Efectividad de las vacunas COVID-19 / Effectiveness of COVID-19 vaccines

La pandemia del SARS-CoV-2, ha generado que se realicen esfuerzos considerables en el desarrollo de las vacunas, para comprobar su efectividad se requiere que ensayos clínicos y emplearlos en la población a nivel mundial. Se realizó una revisión sistemática de literatura (RSL) del COVID-19 y su impacto en el desarrollo de las vacunas desde el 2019 hasta el 2022. La estrategia de búsqueda consiguió obtener 8 646 artículos, escogidos de las 6 fuentes de investigación (Wiley Online Library, Taylor & Francis, THE LANCET Infectious Diseases, National Library of Medicine, Nature Portfolio y Oxford Academic), luego se realizó un filtrado de 4 etapas con 2 criterios de exclusión cada una de ellas, quedando solo 78 artículos, los cuáles se utilizaron para responder tres preguntas de investigación planteadas. Se identificaron en los artículos científicos analizados, los laboratorios más referenciados que desarrollaron vacunas Pfizer/ BioNTech, Moderna, AstraZeneca, Sinovac, Sinopharm y Sputnik V, se identificó la utilización de nanotecnología en el diseño de las vacunas, principalmente utilizaron ARN mensajero, vector viral y subunidades proteicas, según el caso con coadyuvantes que potencia la inmunogenicidad. Los estudios demostraron buena efectivad, en los diferentes grupos priorizados y gracias a la dosificación de las inmunizaciones contra la COVID-19, se ha prevenido el número de casos graves y por ende la tasa de mortalidad. Sin embargo, se recomienda promoción y educación sanitaria a la población en general para incentivar la aceptación(AU)

The SARS-CoV-2 pandemic has generated considerable efforts in the development of vaccines, to verify their effectiveness, clinical trials are required and use them in the population worldwide. A systematic literature review (RSL) of COVID-19 and its impact on vaccine development was carried out from 2019 to 2022. The search strategy managed to obtain 8,646 articles, chosen from the 6 research sources (Wiley Online Library, Taylor & Francis, THE LANCET Infectious Diseases, National Library of Medicine, Nature Portfolio and Oxford Academic), then a 4-stage filter was performed with 2 exclusion criteria each, leaving only 78 articles, which were used to answer three research questions posed. In the scientific articles analyzed, the most referenced laboratories that developed Pfizer/BioNTech, Moderna, AstraZeneca, Sinovac, Sinopharm and Sputnik V vaccines were identified, the use of nanotechnology in the design of the vaccines was identified, mainly using messenger RNA, viral vector and protein subunits, depending on the case with adjuvants that enhance immunogenicity. The studies demonstrated good effectiveness, in the different prioritized groups and thanks to the dosage of the immunizations against COVID-19, the number of serious cases and therefore the mortality rate have been prevented. However, health promotion and education is recommended for the general population to encourage acceptance(AU)

Susceptibility of the elderly to SARS-COV-2 infection: ace-2 overexpression, shedding, and antibody-dependent enhancement (ADE)

The world is currently facing a serious SARS-CoV-2 infection pandemic. </mac_aq>This virus is a new isolate of coronavirus, and the current infection crisis has surpassed the SARS and MERS epidemics</mac_aq> that occurred in 2002 and 2013, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing </mac_aq>5,000 deaths and spreading across more than 130 </mac_aq>countries worldwide. The spreading capacity of the virus clearly demonstrates the potential threat </mac_aq>of respiratory viruses to human health, thereby reiterating to the governments around the world that preventive </mac_aq>health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of the patients need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of the elderly, especially individuals who are older than 60 years of age, and have comorbidities, including hypertension, diabetes, and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow less susceptible and are not considered as a risk group. Therefore, in this review, we discuss some possible molecular and cellular mechanisms by virtue of which the elderly subjects may be more susceptible to severe COVID-19. Toward this, we raise two main </mac_aq>points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 </mac_aq>receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe that these points are pivotal for a better understanding of the pathogenesis of severe COVID-19, and must be carefully addressed by physicians and scientists in the field.

Parasite load, iNOS and cytokine profiles, and histopathological aspects of Leishmania infantum infection in dogs with different clinical presentations / Carga Parasitária, iNOS, citocinas e histopatologia na infecção por Leishmania infantum em cães com apresentações clínicas distintas

ABSTRACT: Visceral leishmaniasis (VL) is a zoonotic disease with a canine urban reservoir in South America. Dogs from an endemic area within Brazil, which were naturally infected with Leishmania infantum, and those presenting severe clinical (SC), mild, or no clinical (MNC) disease, were evaluated. Parasite load, histopathology, and cytokine and iNOS mRNA expressions were assessed in the spleen and liver in order to determine the potential markers for disease susceptibility or resistance. As a result, dogs with both SC and MNC had high parasite loads; IFN-γ was the most expressive cytokine in both organs, along with IL-6 and IL-4 being detected in the spleen and liver, and IL-10 only in liver. The hepatic tissue presented higher medians for IFN-γ and IL-10, and was the main organ to produce cytokines with hepatic IL-10 suggesting a regulatory follow up. Granulomas were detected in both organs; however, when absent in spleen, they were associated with elevated IL-6 levels, thus highlighting the anti-inflammatory role of IL-6. Microscopic lesions in the spleen were predominantly characterized by an extensively disorganized white pulp and splenic response was suggested as sub optimized. Parasite load, tissue damage, and immunological response may vary in the dogs with similar clinical symptoms, which may not be a good parameter for assessing the animal's susceptibility to VL.

RESUMO: A Leishmaniose visceral (LV) é uma doença zoonótica com reservatório canino na América do Sul. Cães oriundos de área endemica brasileira, naturalmente infectados por Leishmania infantum, apresentando doença clínica severa (CS) ou doença branda ou ausente (BA) foram avaliados. Carga parasitária, histopatologia e expressão de mRNA de citocinas e iNOS foram analisados em baço e fígado, buscando determinar possíveis marcadores de susceptibilidade ou resistência à doença. Como principais resultados, tanto cães CS como BA apresentaram alta carga parsitária. IFN-γ foi a citocina mais expressiva em ambos os órgãos, sendo IL-6 e IL-4 também detectadas em baço e fígado e IL-10 em fígado. No tecido hepático foram encontradas as maiores medianas de IFN-γ e IL-10, sendo o fígado o principal órgão produtor de citocinas, com IL-10 sugerindo acompanhamento regulatório. Granulomas foram detectados em ambos os órgãos. Quando de sua ausência no baço, essa foi associada à elevação dos níveis de IL-6, salientando o papel anti-inflamatório dessa citocina. Alterações microscópicas foram principalmente caracterizadas por extensiva desorganização de polpa branca, com a resposta esplência sendo sugerida como subotimizada. Carga parasitária, dano tecidual e resposta immune variaram mesmo em cães com quadros clínicos similares, não sendo, portanto, a análise clínica um bom parâmetro para avaliação de susceptibilidade animal à LV.

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

Clinical significance of bone marrow immunopathologic detection: analyses of 266 newly diagnosed lymphoma cases / 白血病·淋巴瘤

Objective To investigate the clinical significance of bone marrow immunopathogenesis in the diagnosis and staging of lymphoma. Methods Clinical data of 266 patients with newly diagnosed lymphoma admitted to Department of Hematology in the First Hospital of Jilin University from August 2015 to December 2017 were retrospectively analyzed. The results of lymphoma diagnosis and staging in different bone marrow detection methods were compared, SPSS 22.0 software was used to make statistical analysis and χ2 test was used to compare the positive rates of lymphoma bone marrow infiltration in different methods. Results In the 266 patients, 64 cases (24.1 %) were diagnosed with lymphoma by using bone marrow detection on the condition that no lymph node pathology was available and all the immunophenotypes of 64 cases were identified by bone marrow immunopathology. Bone marrow infiltration was identified in 121 patients (45.5 %), among which the rate of bone marrow infiltration was 0 (0/12) in Hodgkin lymphoma (HL) and 47.6 % (121/254) in non-Hodgkin lymphoma (NHL). The rate of bone marrow infiltration was 50.0 % (105/210) and 36.4 % (16/44) in B type and T type NHL respectively. The positive rate of bone marrow infiltration detected by bone marrow smear, bone marrow biopsy, bone marrow flow cytometry and bone marrow immunopathology were 78.5 % (95/121), 87.6 % (106/121), 89.3 % (108/121), 96.7 % (117/121) respectively. Bone marrow immunopathology was more advantageous than any other methods, and there was a statistical difference (χ2＝18.38, 9.09, 3.76; all P < 0.05). Among 121 patients who were identified with bone marrow infiltration by bone marrow detection, the staging of 42 patients (34.7 %) were amended, including the staging of 39 amended patients (32.2 %) through bone marrow immunopathologic detection. Conclusion Bone marrow immunopathology can be used for the diagnosis and classification of lymphoma, which has an obvious advantage in detecting bone marrow infiltration of lymphoma compared with bone marrow smear, bone marrow biopsy, bone marrow flow cytometry, and it can be used to amend the clinical staging.

Treg/Th17 balance and immunology of schistosome infection: a review / 中国血吸虫病防治杂志

Many factors are reported to be involved in regulating the immunopathogenesis of schistosome infection. CD4+ T cell is one of the key players in the regulation of the liver granuloma formation by differentiation into different effector subsets including T helper (Th) 1, Th2, Th17, and T regulatory cells (Treg cells). Treg cells play an important suppressive role in immunopathology control and favor the pathogen to escape from the host immune assault. The functional activity of Tregs has been related to some autoimmune diseases including asthma and inflammatory bowel disease, which suggests that the manipulation of Tregs to restore their numbers and function may be therapeutic. However, interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the pathogenesis of many inflammatory and infectious conditions, including schistosomiasis. Therefore, a deeper understanding of the mechanisms of these immune regulations is necessary for the better control of pathology in schistosomiasis. In this paper, we review the Treg/Th17 balance and the immunology of schistosome infection.

Treg/Th17 balance and immunology of schistosome infection: a review / 中国血吸虫病防治杂志

Many factors are reported to be involved in regulating the immunopathogenesis of schistosome infection. CD4+ T cell is one of the key players in the regulation of the liver granuloma formation by differentiation into different effector subsets including T helper (Th) 1, Th2, Th17, and T regulatory cells (Treg cells). Treg cells play an important suppressive role in immunopathology control and favor the pathogen to escape from the host immune assault. The functional activity of Tregs has been related to some autoimmune diseases including asthma and inflammatory bowel disease, which suggests that the manipulation of Tregs to restore their numbers and function may be therapeutic. However, interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the pathogenesis of many inflammatory and infectious conditions, including schistosomiasis. Therefore, a deeper understanding of the mechanisms of these immune regulations is necessary for the better control of pathology in schistosomiasis. In this paper, we review the Treg/Th17 balance and the immunology of schistosome infection.

Cytotoxic activity in cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is a chronic disease caused by species of the protozoan Leishmania and characterised by the presence of ulcerated skin lesions. Both parasite and host factors affect the clinical presentation of the disease. The development of skin ulcers in CL is associated with an inflammatory response mediated by cells that control parasite growth but also contribute to pathogenesis. CD8+ T cells contribute to deleterious inflammatory responses in patients with CL through cytotoxic mechanisms. In addition, natural killer cells also limit Leishmania infections by production of interferon-γ and cytotoxicity. In this review, we focus on studies of cytotoxicity in CL and its contribution to the pathogenesis of this disease.

La biología molecular en el estudio de la inmunopatología / Molecular Biology in the study of Immunopathology

Las técnicas de biología molecular han tenido un profundo impacto en el campo de la inmunología. Han permitido dilucidar varias interrogantes sobre el funcionamiento del sistema inmune y han aumentado nuestra habilidad para entender, diagnosticar y tratar una gran variedad de enfermedades inmunológicas. Se realizó una revisión de la literatura sobre aspectos generales de la importancia de las técnicas de biología molecular en el estudio de la respuesta inmune, que incluye conceptos generales y clasificación de las metodologías más empleadas, así como la referencia de algunas aplicaciones en el estudio de la inmunología y la inmunopatología. Se muestra información actualizada con enfoque analítico que permite ilustrar las características de los principales métodos empleados en biología molecular y su aplicación en el estudio de la respuesta inmune. La utilidad de las técnicas de biología molecular en el estudio de la respuesta inmune, ha constituido un poderoso instrumento para sus aplicaciones en el desarrollo de mejores alternativas diagnósticas y terapéuticas...

Molecular biology technical methods have caused a high impact in the field of immunology. They have made it possible to know the answer to many questions regarding the immune system function and have increased our ability to understand, diagnose and treat a great deal of immunological diseases. A review of the literature about the importance of molecular biology in the study of immune response was made, including general concepts, classification of the most used technologies, as well as some applications in the study of immunology and immunopathology. Update information with analytic view about the main methods used in molecular biology and its application in the evaluation of immune response is shown. Usefulness of molecular biology techniques are a powerfull instrument to develop new and better alternatives for diagnoses and treatment...

Leprosy, a neglected disease that causes a wide variety of clinical conditions in tropical countries

Leprosy is an ancient disease that remains endemic and continues to be a major public health problem in some tropical countries, where it has been internationally recognized as being linked to the underdevelopment conditions. The natural course of the disease covers a wide variety of clinical conditions with systemic involvement. In this paper, we review the findings obtained in studies of the pathological mechanisms of leprosy, including a survey of the literature and of our own work. The understanding and control of the wide variety of clinical conditions should help improve patient care and thus prevent the onset of physical impairment and the stigma of the disease.

Pathology of lymphatic filariasis

Developing and adult worms of the human lymphatic filarial parasites (Wuchereria bancrofti, Brugia malayi, and Brugia timori) are located mainly in the lymphatic system and occasionally in aberrant sites like subcutaneous and conjunctival cysts. Lymphatic pathology ranging from dilatation of lymphatic channels and lymphangiectasia are detected on ultrasonography in apparently healthy, amicrofilaraemic, but filarial antigen positive individuals in endemic areas. Microfilariae are distributed in various organs and may be associated with immune mediated pathology at these sites; tropical pulmonary eosinophilia is characterized by intense immune mediated destruction of microfilariae in the lung parenchyma. In the spleen and other sites, nodular granulomatous lesions can occur where microfilariae are trapped and destroyed. The finding of Wolbachia endosymbionts in all stages of lymphatic filarial parasites has provided new insight on the adverse reactions associated with anti-filarial chemotherapy. Inflammatory molecules mainly lipopolysaccharide (LPS)-like molecules released from endosymbionts on death of the parasites are largely responsible for the adverse reactions encountered during anti-filarial chemotherapy. Prenatal tolerance or sensitization to parasite derived molecules can immune-modulate and contribute to both pathology and susceptibility/resistance to infection. Pathological responses thus depend not only on exposure to filarial antigens/infection, but also on host-parasiteendosymbiont factors and to intervention with antifilarial treatment. Treatment induced or host mediated death of parasites are associated with various grades of inflammatory response, in which eosinophils and LPS from endosymbionts play prominent roles, leading to death of the parasite, granulomatous formation, organization and fibrosis. The non-human primate (Presbytis spp.) model of Brugia malayi developed for the tertiary screening of anti-filarial compounds has provided unique opportunities for the longitudinal study of the pathology associated with lymphatic filariasis. The pathology in this non-human primate model closely follows that seen in human lymphatic filarial infections and correlates with clinical evidence of lymphatic pathology as detected with ultrasonography. These studies also show that successful treatment as detected by loss of motility and calcification of worms on ultrasonography is associated with reversal of early dilatations of lymphatic channels.

Modelo natural de dicotomía TH1-TH2: La enfermedad de Hansen / Th1-TH2 balance. Natural model: Hansen'disease

La enfermedad de Hansen producida por el Mycobacterium leprae, es una enfermedad infecciosa cuyo amplio espectro clínico e inmunopatológico se correlaciona con los diferentes patrones de respuesta Th1/Th2. La activación preferencial de esas subpoblaciones de linfocitos T CD4 juega un rol importante en su patogenia y constituye un modelo natural de esa dicotomía de la respuesta inmune. Ambas formas polares de la lepra presentan un perfil definido de secreción de citoquinas: Th1 (IL2 e IFN?) en el polo tuberculoide y Th2 (IL4, IL5, IL10) en el polo lepromatoso. En el primer caso, la respuesta celular adecuada estimula la activación macrofágica y lleva a la destrucción del bacilo. Las lesiones son escasas y limitadas a la piel y nervios periféricos. En el segundo en cambio, la respuesta celular es casi nula y los bacilos se multiplican descontroladamente dentro de los macrófagos, llevando a la diseminación de las lesiones y afectación de otros órganos. La inmunidad humoral está exacerbada y hay un alto nivel de anticuerpos que no pueden eliminar el germen intracelular. Los factores que determinan la diferenciación hacia una respuesta Th1 ó Th2 no se han esclarecido totalmente. Se han postulado varias hipótesis que hacen referencia a factores genéticos, prevalencia de citoquinas en el microambiente celular, disfunción macrofágica; alteración en los receptores Toll de la inmunidad innata, en la expresión de moléculas coestimulatorias, etc En los últimos años se han descubierto nuevas subpoblaciones de linfocitos, (CD4+ CD25+, Tr1, Th3 y Th17) que estarían implicadas en la desregulación de estas respuestas inmunes.

Hansen' disease, caused by Mycobacterium leprae, is an infectious illness whose wide clinical and immunopathologic spectrum correl with different Th1/Th2 responses patterns. The prefferencial activation of the CD4 T cells subset play an important rol in it's pathogenia and provides a natural model of that balance. Either polars forms present a defwed citokynes secretion profile: Th1 cells (IL-2 and IFN-g) dominate in tuberculoid form, whereas cytokines typically produced by Th2 cells (IL-4, IL-5 and IL-10) dominate in lepromatous form. In the first case, the macrophagic activation kills M leprae. It's lesions are located in nerves and skin only. In the second case, cell-mediated immunity is absent. The bacilli multiply uncontrolably in macrophages and infection is widely disseminated affecting other organs. Humoral immunity is exacerbated and have high levels of antibodies that cannot reach intracellular germ. The factors that determine whether the proliferation CD 4 T cells differentiate into Th1 or Th2 cell are not fully understood. Several hypothesis include genetics factors, prevail of cytokinesin the microenviroment, macrophagic disfunction; alterations in the coestimulatory molecules, on toll receptors of the innate immunity, etc. In recent years times new limphocytes subsets have been discovery (CD4+CD 25+, Tr1, Th3, Th17) that could be implicated in this desregulated immune reponses.

Manson's schistosomiasis in the undernourished mouse: some recent findings

This paper deals with current knowledge of the interrelationships between Schistosoma infection and malnutrition. It emphasizes the relevance of these investigations in the face of dynamic and evolving changes occurring in population diets and changes in the epidemiological patterns of schistosomiasis in endemic countries. The paper further discusses the basis for continuing the studies on this subject and the reasons why it represents a misunderstood association. This review also focuses on the cellular and humoral immune responses in the undernourished mouse model infected with Schistosoma mansoni, with updated information on the immune response in wild-type and iNOS knockout mice concerning soluble egg antigen specific antibodies and kinetics of IFN-ã, IL-4, IL-10 and IL-13 cytokines, in the chronic phase of Manson's schistosomiasis. There is indication that schistosome-infected undernourished mice are able to develop a humoral immune response, but antibody titres are much lower than in the control animals. Cytokine production (IFN-ã, IL-4, IL-10) is lower in the undernourished mice, but as infection progresses to the chronic phase its kinetics run an antagonistic course when compared to that of well-nourished animals. Marked variation in the secretion of IL-13 (a fibrogenic cytokine) could explain why undernourished mice do not develop liver "pipe-stem" fibrosis described in previous papers on well-nourished animals.

Regulatory T cells are increased in tuberculosis patients and closely correlate with its immunopathology / 中华微生物学和免疫学杂志

Objective To determine whether regulatory T cells(Tr)are increased in patients with tuberculosis and whether they are associated with its immunopathology.Meantime,to investigate the possibility of tuberculosis(TB)as a model for studying Tr functions.Methods The lymphocyte subsets were isolated from peripheral blood mononuclear cells by sorting with flow cytometry.Total cellular RNA was extracted and RT-PCR was performed to detect the Foxp3 mRNA in purified CD3+CIM+T cells,CD3+CD8+T cells and non-CD3+CD4+CD8+T cells.Using FACS analysis.we further investigated the distribution of Foxp3+ population in CD4+ CD25+T cells.Finally,we compared the percentage of CD4+CD25highFoxp3+T cells present in 51 active patients with tuberculosis and 40 uninfected healthy control subjects by FACS.The detection of Tr infiltration of Foxp3+ cells were performed with immunohistochemistry(IHC)method on tuberculosis pathological sections.Results Foxp3 was specific expressed in CD3+CD4+T cells,either in tuberculosis patients or healthy control subjects.Foxp3+ T cells took about 85%fraction of CD4+ CD25highpopulation.We used CD4+CD25high Foxp3+as a detective markers for Tr in the FACS analysis.The results showed that patients with active TB had a 4.4 fold higher percentage within the CD4+T cells in peripheral blood compared to healthy control group(modian,1.01%vs 0.23%,P<0.01).Much higher frequency of Tr were found along with T cells infiltration at the tuberculosis pathological tissues.A few individuals that we can followed indicated the expanded Tr was declined after curative treatment with operation.Conclusion Tr cells are increased in tuberculosis patients and closely correlate with its immunopathology.Tuberculosis should be a valuable model for Tr functional study.

Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-gama, IL-2, IL-4 and IL-10) by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.

Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system (CNS) and one of the most common disabling neurological diseases of young adults. Although the exact mechanisms involved in MS pathogenesis remain unclear, MS is believed to be caused by interactions between as yet unidentified environmental factors and susceptibility genes. Symptoms commonly occurred in MS include visual disturbance; weakness; spasticity; sensory disturbances; ataxia; bladder, bowel, and sexual dysfunction; fatigue; affective symptoms; and cognitive impairment. Most patients initially undergo a relapsing-remitting course, however, without treatment, the majority of them make a transition to the secondary progressive form. The clinical diagnosis is based on demonstrating neurological lesions, predominantly in the white matter, that are disseminated over space with the lapse of time. The key to the successful MS management is to prevent disability. Although there is no effective cure for MS, therapies are available that mitigate the course of the disease, treat relapses and improve symptoms, all of which place a significant impact on patients' quality of life. Recent clinical trials suggest that early identification and treatment are critical to optimize the treatment benefit. Currently six agents have been specifically approved for mitigating the course of MS. These include three formulations of interferon beta, glatiramer acetate, mitoxantrone, and natalizumab. Recent advances in understanding of immune pathogenesis lead us to new therapeutic approaches focused on precise target mechanisms. Many ongoing clinical trials will provide better treatment protocols in near future.

Cytokine profile in Montenegro skin test of patients with localized cutaneous and mucocutaneous leishmaniasis / Perfil de citocinas na intradermorreação de Montenegro em doentes de leishmaniose cutânea localizada e cutâneo-mucosa

American tegumentary leishmaniasis presents as two major clinical forms: localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). The immune response in leishmaniasis is efficiently evaluated by the response to Leishmania antigen through the Montenegro skin test (MST). Both LCL and MCL present positive response to MST, indicating that the patients present cell-mediated immunity against the parasite - Leishmania. In spite of the presence of immunity in MCL, this is not sufficient to stop disease progression and prevent resistance to treatment. In this study we demonstrated interleukin (IL) 2, 4, 5 and interferon (IFN) gamma expression in biopsies of MST of ten patients with American tegumentary leishmaniasis. The obtained results were compared between LCL (n = 5) and MCL (n = 5) patients. The MST of MCL patients displayed a higher expression of IL-2, IL-4 and IL-5, in comparison to LCL. There was no significant difference in IFN-gamma expression between groups. The obtained results suggest the role of IL-4 and IL-5 in the maintenance of the immunopathogenic mechanism of the destructive lesions that characterize MCL.

A leishmaniose tegumentar americana apresenta duas formas clínicas mais comuns: a leishmaniose cutânea localizada e a leishmaniose cutâneo-mucosa. A imunidade da leishmaniose é avaliada pela resposta ao antígeno Leishmania através da Intradermorreação de Montenegro. Estas duas formas apresentam resposta positiva, indicando que o paciente apresenta imunidade celular contra o parasita Leishmania. Apesar da presença da imunidade celular na leishmaniose cutâneo-mucosa, esta não é suficiente para barrar a progressão da doença e a resistência ao tratamento. Neste estudo, detectamos quatro citocinas por imunohistoquímica, IL-2, IL-4, IL-5 e IFN-gama nas biópsias da intradermorreação de Montenegro de pacientes com leishmaniose tegumentar americana (n = 10), cinco com leishmaniose cutânea e cinco com cutâneo-mucosa. Os resultados mostraram uma alta expressão significativa de IL-2, IL-4, IL-5 na leishmaniose cutâneo-mucosa comparada com a leishmaniose cutânea localizada, mas sem diferença significante na expressão do IFN-γ entre os grupos. Estes resultados sugerem a importância da participação da citocina IL-4 e IL-5 na manutenção do mecanismo imunopatogênico das lesões destrutivas da forma cutâneo-mucosa.

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.

Childhood Henoch-Sch(o)nlein Purpura Nephritis and IgA Nephropathy:One Disease Entity?--A Clinico-pathologically Comparative Study / 华中科技大学学报（医学）（英德文版）

In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schonlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 %children with IgA nephropathy, but only 10 % in HSPN (P＜0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia,compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6% of HSPN and 29 % of IgA nephropathy (all P＜0.01). Thin basement membrane nephropathy was only found in 6.5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2 %of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits,moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9 % of HSPN had IgG deposits in glomeruli and only 19.4 % of IgA nephropathy showed glomerular IgG deposits (P＜0.01). No IgG deposit was observed in 81.6 % of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn't be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5 % of HSPN, but only 19.4 % in IgA nephropathy after 34 months follow-up. Moreover, 64.5 % of IgA nephropathy had consistent hematuria and proteinuria and 16.1% had active nephritides (P＜0.05). It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn't support the one disease entity hypothesis.HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities.