Development Of Specific Immunity Research Articles

Surfactant proteins and innate immunity of otitis media.

Otitis media (OM) is the most common disease among young children and one of the most frequent reasons to visit the pediatrician. Development of OM requires nasopharyngeal colonization by a pathogen which must gain access to the tympanic cavity through the eustachian tube (ET) along with being able to overcome the defense mechanisms of the immune system and middle ear mucosa. OM can be caused by viral or bacterial infection. The three main bacterial pathogens are Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis. Innate immunity is important in OM resolution as the disease occurs in very young children before the development of specific immunity. Elements of innate immunity include natural barriers and pattern recognition receptors such as Toll like receptors (TLRs), and Nod like receptors (NLRs). Surfactant proteins A (SP-A) and D (SP-D) act as pattern recognition receptors and are found in the lung and many other tissues including the ET and the middle ear where they probably function in host defense. Surfactant has a potential for use in the treatment of OM due to surface tension lowering function in the ET, and the possible immune functions of SP-D and SP-A in the middle ear and ET.

Different Transcriptomic Response to T. cruzi Infection in hiPSC-Derived Cardiomyocytes From Chagas Disease Patients With and Without Chronic Cardiomyopathy.

Chagas disease is a tropical zoonosis caused by Trypanosoma cruzi. After infection, the host present an acute phase, usually asymptomatic, in which an extensive parasite proliferation and intense innate immune activity occurs, followed by a chronic phase, characterized by low parasitemia and development of specific immunity. Most individuals in the chronic phase remain without symptoms or organ damage, a state called indeterminate IND form. However, 20 to 40% of individuals develop cardiac or gastrointestinal complications at any time in life. Cardiomyocytes have an important role in the development of Chronic Chagas Cardiomyopathy (CCC) due to transcriptional and metabolic alterations that are crucial for the parasite survival and replication. However, it still not clear why some infected individuals progress to a cardiomyopathy phase, while others remain asymptomatic. In this work, we used hiPSCs-derived cardiomyocytes (hiPSC-CM) to investigate patterns of infection, proliferation and transcriptional response in IND and CCC patients. Our data show that T. cruzi infection and proliferation efficiency do not differ significantly in PBMCs and hiPSC-CM from both groups. However, RNA-seq analysis in hiPSC-CM infected for 24 hours showed a significantly different transcriptional response to the parasite in cells from IND or CCC patients. Cardiomyocytes from IND showed significant differences in the expression of genes related to antigen processing and presentation, as well as, immune co-stimulatory molecules. Furthermore, the downregulation of collagen production genes and extracellular matrix components was significantly different in these cells. Cardiomyocytes from CCC, in turn, showed increased expression of mTORC1 pathway and unfolded protein response genes, both associated to increased intracellular ROS production. These data point to a differential pattern of response, determined by baseline genetic differences between groups, which may have an impact on the development of a chronic outcome with or without the presentation of cardiac symptoms.

Development of specific immunity in laboratory animals after co-immunization against seasonal influenza and COVID-19

Introduction. In clinical practice, the differential diagnosis of COVID-19 can be challenging during the flu season, entailing serious consequences such as delays in appropriate control measures against the SARS-CoV-2 pandemic. Another problem is posed by co-infection of SARS-CoV-2 and influenza virus (IV), which significantly contributes to the severity of the COVID-19 disease. This study was aimed to explore the cross-impact of co-administration of Russian influenza and COVID-19 vaccines on development of specific immunity in laboratory animals.Materials and methods. The study was conducted on BALB/c mice. The animals were inoculated intramuscularly with the vaccine for COVID-19 prevention (CoviVac) and the vaccine for influenza prevention (Flu-M). The sera from the immunized animals were examined separately. Three IV strains were used in the hemagglutination inhibition assay. Antibodies (Abs) against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA). The neutralization test was performed to detect virus neutralizing antibodies against SARS-CoV-2 and IV.Results. Relatively high titers of specific Abs were found in the groups of animals inoculated with one vaccine and with two vaccines concurrently. In the groups of animals inoculated with CoviVac and with two vaccines concurrently, both in the ELISA test and in the neutralization test, the average titers of specific Abs against SARSCoV- 2 did not demonstrate any statistical difference. The group of animals inoculated concurrently with two vaccines demonstrated statistically higher titers of Abs against IV after the second immunization compared to the group of animals inoculated with Flu-M.Discussion. The study has shown that post-vaccination immunity both to IV and to SARS-CoV-2 develops after co-vaccination with two vaccines. The observed enhanced post-vaccination immune response to IV in the coimmunized laboratory animals needs further research.Conclusion. The performed studies suggest the possibility of co-administration of two vaccines to prevent influenza and COVID-19.

Staphylococcus aureus Protein A Induces Human Regulatory T Cells Through Interaction With Antigen-Presenting Cells.

Despite continuous exposure and development of specific immunity, Staphylococcus aureus (Sa) remains one of the leading causes of severe infections worldwide. Although innate immune defense mechanisms are well understood, the role of the T cell response has not been fully elucidated. Here, we demonstrate that Sa and one of its major virulence factors protein A (SpA) induce human regulatory T cells (Tregs), key players in immune tolerance. In human PBMC and MoDC/T cell cocultures CD4+CD25+CD127dim Tregs were induced upon stimulation with Sa and to a lower extent with SpA alone. Treg induction was strongly, but not exclusively, dependent on SpA, and independent of antigen presentation or T cell epitope recognition. Lastly, soluble factors in the supernatant of SpA-stimulated MoDC were sufficient to trigger Treg formation, while supernatants of MoDC/T cell cocultures containing Sa-triggered Tregs displayed T cell suppressive activity. In summary, our findings identify a new immunosuppressory function of SpA, which leads to release of soluble, Treg-inducing factors and might be relevant to establish colonization.

THE ROLE OF CYTOKINE GENES POLYMORPHISM IN HEPATITIS C VIRUS INFECTION

Abstract. The outcome of hepatitis C virus (HCV) infection depends on the immune response caused by the host genetic factors. Cytokines are key mediators of inflammation and development of specific immunity, which is responsible for the elimination of HCV. It has been found that the polymorphisms in several cytokine genes play role in human susceptibility to HCV infection, determine its differences in response to HCV and treatment-induced HCV clearance. This review summarizes the results of studies on the single-nucleotide polymorphisms of cytokine genes that complete our knowledge of the pathogenesis of HCV infection.

ПРИМЕНЕНИЕ КОРМОВОЙ ДОБАВКИ ВИНИВЕТ В ПТИЦЕВОДСТВЕ. СООБЩЕНИЕ I. РАЗВИТИЕ СПЕЦИФИЧЕСКОГО ИММУНИТЕТА У ЦЫПЛЯТ

A composition and technology for feed additive Vinivet production from renewable by-products of beekeeping have been developed and patented firstly in the world. Study of the effect of feed additive Vinivet on the development of specific immunity in chicken of Bovans cross, vaccinated with a dry virus-vaccine against Newcastle’s disease (LA-Sota strain) at the age of 30 days located at the reproduction facility Udinsky JSC (Tatarstan Republic)), demonstrated that the humeral and cellular immunity improved. The growth of the number of sulphahydrate groups by 58.3 % and I-globuline fraction by 55.3 % were recorded, and the activation of blood neutrophil function was confirmed as the number of active cells at stimulated test increased by 25.7 %.

Adult stem cell plasticity: will engineered tissues be rejected?

The dogma that adult tissue-specific stem cells remain committed to supporting only their own tissue has been challenged; a new hypothesis, that adult stem cells demonstrate plasticity in their repertoires, is being tested. This is important because it seems possible that haematopoietic stem cells, for example, could be exploited to generate and perhaps deliver cell-based therapies deep within existing nonhaematopoietic organs. Much of the evidence for plasticity derives from histological studies of tissues from patients or animals that have received grafts of cells or whole organs, from a donor bearing (or lacking) a definitive marker. Detection in the recipient of appropriately differentiated cells bearing the donor marker is indicative of a switch in phenotype of a stem cell or a member of a transit amplifying population or of a differentiated cell. In this review, we discuss evidence for these changes occurring but do not consider the molecular basis of cell commitment. In general, the extent of engraftment is low but may be increased if tissues are damaged. In model systems of liver regeneration, the repeated application of a selection pressure increases levels of engraftment considerably; how this occurs is unclear. Cell fusion plays a part in regeneration and remodelling of the liver, skeletal muscle and even regions of the brain. Genetic disease may be amenable to some forms of cell therapy, yet immune rejection will present challenges. Graft-vs.-host disease will continue to present problems, although this may be avoided if the cells were derived from the recipient or they were tolerized. Despite great expectations for cellular therapies, there are indications that attempts to replace missing proteins could be confounded simply by the development of specific immunity that rejects the new phenotype.

Interactions Between NK Cells and B Lymphocytes

Publisher Summary This chapter focuses on interactions between natural killer (NK) Cells and B Lymphocytes. Through studies of the extent of NK cell participation during the early phases of infection by a number of organisms, NK cells have long been well established as being an important element of innate immunity that can boost immune resistance before the development of specific immunity. They are also important in shaping the nature of the B- and T-cell responses. Natural killer cells constitute one of the key components of the innate immune system in that they can be rapidly activated without the need for expansion of antigen-specific clones. B lymphocytes, by contrast, are important constituents of the specific immune system because of the presence of clonally distributed antigen receptors and the persistence of the progeny of specific clones that can continue to produce the relevant antibodies. The most direct way of demonstrating that NK and B cells can interact is to isolate purified populations of each cell type, coculture them, and determine the effect of these interactions on parameters of cellular activation, such as induction of activation markers, proliferation, cytokine production, and in the case of B lymphocytes, immunoglobulin secretion, and isotype switching.

Immune defense at the ocular surface.

The ocular surface is constantly exposed to a wide array of microorganisms. The ability of the outer ocular system to recognize pathogens as foreign and eliminate them is critical to retain corneal transparency, hence preservation of sight. Therefore, a combination of mechanical, anatomical, and immunological defense mechanisms has evolved to protect the outer eye. These host defense mechanisms are classified as either a native, nonspecific defense or a specifically acquired immunological defense requiring previous exposure to an antigen and the development of specific immunity. Sight-threatening immunopathology with autologous cell damage also can take place after these reactions. This article discusses the innate and acquired corneal elements of the immune defense at the ocular surface. The relative roles of the various factors contributing to prevention of eye infection remain to be fully defined.

Genetic and management factors that influence the susceptibility of cattle to Mycobacterium bovis infection.

Genetic variation in the susceptibility of cattle to Mycobacterium bovis infection exists in differences between families and species, but not breeds. Susceptibility to M. bovis infection increases with age of cattle. Natural exposure to M. bovis or environmental mycobacteria may assist in the development of specific immunity, but there is no direct evidence for such immunological priming of tuberculosis resistance in cattle. This has, however, been demonstrated in humans and other animals. Since non-specific mechanisms have a role in protective immunity, developing an effective vaccine will be difficult, even though some protection of other species has been achieved. Immunological suppression in the periparturient period can produce anergic reactors, which may act as a constant source of infection for cattle-to-cattle transmission. Circumstantial evidence suggests that an adequate intake of mineral, vitamin and protein reduces the susceptibility of cattle. Although weather patterns have been implicated in the susceptibility of herds to M. bovis infection, there is insufficient information to determine the risk factors precisely. It is concluded that some reduction in the susceptibility of cattle to M. bovis infection can be achieved by modifications to the management system to minimize risk factors, but that a considerable amount of further research is required.

Limited role of polymorphonuclear neutrophils in a pregnant mouse model of secondary infection by Chlamydophila abortus (Chlamydia psittaci serotype 1)

The aim of this work was to study the role of polymorphonuclear neutrophils (PMNs) in the clearance of infection, and in the development of specific immunity against Chlamydophila abortus (Chlamydia psittaci serotype 1) secondary infection. A pregnant mouse model depleted of neutrophils by the RB6-8C5 monoclonal antibody was used. No clinical signs were observed in depleted or non-depleted mice after secondary infection and no significant differences were observed in the litter size between the infected and control groups. In PMN-depleted mice C. abortus was not detected in the materno-fetal unit but merely produced low, persistent levels of infection in spleen and liver. In the non-depleted mice the level of infection was significantly lower, being resolved during the first few days post-reinfection. In both infected mice groups the immune response in the liver was quickly established and was seen to be composed mainly of CD4+T lymphocytes and macrophages. A Th1 response characterized by the presence of IFN-γ and TNF-α in serum was observed during early infection, with significantly higher levels in the non-depleted animals. Our results suggest that PMNs have little influence on the control ofC. abortus secondary infection, although they are a first line of defense and may influence the early production of TNF-α and IFN-γ.

Antibacterial protection of the ocular surface.

The outer surface of the eye is constantly exposed to a wide array of microorganisms. To protect the integrity or the ocular surface and to retain corneal transparency, a number of defense mechanisms have evolved. This article discusses the host mechanisms of the eyelids-, tears, cornea and conjunctiva. These host defense mechanisms are identified as either a native, nonspecific defense or a specifically acquired immunological defense requiring previous exposure to an antigen and the development of specific immunity. Nonspecific components that protect the eye include the eyelids, ocular surface epithelium, normal flora and tear proteins. Specifically acquired immunity in tears, cornea and conjunctiva involves the interaction of antigen-presenting cells, lymphocytes and humoral components of the immune system.

Viral replication and development of specific immunity in macaques after infection with different measles virus strains.

Cynomolgus monkeys (Macaca fascicularis) were experimentally infected with a wild type measles virus (MV) strain (MV-BIL). Following intratracheal inoculation with different infectious doses, the virus could be isolated from peripheral blood mononuclear cells (PBMC), lung lavage cells, and pharyngeal cells. The kinetics of the cell-associated viremia was similar in all infected animals. They developed specific serum IgM, IgG, and neutralizing antibody responses as well as MV-specific T cell-mediated immunity. Monkeys infected intratracheally or intramuscularly with the wild type MV-Edmonston or the attenuated MV-Schwartz strain showed a lower level of PBMC-associated viremia and less pronounced specific IgM responses. Nine months after infection with MV strains, all of the monkeys were protected from intratracheal reinfection with MV-BIL. This monkey model is suitable for study of new generations of vaccines and vaccination strategies for measles.

Pulmonary host defenses and oropharyngeal pathogens

The lower respiratory tract is repetitively inoculated with oropharyngeal bacteria and yet pneumonia is an infrequent event. Efficient mechanisms of antibacterial defense are present in the respiratory tract that eliminate microbes before their presence or multiplication leads to disease in the majority of instances. Resident pulmonary defenses consist of aerodynamic defenses, the mucociliary apparatus, alveolar macrophages, complement, and surfactant. These resident defenses can be augmented by the development of an inflammatory response or the development of specific immunity. Significant species variability exists in the efficiency and mechanisms of clearance for oropharyngeal organisms. Streptococci are cleared promptly, Branhamella catarrhalis is cleared slowly, whereas non-typable Haemophilus influenzae multiply before being cleared. A dual phagocytic system of alveolar macrophages and recruited polymorphonuclear leukocytes is required for clearance of most oropharyngeal microbes. Systemic immunization can significantly enhance clearance of non-typable H. influenzae, suggesting immunoprophylaxis might be possible for this organism.

Immunological aspects of chronic inflammation and repair

Macrophages and lymphocytes play essential roles in cell-mediated mechanisms involved in chronic inflammation. During the development of specific immunity, macrophages are required to process and present antigen to immunocompetent T cells. They also serve as "accessory" cells to lymphocytes by releasing soluble factors involved in host defense. In order to carry out their role more effectively, macrophages have the property of being activated, a process that provides them with greater ability to phagocytose and kill ingested microorganisms. Activated T cells serve as key effector cells that are capable of producing lymphokines which modify the behavior of other cells. In this way, they are able to facilitate or suppress an immune response. Chronic inflammation is often associated with irreversible destruction of parenchymal tissue, and fibrous connective tissue fills the resultant defect. Proliferation of fibroblasts, collagen production, and neovascularization are enhanced by the secretion of cytokines by T cells and macrophages.

Pathogenesis of renal lesions in haemoglobinaemic and non-haemoglobinaemic leptospirosis

Hamsters were infected with Leptospira interrogans serovar ballum or Leptospira interrogans serovar pomona and the kidney lesions were compared by light and electron microscopy. Ballum and pomona both caused severe clinical signs and death within 6 days in some animals, although only ballum was associated with red blood cell destruction and haemoglobinaemic nephrosis. With ballum infections it is difficult to distinguish degenerate changes resulting from leptospiral “toxins” from those resulting from hypoxia and haemoglobinaemic nephrosis because large numbers of organisms and haemoglobinaemia coincide shortly before death. Although large numbers of leptospires were seen within the renal interstitium and blood vessels in animals dying shortly after infection, organisms were seen only in the proximal convoluted tubules of those surviving until 14 days. It is thought that leptospires are carried by the bloodstream and migrate at random throughout all body tissues. When antibody develops, only those in the renal tubules remain. The random migration results in some leptospires entering tubules at all levels of the nephron but there are good grounds for believing that the normal changes in composition of the glomerular filtrate as it passes through the nephron are increasingly deleterious to leptospiral survival. This probably explains why leptospires are found predominantly in the proximal convoluted tubules of animals after the development of specific immunity.

Immunology and Immunopathology of the Intestines: Immunization of the Gastrointestinal Tract with Bacterial and Viral Antigens: Implications in Mucosal Immunity

The effects of oral immunization with Pseudomonas aeruginosa (PAOI), Chlamydia trachomatis or respiratory syncytial virus (RSV) on the development of specific antibody responses in the intestine, respiratory tract and genital secretions was studied in several animal models. Oral immunization resulted in the development of specific immunity in distant mucosal sites. However, its role in influencing the outcome of reinfection challenge at the distant site varied with the antigen. Little or no protection was observed against infection with Pseudomonas aeruginosa in the respiratory tract. Limited protection was observed against respiratory tract infection with RSV. On the other hand oral immunization appeared to be quite effective in preventing respiratory or genital infection with Chlamydia trachomatis. Finally, preliminary studies have suggested that intestinal immunization via the process of breast feeding can also be employed as an effective means to induce anti-idiotypic immunity against RSV in the breast feeding neonates.

Current concepts: immunology. Monocytes and macrophages.

MACROPHAGES play a central and essential part in the immune response by presenting antigen to lymphocytes during the development of specific immunity and by serving as supportive, accessory cells...

The intranasal infection of mice with Bordetella pertussis.

Bordetella pertussis instified by the intranasal route into the lungs of mice multiply without difficulty even from small inocula, although B. pertussis is not a natural pathogen for mice and mouse to mouse infection could not be demonstrated. When the initial dose was large the bacilli multiplied until the number in the lungs reached a critical level at which the mouse died. With smaller doses the critical level was never reached; a maximum count was achieved in 10–14 days, after which the number of viable bacilli declined. These smaller doses were consistently non-lethal and the figures for the viable counts when plotted gave curves of typical shape which were called ‘sublethal curves’. The decline corresponded in time with the development of specific immunity. Growth in the lung during the first 4 days of the infection was exponential, the rate of increase in the viable count depending on the size of the inoculum; the smaller the inoculum the faster the increase. With infecting doses at about the critical level, the numbers did not increase during the first 3–4 days, and with larger doses they decreased during the first 2–4 days of infection.Antiserum given with the inoculum reduced the number of viable organisms in the lung at once. Its effect was short-lived, because after 24 hr. the lung count rose; nevertheless, the initial check on the bacteria had converted a lethal in fection into a sublethal infection.

Studies on Tissue Reactions in Immunity

Abstract The injection of killed cultures of bacteria in animals leads to their development of specific immunity and tissue hypersensitiveness. Much is known regarding the nature of acquired immunity, especially with reference to antibody production, but relatively little appears to be known regarding acquired sensitivity. For over a year we have been investigating quantitative aspects of sensitization to different organisms, utilizing the albino rabbit as the experimental animal. During that period we have become more and more impressed with the extent to which sensitivity or, to use the widely accepted term, allergy is a marked and constant response of the rabbit to repeated injections of bacterial suspensions in the tissue. It was stated in connection with our studies on sensitization to proteins (1), that tissue hypersensitiveness frequently exists in the absence of serum precipitins.