Factors influencing phagocytosis of malaria parasites: the story so far

There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.

Аllergic Basal Deciduitis as a Reason of Recurrent Antenatal Fetal Death

BACKGROUND: Allergic diseases of pregnant women are associated with chronic placental insufficiency and the development of immunopathological conditions of unknown etiology in a child in postnatal life. Pregnancy with bronchial asthma is often complicated by intrauterine growth retardation, preeclampsia, and antenatal fetal death. AIM: The objective was to present a clinical case of recurrent antenatal fetal death in the third trimester in women with bronchial asthma under controlled course. CASE REPORT: Pregnancy proceeded without clinical signs of exacerbation of bronchial asthma and allergic status. However, chronic inflammation with eosinophilia in the intervillous space and the basal lamina was revealed in the placenta tissue. Eosinophilia of the intervillous area was accompanied by obliteration of the intervillous area by fibrin deposits. CONCLUSION: We suppose that immunological inflammation at the fetoplacental unit level can occur regardless of the mother’s allergic status. Moreover, it is likely that the objective state of the mother in the presence of an allergic disease does not reflect the presence/absence of an immunological process in the placenta, as the immunological inflammatory process can develop in different compartments (at the level of the mother’s body and the placental-fetal compartment) with varying degrees of severity.

Pembrolizumab-Induced Thyroiditis Shows PD-L1Expressing Histiocytes and Infiltrating T Cells in Thyroid Tissue - A Case Report

ContextImmune-related adverse events frequently take place after initiation of immune checkpoint inhibitors (ICI) therapy. The thyroid gland is the endocrine organ most commonly affected by ICI therapy, the pathological mechanism is still poorly understood.Case DescriptionA 60-year old Upper Austrian male melanoma patient under pembrolizumab therapy received thyroidectomy because of a suspicious FDG avid thyroid nodule. Histopathology showed a pattern comparable with thyroiditis de Quervain. The inflammatory process consisted predominantly of T lymphocytes with a dominance of CD4+ T helper cells. In addition CD68+ histiocytes co-expressing PD-L1 were observed.ConclusionClusters of perifollicular histiocytes expressing PD-L1 were observed in this case of pembrolizumab induced thyroiditis - probably induced by the former ICI therapy. This finding might indicate the initial target for the breakdown of self tolerance. In context with other data the immunological process seems to be driven by CD3+ lymphocytes infiltrating the thyroid.

From Flies to Men: ROS and the NADPH Oxidase in Phagocytes

The cellular formation of reactive oxygen species (ROS) represents an evolutionary ancient antimicrobial defense system against microorganisms. The NADPH oxidases (NOX), which are predominantly localized to endosomes, and the electron transport chain in mitochondria are the major sources of ROS. Like any powerful immunological process, ROS formation has costs, in particular collateral tissue damage of the host. Moreover, microorganisms have developed defense mechanisms against ROS, an example for an arms race between species. Thus, although NOX orthologs have been identified in organisms as diverse as plants, fruit flies, rodents, and humans, ROS functions have developed and diversified to affect a multitude of cellular properties, i.e., far beyond direct antimicrobial activity. Here, we focus on the development of NOX in phagocytic cells, where the so-called respiratory burst in phagolysosomes contributes to the elimination of ingested microorganisms. Yet, NOX participates in cellular signaling in a cell-intrinsic and -extrinsic manner, e.g., via the release of ROS into the extracellular space. Accordingly, in humans, the inherited deficiency of NOX components is characterized by infections with bacteria and fungi and a seemingly independently dysregulated inflammatory response. Since ROS have both antimicrobial and immunomodulatory properties, their tight regulation in space and time is required for an efficient and well-balanced immune response, which allows for the reestablishment of tissue homeostasis. In addition, distinct NOX homologs expressed by non-phagocytic cells and mitochondrial ROS are interlinked with phagocytic NOX functions and thus affect the overall redox state of the tissue and the cellular activity in a complex fashion. Overall, the systematic and comparative analysis of cellular ROS functions in organisms of lower complexity provides clues for understanding the contribution of ROS and ROS deficiency to human health and disease.

HEMATOLOGICAL INTEGRATED INDICATORS IN ASSESSING THE CELLULAR REACTIVITY OF THE BODY IN COVID-19 CORONAVIRUS INFECTION

The article analyzes the disorders in homeostasis diagnosed during the development of acute viral infection SARS-CoV-2 in patients. Hematological changes in patients with coronavirus infection were characterized by the development of disintegration of humoral mechanisms of regulation with the initiation of a systemic inflammatory reaction with an increase in the leukocyte index of intoxication, activation of necrobiotic processes, an increase in the activity of macrophage-microphage nonspecific protection with a predominance of effector links of the immunological process. The development of immunocompromise in patients with a new strain of coronavirus infection is one of the determining factors in the course of the disease.

LEVEL OF PROCALCITONIN PLASMA AS AN EARLY SEPSIS BIOMARKER IN POLYTRAUMA PATIENTS IN DR HASAN SADIKIN GENERAL HOSPITAL BANDUNG

Background: Polytrauma patients have a risk of progressive organ dysfunction due to uncontrolled immunological process. Sepsis and multiple organ failure are the most common causes of morbidity and mortality in late death of polytrauma patients. Clinical diagnosis and routine laboratory test are not specific until the patient entered a critical state. Delayed diagnosis of sepsis is caused by difficulties in diagnosing. Procalcitonin is a biomarker that is useful in predicting the onset of sepsis. The aim of this research is to determine the level of procalcitonin as early biomarker sepsis in polytrauma patients in RSHS Bandung. Methods: A diagnostic study using secondary data from the Academic Leadership Grant (ALG) study on polytrauma patients in Emergency Room of RSHS Bandung from January-June 2017. This study determined the cut of point, sensitivity, spesificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and accuracy to diagnosis sepsis.Result: A total of 70 subjects were enrolled in this study, 92.9% were male gender with average age 33.21±13.395 years old. Twenty-one patients (30%) were diagnosed with sepsis. Based on receiver operating characteristic (ROC) curve showed the level of procalcitonin was given in the area under curve (AUC) 0.96 with Confidence Interval 0.923-1.00 (p < 0.05). The Procalcitonin cut of point was 1.46 ng/mL with a sensitivity of 90.5%, specificity of 89.8%, PPV of 79.2%, NPV of 95.7%, and accuracy of 90.0%.Conclusion: Plasma Procalcitonin 1.46 ng/mL is a good predictor for early diagnosis sepsis toward polytrauma patients.

Reduced humidity induces skin barrier dysfunction and secretion of dipeptidyl peptidase-4 (DPP-4) in a skin-equivalent model

Seasonal changes can affect the physiological condition of the skin and cause various cutaneous disorders. The skin barrier function tends to worsen during winter when humidity is lower compared to other seasons. To determine the influence of relative humidity (RH) on the function of the skin barrier, we performed biological and histological assays using skin equivalents that were cultured under reduced humidity in an environmental humidity chamber. We found that reduced humidity led to decreased epidermal thickness and disruption of the skin barrier. Reduced humidity induced the decrease of filaggrin, loricrin and damage to tight junction. In addition, dipeptidyl peptidase-4 (DPP4), which has roles in the immunological process, was upregulated in a skin-equivalent model under reduced humidity. These results suggest that reduced humidity affects the skin barrier function and regulates the secretion of DPP4 in a skin-equivalent model.

Effects of X-Ray Exposure on Some CMI Regulatory Cytokines in Technicians Serum Samples

Ionizing radiation considered as an immunosuppressive factor upon over dose of exposure. Radiation field workers usually following a periodic checkup to monitor changes in their clinical status. Cell Mediated Immunity (CMI) has an important cytokines that regulate this specific immunological process. This study estimated the Interleukins (IL-2, IL-12 and IL-18) levels in serum samples using ELISA technique. Serum samples were collected from X-ray Technicians (Radiography, Fluoroscopy and Computed Tomography Scan Technicians) working in AL-Muthanna governorate hospitals. A total of (60) technicians and (30) control were involved in this research. Results showed significant decrease in IL-2 levels and increase in IL-18 levels in test groups (technicians) as compared with controls. While, IL-12 levels did not show a difference; all obtained values were within normal range. Overdose of X-ray exposure caused CMI suppression via disturbing the levels of critical cytokines (IL-2 and IL-18) leading to CMI loss regulation.

Treatment Standards and Individualized Therapy of Myasthenia Gravis

A wide range of established treatment options is currently available for myasthenia gravis. These include cholinesterase inhibitors for symptomatic treatment and a broad spectrum of immunosuppressive, immunomodulating or cell-depleting options to modify the underlying immunological process. Appropriate use allows the great majority of patients to lead a normal life. Specialized centers integrating outpatient and in-hospital resources as well as interdisciplinary competences offer important advantages for optimum individualized therapy.