Correction Of Immunodeficiency Research Articles

EFFECTIVENESS OF MICROELEMENTS IN THE FORMATION OF MECHANISMS OF PROTECTION OF THE BODY UNDER THE INFLUENCE OF ENVIRONMENTAL STRESS FACTORS

Analysis of literature data and the results of our own research show that even with intensive rearing of animals with the use of balanced feeding and keeping them in accordance with the technology - it is almost impossible to avoid stress. And especially, excessive man-made load on agroecosystems also has a negative impact on animal life.
 Factors that cause a decrease in immune status and the emergence of immune pathology in animals include: industrial technology of animal husbandry, chemicalization in crop and livestock production, man-made pressure, dietary imbalance in nutrients and biologically active substances. This increases the impact on the body of heavy metals, which displace nutrients from body tissues, in particular trace elements and replace them in metabolic processes, which is a potential prerequisite for the development of oxidative stress. The mechanism of development of stress reaction of an organism is closely connected with activity of POL (lipid peroxidation) and depression of antioxidant potential. Under these conditions, the ability of the organism to mobilize protective and adaptive capabilities in response to the action of negative factors becomes especially important. Keeping productive animals in adverse conditions, unbalanced feeding are components of immobilization stress, which reduces their productivity, affects reproductive function, metabolic and functional disorders, reducing nonspecific and specific resistance of the organism (Fedoruk & Kravtsiv, 2003; Velychko, 2008; Velychko, 2011).
 Under conditions of man-caused load on the environment, respectively, and animals – it is promising to develop effective methods for regulating the activity of the enzymatic system of antioxidant protection with the help of biologically active substances, in particular trace elements. The results of research confirm that this has a positive effect on the formation of productive and adaptive properties of animals.
 The system of antioxidant protection is a necessary part of non-specific reactions of the organism, a component of the processes of its adaptation to environmental conditions, a component of normal life, a factor in maintaining homeostasis. Widespread immunodeficiency and elucidation of the main links of their pathogenesis have exacerbated the problem of regulating disorders of the immune system. Therefore, knowledge of the patterns of formation of the immune status of animals, especially in the early postnatal period, is important in the development of methods for the correction of immunodeficiency, antioxidant protection.

Correction of immunodeficiency in mice with a biologically active substance of tissue origin

Correction of immunodeficiency in mice with a biologically active substance of tissue origin

BIOTECHNOLOGICAL PREPARATIONS FOR MEDICINE AND VETERINARY MEDICINE IN PROGRAMS PRODUCTION OF ENVIRONMENTALLY FRIENDLY FOOD

A proposal is being considered for the use of BAS preparations developed in the Institute of medical biotechnology OF the FBU SSC VB «Vector» in the programs of ensuring the country’s security in the field of medicine, veterinary medicine and obtaining environmentally friendly food products. On the basis of biotechnological methods, a technology for obtaining a complex of biologically active preparations of double-stranded and single-stranded RNA from yeast and phages that can provide a solution to the above problems has been created. The» ideology «of the development consisted in a deep study of the EN-Dogen induction of interferons by the organism itself using evolutionarily formed mechanisms. The basis was taken of inter-veronicaceae mechanisms of action of viruses. Such drugs when injected into the human body and animals can act as viruses, inducing the synthesis of interferons and other proteins-cytokines in the body, but unlike viruses, they do not produce destructive effects. Activation of the endogenous cytokine network in this case at the systemic level can form a state of non-specific resistance against viruses, bacteria and their toxins. Injectable and ointment forms of these drugs based on RNA were developed, tested and approved by the Ministry of health of the Russian Federation and the Department of veterinary medicine of the Russian Federation. Introduction of effective methods of application of the developed preparations allows to use them as etiotropic means of emergency prevention and treatment of viral diseases of the person, calves, pigs, carnivores, birds and fishes, correction of immunodeficiency, strengthening of protective properties of vaccines.

Toward Gene Therapy for Cystic Fibrosis Using a Lentivirus Pseudotyped With Sendai Virus Envelopes

Gene therapy for cystic fibrosis (CF) is making encouraging progress into clinical trials. However, further improvements in transduction efficiency are desired. To develop a novel gene transfer vector that is improved and truly effective for CF gene therapy, a simian immunodeficiency virus (SIV) was pseudotyped with envelope proteins from Sendai virus (SeV), which is known to efficiently transduce unconditioned airway epithelial cells from the apical side. This novel vector was evaluated in mice in vivo and in vitro directed toward CF gene therapy. Here, we show that (i) we can produce relevant titers of an SIV vector pseudotyped with SeV envelope proteins for in vivo use, (ii) this vector can transduce the respiratory epithelium of the murine nose in vivo at levels that may be relevant for clinical benefit in CF, (iii) this can be achieved in a single formulation, and without the need for preconditioning, (iv) expression can last for 15 months, (v) readministration is feasible, (vi) the vector can transduce human air-liquid interface (ALI) cultures, and (vii) functional CF transmembrane conductance regulator (CFTR) chloride channels can be generated in vitro. Our data suggest that this lentiviral vector may provide a step change in airway transduction efficiency relevant to a clinical programme of gene therapy for CF.

985. Lentiviral Vector Mediated Correction of Immunodeficiency in a Murine Model of Artemis-Deficient SCID

985. Lentiviral Vector Mediated Correction of Immunodeficiency in a Murine Model of Artemis-Deficient SCID

Analysis of the mucosal microenvironment: factors determining successful responses to mucosal vaccines

The predominance of IgA antibodies in mucosal sites reflects a combination of high rate IgA isotype switching among precursor cells in induction sites, their selective localisation in mucosal effector tissues and vigorous proliferation of these cells after extravasation. Each of these steps leading to IgA expression at the mucosa is under cytokine control. This paper will address the role of cytokines in induction and expression of IgA responses, the contribution of various precursor cell subsets and their differential responses to cytokine signals and strategies for manipulating cytokine expression. With respect to IgA antibody production in the gut whereas IL-4 and TGF-β have been implicated in isotype switching of precursor cells to IgA commitment, their subsequent localisation, proliferation and effector activity expression is dependent on IL-5 and IL-6 expression locally. Most IgA plasma cells in the intestine derive from cells of the B2 lineage in the Peyer’s patch, but a subpopulation of cells derived from the peritoneal cavity (B1 cells) also contribute to the IgA plasma cell population in the intestinal lamina propria. Whereas IgA + cells of the B2 lineage are IL-6 dependent but IL-5 independent, B1-derived IgA + cells are IL-5 dependent and IL-6 independent. On the other hand, cell mediated immune responses in the gut are highly dependent on IFN-γ production by both Th1 CD4 cells and CD8 cells and in enteric Salmonella infection IFN-γ production is essential but antibody has little effect on this process. Therapeutic interventions based on the information emerging from these studies will lead to improved vaccination responses and correction of immunodeficiencies especially in young animals.

Cytokine mediated effects in mucosal immunity

The predominance of IgA antibodies in mucosal sites reflects a combination of high rate IgA isotype switching among precursor cells in induction sites, their selective localization in mucosal effector tissues and vigorous proliferation of these cells after extravasation. Each of these steps leading to IgA expression at the mucosa is under cytokine control. This paper will address the role of cytokines in induction and expression of IgA responses and strategies for manipulating cytokine expression. Therapeutic interventions based on this information may not only lead to improved vaccination responses and correction of immunodeficiencies but also, by invoking the phenomenon of oral tolerance, may assist in the management of autoimmune, allergic and alloreactive disease.

Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report

Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti- LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus- induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.

Reduction of Graft Failure by a Monoclonal Antibody (Anti-LFA-1 CD11a) After HLA Nonidentical Bone Marrow Transplantation in Children With Immunodeficiencies, Osteopetrosis, and Fanconi’s Anemia: A European Group for Immunodeficiency/European Group for Bone Marrow Transplantation Report

Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.

Advances in the correction of immunodeficiency by bone marrow transplantation.

Advances in the correction of immunodeficiency by bone marrow transplantation.

Correction of immunodeficiency in aged mice by levamisole and bestatin administration.

An attempt to correct the impaired immune functions of aged mice was made by injecting repeatedly (over a 6-month period) two chemically defined immunostimulating agents, levamisole and bestatin, into 12- to 16-month-old hybrid mice. Continuous treatment with levamisole restored T-cell-dependent functions (delayed-type hypersensitivity reaction and antibody response to T-dependent antigens) and prevented the appearance of suppressor cells induced by aging. In aged animals, this treatment led to macrophage activation and to a significant reduction of ADCC activity near the baseline value of young animals. Weekly injections of bestatin resulted in varying effects, depending on the dose administered. Small doses (10 microgram/injection) were more effective in restoring humoral response to SRBC rather than delayed-type hypersensitivity reaction, whereas large doses (100 microgram/injection) had the opposite effect. Macrophage activation was obtained only after the administration of the high dose of bestatin. Continuous treatment with bestatin did not eliminate suppressor cell activity, but decreased the ADCC normally elevated in aged animals. A significant reduction of spontaneous tumors and prolongation of median survival was observed in mice given repeated injections of levamisole and of 100 microgram bestatin, compared with untreated aged mice and with mice given low doses of bestatin.