Análisis de la inmunidad de las mujeres infectadas por el virus del papiloma humano y su relación con la lesión intraepitelial cervical / Immunity analysis in women infected with human papillomavirus and its link with cervical intraepithelial lesion (IMVIR study)

Introducción: El objetivo principal es estudiar los marcadores de NK memoria presentes en sangre periférica en pacientes con lesiones cervicales intraepiteliales de alto grado CIN2/3 frente a mujeres sin lesiones o con lesiones de bajo grado. Los objetivos secundarios son estudiar la relación entre el perfil de las células NK memoria y la infección o no por VPH, así como la persistencia viral en las mujeres infectadas por VPH. Material y métodos: Se trata de un estudio observacional prospectivo de una cohorte de mujeres reclutadas desde el año 2019, durante un periodo de 2años, en la unidad del tracto genital inferior en las consultas de ginecología general del Instituto de Salud de la Mujer del Hospital Clínico San Carlos. Los grupos de pacientes incluidos en el estudio son el grupo de estudio: mujeres con infección por VPH y con lesión cervical de alto grado (CIN2+); el grupo control1: mujeres con infección por el VPH sin lesión cervical de alto grado, y el grupo control2: mujeres sin infección por el VPH y sin lesión. Resultados: Durante el estudio se han reclutado 115 pacientes. Nos encontramos con un mayor número de NK «memoria» en pacientes infectadas, tanto en el grupo control1 como en el grupo de estudio, en comparación con el grupo control2. Además, cuando se analizan las pacientes no fumadoras, la expresión de NKp30 es significativamente menor en el grupo control1. Conclusiones: Los resultados ponen de manifiesto una probable menor capacidad para desarrollar funciones adaptativas por parte de las células NK en estas pacientes fumadoras frente a las no fumadoras. Un mejor conocimiento de la biología de las células NK y su papel en la infección por el VPH podría permitir el desarrollo de estrategias para manipular su funcionamiento (inmunoterapias) con un propósito pronóstico y terapéutico.(AU)

Introduction: The main objective is to study the NK markers present in circulating blood in patients with high grade intraepithelial cervical lesions compared with women without lesions or low grade lesions. The secondary objectives of the study are to understand the relationship between the NK memory like cells and the infection with HPV, as well as the persistence of the infection. Methods and materials: It is an observational prospective study that studies women from 2019 for 2years seen in ginecology rooms in Hospital Clínico San Carlos. The group of patients studied are: women with infection by HPV and high grade lesions, women with infection by HPV but no lesion or low grade lesion and women without lesion or infection. Results: We have recruited 115 patients. We have found more memory like NK cells in patients infected by HPV. And when we analyze the non-smoking patients, the expression of NKp30 is lower in patients infected without lesion. Conclusions: The results show that there could be less capacity to generate an adaptative function by NK in smoking patients than in non-smoking. A better knowledge of the NK cells biology and its role in the infection by HPV could allow us to manipulate with a therapeutic and prognostic end.(AU)

Molecular Aspects of Regeneration Mechanisms in Holothurians.

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation).

Protective effect of procyanidins extracted from the lotus seedpod on immune function injury induced by extremely low frequency electromagnetic field.

This study aimed to evaluate the protective effect of Lotus seedpod procyanidins (LSPCs) from extremely low frequency electromagnetic field (ELF-EMF) exposure (50Hz, 8mT, 28 days) and their protective mechanism against radiation damage. The results showed that LSPCs increased the organ index of mice and made the damaged blood-producing function and cytokine(INF-γ, TNF-α, IL-2, IL-6 and IL-10 in spleen) levels by ELF-EMF-irradiation recovered to normal appearance. And experimental results proved that dosing LSPCs inhibit more stagnation of splenocytes in G0/G1 phase caused by ELF-EMF, thus the spleen cells from G0/G1 phase to S phase shift, restore normal cell metabolism, promote the splenocytes proliferation, reduced the apoptosis of spleen cells, effective protect the damage induced by the ELF-EMF radiation. In addition, LSPCs prevented the decline of DNA content caused by ELF-EMF. Western blot determinated the levels of apoptosis genes including Bcl-2, Bax, Bcl-cl, Caspase-3 and Caspase-9. The results revealed that a significant suppression in Bcl-2 expression and increase in Bax, Caspase-3 and Caspase-9 expression in splenic cells in ELF-EMF group. However, LSPCs restored these changes. Taking these results together, it may be summarized that LSPCs could protect hematopoietic tissues and the immune system from ELF-EMF. And it may be hypothesized that ELF-EMF-induced apoptosis in splenocytes might occur via triggers the trans-activation of Bax and activates caspases-3 and -9, which then cleaves the death substrates, leading to apoptosis in splenocytes of mice treated with ELF-EMF.

Respuesta inmune contra antígenos menores de histocompatibilidad en el trasplante alogénico de progenitores hematopoyéticos / Immunologycal response under antigens hematopoietic stem cell transplantation

Patients who receive allo hematopoietic stem cell transplantation (SCT) could develop graft versus host disease and/or graft versus tumour effect. These immunological responses can happen even with perfect fully HLA matched haematopoietic stem cells. Moreover, the engraftment of the donor’s cells depends on the immunological conditions of both donor and recipient. The development of alloreactivity occurs in the context of the polymorphisms of the human genome, these genomic differences results in proteins with antigenic properties which trigger immune responses. Considering this, the SCT is a powerful tool to heal the patient disease, because all of them become chimeras. In other words, into individuals with two different genomic sets, which will develop a strong immunological response that cannot exist in natural conditions.

Marathon training and immune function.

Many components of the immune system exhibit adverse change after marathon-type exertion. These immune changes occur in several compartments of the immune system and body (e.g. the skin, upper respiratory tract mucosal tissue, lung, peritoneal cavity, blood and muscle). Of all immune cells, natural killer (NK) cells, neutrophils and macrophages (of the innate immune system) exhibit the greatest changes in response to marathon competition, both in terms of numbers and function. Many mechanisms appear to be involved, including exercise-induced changes in stress hormone and cytokine concentrations, body temperature changes, increases in blood flow and dehydration. During this 'open window' of immune dysfunction (which may last between 3 and 72 hours, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. Of the various nutritional and pharmacological countermeasures to marathon-induced immune perturbations that have been evaluated thus far, ingestion of carbohydrate beverages during intense and prolonged exercise has emerged as the most effective. However, carbohydrate ingestion during a marathon attenuates increases in plasma cytokines and stress hormones, but is largely ineffective against changes in other immune components including suppression of NK and T-cell function, and salivary IgA output. Other countermeasures, such as glutamine, antioxidant supplements and ibuprofen, have had disappointing results and thus the search for companion agents to carbohydrate continues.

Enfermedad periodontal e infección por VIH: estado actual / Periodontal disease and HIV infection: up to date

La infección por el virus de la inmunodeficiencia humana (VIH) puede tener influencia a nivel periodontal. El deterioro del sistema inmune por una disminución de los linfocitos TCD4+ puede comprometer las defensas del huésped a nivel sistémico por lo que se puede aumentar la susceptibilidad a padecer diferentes patologías en la cavidad oral. En este trabajo de revisión se recoge el estado actual de la enfermedad periodontal en pacientes VIH+ y trata de abordar como el VIH puede influir en la microbiota subgingival aumentando el riesgo de padecer periodontitis. La presencia de otros factores coadyuvantes podría favorecer la aparición de patología o incluso agravarla independiente de la presencia del VIH (AU)

Human immunodeficiency virus (HIV) infection can be related with the periodontal status. The damage of the immunological system by decreasing TCD4+ lymphocytes may compromise host defenses therefore the susceptibility of suffering from several diseases in the oral cavity can also be increased. This review manuscript addresses the current aspects concerning to the periodontal disease in HIV infected patients and tries to explain how HIV may influence the subgingival microflora, increasing the risk of suffering periodontal problems. Others concomitant factors, not related with HIV infection, might help either the onset or increase the severity of the disease (AU)

Lupus miliar diseminado de la cara asociado a quistes epidérmicos / Lupus miliaris disseminatus faciei associated with epidermal cysts

El lupus miliar diseminado de la cara (LMDF) es una enfermedad granulomatosa crónica, con predisposición a localizarse en el área central de la región facial. Su imagen histológica característica corresponde a granulomas epitelioides con necrosis caseosa. Su asociación con quistes epidérmicos se ha descrito en escasas ocasiones en la literatura médica. Se presenta un caso de LMDF asociado a quistes epidérmicos en una paciente de raza caucasiana. Esta asociación sugiere que la rotura de los quistes epidérmicos podría estar relacionada con la aparición de LMDF. Sin embargo, existen probablemente otros factores que pueden también contribuir a su patogénesis

Lupus miliaris disseminatus faciei (LMDF) is a chronic granulomatous disease, which tends to be located on the central part of the face. Its typical histological image is one of epithelioid granulomas with caseous necrosis. Its association with epidermal cysts has been described on few occasions in literature. We present a case of LMDF associated with epidermal cysts in a female Caucasian patient. This association suggests that the rupture of the epidermal cysts may be related to the appearance of LMDF. However, there are probably other factors that may also contribute to its pathogenesis

Accommodation: preventing injury in transplantation and disease.

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as "accommodation." In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.

Injury primes the innate immune system for enhanced Toll-like receptor reactivity.

Severe injury causes a dramatic host response that disrupts immune homeostasis and predisposes the injured host to opportunistic infections. Because Toll-like receptors (TLRs) recognize conserved microbial Ags and endogenous danger signals that may be triggered by injury, we wanted to determine how injury influences TLR responses. Using an in vivo injury model, we demonstrate that injury significantly increased TLR2- and TLR4-induced IL-1beta, IL-6, and TNF-alpha production by spleen cells. This influence of injury on TLR reactivity was observed as early as 1 day after injury and persisted for at least 7 days. The outcome of similar studies performed using TLR4-mutant C57BL/10ScN/Cr mice revealed that TLR2 responses remained primed, thus suggesting that injury-induced priming can occur independently of endogenous TLR4 signaling. Increased TLR4 reactivity was also observed in vivo, because LPS-challenged injured mice demonstrated significantly higher cytokine expression levels in the lung, liver, spleen, and plasma. Macrophages and dendritic cells were the major source of these cytokines as judged by intracellular cytokine staining. Moreover, ex vivo studies using enriched macrophage and dendritic cell populations confirmed that T cells did not contribute to the enhanced TLR2 and TLR4 responses. The results of flow cytometry studies using TLR2- and TLR4-MD-2-specific Abs indicated that injury did not markedly alter cell surface TLR2 or TLR4-MD-2 expression. Taken together, these findings establish that injury primes the innate immune system for enhanced TLR2- and TLR4-mediated responses and provides evidence to suggest that augmented TLR reactivity might contribute to the development of heightened systemic inflammation following severe injury.

Long-term monitoring of the immune reactivity of stainless steel welders.

The immune reactivity of stainless steel welders (n = 22-53) was evaluated in a three year's study. The results (phagocytic activity, cellular and humoral immunity) were statistically compared with those in control group of non-exposed persons from the same plant (n = 14-23) and with long-term laboratory reference values (LRV) (n = 14-311). In welders several changes were found when compared to the LRV: in humoral response there were higher prealbumin, lysozyme, circulating immune complexes and lower IgG. In phagocytic tests there were lower ingestion, bactericidal activity and higher metabolic activity of peripheral mononuclear leucocytes. In cellular immunity the marked lymphocytosis, higher counts of T-lymphocytes, CD4+ and CD8+ lymphocytes were noticed. After lowering the concentrations of metals in the working area there were trends to normal values in some parameters [relative numbers of T-lymphocytes, relative number of CD4+ lymphocytes, phagocytic activity, metabolic activity of leucocytes (INT index), IgA, complement C3, transferrin]. The extent and the length of the exposure to welding fumes, smoking and changed conditions at working place were followed as well.