Components Of Nonspecific Immunity Research Articles

Markers of Local and Systemic Inflammation in the Diarrhea Syndrome Associated with the Coronavirus Disease (COVID-19)

Introduction: Fecal calprotectin is known to be a biomarker of inflammatory bowel problems. An increase in its level has been also noted in COVID-19 patients, which is associated with the pathogenic effect of the virus on the intestinal epithelium involving components of nonspecific immunity. Objective: To evaluate markers of local and systemic inflammation and their relationship in the diarrhea syndrome associated with the novel coronavirus disease (COVID-19). Materials and methods: We have analyzed medical histories of 90 laboratory-verified SARS-CoV-2 patients aged 35 to 70 years and divided them into three equal groups of 30 cases each by the measured level of fecal calprotectin (Group 1: CPT > 200 μg/g, Group 2: CPT = 50 to 200 μg/g, and Group 3: CPT < 50 μg/g). Results: In Group 1 patients with CPT > 200 μg/g, we observed a 1.5 times more frequent severe course of the coronavirus disease, pulmonary damage over 50 % (p < 0.05), fever and diarrhea that persisted up to 14.8 ± 0.5 and 8.7 ± 0.4 days, respectively (p < 0.05). Conclusions: We established a direct relationship between markers of local and systemic inflammation. Clinical manifestations of COVID-19 correlated with the severity of intestinal inflammation. A positive correlation was found between fecal calprotectin levels and diarrhea syndrome duration. The landscape of opportunistic intestinal microbiota also correlated with the severity of the inflammatory process in the intestine.

Activation of Innate Immunity and Autophagy in Brain Tissues with Prion Disease and Degradation of Abnormal PrPs in Cells - China's Studies.

Unlike infectious diseases caused by conventional microbes, there are no detectable specific humoral or cellular immunoresponses to prion infection. However, extensive and active gliosis is observable in affected brain regions along with significant deposits of scrapie-like prion protein (PrPSc). Here, we summarize our studies of vibrant activation of host non-specific immune components and autophagy in the microenvironment of prion infected brains. Activation of the brain’s innate immunity and autophagy upon prion infection reflect non-specific host defense systems attempt to dispose of accumulated prions. Vibrant elevation of neuroinflammation leads to neuron injury.

Lactoferrin and Peptide-derivatives: Antimicrobial Agents with Potential Use in Nonspecific Immunity Modulation.

Lactoferrin (Lf) is a conserved cationic non-heme glycoprotein that is part of the innate immune defense system of mammals. Lf is present in colostrum, milk and mucosal sites, and it is also produced by polymorphonuclear neutrophils and secreted at infection sites. Lf and Lf N-terminus peptide-derivatives named lactoferricins (Lfcins) are molecules with microbiostatic and microbicidal action in a wide array of pathogens. In addition, they display regulatory properties on components of nonspecific immunity, including toll-like receptors, proand anti-inflammatory cytokines, and reactive oxygen species. Mechanisms explaining the ability of Lf and Lfcins to display both up- and down-modulatory properties on cells are not fully understood but result, in part, from their interactions with membrane receptors that elicit biochemical signal pathways, whereas other receptors enable the nuclear translocation of these molecules for the modulation of target genes. The dual role of Lf and Lfcins as antimicrobials and immunomodulators is of biotechnological and pharmaceutical interest. Native Lf and its peptide-derivatives from human and bovine sources, the recombinant versions of the human protein, and their synthetic peptides have potential application as adjunctive agents in therapies to combat infections caused by multi-resistant bacteria and those caused by fungi, protozoa and viruses, as well as in the prevention and reduction of several types of cancer and response to LPS-shock, among other effects. In this review, we summarize the immunomodulatory properties of the unique multifunctional protein Lf and its N-terminus peptides.

Increased activity of lysozyme and complement system in Atlantic halibut exposed to elevated CO2 at six different temperatures

Ocean acidification and rising seawater temperature are environmental stressors resulting from the continuous increase of the atmospheric CO2 concentration due to anthropogenic activities. As a consequence, marine fish are expected to undergo conditions outside of their tolerance range, leading to physiological challenges with possible detrimental implications. Our research group has previously shown that exposure to elevated CO2 modulated the immune system of the Atlantic halibut. To further investigate this finding, we analysed non-specific immune components in blood plasma of Atlantic halibut (Hippoglossus hippoglossus) juveniles acclimated to six different temperatures (5, 10, 12, 14, 16 and 18 °C), and to water pH of 8.0 (control) or 7.6 (predicted for year 2100) for three months. Plasma ions (K+, Na+, Ca++, Cl−) and lactate concentrations were also measured. The analysis of plasma ions did not show any trends related to temperature or CO2 exposure, and the majority of the experimental fish were able to maintain ionic balance. The results show that both innate immune components (lysozyme and alternative complement system) had increased activities in response to elevated CO2, representing a CO2-related impact on the halibut's immune system. The increased activity of lysozyme and complement system is possibly part of the acclimatization process, and might be protective.

The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

Newcastle disease (ND) is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius) and cellular (thymus and spleen) lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa), phagocytic cells (macrophages and natural killer), protein complement and the mediator of inflammation and cytokines. Interferons (IFNs) belong to a group of cytokines that play a major role in the nonspecific or innate (natural) immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity) when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI) and cell-mediated immunity (CMI). The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

Use of Canonical Correfslation Analysis to Evaluate the Strength of Relationships between Clinical and Biological Parameters

Studies were performed using, an example, the relationship between nonspecific immunity factors and therapeutic efficacy in endogenous psychosis. The canonical correlations method demonstrated a strong and significant (Canonical, R > 0.8; p = 0.02) positive relationship between the efficacy of treatment with neuroleptics (haloperidol and clozapine) and pretreatment nonspecific immunity factors in a group of juvenile and young adult (16–34 years) men with schizophrenia (34 patients), with first onset of manifest endogenous psychosis. Treatment efficacy was assessed in terms of the reduction (%) in total points on the PANSS or the numbers of points on PANSS subscales for positive, negative, and psychopathological disorders between the beginning and end of treatment (60 days). Initial values for nonspecific immunity factors (T-lymphocyte γ-interferon production levels, proportion of phagocytosing neutrophils and monocytes, and lymphocyte natural killer cytotoxic activity) were found to account for 67.3% (i.e., more than two thirds) of treatment efficacy. The contribution of nonspecific immunity factors resulted mainly from their essentially identical influences on decreases in positive and psychopathological symptoms and was minimal in relation to decreases in negative symptoms on the PANSS. The strongest relationships were seen with weighting coefficients for nonspecific immunity factors (in decreasing order) of 0.567 for the proportion of phagocytosing neutrophils and monocytes, 0.518 for T-lymphocyte γ-interferon production levels, and 0.334 for lymphocyte natural killer cytotoxic activity. It is suggested that there are reductions in the activities of factors of the cellular components of nonspecific immunity before manifestation of disease, which create the conditions for activation of persistent latent microorganisms (in the present case cytomegalovirus infection) in the patient’s body, with formation of therapeutic resistance. This method may find wide use in clinical and biological psychiatry and neurology.

Modulation and Interaction of Immune‐Associated Parameters with Antioxidant in the Immunocytes of Crab Scylla paramamosain Challenged with Lipopolysaccharides

Invertebrates are dependent on cellular and humoral immune defences against microbial infection. Scylla paramamosain is an important commercial species, but the fundamental knowledge on its immune defense related to the antioxidant and immune-associated reactions is still lacking. The study was to differentiate the responses of immune-associated parameters of haemolymph components in S. paramamosain when challenged with bacterial lipopolysaccharides (LPSs). The immunostimulating effects of LPS in crab by triggering various immune parameters (phagocytosis, lysozyme, antibacterial activity, phenoloxidase, and the generation of superoxide and nitric oxide) were investigated. Results showed that the generation of free radicals, phenoloxidase, lysozyme and antibacterial activities was significantly increased through the exposure periods. Conversely, total hemocyte count and lysosomal membrane stability decreased significantly as the exposure period extended to 96 h. The relationship between the antioxidant enzymes and immune reactions due to LPS was highly significant. In addition, ROS production was positively correlated with antioxidant showing immediate response of antioxidant defense to the oxyradicals generated. Overall, the study indicated that nonspecific immune components in hemocytes of crab showed active response to the LPS stimulation, and their responses suggested that many immune-associated parameters could be modulated and interrelated with the influence of antioxidants in crustaceans.

Evaluation of non-specific immune components from the skin mucus of olive flounder ( Paralichthys olivaceus)

The innate immune system, particularly the external body surface, plays a frontier role in protecting fish under intensive aquaculture and at prolonged low temperatures from relevant infections due to inadequate adaptive immune responses. In the present study we aimed to understand the mucosal immunity of an economically important mariculture fish, olive flounder ( Paralichthys olivaceus) by evaluating the immune components from its skin mucus. The activities of lysozyme (233.33 ± 171.82 units mg −1), trypsin-like protease (42.84 ± 1.249 units mg −1), alkaline phosphatase (0.376 ± 0.005 units mg −1) and esterase (0.170 ± 0.006 units mg −1) were detected in the skin mucus. Transferrin was identified by MALDI-TOF/MS analysis. ELISA and immunoblot assays using anti-flounder IgM monoclonal antibody showed the presence of a significant level (1.80 ± 0.001, n = 3) of monomer immunoglobulin M (IgM) with approximate molecular weight of 160 and 25 kDa under non-denaturing and denaturing states, respectively. Skin mucus showed strong antibacterial activity against tested fish pathogenic bacteria. In addition, skin mucus successfully agglutinated (HA titre 2 8), but completely failed to haemolyse, rabbit erythrocytes. In conclusion, the major immune components of the skin mucus, identified in the present study, are possibly involved in the broad spectrum non-specific immunity of olive flounder.

In vitro combined effect of co-amoxiclav concentrations achievable in serum after a 2000/125 mg oral dose, and polymorphonuclear neutrophils against strains of Streptococcus pneumoniae exhibiting decreased susceptibility to amoxicillin

The in vitro effect that the presence of components of non-specific immunity (serum plus polymorphonuclear neutrophils) has on the bactericidal activity of co-amoxiclav was explored against Streptococcus pneumoniae strains exhibiting an amoxicillin MIC ≥4 mg/L. Eight penicillin-resistant clinical isolates non-susceptible to co-amoxiclav with MICs of 4 (two strains), 8 (four strains) and 16 mg/L (two strains) were used. Values of MBC were identical to MIC values in all cases. Time-kill curves were performed with co-amoxiclav concentrations achievable in serum after a single oral dose administration of the new 2000/125 mg sustained-release formulation. Results were expressed as percentage of reduction of initial inocula after 3 h incubation. Control curves showed growth with no reduction of initial inocula. Against strains with MIC of 4 and 8 mg/L, the results obtained with the antibiotic alone or with the presence of factors of non-specific immunity were similar, with a weak combined effect due to the intrinsic activity of co-amoxiclav (reductions of initial inocula ranging from 70 to 99.16%). Against strains with MIC of 16 mg/L, the addition of PMN in the presence of serum increased the reduction of bacterial load provided by the aminopenicillin, even at sub-inhibitory concentrations (25.8% versus 51.1% at 0.5×MIC concentration − 8/0.5 mg/L). This combined activity against strains with an amoxicillin MIC of 16 mg/L which decreased the bacterial load may be important in preventing bacterial proliferation within the host and the transmission of resistant clones to others.

Maternal modulation of specific and non-specific immune components of colostrum and mature milk.

The neonates of most mammalian species cannot survive on an adult diet or exposure to an array of adult pathogens. Lactation provides a transitional period for the immature newborn to adapt to the adult environment. However, there is immense variation in the metabolic maturity of mammals at birth, as well as in the rate of postnatal growth and development during the lactation period. As a result, large differences in milk composition have evolved among mammals (Oftedal and Iverson, 1995). Furthermore, large progressive changes in milk composition occur during lactation to meet the changing metabolic needs of the young (Nicholaset al.1997). For example, the Tammar Wallaby has a relatively short gestation period, during which Phase 1 of mammary development occurs. The animal weighs only 400 mg at birth and remains permanently attached to the teat for the next 130 days, while growing to 100 g (Phase 2A). The pouch young (PY) then detaches from the teat and sucks intermittently to reach a weight of 400500 g by 200 days of age (Phase 2B). The PY then leaves the pouch intermittently until 260 days when it exits the pouch permanently, finally weaning at 300 days, at a weight of 1.6-2.5 kg (Phase 3). The increase in body weight of the young from about 0.5 g to 2000 g during lactation is associated with major changes in milk composition that define phases 2A, 2B and 3 of lactation. Both mammary gland size and milk production increase commensurate with the rate of growth of the young.

Antigen specific and nonspecific modulation of the immune response by aminolevulinic acid based photodynamic therapy

Photosensitizers used normally in treating cancers have considerable potential for treatment of other diseases. One such photosensitizer is the endogenously synthesized photosensitizer protoporphyrin IX (PpIX). To better understand how protoporphyrin might be used in transplantation or in treating autoimmune diseases, information must be obtained on how the photosensitizer affects all immune cells. We used a combination of flow cytometry and in vitro activation assays (recall assays and mixed-lymphocyte reactions) to examine the effects of PpIX on the antigen specific component, lymphocytes and the non-antigen specific component, the macrophages/monocytes and dendritic cells of the immune system. Whereas, lymphocytes accumulate PpIX only when activated, both macrophages and dendritic cells accumulated PpIX immediately, without in vitro activation, as measured by flow cytometry. ALA–PDT (aminolevulenic acid–photodynamic therapy) treated adherent cells in the recall assay had a decreased capability to activate lymphocytes. By increasing the light dose in the recall assay, antigen primed lymphocytes were selectively eliminated from a population of cells. Stimulator cells in an MLR had a decreased stimulatory capacity following ALA–PDT treatment. Functional alterations are seen in both the antigen specific and nonspecific immune components.

Disease resistance in rainbow trout ( Oncorhynchus mykiss) selected for stress response

Two lines of rainbow trout, selected for either high or low stress response as measured by blood cortisol levels, were challenged by two bacterial pathogens, Aeromonas salmonicida, causing furunculosis and Vibrio anguillarum, causing vibriosis. In both challenge experiments, the survival rates during the experiment, and the total accumulated mortality at termination of the experiment, were significantly different between the two lines. Whereas in the furunculosis challenge the death rate in the high-stress response line was higher than in the low-stress response line, the opposite was true for the vibriosis challenge. Two non-specific immune components were analysed in the challenged fish: serum haemolytic activity, which was higher in low-stress fish than in high-stress fish; and lysozyme, which had higher measures in high-stress fish. The results of the present study indicate that selection for stress response affects the disease resistance of rainbow trout, albeit not in an unambiguous direction in respect to different diseases.

Avian Inflammatory Response: Mediation by Macrophages

The inflammatory response is one of the best defined components of nonspecific immunity in birds. Introduction of an immunogen into the skin or peritoneal cavity results in a characteristic series of local and systemic responses. Initially, locally produced chemotactic substances cause heterophils and monocytes to emigrate from the blood through postcapillary venules to the site of immunogen. Monocytes and heterophils phagocytize the immunogen and monocytes can initiate specific immunity mediated by lymphocytes. Monocytes release a variety of hormone-like substances (monokines) that act locally to coordinate the localized inflammatory response and facilitate lymphocyte responses. These same monokines can gain entrance into the circulation and act systemically to orchestrate the acute phase response. Monokine activities characterized to date are similar to mammalian interleukin-1, interleukin-2, tumor necrosis factor, and granulocyte-stimulating factor. The inflammatory response is active in the embryo midway through incubation and is probably instrumental in protection of the embryo. Inappropriate or overexuberant inflammatory responses can lead to a variety of pathologies in the chicken, demonstrating the importance of precise regulation of the inflammatory response.

THE STATE OF INNATE IMMUNITY IN NORMOTROPHIC PIGLETS IN THE EARLY POSTNATAL PERIOD

The article presents the dynamics of changes in the performance of hematological, biochemical, humoral and cellular components of nonspecific immunity in normotrophic piglets from its birth to weaning from sows. The age-related changes in the performance in all the components of nonspecific immunity in piglets, connected with the adaptation of the organism to the new existence conditions and the activation of the duties of their organs and systems, have been established. In the hematological component, the changes were manifested by a higher content of white blood cells and lymphocytes in piglets, starting from the daily age and in the following terms of cultivation, relative to such before intake of colostrum. For the biochemical state of piglets before intake of colostrum, the most definitive were low total protein, but high albuminous and high nitrogen oxide, essential to the adaptation of animals to new existence conditions, Hypoglobulinemia. In piglets, starting from the daily age, the total protein, globulins, and especially gamma globulins, promoting the humoral defense, are increased, and the albuminous is decreased. The humoral performance of non-specific defense for piglets before colostrum intake is characterized by a low activity of the complement system, which increases up to 14 days-age, followed by its thereafter decrease. Serum bactericidal activity is decreased on the 22nd, and lysozyme activity - on the 26th day of age. From the daily age and in the days following, neutrophil phagocytic activity; stimulated NBT test, and phagocyte reserve number exceeded like that before intake of colostrum. Absorbtivity of neutrophils and spontaneous NBT test increased only in daily age piglets. The lowest level of nonspecific immune defense in piglets during the last week of the suckling period, manifested by a decrease of the bactericidal activity, of lysozyme activity, and of complementary activity of blood serum, of monocytes, and of gamma-globulins, is due to a decrease in sow productivity.