Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts

Abstract Background: Anogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. Objective: To assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. Methods: This is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. Results: 48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p < 0.001). Study limitations: Small number of patients analyzed. Conclusion: There was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.

Immunohistochemical staining of Langerhans cells in HPV-positive and HPV-negative cases of oral squamous cells carcinoma

The Human Papillomavirus (HPV) has been strongly implicated in development of some cases of oral squamous cell carcinoma (OSCC). However, the immunological system somehow reacts against the presence of this virus. Among the cells involved in such mechanism of defense Langerhans cells (LC) stand out, which are responsible for processing and presenting antigens. OBJECTIVES: The purposes of this study were to investigate the presence of HPV DNA and to evaluate the immunohistochemical reactivity for Langerhans cells between HPV-positive and HPV-negative OSCC. Twenty-seven cases of OSSC were evaluated. MATERIAL AND METHODS: DNA was extracted from paraffin-embedded tissue samples and amplified by Polymerase Chain Reaction (PCR) for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the Streptavidin-biotin technique. RESULTS: From the 27 cases, 9 (33.3 percent) were HPV-positive and 18 (66.0 percent) HPV-negative. HPV 18 was the most prevalent viral type (100 percent cases) and infection with HPV-16 (co-infection) was detected in only 1 case. In the OSCC specimens examined, immunoreactivity to S-100 antibody was detected in all cases, with a mean number of 49.48±30.89 Langerhans cells positive for immunostaining. The mean number of immunostained Langerhans cells was smaller in the HPV-positive cases (38 cells/case) than in the HPV-negative cases (42.5 cells/case), but this difference was not significant (p=0.38). CONCLUSIONS: The low frequency of detection of HPV DNA in OSCC indicates a possible participation of the virus in the development and progression of only a subgroup of these tumors. There was no association between the immunohistochemical labeling for Langerhans cells (S-100+) and HPV infection of in OSSC. These findings suggest that the presence of HPV in such OSCC cases could not alter the immunological system, particularly the Langerhans cells.

Langerhans cells in periodontal disease of HIV- and HIV+ patients undergoing highly active antiretroviral therapy

The aim of this study was to assess and compare quantitatively the presence of S100+ Langerhans cells (LC) by immunochemistry techniques in HIV+ and HIV- gingivitis and periodontitis subjects. Additionally, it aimed to evaluate the correlation among densities of these cells with CD4+ and CD8+ T cells, and viral load levels in HIV+ subjects, all using Highly Active Antiretroviral Therapy (HAART). The samples were allocated into four groups: 1) 15 subjects with moderate chronic periodontitis (MCP), HIV+; 2) 15 subjects with MCP, HIV-; 3) 10 subjects with gingivitis (G), HIV+; and 4) 10 subjects with G, HIV-. The S100+ cells were assessed in the pocket epithelium, gingival epithelium, and lamina propria. A statistically significant increase of total S100+ cells in HIV+ periodontitis subjects was observed in relation to HIV- periodontitis subjects. No increase of S100+ cells with increased inflammation was observed. No statistically significant correlation among S100+ cells and blood levels of CD4, CD8, and viral load was observed. In conclusion, the use of HAART can aid in achieving viral loads, and it is suggested that it may prevent the destruction of the LC.

Imunopatologia da dermatite de contato alérgica / Immunopathology of allergic contact dermatitis

A dermatite de contato alérgica é consequência de uma reação imune mediada por células T contra químicos de baixo peso molecular, denominados haptenos. É uma condição frequente que ocorre em todas as raças e faixas etárias e afeta a qualidade de vida de seus portadores. O mecanismo imunológico desta doença vem sendo revisto nas últimas décadas com significativo avanço no seu entendimento. A metabolização e o caminho dos haptenos, bem como a formação e o mecanismo de ação das células responsáveis tanto pela reação quanto pelo seu término, são discutidos neste artigo.

Allergic contact dermatitis is the consequence of an immune reaction mediated by T cells against low molecular weight chemicals known as haptens. It is a common condition that occurs in all races and age groups and affects the quality of life of those who present it. The immunological mechanism of this disease has been reviewed in recent decades with significant advance in its understanding. The metabolism and pathway of the haptens as well as the activation and mechanism of action of the cells responsible for both the immune reaction and its completion are discussed in this article.

American tegumentary leishmaniasis: langerhans cells in montenegro skin test / Leishmaniose tegumentar americana: células de Langerhans na reação intradérmica de Montenegro

This work analyzed the histopathology and epidermal Langerhans cells (LC) of Montenegro skin test (MST) in patients with American tegumentary leishmaniasis (ATL) in order to in situ characterize and compare the immunological reaction of the two major clinical forms of ATL, localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). MST histopathology of both LCL and MCL showed superficial and deep perivascular inflammatory infiltrate composed mainly of lymphocytes and histiocytes. Epidermal LC population was higher in MST biopsies taken from LCL patients when compared to MCL group, at 48 and 72 hours after antigen inoculation. Increased number of epidermal LC displayed in MST biopsies of LCL patients represents specific cellular immunity against parasites. The decrease of LC in MST biopsies of MCL patients does not necessarily indicate a worse specific cellular immunity in this clinical form of leishmaniasis.

Este trabalho analisou e quantificou as células de Langerhans e as características histopatológicas da reação de Montenegro nos pacientes com leishmaniose tegumentar americana (LTA) para caracterizar seu comportamento imunológico nas duas formas clínicas mais comuns da LTA, a leishmaniose cutânea localizada (LCL) e a leishmaniose cutâneo-mucosa (LCM). O exame histopatológico apresentou infiltrado inflamatório perivascular superficial e profundo, com predomínio de histiócitos e linfócitos, sem diferença significante entre as duas formas da doença. O resultado da quantificação das CL apresentou aumento das CL na LCL e diminuição na LCM em 48 e 72 horas após a inoculação do antígeno (p < 0,001). O aumento das células de Langerhans epidérmicas na reação de Montenegro da LCL demonstra a presença de imunidade celular específica, enquanto a diminuição das mesmas células na LCM não necessariamente demonstra uma diminuição da imunidade celular específica.

Interstitial and Langerhans' dendritic cells in chronic periodontitis and gingivitis

The aim of the present study was to compare quantitatively the distribution of dendritic cell subpopulations in chronic periodontitis and gingivitis. Fourteen biopsies from patients with chronic periodontitis and fifteen from patients with gingivitis were studied. An immunoperoxidase technique was used to quantify the number of Langerhans' cells (CD1a) and interstitial dendritic cells (factor XIIIa) in the oral and sulcular and junctional/pocket epithelia and in the lamina propria. A greater number of factor XIIIa+ dendritic cells in the lamina propria and CD1a+ dendritic cells in the oral epithelium were observed in gingivitis compared to the periodontitis group (p = 0.05). In the sulcular and junctional/pocket epithelia and in the lamina propria, the number of CD1a+ dendritic cells was similar in the gingivitis and periodontitis groups. In conclusion, the number of Langerhans' cells in the oral epithelium and interstitial dendritic cells in the lamina propria is increased in gingivitis compared to periodontitis, which may contribute to the different pattern of host response in these diseases.

Resposta imune local nas lesões do colo uterino induzidas pelo HPV em mulheres soropositivas para o HIV / Local immune response in uterine cervix injuries induced by HPV in HIV-infected women

Os autores relatam a participação da imunidade local, representada pelas células de Langerhans, e a posterior ativação da resposta imunológica, como mecanismos importantes no controle das lesões intraepiteliais cervicais. Acredita-se que a depleção das células de Langerhans (quantitativa) ou a alteração na morfologia (qualitativa) possam ter participação no mecanismo de progressão ou persistência das lesões HPV induzidas, tendo em vista que poderão determinar alteração na resposta imunológica local independente na contagem de linfócitos TCD4+. Por outro lado, uma resposta imunológica local adequada pode ser a responsável pela regressão dessas lesões.

Células de Langerhans en la inmunidad cutánea / Langerhan cells in cutaneous inmunity

Las células de Langerhans (CL) se derivan de precursores de la médula ósea y pertenecen a la familia de células presentadoras de antígenos. Se encuentran en la epidermis y son las encargadas de la captación, procesamiento y presentación de antígenos a los linfocitos en los ganglios linfáticos locales. Su densidad y función varían en condiciones normales en la piel de acuerdo con la edad, el área anatómica, la exposición solar y se encuentran alteradas en las diversas enfermedades de la piel.

The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence

Chromoblastomycosis (CR) is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68), Langerhans'cells (S100), lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56) and neutrophils (CD15). The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha), chemokine receptors (CXCR3 and CCR1) and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS) was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15+ and CD56+ were significantly lower than CD3+, CD4+, CD20+ and CD68+ cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.

A cromomicose é micose subcutânea crônica sistêmica caracterizada por resposta inflamatória crônica granulomatosa. No entanto, existem poucos dados a respeito do padrão de subtipos de leucócitos na cromomicose e sobre as vias envolvidas no recrutamento destas células. O objetivo deste trabalho foi avaliar os tipos celulares, bem como a expressão de quimiocinas, receptores de quimiocinas e enzimas em lesões de cromomicose. O infiltrado inflamatório foi caracterizado por meio de técnica imuno-histoquímica utilizando os seguintes marcadores CD68 (macrófagos), S100 (células de Langerhans), CD3, CD4, CD8, CD45RO, CD20 e CD56 (linfócitos) e CD15 (neutrófilos). A expressão de MIP-1alfa (Proteína Inflamatória do Macrófago-1alfa), receptores de quimiocinas (CXCR3 e CCR1) e enzimas (superóxido dismutase-SOD e óxido nítrico sintase induzida-iNOS) foi avaliada pelo mesmo método. Observou-se um aumento de todas as populações celulares avaliadas em relação às amostras controle. As populações de células CD15+ e CD56+ foram significativamente menores que células CD3+, CD4+, CD20+ e CD68+. A análise estatística revelou uma correlação positiva entre o número de fungos com as células CD3, CD45RO e iNOS-positivas. A expressão de MIP-1alfa foi também associada às populações de células CD45RO, CD68, iNOS e CXCR3 positivas. Nossos resultados apontam para um possível papel de MIP-1alfa e da persistência fúngica na infiltração de células inflamatórias nos sítios de cromomicose.

Las células de Langerhans en la inmunidad a leishmaniasis / Role of Langerhans cells in the immunity of leishmaniasis

En la respuesta inmune a parásitos del género Leishmania influyen múltiples factores entre los que se encuentran no sólo los relacionados con el parásito sino también aquéllos relacionados con el hospedero; de particular importancia es el tipo participante de célula presentadora de antígenos. En la piel, lugar donde el vector inocula el parásito, se encuentran las células de Langerhans que tienen como principal función servir como centinelas para la detección de microorganismos invasores. El estímulo que genera el microorganismo o las células circundantes induce la activación de las células de Langerhans, su maduración y migración hacia el tejido linfoide local (regional) donde presentan los antígenos a las células T para la posterior activación y diferenciación de subpoblaciones de células T específicas, responsables de la resolución de la infección o de la cicatrización. Se ha observado que durante la fase temprana de la infección con Leishmania hay muy pocas células T en el sitio de la infección lo cual sugiere que los macrófagos infectados tienen pocas probabilidades de encontrar allí células T con la especificidad requerida para eliminar el parásito y que, por tanto, son las células de Langerhans las que proporcionan la señal que activa las células T específicas para Leishmania en los ganglios linfáticos locales que drenan de la lesión e inducen su migración al sitio de la lesión. En la presente revisión se abordan las principales características de las células de Langerhans, se hace especial énfasis en la participación en la respuesta inflamatoria cutánea y se presentan los hallazgos más relevantes del papel de estas células en el modelo de infección por parásitos del género Leishmania

Conociendo a la célula de Langerhans / Meet the Langerhans cell

La célula de Langerhans (CL) representa uno de los elementos más eficaes del sistema inmunológico. Presentes desde las primeras etapas de la vida embrionaria, no sólo endocitan, procesan a los antígenos tópicos o ambientales, sino que tienen la capacidad de migrar hacia ganglios linfáticos para presentar los mismos a los linfocitos TCD4. Si bien su estructura y funcionalidad aún no están bien establecidas, se conoce que el gránulo de Bierbeck posee entre otras una proteína denominada Langerina, la cual estaría implicada en el proceso de endocitosis. Muchas líneas de investigación están abocadas al análisis de estos elementos, debido a que podrían estar implicadas en la génesis de diferentes neoplasias como linfomas, melanomas y carcinoma de cuello uterino, y a partir de ésto, la generación de vacunas antitumorales es un área donde el desarrollo de la inmunología, aunada a la biología molecular, avanzan en forma continua

Histiocitose de células de Langerhans: o papel do sistema imunológico na sua etiopatogenia / Langerhans cell histiocytosis: the immunology role in its etiopathogeny

A histiocitose das células de Langerhans é uma condiçäo reativa na qual células com um fenótipo de células de Langerhans acumulam-se em vários tecidos, lesando-os. A doença está relacionada a alteraçöes imunológicas, podendo causar lesöes em um ou mais órgäos. O objetivo deste trabalho foi relatar um caso de histiocitose de células de Langerhans numa criança de dois anos de idade que desenvolveu a doença após ter recebido uma dose da vacina tríplice, e discutir os prováveis mecanismos etiopatogênicos.

Frequency of epidermal langerhans cells in site of intradermal injection promastigotes of leishmania braziliensis in mice

We utilized inmunostaining assay with avidein boitin peroxidase technique and primary rat monoclonal antibody NLDC-145 specific for mouse dentritic cell, characterized langerhans cells (LC) in epidermis sheet of 1 mm² of skin of the footpads of inbred females BALB/c mice, intradermally (id) injected with 1.10ü cultured promastigotes of leishmania braziliensis. The result showed that the injection of the parasites in the skin of the animals produced a progressive increment of epidermal LC in the site of the previus injection, and statistically significant (P<0.05) in each study period. The density of epidermal LC was going up by parasite insult in early time, after the 15 minutes (m) post-infection (pi) with 162ñ31.2 LC/mm², reaching a maximal value of 4503ñ713 LC/mm² to 2 week (w) pi until 898ñ481 LC/mm² to 6 w pi. The number of LC was always higher in epidermis of the control healthy mice, these skin samples showed 120ñ28.9 LC/mm². Morphological changes of the promastigotes injected could to be detected in skin giemsa-stained imprints, the parasite showed form ovoid and a short flagel, between 15m and 2 hour (hr) pi. No parasites were even seen in the imprint samples than of as: activated macrfophages (33 percent) to 15 m pi, neutrophils (46,33 percent) to 4 hr pi, eosinophils (2,33 percent) to 4 hr pi, lymphocytes (15,67 percent) to 6 hr pi, degraded lymphocytes (8,33 percent) to 1 w pi, monocytes (4,33 percent) to 4 day (d) pi and activated monocytes (19,33 percent) to 1 d pi. The stained sections of skin inoculated, revealed amastigotes into macrophages dermal near of the perivascular area and inflammatory process in the dermis consisted of lymphocytes, monocytes, plasma cell and polymorphonuclear cells between 1 w and 6 w pi. No parasites were detected in the epidermis. the results showed that the promastigotes in the skin survived the first 2 hr out of the macrophages, and on the other hand, stinuled various cell types in sites of injection of the parasites, and the proliferation of antigen presentation by epidermalk langerhans cells, necessary for the initiation of the specific T cell inmune response

Celulas dendriticas y su papel en patologia / Dendritic cells: their role in pathology

La finalidad de esta revisión es aportar un conocimiento general sobre las células dendríticas (CD), células accesorias de la respuesta inmune. Se las reconoce como las células presentadoras de antígenos por excelencia (APC) y por lo tanto expresan antígenos clase II del complejo mayor de histocompatibilidad (MHC). Los diversos tipos de CD tienen un origen común en la médula ósea diferenciándose luego bajo la influencia de variados estímulos y distribuyéndose en órganos linfoideos y no linfoideos. Desde los tejidos periféricos migran a los ganglios linfáticos donde presentan el antígeno a los linfocitos T. Dependiendo del microambiente expresan diversos marcadores de superfície siendo capaces de la secreción de citoquinas como IL-12, IL-1 y TNFalpha. Como APC cumplen un importante papel en la patogenia de enfermedades autoinmunes y virales destacándose su participación en la infección por HIV. Se las encuentran en el infiltrado de numerosos cánceres humanos donde actuando como APC podrían incluir una respuesta inmune antitumoral. En esta propiedad se basa su utilización para el tratamiento de linfomas y melanomas llevada a cabo actualmente en diversos laboratorios.