Oral bacillus Calmette-Guérin vaccine against tuberculosis: why not?

The bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine for human use against tuberculosis (TB). Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB.

Tejido linfático asociado a mucosas: Células presentadoras de antígenos / Mucose associated lymphoid tissue: Antigen presenting cells

Se estudiaron al microscopio electrónico biopsias de mucosas normales y patológicas (cavidad bucal y cuello uterino), con especial atención a los sistemas de defensa existentes en las células epiteliales (CE) y en las células dendríticas (CD). Las CE, cuando están activadas, muestran su capacidad de fagocitar y procesar antígenos con la finalidad de presentarlos luego a las CD; los elementos implicados en esta función son vesículas de micropinocitosis, cuerpos multivesiculares, lisosomas, fagosomas, vesículas recubiertas por clatrina, gránulos de contenido denso recubiertos por una unidad de membrana, gránulos en cuyo interior se aprecian láminas que simulan hojas de cebolla, microcuerpos y gránulos con actividad de fosfatasa ácida. Las CD que recién han ingresado al interior del epitelio son de baja densidad electrónica y poseen grandes prolongaciones citoplasmáticas, que luego se reducen de tamaño, a la vez que aumenta la densidad de su citoplasma. Muestran vesículas de micropinocitosis, algunas recubiertas por clatrina, lisosomas y corpúsculos de Birberk. En este momento son reconocidas como células de Langerhans. Tanto en las CE como en las CD existen abundantes “pliegues marginales o de superficie“ (surface folds), conteniendo numerosas vesículas de micropinocitosis. Entre la CE y la CD se establecen íntimos contactos a través de los cuales las primeras presentan los antígenos fagocitados y tratados a las CD donde son terminados de procesar y se unen a las moléculas del complejo principal de histocompatibilidad y/o a moléculas con función similar (CD1). Las CD migran a los ganglios linfáticos donde presentan los antígenos a los linfocitos T y empieza el proceso de activación de estos, que conduce a la defensa frente a las noxas que han ingresado al organismo. De esta manera tanto las CD como las CE son un lazo de unión entre los sistemas de defensa innata y la adquirida.

We studied samples of normal and abnormal human mucosae, including oral tissue and uterine cervix, using electron microscopy. Special attention was given to the functions and mechanisms of defense carried out by the epithelial (EC) and dendritic cells (DC). Activated epithelial cells posses the capacity to uptake and process antigens, in order to present them, subsequently, to the dendritic cells. The structures and elements of the cells intervening on this function are: micropinocytic vesicles, multivesicular bodies, lysosomes, phagosomes, clathrin-covered vesicles, dense granules covered by a unit membrane, granules with onion likes leaves, microbodies, and dense granules with acid phosphatase activity. When they first arrive within the epithelial layers, the DC are clear with long cytoplasmic projections, which later become short, and the density of their cytoplasm increases. They possess mycropinocytic vesicles, some clathrine-covered vesicles, lysososmes and Birbeck granules. At this moment, they are known as Langerhans cells. EC and DC present many surface folds rich in micropynocytic vesicles. Between EC and DC there are many contacts (close junctions or tight junctions), through which antigens, phagocitized and processed by the EC, are given to the DC. These cells join them to major histocompatibility complex molecules or to other molecules with similar functions (CD1). Then the Langerhans cells travel to the lymphatic node to activate T cells and continue the immunologic task. So, in this way, both the EC and the DC are a link between the natural and the acquired immunological mechanisms.

Antiviral effect of dietary germanium biotite supplementation in pigs experimentally infected with porcine reproductive and respiratory syndrome virus

Germanium biotite (GB) is an aluminosilicate mineral containing 36 ppm germanium. The present study was conducted to better understand the effects of GB on immune responses in a mouse model, and to demonstrate the clearance effects of this mineral against Porcine reproductive and respiratory syndrome virus (PRRSV) in experimentally infected pigs as an initial step towards the development of a feed supplement that would promote immune activity and help prevent diseases. In the mouse model, dietary supplementation with GB enhanced concanavalin A (ConA)-induced lymphocyte proliferation and increased the percentage of CD3+CD8+ T lymphocytes. In pigs experimentally infected with PRRSV, viral titers in lungs and lymphoid tissues from the GB-fed group were significantly decreased compared to those of the control group 12 days post-infection. Corresponding histopathological analyses demonstrated that GB-fed pigs displayed less severe pathological changes associated with PRRSV infection compared to the control group, indicating that GB promotes PRRSV clearance. These antiviral effects in pigs may be related to the ability of GB to increase CD3+CD8+ T lymphocyte production observed in the mice. Hence, this mineral may be an effective feed supplement for increasing immune activity and preventing disease.

Distribution and Quantification of Lymphocytes in the Major Lymphoid Organs of Naturally Gumboro Infected Broilers / Distribución y Cuantificación de Linfocitos en los Órganos Linfoides Principales de Pollos de Engorda Infectados Naturalmente con Gumboro

Gumboro disease is caused by the infectious bursal disease virus (IBDV) which rapidly destroys immature B-lymphocytes of bursa of Fabricious, and causes immune suppression and high mortality in commercial broiler farms in Bangladesh. To investigate the possible effect of IBDV on lymphocytes and its distribution in the major lymphoid organs, bursa of Fabricious including spleen and thymus of naturally Gumboro-infected broilers, a research was conducted in the Department of Anatomy and Histology, collaboration with the Department of Pathology, Bangladesh Agricultural University, Bangladesh. Bursa of Fabricious, spleen and thymus of 21-days-old Gumboro-infected and non-infected broilers of same age (control) were routinely processed and stained by hematoxylin and eosin to examine the distribution of lymphocytes in the major lymphatic organs as well as quantified the number of lymphocytes under high power magnification field and compared with those of control. The number of lymphocytes in bursa of Fabricious, spleen and thymus of Gumboro-infected broilers were 27.20 ± 1.53, 66.50 ± 2.70 and 79.30 ± 3.92 whereas 121 ± 3.82, 89.90 ± 2.09 and 106.30 ± 4.07 were in non-infected control respectively. The numbers of lymphocytes were significantly (p < 0.05) lower in all lymphatic organs of Gumboro-infected broilers than those of non-infected control. The significant numbers of lymphocytes decrease in spleen and thymus suggest that IBVD not only destroy lymphocytes in bursa of Fabricious, but also in spleen and thymus and thus may severely suppress the immune response of IBVD affected broilers.

La enfermedad de Gumboro es causada por el virus de la bursitis infecciosa (VBI), que destruye rápidamente los linfocitos B inmaduros de la bolsa de Fabricio, y causa supresión inmune y la elevada mortalidad en las granjas comerciales de pollos de engorde en Bangladesh. Para investigar el posible efecto del VBI en los linfocitos y su distribución en los órganos linfoides principales, la bolsa de Fabricio, incluyendo el bazo y el timo de pollos de engorde naturalmente infectados con Gumboro, se realizó una investigación en el Departamento de Anatomía e Histología, y el Departamento de Patología, Universidad Agrícola de Bangladesh, Bangladesh. Tanto la bolsa de Fabricio, bazo y el timo de pollos de engorde con 21 días de edad infectados con Gumboro y no infectados de la misma edad (control) se procesaron de forma rutinaria y se tiñeron con H & E para examinar la distribución de los linfocitos en los órganos linfáticos principales, así cuantificar el número de linfocitos bajo campo de alta magnificación y compararlos con los de control. El número de linfocitos en la bolsa de Fabricio, bazo y timo de pollos infectados con Gumboro fue 27,20 ± 1,53, 66,50 ± 2,70 y 79,30 ± 3,92, respectivamente, mientras que en los controles no infectados fue 121 ± 3,82, 89,90 ± 2,09 y 106,30 ± 4,07 respectivamente. El número de linfocitos fue significativamente (p < 0,05) más bajo en todos los órganos linfáticos de pollos de engorde infectados con Gumboro que los no infectados. La disminuición significativa de linfocitos en el bazo y timo, sugiere que el VBI no sólo destruye linfocitos en la bolsa de Fabricio, sino también en el bazo y el timo y, por tanto, puede suprimir severamente la respuesta inmune de pollos de engorde afectados por VBI.

Mucosa-associated lymphoid tissue in individuals with AIDS / Tecido linfoide associado à mucosa em indivíduos com AIDS

Vestibular folds (VF) protect upper airways, but contain fewer immune cells in AIDS patients, which affects the structure of lymphoid follicles (LF). OBJECTIVE: To characterize fibrosis and immunoglobulin production in vestibular fold lymphoid tissues of AIDS patients with or with no infection and malnutrition. MATERIALS AND METHODS: A retrospective study of 71 adult vestibular fold autopsy specimens. The morphological analysis was done using the picrosirius staining method. Immunohistochemical methods consisted of anti-IgA, anti IgG, and anti IgM antibodies. RESULTS: Fibrosis was less intense in AIDS patients compared to subjects without AIDS; the same applied to patients with infection or malnutrition. IgA and IgG titers were higher in AIDS patients; IgM titers were higher in cases with infection. CONCLUSION: This study helps understand variations in lymphoid follicle components of AIDS patients; it also shows the influence of architectural changes and the effect of associated respiratory infection and malnutrition on lymphoid follicle function.

Pregas vestibulares (PV) são responsáveis pela proteção das vias aéreas superiores e, nos indivíduos com AIDS, apresenta diminuição das células imunes, o que influencia na estrutura dos folículos linfoides (FL). OBJETIVO: Caracterizar a fibrose e a produção de imunoglobulinas nos FL das PV nos indivíduos com AIDS, com e sem infecções e subnutrição associadas. MATERIAIS E MÉTODOS: Foi realizado um estudo retrospectivo transversal em 71 PV de adultos autopsiados. Para a análise morfológica foi usada a coloração picro-sirius. A imuno-histoquímica foi realizada com os anticorpos: anti-IgA, anti-IgG, anti-IgM. RESULTADOS: Nos pacientes com AIDS, a quantidade de fibrose foi menor quando comparados com aqueles que não possuíam AIDS, o mesmo sendo encontrado nos pacientes com infecções ou subnutrição. As quantidades de IgA e IgG foram maiores nos indivíduos com AIDS, e os valores de IgM foram maiores nos casos com infecção. CONCLUSÃO: Este estudo contribui para o melhor conhecimento da variação dos constituintes dos FL das PV nos indivíduos com AIDS, bem como da influência de modificações arquiteturais, e da associação de outras entidades, como infecções respiratórias e a subnutrição, sobre a função destes FL.

Distribution and characterization of IL-10-secreting cells in lymphoid tissues of PCV2-infected pigs

Distribution and characterization of interlukin-10 (IL-10)-secreting cells in lymphoid tissues of pigs naturally infected with porcine circovirus type 2 (PCV2) were evaluated in accordance with PCV2 antigen detection. After screening a total of 56 pigs showing the symptoms of postweaning multisystemic wasting syndrome (PMWS), 15 pigs were PCV2 positive and 5 pigs, which showed stronger positive signals over multiples tissues were further investigated. This study showed that in PCV2-infected lymphoid tissues, particularly mandibular lymph node, spleen and tonsil, IL-10 expression was mainly localized in T-cell rich areas but rarely in B cell rich areas. IL-10 was highly expressed in bystander cells but rarely in PCV2-infected cells. Elevated IL-10 expression was predominantly associated with T cells, but rarely with B cells or with macrophages. The results of this study provide evidence for the role of IL-10 in chronic PCV2 infection and its relation to PCV2 antigen in affected tissues. Constantly elevated levels of IL-10 lead to immunosuppression in persistent and chronic viral infections. The increased IL-10 expression observed in PCV2 infection in this study suggests that IL-10-mediated immunosuppression may play an important role in the pathogenesis and maintenance of naturally occurring PCV2 infection.

Avaliação imunológica nas pregas vestibulares de pacientes autopsiados com a Síndrome da Imunodeficiência Adquirida / Immunological evaluation of vestibular folds in autopsies of patients with the Acquired Immunodeficiency Syndrome

Em pacientes com Síndrome da Imunodeficiência Adquirida há uma diminuição das células envolvidas na resposta imune, o que influencia na população celular dos folículos linfóides encontrados nas pregas vestibulares, favorecendo o aparecimento de infecções nas vias aéreas destes pacientes. Estas infecções são a principal causa de mortalidade e morbidade nestes pacientes. OBJETIVO: Caracterizar a população de células nos folículos linfóides localizados nas pregas vestibulares de adultos autopsiados com Síndrome da Imunodeficiência Adquirida, com e sem infecções respiratórias associadas. MATERIAIS E MÉTODOS: Foi realizado um estudo retrospectivo transversal em 64 laringes de adultos coletadas na rotina das autopsias. Para a imunohistoquímica foram utilizados os anticorpos: Anti-B cells, Anti-CD3, Anti-CD68 e Anti-follicular dendritic cells. RESULTADOS: 46 (71,87 por cento) dos pacientes estudados tinham diagnóstico de Síndrome da Imunodeficiência Adquirida. Nestes pacientes, a celularidade dos folículos linfóides foi estatisticamente menor em relação ao grupo controle em todos os fenótipos estudados. Nos pacientes imunodeprimidos com infecção respiratória associada, o número de células estava diminuído, sendo significante no caso dos linfócitos T (p=0,024). CONCLUSÃO: Em nosso estudo demonstramos que os folículos linfóides das pregas vestibulares são afetados pela infecção viral e representam com fidedignidade o estado imunológico de imunodepressão destes pacientes.

Immune response cells are decreased in patients with the Acquired Immunodeficiency Syndrome. This alters the cell population in vestibular fold lymphoid follicles, leading to respiratory infections in these patients. Such infections are the main cause of mortality and morbidity in these patients. AIM: to characterize lymphoid follicle cell populations in the vestibular folds of adults with the Acquired Immunodeficiency Syndrome and associated or not respiratory infection. MATERIALS AND METHODS: A retrospective study was made of 64 adult larynges harvested during routine autopsies. Anti-B cell, Anti-CD3, Anti-CD68 and Anti-follicular dendritic cell antibodies were used for immunological testing. RESULTS: 46 (71.87 percent) of the sample patients had the Acquired Immunodeficiency Syndrome. In these patients, lymphoid follicle cellularity was lower compared to the control group. The cell number was decreased in patients with the Acquired Immunodefficiency Syndrome and associated respiratory tract infection. CONCLUSION: We demonstrated in this study that vestibular fold lymphoid follicles were affected by viral infections, and may be considered as a reliable marker of immunodepression in these patients.

Nasal associated lymphoid tissue & M cells, a window to persistent streptococcal infections.

BACKGROUND & OBJECTIVES: Intranasal infection of mice has been used as a model of streptococcal pharyngitis, as nasal associated lymphoid tissue (NALT) in this animal is structurally and functionally analogous to human tonsils. The present study was carried out to determine whether group A streptococci preferentially colonized or invaded NALT. METHODS: Lux(+) strain Sp3 was created and exponential phase bacteria were introduced intranasally into BALB/C female mice, total photon emission from selected areas was quantified, sections of NALT tissues were used for immunofluorescent staining and M cell staining. RESULTS: Intranasal infection of mice with bioluminescent group A streptococci or unlabeled streptococci demonstrated that NALT was a primary target of this pathogen. Streptococci readily gained access to the blood stream from this site of infection. Immunofluorescence microscopy studies showed that M cells, dispersed along the mucosal epithelium adjacent to NALT, were preferentially infected and likely to provide the window through which streptococci reached the underlying tissue. INTERPRETATION & CONCLUSION: The present study suggests that this upper respiratory Gram positive pathogen uses a mechanism similar to that of enteric pathogens in the intestine to gain access to underlying tissue, lymphatics and blood.

Células y órganos del sistema inmune / Cells and organs of the immune system

Las células del sistema inmune que incluyen linfocitos, granulocitos y monocitos-macrófagos, se forman en la médula ósea a partir de células pluripotentes, a través de un proceso finamente regulado y el que participan varias citoquinas. Los granulocitos (neutrófilos, eosinófilos y basófilos) presentan particularidades morfológicas y funcionales. La principal función de los neutrófilos es su capacidad fagocítica. En el capítulo se explican los procesos de activación, quimiotaxis, fagocitosis y bacteriolisis. Las células del sistema fagocítico mononuclear (monocitos y macrófagos) tienen como función fagocitar; actividad más desarrollada en los macrófagos, que son células tisulares derivadas de los monocitos circulantes. Los linfocitos son las células que participan en la inmunidad adquirida o específica. Las células T participan en la inmunidad celular y las células B en la inmunidad humoral. Una tercera subpoblación de linfocitos, las células NK, participan en la inmunidad celular de tipo innata. Los órganos linfoides se pueden clasificar en primarios (timo y médula ósea) y secundarios (bazo, ganglios linfáticos y tejido linfoide asociado a mucosas). En el timo maduran los LT y en la médula ósea los LB. En los órganos linfoides secundarios los linfocitos y otras células del sistema inmune toman contacto con los antígenos y es en ellos donde se genera la respuesta inmune específica. En estos órganos existen zonas ricas en células T, y otras en que, principalmente, existen células B. La capacidad de los linfocitos de recircular entre los órganos linfoides secundarios, vasos linfáticos, conducto torácico y vasos sanguíneos le permiten tomar contacto con antígenos en diferentes lugares del organismo

Differential expression of leukocyte common antigen in human fetal lymphoid organs

To investigate the differential expression of various types of leukocyte common antigen (LCA) isoforms during development, we analyzed human fetal lymphoid organs, including the thymus, liver, spleen, and bone marrow from 14 weeks to 29 weeks of gestational age by immunohistochemical and flow cytometric methods. In fetal thymus, over 90% of thymocytes throughout the entire fetal life expressed CD45RO and CD45RB, while CD45RA was expressed only in less than 5% of thymocytes. This expression pattern of LCA isoforms was established by a gestational age of 14 weeks or earlier, and persisted throughout the fetal period. The tissue distribution was different from each isoform; CD45RO-positive thymocytes were found in both the cortex and medulla at the 14th week with low intensity, but was localized in the cortex with increasing fetal age. CD45RB-positive thymocytes distributed mainly in the medulla from early gestational age. Among extrathymic lymphoid organs, a small portion of lymphoid cells expressing leukocyte common antigens appeared first in the liver at 10-12 weeks of gestational age and was followed by a small number in the spleen and bone marrow by 13-15 weeks. All lymphoid cells in these extrathymic lymphoid organs at this stage were CD19+ B cells. The number of these CD19+ cells increased abruptly during the early period of mid-gestational age. The pattern of tissue distribution of each LCA isoform in the fetal liver and spleen correlated well with the patterns of quantitative analysis by flow cytometry. In summary we found that different LCA isoforms expressed in cell-type-specific pattern and showed different tissue distribution during the period of fetal development, and that LCA was the earliest antigen expressed by lymphocytes in the thymus and extrathymic lymphoid organs in our series.

Imunologia das dermatofitoses / Immunology of dermatophytosis

Revisäo das respostas imunológicas na infecçäo por dematófitos, tanto no que se refere à imunidade mediada por células como à humoral. Discussäo quanto à inexistência de antígenos de dermatófitos padronizados e as dificuldades decorrentes deste fato

Expansion of a subset of TCR gamma/delta human lymphocytes from various lymphoid organs cultured with recombinant IL-2

1. TCR1 cells are a minor component of CD3+ lymphocytes which bear the gamma/delta T-cell receptor. There are limited data concerning the activation of TCR1 cells or TCR1 cell subsets in human lymphoid organs. We analyzed a subset of TCR1 cells (delta TCS1+) in peripheral blood (PBL), spleen (SPL), lymph nodes (LN), bone marrow (BM), and thymus (THY) after activation with IL-2. Lymphoid cells from these organs were cultured with 1500 U/ml IL-2 for 14 days and analyzed at periodic intervals for delta TCS1+ cells. 2. We found increased numbers of delta TCS1+ cells in 6- and 14-day cultures from SPL (20.8 +/- 11.8 per cent positive cells after 14 days of culture), LN, BM and THY but not in peripheral blood (1.8 +/- 0.9 per cent ). These delta TCS1+ cells coexpressed CD2, CD3, CD8 and CD56, but were negative for TCR alpha/beta and CD4. We also detected an expansion of TCR1+ cells in IL-2-stimulated PBL employing the pan-gamma/delta marker TCR delta 1; however, in contrast to solid organs, these TCR1+ cells were delta TCS1 negative. 3. Sorting experiments demonstrated directly that delta TCS1 cells from spleen cultures mediate high cytotoxic activity against K562 cell targets (39.4 per cent median specific cytotoxicity) and low activity against Daudi (9.6 per cent ), COLO (2.7 per cent ) and an antibody-sensitized human B-cell line (17 per cent ). 4. These results show expansion and cytotoxic activation by IL-2 of a subset of human TCR1 cells in solid lymphoid organs

Imunofisiologia do anel linfatico de Waldeyer / Imunnophisiology of Waldeyer's linfatic ring

O anel linfatico de Waldeyer (ALW), descrito pelo anatomista alemao Wilhelm Von Waldeyer, consiste em um aglomerado de tecido linfoide localizado de forma a circundar o istmo da orofaringe e a transicao entre a naso e orofaringe. Seus componentes sao tonsila faringea (adenoides), localizada na regiao mediana mais superior da parede superior da rinofaringe, estendendo-se lateralmente ate o ostio tubareo, encontrando o tecido que ai forma a tonsila tubarea. Abaixo e laterlamente a estes componentes, na abertura da orofaringe, encontra-se a tonsila palatina. O anel e completado pelas tonsilas linguais, que ocupam quase toda a extensao mais posterior do 1/3 posterior da lingua

Milky spots reactions to schistosomal mansoni infection

Milky spots (MS), considered by the authors as a Coelomatic Lympho-myelopoietic Organ (CLMO), present a strong reactivity during experimental schistosomal mansoni infection, characterized by an increase of lymphocytes, macrophages, plasmocytes, mast cells, neutrophils and expression of eosinophil metaplasia. Intraperitoneal injection of purified Schistosoma mansoni (Sm) eggs provoked a rise in the number and size of MS, which developed the sessile marginal and pedunculated types. The authors conclude that egg antigens are, at least partially, responsible for MS reactivity during Sm infection

Effect of acute heat stress on certain immunological parameters in albino rats.

The effect of acute heat stress on certain immunological parameters were studied in male albino rats. The test rats were exposed to an ambient temperature of 40 degrees celsius for 30 minutes and sacrificed immediately. Total WBC count, Differential count, Phagocytic index, NBT reduction, organ weight body weight ratio of spleen, thymus, and popliteal lymph nodes, and soluble immune complex levels were measured in control group and the heat stressed animals. The heat stressed animals show decrease in total WBC count, and neutrophilia, eosinophilia, and lymphocytopenia. The phagocytic index showed a significant increase whereas the avidity index showed a decrease from the control value. NBT reduction was also significant. The soluble immune complex level was not altered. The heat stressed animals showed a decrease in the thymus and spleen weight/body weight ratio while the lymph node/body weight ratio showed an increase compared to the control animals.

Immunologic response of guinea pigs (Cavia porecellus) by treatment with antithymocyte serum, gamma-irradiation of gastrointestinal tract, lymphoid tissue and bone marrow.

The immunologic status of the guinea pigs was modified by treatment with antithymocyte serum (ATS): irradiation of gastrointestinal tract lymphoid tissue (GALT) and bone marrow (BM) by gamma-rays. These animals were injected with homologous testes, kidney and heterologous sheep red blood cells respectively in complete Freund's adjuvant. Cell mediate immune response (CMI) and humoral immune response was studied after first, third, fifth and eighth week of allergization. CMI was completely suppressed in guinea pigs treated with ATS, whereas humoral response suppressed to a lesser extent. In GALT and BM irradiated guinea pigs, CMI develops normally. However, marked suppression in the production of antibody titre both against homologous testes, kidney and heterologous sheep red blood cells was observed. Thymic lymphocytes "T' are destroyed by antithymocyte serum which are the mediators of cell mediated immune response. Irradiation of GALT and BM suppresses humoral response thereby supports that these are populated by "B' lymphocytes.