and controls, as also corroborated by a recent meta-analysis. [sup][9] In summary, the existing data is inconsistent regarding the role of immunological mechanisms in the pathogenesis of OCD. The evidence does not conclusively suggest a role of immunological mechanisms in the pathogenesis for OCD in general, and, at the same time, does not rule out its possible role in a subgroup of OCD. Few possible reasons for the inconsistency are methodological. First, OCD is a heterogeneous disorder with varying age at onset, and pediatric OCD may be distinctly different from adult OCD. While pediatric OCD studies have implicated possible role for immunological mechanisms, results of studies in adult OCD are equivocal. In one study, age at onset had negative correlation with tumor necrosis factor-a levels, [sup][10] further supporting this view. Second confounding factor is the presence of comorbid diagnosis, importantly depression. Only few studies have examined OCD patients without comorbid diagnosis, and because immunological mechanisms are implicated in pathogenesis of other psychiatric disorders as well, it is difficult to delineate the effects specific to OCD. …

The association of adenosine deaminase with coronary artery disease: Effect of gender and diabetes

An association between ADA1 and Coronary Artery Disease (CAD) has been observed in Polish and in Italian populations but in Italian population the association was present in males only. In order to enlighten these differences we have carried out a collaborative study in the two populations. In Italy 215 subjects admitted to the Hospital for CAD, 275 subjects with Type 2 Diabetes (T2D) without CAD and 398 healthy new-borns were studied. In Poland 173 subjects with CAD and 200 healthy newborns were studied. Written informed consent was obtained from all subjects or from their mothers to participate to the study that was approved by the I.R.B. ADA1 polymorphism was determined by DNA analysis. Three way contingency table analysis was performed by a log linear model. The association between CAD and ADA1 is present in non diabetic male subjects only: OR = 0.195, p = 0.007 in the Italian population and OR = 0.163, p = 0.004 in the Polish population. The data suggest a significant role of immunological mechanisms in the pathogenesis of CAD without diabetes. Gender differences in immune diseases could explain the lack of association in females.

Severe herpes simplex virus encephalitis in a pediatric patient – the role of immunological mechanisms in diagnosis and treatment

Introduction Herpes simplex encephalitis (HSE) is the most common sporadic viral encephalitis in children in Western countries. Only early administration of antiviral drugs can improve the mortality rate, which goes up to 70% without treatment. In different pediatric studies on children with HSE treated by acyclovir about 50% of patients recovered fully, whereas about 40% stayed with moderate to severe neurological impairment. Recent studies reported that specific genetic immunodeficiencies lead to increased HSE susceptibility and that secondary immune-mediated processes can modify disease evolution. Some of these immunodeficiencies such as defects in Toll-like receptor signalling can be detected by cheap and fast tests.

Rate of progression determines the clinical outcome after neural transplantation in Parkinson's disease

Sir, I read with great interest the article by Piccini et al . (2005) analysing factors affecting the clinical outcome after foetal neural transplantation in Parkinson's disease. A recent review on the same topic emphasized the role of immunological mechanisms, tissue manipulation before grafting and graft placement (Winkler et al ., 2005), which can be of utmost relevance in explaining the negative final outcome shown by double-blind studies (Freed et al ., 2001; Olanow et al ., 2003). By using PET technology, Piccini et al . determined the amount of 18F-dopa uptake and 11C-raclopride binding in the grafted putamen, as well as in other areas that receive dopamine innervation, and correlated them with the clinical outcome during the first 2 years after transplantation. They found an increased 18F-dopa uptake in the grafted putamen in all patients. Patients with the worst outcome showed a parallel progressive reduction of 18F-dopa uptake in substantia nigra and median raphe region, as well as in the ventral striatum in which the uptake was reduced even before grafting. These areas are innervated by dopamine neurons located on the dorsal tier of the substantia nigra pars compacta and the ventral tegmental area. This suggests a continuing loss of dopaminergic neurons in substantia nigra despite a functioning graft that could affect the evolution of symptoms after transplantation. Thus, Piccini et al . state that the overall functional impact of dopamine neuron replacement is less pronounced in patients with more widespread …

Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants.

Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level >1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. Of the 57 haploidentical patients, there were 33 males and 24 females. The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058). Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients.

Changes in interleukin-1 and tumor necrosis factor production by peripheral blood monocytes after specific bronchoprovocation test in occupational asthma.

The pathogenetic mechanisms of occupational asthma (OA) due to low-molecular-weight compounds have been poorly defined, and further studies are required to clarify the role of immunologic mechanisms in OA. Until now cellular mechanisms have been less investigated than humoral ones. We have evaluated interleukin-1 (IL-1) and tumor necrosis factor (TNF) production by peripheral blood monocytes (PBM), and peripheral T-cell subpopulations in 22 subjects with possible OA before and after specific bronchoprovocation test (SBPT). After SBPT, three subjects had an immediate reaction, seven a late reaction, and two a dual reaction. Ten subjects had no asthmatic reaction to SBPT. Spontaneous release of IL-1 from PBM did not change significantly after SBPT. TNF activity was increased 48 h after SBPT in immediate reactions and 72 h after SBPT in late-dual reactions. These results suggest that exposure to occupational agents may induce activation of PBM with increased spontaneous release of cytokines, such as TNF.

IMMUNOLOGIC AND CLINICAL FEATURES OF TOXIC INHALATIONS

Irritant gases and dusts can cause intense damage to the airway. Some authors have speculated that the irritant effects of these gases in the airway are the mechanism for the development of bronchial hyper-responsiveness and occupational asthma in patients exposed to sensitizing chemicals. Others have postulated that toxic inhalation produces airway damage that increases the susceptibility to antigen entrance into the subepithelial layer of the bronchial mucosa, which, in some unexplained way, increases the risk for subsequent hypersensitivity to that antigen. Other toxic gases, such as chlorine, produce airway damage that may take months or years to develop through unknown mechanisms. Toxic dusts may produce an atypical form of hypersensitivity pneumonitis, most likely nonimmunologically mediated, related to the effects of high concentrations of microbial and mycotoxins. The role of immunologic mechanisms in a variety of toxic inhalation syndromes is unclear.

Immunological abnormalities in patients with untreated retinal vasculitis.

Peripheral blood immunological features were assessed in 21 patients with clinical and angiographic evidence of retinal vasculitis (RV). Abnormalities of humoral and cellular immunity were frequent in this group of patients. Lymphopenia was the most common immunological abnormality, being present in 76% of patients at presentation (p less than 0.05). Peripheral blood T and B cells were decreased with a normal helper (OKT4) to suppressor (OKT8) T cell ratio in 11 patients tested (five with Behçet's syndrome and six with idiopathic RV). Significantly increased concentrations of serum immune complexes were present in 55% of patients (p less than 0.05). Results of the present study indicate the frequent association of peripheral blood immunological abnormalities in patients with active RV and indicate the possible role of immunological mechanisms in its pathogenesis.

Role of immunologic mechanisms in tubulointerstitial nephropathies.

The immunologic basis of various glomerulonephropathies has been widely investigated and highly publicized. Little recognition, however, has been given to the possible role of the immune system in the genesis of tubulointerstitial nephropathies. Considerable clinical and experimental data have recently appeared suggesting the possible role of immunologic mechanisms in the genesis of various tubulointerstitial nephropathies. This article is intended to review the available clinical and experimental data pertaining to this issue.

Liver membrane antibodies in alcoholic liver disease. II. Antibodies to ethanol-altered hepatocytes.

Using an indirect immunofluorescence technique, circulating liver membrane antibodies against normal rabbit hepatocytes and ethanol-altered rabbit hepatocytes have been sought in a series of patients with histologically confirmed alcoholic liver disease. Liver membrane antibodies against normal hepatocytes were found in 18 (28%) of the 65 sera examined, but with ethanol-altered hepatocytes as substrate liver membrane antibodies were found in 48 (74%) of the sera. Isolation of F(ab')2 fragments confirmed that the positive results were due to antibody binding. Liver membrane antibodies against ethanol-altered hepatocytes are peculiar to alcoholic liver disease, and there is a similar incidence in the various histological types of alcoholic liver disease. Absorption studies suggest that the liver membrane antibodies are directed against new or altered antigens which are not present in normal hepatocytes. These new or altered antigens may also appear after pretreatment with other primary alcohols and seem likely to be induced by a haptenic effect of the alcohol or a metabolic break-down product. These studies represent a novel approach to the further investigation of the possible role of immunological mechanisms in alcohol-induced liver injury.

Idiopathic Inflammation Bowel Disease: is there a role for immunological mechanisms in etiopathogenesis?

From this review it seems that modest but tantalizing clues exist to support a hypothesis that microbial agents (particularly Enterobacteriaceae), host immune responses and related genetic factors are involved in the etiopathogenesis of IBD. My last slide presents such a hypothesis31) schematically in the hope that future studies to test this will ultimately resolve the enigma of these diseases.

‘Neuroimmunologic’ Diseases: Conference Provides an Interdisciplinary Overview

Increasingly. the role of immunologic mechanisms in the etiology and progression of neurologic diseases, particularly those involving demyelination, is being recognized. In appreciation of this, the Rockefeller Foundation recently convened a small group of neurologists and immunologists to exchange their views not only with respect to pathogenesis, but also with emphasis on the application of immunologic modalities to the treatment of these diseases. Among the participants was Sir Peter B. Medawar, Nobel Laureate, of the Medical Research Council, Clinical Research Centre at Harrow, England.The following special report on the conference in Bellagio. Italy, was prepared by Dr. Medawar.

Comparison of Cell-mediated Immunity to Melanoma Cells in Patients with Vitiligo, Halo Nevi or Melanoma

Cell-mediated immunity of partially purified lymphocytes to cultivated melanoma cells was measured in vitro in patients with melanoma, vitiligo or halo net, or with nonpigmentary skin disorders, and in normal individuals. With a long-term line of melanoma cells labeled with 125 I-IUDR it was impossible to discern a difference among the various groups. However, with 3 ;H-proline labeled, recently explanted melanoma cells significant differences in cell-mediated immunity were demonstrable. Twelve melanoma patients reacted to target melanoma cells, with a mean of 32.6% (SE 2.6%). In contrast, 29 patients with vitiligo had a mean reactivity of −10.3% (SE 4.5%). Seven patients with halo nevi had a mean reactivity of 51.4% (SE 7%). There was essentially no reactivity among individuals with nonpigmentary disorders or normal volunteers (mean = −9.8%, SE 8.2%). Autologous serum did not affect cell-mediated reactivity in any group. Reactivity of lymphocytes from melanoma or halo nevi patients to neuroblastoma cells and fibroblasts was slight (mean = 19% and 5%, respectively), indicating a degree of specificity, probably against pigment-containing cells. These studies indicate that idiopathic vitiligo in contrast to halo nevi is not characterized by cell-mediated immunity of peripheral blood lymphocytes against pigmented tumor cells. Other tests of immunity must be brought to bear in these disorders before the role of immunological mechanisms in vitiligo can be definitively resolved.

Immunologic Lung Disease

IN 1972, McCombs published an elegant review of diseases due to immunologic reactions in the lungs.1 Since then, intense interest in pulmonary immunology has provided new insights into the role of immunologic mechanisms in many pulmonary diseases. It is the purpose of this review to survey the diseases of the lung in which immunologic mechanisms seem important and to present current concepts regarding their immunopathogeneses.Diseases Related to Single Immunologic MechanismsAlthough it is probably an oversimplification to consider any immunologic disorder a manifestation of only one mechanism, there are several pulmonary diseases in which one type of immunologic reaction . . .