T regulatory cells and allergy

Anergy, tolerance and active suppression may not be independent events, but rather involve similar mechanisms and cell types in immune regulation. Induction of allergen-specific T(Reg) cells seems essential for maintaining a healthy immune response towards allergens. By utilizing multiple secreted cytokines and surface molecules, antigen-specific T(Reg) cells may re-direct an inappropriate immune response against allergens or auto-antigens.     

In Situ Immune Response in Human Chromoblastomycosis – A Possible Role for Regulatory and Th17 T Cells

Background

Chromoblastomycosis is a chronic fungal infection that affects skin and subcutaneous tissue. Lesions can be classified in tumorous, verrucous, cicatricial and plaque type. The cellular immune response in the severe form of the disease seems to correlate with a Th2 pattern of cytokines. The humoral immune response also seems to play a role. We intended to explore the populations of regulatory T cells and the Th17 pattern.

Methodology

Twenty-three biopsies of verrucous form were obtained from patients with clinical, culture and histopathological diagnostic of chromoblastomycosis, without treatment. It was performed an immunohistochemistry method to detect Foxp3, CD25, TGF-β, IL-6, IL-17 and IL-23.

Principal findings

IL-17 was the only cytokine with high expression in CBM when compared to normal skin. The expression of Treg cells, TGF- β, IL-6 and IL-23 were similar to normal skin.

Conclusions/Significance

The constitution of a local immune response with high expression of IL-17 and low expression of other cytokines could be at least in part, an attempt to help the immune system against fungal infection. On the other hand, high levels of local immune response mediated by Th17 profile could overcome the role of Treg cells. The inefficient immunomodulation as a consequence of the unbalance by Treg/Th17 cells seems to corroborate with the less effective immune response against fungi.     

Cell-mediated immunity predicts the probability of local recruitment in nestling blue tits

We investigated whether the variation in T-cell-mediated immune function of blue tit nestlings affected their fledgling success and the probability of local survival. We studied the relationship between immune function and survival under two rearing conditions: control, unmanipulated, and experimentally enlarged broods. Brood enlargement had negative effects on nestling immune response. Immune response was positively related to fledgling success and it predicted the probability of local recruitment. However, the relationship between immune response and the probability of recruitment was significantly positive only among control broods and nonsignificant among enlarged broods. The effect of immune response on the recruitment probability was not affected by variation in body mass. Our study suggests that selection for immune responsiveness seems to be weak or even absent under unfavourable rearing conditions as simulated by brood size enlargement. Therefore, year-to-year environmental variation and environmental heterogeneity may constrain evolution towards higher immune responsiveness.     

Humoral primary immune response in vitro in a homologous mouse system: replacement of fetal calf serum by a 2-mercaptoethanol or macrophage-activated fraction of mouse serum.

The primary immune response in mouse spleen cell cultures against heterologous red cell antigens is dependent on the medium being supplemented with selected batches of fetal calf serum. Mouse serum itself is not able to support this response. The active immune response-supporting component in fetal calf serum seems to be a distinct factor (s), which has been partially purified by Sephadex G-100 filtration and termed MaSF-2-mercaptoethanol-activated serum factor. In this report it is demonstrated that MaSF is also present in mouse serum. For functional detection, mouse MaSF has to be separated from higher m.w. inhibitors, and has to be activated by 2-ME. After separation and activation mouse MaSF can support the primary immune response in a completely homologous in vitro culture system. Evidence is presented that MaSF can also be activated by macrophages. It is concluded that macrophages and 2-ME have the same mode of action in the primary immune response in vitro, i.e., induction of lymphocyte competence by activation of a serum factor.     

Participation of the rat caudate nucleus in the immunostimulating effect of DAGO

The data obtained suggest that administration of the DAGO increased the number of plaque- and rosette-forming cells after immunisation with the sheep red blood cells in the sham-operated Wistar rats. Following destruction of the caudate nucleus, the DAGO administration prevented the immune activation. Bilateral destruction of the caudate nucleus resulted in a considerable inhibition of the immune response as compared with the control rats. Thereupon the caudate nucleus seems to be involved in realisation of the DAGO-induced immune activation.     

The role of N-beta-alanyldopamine synthase in the innate immune response of two insects

Insects trigger a multifaceted innate immune response to fight microbial infections. We show that in the yellow mealworm, Tenebrio molitor, septic injuries induce the synthesis of N-beta-alanyldopamine (NBAD), which is known as the main sclerotization precursor of insect brown cuticles. We demonstrate that NBAD synthase is induced in the epidermis of the mealworm and of the Medfly, Ceratitis capitata, by infection with Escherichia coli. Our results indicate that synthesis of NBAD seems to be a novel component of the overall innate immune response in insects.     

Chlamydiales and the innate immune response: friend or foe?

Pathogenicity of Chlamydia and Chlamydia-related bacteria could be partially mediated by an enhanced activation of the innate immune response. The study of this host pathogen interaction has proved challenging due to the restricted in vitro growth of these strict intracellular bacteria and the lack of genetic tools to manipulate their genomes. Despite these difficulties, the interactions of Chlamydiales with the innate immune cells and their effectors have been studied thoroughly. This review aims to point out the role of pattern recognition receptors and signal molecules (cytokines, reactive oxygen species) of the innate immune response in the pathogenesis of chlamydial infection. Besides inducing clearance of the bacteria, some of these effectors may be used by the Chlamydia to establish chronic infections or to spread. Thus, the induced innate immune response seems to be variable depending on the species and/or the serovar, making the pattern more complex. It remains crucial to determine the common players of the innate immune response in order to help define new treatment strategies and to develop effective vaccines. The excellent growth in phagocytic cells of some Chlamydia-related organisms such as Waddlia chondrophila supports their use as model organisms to study conserved features important for interactions between the innate immunity and Chlamydia.     

Cell-mediated Control of an Antibody Response

THERE is an increasing recognition of the cellular interactions which may influence immune responses. Here we report the in vitro demonstration of one such type of phenomenon, which seems to be a cell-mediated effect, displaying both high potency and unusual dose response characteristics in terms of its capacity to inhibit an antibody response.     

Ki-M7 monoclonal antibody specific for myelomonocytic cell lineage and macrophages in human

We describe a new monoclonal antibody, termed Ki-M7, which is specific to human myelomonocytic cell lineage and macrophages, as tested by immunohistochemical methods. Ki-M7 recognizes an intracytoplasmic antigen of molecular weight 29,000. Ultrastructurally, the antigen is localized in the lysosome and phagosome compartments and seems to be involved in generation of oxygen radicals during the respiratory burst. Dendritic cells, such as dendritic reticulum cells of lymphoid follicles and interdigitating reticulum cells of lymphoid T-zones, considered as accessory cells of the B- and T-cell immune response, respectively, do not show any reactivity with monoclonal antibody Ki-M7. Ki-M7 seems to be an appropriate reagent to clearly differentiate between the phagocytosing and the immune accessory population of the human monocyte/macrophage system.     

CD38 plays a role in effective containment of mycobacteria within granulomata and polarization of Th1 immune responses against Mycobacterium avium

CD38 is a multifunctional ectoenzyme that behaves either as an enzyme, a cell adhesion molecule or as a cell surface receptor involved in cell signalling. It is expressed in cells of several lineages, including B and T lymphocytes, and macrophages. CD38 was shown to be important for the development of T-cell dependent humoral immune responses against extracellular pathogens. It also appears to be functionally important in macrophages, which are the host cells of Mycobacterium avium, an intracellular parasite that survives within these cells by avoiding a number of their microbicidal strategies. The present work aimed at investigating whether CD38 had any role on the immune response against mycobacterial infection. After intraperitoneal M. avium infection, the immune response of CD38KO mice was compared to that of their parental strain, C57Bl.6 mice. Absence of CD38 rendered mice more susceptible to mycobacterial infection. This susceptibility seems to be due to ineffective Th1 differentiation and polarization, which is essential for the control of M. avium infection. In addition, absence of CD38 seems to compromise the maintenance of the granulomatous barrier, leading to dissemination and unrestrained growth of mycobacteria.     

Cancer despite immunosurveillance: immunoselection and immunosubversion

Numerous innate and adaptive immune effector cells and molecules participate in the recognition and destruction of cancer cells, a process that is known as cancer immunosurveillance. But cancer cells avoid such immunosurveillance through the outgrowth of poorly immunogenic tumour-cell variants (immunoselection) and through subversion of the immune system (immunosubversion). At the early stages of carcinogenesis, cell-intrinsic barriers to tumour development seem to be associated with stimulation of an active antitumour immune response, whereas overt tumour development seems to correlate with changes in the immunogenic properties of tumour cells. The permanent success of treatments for cancer might depend on using immunogenic chemotherapy to re-establish antitumour immune responses.     

Types of immunological failure in the "slow-virus" encephalopathies and multiple sclerosis.

The pathogenesis of the slow virus encephalopathies and multiple sclerosis is reviewed within the framework of the immune response. The diseases are analyzed for the component of the immune response that appears to be crucial to the host''s failure to control the disease. Thus, the absence of an immune response in the spongiform encephalopathies appears to reflect a failure of antigen recognition. Progressive multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), and progressive rubella panencephalitis (PRP) may result principally from a failure of effector mechanisms. In PML the failure usually occurs within the setting of an immunosuppressive illness. Conversely, in SSPE and PRP the effector failure seems to result from the nature of the host-virus interaction itself. Finally, evidence is accumulating that a defect of immunoregulation plays a significant role in multiple sclerosis.     

Cellular immune findings in Lyme disease

From 1981 through 1983, we did the first testing of cellular immunity in Lyme disease. Active established Lyme disease was often associated with lymphopenia, less spontaneous suppressor cell activity than normal, and a heightened response of lymphocytes to phytohemagglutinin and Lyme spirochetal antigens. Thus, a major feature of the immune response during active disease seems to be a lessening of suppression, but it is not yet known whether this response plays a role in the pathophysiology of the disease.     

B cells in rheumatoid arthritis

Normally the immune response is restricted to the peripheral secondary lymphoid organs. However, additional ectopic lymphoid tissue may develop at chronic sites of inflammation. In the synovium of rheumatoid arthritis patients the local production of proinflammatory cytokines seems to support the formation of a precisely structured microenvironment, which allows an antigen dependent immune response to take place. The analysis of the V-gene repertoire expressed in synovial B cells demonstrated that in the inflamed synovium a germinal centre reaction takes place. Antigen presented by a network of follicular dendritic cells may activate synovial B cells and support their differentiation into plasma cells secreting high affinity antibodies. The specificity of these antibodies remains to be determined.     

The role of IL-15 in gastrointestinal diseases: A bridge between innate and adaptive immune response

IL-15 is a member of the IL-2 family of cytokines whose signaling pathways are a bridge between innate and adaptive immune response. IL-15 is part of the intestinal mucosal barrier, and functions to modulate gut homeostasis. IL-15 has pivotal roles in the control of development, proliferation and survival of both innate and adaptive immune cells.IL-15 becomes up-regulated in the inflamed tissue of intestinal inflammatory disease, such as IBD, Celiac Disease and related complications. Indeed, several studies have reported that IL-15 may participate to the pathogenesis of these diseases. Furthermore, although IL-15 seems to be responsible for inflammation and autoimmunity, it also may increase the immune response against cancer. For these reasons, we decided to study the intestinal mucosa as an ‘immunological niche’, in which immune response, inflammation and local homeostasis are modulated.Understanding the role of the IL-15/IL-15R system will provide a scientific basis for the development of new approaches that use IL-15 for immunotherapy of autoimmune diseases and malignancies. Indeed, a better understanding of the complexity of the mucosal immune system will contribute to the general understanding of immuno-pathology, which could lead to new therapeutical tools for widespread immuno-mediated diseases.     

Interactions of lactoferrin with cells involved in immune function.

The antimicrobial activities of lactoferrin (Lf) depend on its capacity to bind iron and on its direct interaction with the surface of microorganisms. Its protective effect also extends to the regulation of the host response to infections. Depending on the immune status of an individual, Lf can have anti-inflammatory properties that downregulate the immune response and prevent septic shock and damage to tissues. It also acts as a promoter of the activation, differentiation, and (or) proliferation of immune cells. Although most of the anti-inflammatory activities are correlated with the neutralization of proinflammatory molecules by Lf, the promoting activity seems to be related to a direct effect of Lf on immune cells. Although the mechanisms that govern these activities are not clearly defined, and probably differ from cell to cell, several cellular targets and possible mechanisms of action are highlighted. The majority of the molecular targets at the surface of cells are multiligand receptors but, interestingly, most of them have been reported as signaling, endocytosis, and nuclear-targeting molecules. This review focuses on the known and putative mechanisms that allow the immunoregulating effect of Lf in its interactions with immune cells.     

Das Miteinander im Tumor

Interactions in the tumor Cancer has long been regarded as a mass of cells growing aberrantly due to mutations leading to constant cell proliferation and inhibition of cell death. Meanwhile, it has been acknowledged that not only tumor cells but also stroma plays an important role in tumorigenesis and progression. Although infiltrating immune cells are found in many tumors, an effective response to the tumor often seems to fail. One of the reasons discussed in this context is the modulation and suppression of immune cells by the tumor environment. Tumor cells show an altered metabolism leading to the secretion of metabolites that have been shown to act on stromal cells such as immune cells. Therefore, tumor metabolism is a promising therapeutic target to inhibit tumor growth and reactivate an effective anti‐tumor immune response.     

Cell-mediated immune response after vasectomy in rats.

This study investigated the development of a cell-mediated immune response after vasectomy in Swiss Albino rats, by comparing the development of the thymus-dependent lymphoid tissue of the regional testicular lymph node and the spleen in vasectomized and in sham-operated control animals. Frozen sections were used and thymus-dependent regions were stained by immunocytochemistry. After vasectomy, the areas occupied by the paracortex in the lymph node sections showed a significant increase in size; the thymus-dependent regions of the spleen, in contrast, showed no change. The regional lymph node, rather than the spleen, seems to be important in cell-mediated and humoral immune responses to vasectomy.