The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll-like receptor (TLR)-4 on CD4(+) cells in nasal mucosa.
To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4(+) leucocytes.
Peripheral blood mononuclear cells from children (aged 2-18) and adults with or without a history of atopic conditions were cultured with/without IL-4 or LPS for up to 24 h. Expression of surface TLR-4, CD14, CD4, CD3, as well as of intracellular phosphorylated (p42/p44) ERK and p38 mitogen-activated protein kinase (MAPK) were assessed by flow cytometry.
A history of atopy in children was associated with impaired LPS-induced TLR-4-dependent phosphorylation of (p42/44) ERK and p38 MAPK by CD4(+) monocytes. Decreased LPS signalling was reproduced by pre-incubation of control cells with recombinant IL-4. LPS stimulation also decreased TLR-4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4(+) T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non-atopic children, TLR-4 expression on monocytes of children with atopic histories decreased as a function of age.
This study provides evidence for defective LPS recognition on circulating CD4(+) leucocytes of subjects with atopic histories compared with those from non-atopic children. CD4(+) TLR4(+) monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR-4-mediated innate immune function compared with non-atopic children.
A total of 300 workers engaged in viscose industry were examined for leukocyte blast transformation, spontaneous and complement rosette-formation, blood serum immunoglobulins, bactericidal activity of blood serum, lysozyme titre, phagocytic activity of neutrophils, and the NBT test. The data obtained attest to the changes in the total nonspecific body responsiveness of the workers examined. The character and degree of the changes in cellular and humoral immunity were marked by cycles, depending on the workers' record. The changes in the total nonspecific responsiveness were found to persist for a long time even after discontinuation of the contact with carbon disulfide.
Immunomodulation properties of the composition which contains live cells of bacteria of genus Lactobacillus: L. delbrueckii subsp. bulgaricus LB86 VKPM B-5788, L. delbrueckii subsp. delbrueckii DSM20074, L. rhmanosus LB3 IMB B-7038, L. acidophilus, L. rhamnosus VR were studied. Stimulation of phagocytic system under the influence of lactobacteria composition correlated with an increase of cytotoxic activity of natural killer cells and with their influence on synthesis of cytokines: interferon and tumor necrosis factor was shown.
The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-a in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.
[The effect of etimizol on the functional status of the blood coagulation systems and fibrinolysis in workers on expedition-duty watches working under the climatic conditions of northern Tyumen Province].
The study was undertaken to reveal the effects of ethymisole on the functional status of blood coagulation and fibrinolytic systems, the body's adaptative reserves of workers from expeditionary-duty teams. Ethymisole was found to normalize the functional status of blood coagulation and fibrinolytic systems, to restore conjunction of their functioning. The use of the drug was ascertained to normalize the activity of lipid peroxidation products, to enhance the adaptative reserves of expeditionary-duty workers by prolonging the resistance phase. It is concluded that ethymisole may be used as an agent that enhances the body's adaptative reserves.
As possible alternative to a complex of sanitary-hygienic measures, directed on the infectious diseases prevention, not specific prophylaxis with the aid of immunomodulative preparations is offered. Prospects of the immunomodulative preparations application is defined by transition to popularized epidemiological thinking planned in modern conditions. Strategy of total and selective not specific prophylaxis, results of own researches on estimation of preventive efficiency of dibazolum and prodigiosanum during acute respiratory disease and virus hepatitis A are described.