O feto é um ser alogênico de sucesso / The fetus is a successful allogeneic being

O feto é um ser alogênico de sucesso. O feto é um aloenxerto natural bem tolerado pelo organismo materno. Vários fatores contribuem para a tolerância materna ao feto: 1. O útero é um local do corpo imunologicamente privilegiado, protegido por uma barreira tecidual não imunogênica; 2. A promoção de uma resposta imunossupressora local pela mãe: a. A molécula HLA-G do MHC de classe Ib, expressa nas células da placenta, impede que as células NK matem a placenta; b. A catabolização do aminoácido essencial triptofano pela placenta impede que as células T da mãe tenham acesso ao feto; c. A secreção das citocinas TGF-ß, IL-4 e IL-10, pelo epitélio uterino e trofoblasto, tende a suprimir as respostas das células T da mãe; d. A secreção das citocinas TGF-ß e IL-10, pelas células T reguladoras, também inibe as respostas de células T maternas.(AU)

The fetus is a successful allogeneic being. The fetus is a natural allograft well tolerated by the maternal organism. Several factors contribute to maternal fetal tolerance: 1. The uterus is an immunologically privileged body site, protected by a non-immunogenic tissue barrier. 2. Promoting a local immunosuppressive response by the mother: a. The MHC class Ib HLA-G molecule, expressed on placental cells, prevents NK cells from killing the placenta; b. The catabolization of the essential amino acid tryptophan by the placenta prevents the mother's T cells from accessing the fetus; c. Secretion of TGF-ß, IL-4 and IL-10 cytokines by the uterine and trophoblast epithelium tends to suppress the T-cell responses of the mother; d. Secretion of TGF-ß and IL-10 cytokines by regulatory T cells also inhibits maternal T cell responses.(AU)

Infecção congênita em cabritos por Mycoplasma agalactiae / Congenital infection by Mycoplasma agalactiae in goat kids

This study aimed to report three cases of contagious agalactia (CA) by Mycoplasma agalactiae in goat kids born with polyarthritis. The nanny goats belonging to two different herds presented clinical signs of CA during pregnancy and in parturition they were apparently healthy. The carpal articulations of the three goat kids, the tarsus articulation in one, and thigh-femoral articulation in another showed swelling, pain and impairment of the flexion-extension movements. The articular liquid was collected from two goat kids at birth and revealed a content which varied from transparent to fibrinopurulent, presenting a yellow coloring. The samples were plated on modified Hayflick. The colonies had the appearance of "fried egg" and were confirmed as being M. agalactiae by biochemical tests and 16S rRNA PCR. Blood was collected from three animals soon after birth and submitted to the indirect ELISA test for the determination of the titration of the anti- M. agalactiae antibodies. The results confirmed that the goat kids were infected during pregnancy by M. agalactiae and resulted in the birth of an offspring with clinical signs of CA being immune tolerant...

Avances en inmunidad gestacional / Advances in gestational immunity

El inicio y establecimiento de la gestación en los mamíferos dependen de la adaptación del sistema inmunológico de la madre para tolerar un feto semi-alogénico. La gestación en sí misma constituye un acontecimiento de equilibrio inmunológico, ya que mientras el sistema inmune mantiene la competencia para la defensa contra antígenos foráneos, mecanismos de tolerancia local y periférica previenen una respuesta inapropiada contra alo-antígenos fetales de origen paterno lo que pudiera provocar el rechazo del feto. La interacción materno-fetal es extremadamente compleja y es difícil determinar todos los componentes del sistema inmune involucrados. Hasta ahora se ha demostrado la participación activa de las células T y sus productos, las citoquinas y también se ha involucrado a las moléculas del complejo mayor de histocompatibilidad, los antígenos paternos y algunos inmunomoduladores como progesterona, indoleamina 2,3-dioxigeneasa y glicodelina, entre otros. Todos estos elementos parecen confluir para producir un gran cambio sistémico en el sistema inmune materno, promoviendo por una parte la tolerancia materno-fetal, crucial para finalmente permitir una gestación exitosa y, por otro lado, manteniendo una activa vigilancia inmune contra las infecciones que pondrían en riesgo la gestación y sobrevivencia de diversas especies. Se revisó la literatura más reciente acerca de los diferentes componentes del sistema inmune que han demostrado ser clave en el inicio y mantención de la gestación en mamíferos.

The initiation and establishment of pregnancy in mammals depends on the adaptation from maternal immune system to tolerate a semi-allogeneic fetus. Pregnancy itself constitutes an event of immune balance because, while the immune system maintains the capacity for defense against foreign antigens, mechanisms of local and peripheral tolerance may prevent an inappropriate response against fetal alloantigens of paternal origin which could lead to rejection of the fetus. The maternal-fetal immune interaction is extremely complex and it has therefore been difficult to identify all the immune components involved. So far, it is known that the active participation of T cells and their products, cytokines, and has also involved molecules from the major histocompatibility complex, other paternal antigens and some immunomodulators molecules such as progesterone, glycodelin and indoleamine 2,3-dioxigenase among others. All these elements seem to converge to produce a major systemic change in the maternal immune system, promoting on one hand the maternal-fetal tolerance, crucial to allow a successful pregnancy and on the other hand, maintaining an active immune surveillance against infections that might endanger pregnancy and survival of diverses species. A review of recent literature about the different components of the immune system that have proven key in the beginning and maintenance of pregnancy in mammals.

Placental transfer of Haemophilus influenzae type b antibodies in malnourished pregnant women

This study evaluated the vaccination response to Haemophilus influenzae type b (Hib) in malnourished pregnant women (MN), cord blood (CB) and in infants at two and six months of age for comparison with a control group (C). Twenty-eight malnourished pregnant women and 29 pregnant controls were immunized with conjugated Act-HIB® in the third trimester of pregnancy. Blood samples were collected from all before the immunization, during labor (post immunization), and from CB. All infants were immunized with Hib vaccine according to normal vaccine schedule and sera were collected at two and six months of age. Antibody levels to polyribosylribitol phosphate (PRP) were similar for both groups. Preimmunization: MN 1.94 µg/mL, C 1.68 µg/mL; post-vaccination: MN 18.53 µg/mL and C 17.55 µg/mL; in CB from MN 14.46 µg/mL and from C 17.04 µg/mL. Infants from MN and C mothers presented respectively at two months: 5.18 µg/mL and 8.60 µg/mL and at six months: MN 3.42 µg/mL and C 2.18 µg/mL. Antibody levels were similar in both groups studied (p = 0.485), however the vertical transmission rate was 14 percent lower in the MN pregnant group. Levels of antibodies > 0.15 µg/mL were found in all newborns from the MN pregnant group. Pregnant MN presented an immunological response to Hib vaccine similar to group C, however, vertical transmission rate of antibodies to PRP in the MN pregnant group was 14 percent lower than that in C, suggesting a less efficient passage of antibodies within this group.

Papel inmunológico de la progesterona en el mantenimiento del embarazo / Immunological role of progesterone in the maintenance of pregnancy

Progesterone is an essential hormone for pregnancy maintenance. This hormone acts by binding to its intracellular receptor or by rapid non-genomic actions to regulate a wide variety of biological functions in the feto-placental unit. Progesterone regulates blastocyst implantation and placental development by inducing immunosupression through type Th2 cytokines secretion. This review summarizes current research about the role of progesterone as critical regulator of expression and secretion of cytokines by T-cell and other placental cells.

La progesterona es una hormona esteroide muy versátil y esencial para el mantenimiento del embarazo. El principal mecanismo de acción de la progesterona es el clásico, vía receptor intracelular, regulando diversas funciones, aspectos celulares y vías moleculares implicadas en el proceso de la implantación. Asimismo existen mecanismos adicionales que no dependen de la interacción del complejo hormona receptor con la maquinaria transcripcional y que son capaces de regular rápidamente cascadas de señalización que determinarán la respuesta de la célula. En particular se ha demostrado que la progesterona ejerce efectos inmunosupresores durante la gestación al favorecer la secreción de citocinas de tipo Th2 por los linfocitos T, evento importante para regular el sistema inmunológico materno y evitar el rechazo de la placenta. El objetivo de esta revisión se centra en analizar la influencia de la progesterona en la interfase materno-fetal sobre la expresión y secreción de citocinas por las células T y no T como es el caso del trofoblasto.

Impact of diet on the immunological microenvironment of the pregnant uterus and its relationship to allergic disease in the offspring: a review of the recent literature

Medical progress has reduced the mortality from infectious diseases in most countries, but allergic diseases have become more prevalent worldwide over the same period, especially in industrialized countries. This has prompted speculation that modern lifestyles have altered the relationship between heredity and environment so as to promote development of an atopic phenotype when exposure to infection decreases. A healthy uterine microenvironment is known to favor Th2 lymphocyte development. However, some evidence suggests that persistence of the Th2 pattern of immunity directs the developing organism's immune response towards a long-lasting atopic phenotype. Even though the outcome also depends on other factors (such as infection, functional state of the intestinal microflora, and exposure to environmental allergens at times critical to development), it seems that the immune system during the perinatal period is responsive to interventions that are no longer effective in adulthood. We have reviewed the literature accessible through Medline to identify recent advances in the prevention of allergic disease through interventions in the fetal-maternal relationship. Diet seems to have a significant impact on the immunological profile of the pregnant uterus, as well as on the postnatal development of allergic disease in the offspring, as suggested by the effects of probiotic bacteria and by manipulations of the dietary content of polyunsaturated fatty acids and antioxidants. This highlights the need for further studies, in order to define the best intervention methods, the most appropriate time interval and the individuals who will most likely benefit from them.

Progressos médicos reduziram a mortalidade por doenças infecciosas em muitos países, mas doenças alérgicas tornaram-se mais prevalentes no mundo inteiro, no mesmo período, especialmente nos países industrializados, levando alguns a postular que a vida moderna influencia as relações entre hereditariedade e meio ambiente de forma a favorecer o desenvolvimento de atopia quando a exposição a agentes infecciosos diminui. O micro-ambiente fisiológico do útero gravídico favorece o desenvolvimento de linfócitos Th2. Contudo, a evidência sugere que um padrão persistente de imunidade Th2 direciona a resposta imune do organismo em desenvolvimento para um fenótipo atópico duradouro. Embora o resultado dependa de outros fatores, incluindo infecções, o estado funcional da microflora intestinal, e a exposição a alergenos ambientais em momentos críticos do desenvolvimento, o sistema imune no período perinatal permanece suscetível a intervenções que não têm efeito no adulto. Fizemos uma revisão da literatura acessível através da Medline para identificar avanços recentes na prevenção de doenças alérgicas por meio de intervenção na relação materno-fetal. A dieta parece ter um impacto significativo sobre o perfil imunológico do útero gravídico, assim como sobre o desenvolvimento pós-natal de doença alérgica, como sugerido pelos efeitos de bactérias probióticas e pela manipulação do conteúdo de ácidos graxos poli-insaturados e de antioxidantes na dieta. Isso reforça a necessidade de estudos mais amplos para determinar o melhor tipo de intervenção, o momento mais adequado e os indivíduos que mais serão beneficiados.

A Case of Neonatal Alloimmune Neutropenia Associated with Anti-Human Neutrophil Antigen-1a (HNA-1a) Antibody

Neonatal alloimmune neutropenia (NAN) is an uncommon disease of the newborn provoked by the maternal production of neutrophil-specific alloantibodies, whereby neutrophil IgG antibodies cross the placenta and induce the destruction of fetal neutrophils. Affected newborns are usually identified by the occurrence of bacterial infections. The most frequent antigens involved in NAN are the human neutrophil antigen-1a (HNA-1a), HNA-1b, and HNA-2a. We report a neonate who was delivered at 36 weeks and had a severe neutropenia but who responded well to recombinant human granulocyte colony-stimulating factor (rhG-CSF). Anti-HNA-1a antibody was identified by mixed passive hemagglutination assay in both the sera of the baby and the mother. The baby had HNA-1a and HNA-1b but the mother had only HNA-1b on granulocytes. This is the first Korean report of NAN in which the specificity of the causative antibody was identified.

Inmunología de la relación materno fetal / Immune responses during pregnancy

Desde hace 40 años se consideraba que durante el embarazo los antígenos fetales se expresan de forma diferente a cualquier injerto; los datos actuales indican que la aceptación del feto por la madre depende de la falta de expresión de antígenos polimórficos, además de la producción de hormonas que actúan como inmunosupresoras. Durante el embarazo hay reconocimiento inmunológico de antígenos del trofoblasto; estos antígenos expresados por el trofoblasto no son polimórficos y previenen el reconocimiento de células T citotóxicas y células NK; además, esta estructura produce hormonas que también contribuyen a la disminución en la producción y proliferación de células T. Se ha demostrado que existe aumento en la producción de inhibidores del complemento de parte del trofoblasto (DAF, CD46) así como aumento en la secreción de hormonas como la progesterona, alfafetoproteína, esteroides y prostaglandinas. La identificación de estos factores y mecanismos inmunológicos puede ser fundamental en la búsqueda de tratamiento para padecimiento como cáncer, abortos espontáneos, infertilidad y trasplantes

Efecto de medio condicionado de placenta humana sobre linfocitos periféricos in vitro / Effects of human placenta conditioned media on peripheric lymphocytes in vitro

En este trabajo se investiga la acción del medio condicionado de placenta humana (MCPH) sobre linfocitos periféricos in vitro. Se cultivaron leucocitos periféricos de varones, mujeres con diferente número de partos, gestantes y nulíparas, en su propio plasma sin y con MCPH al 5, 10 y 20 por ciento. Luego de 120 h de cultivo se determinó la Transformación Blástica Linfocitaria (TBL, valores ò 0,5 indican estimulación) por observación de la morfología celular. Los linfocitos de varones y mujeres nulíparas no responden a ninguna de las concentraciones de MCPH ensayadas. En mujeres que han tenido hijos, la más alta transformación blástica linfocitaria se observa con MCPH al 10 por ciento, siendo esta respuesta correlativa con el número de partos (r = 0,73). En gestantes, si bien la máxima respuesta se obtiene con MCPH al 10 por ciento, el agregado de 5 por ciento del extracto es suficiente para producir estimulación linfocitaria (TBL x = 0,54 ñ 0,05). En conclusión, MCPH al 10 por ciento sigue siendo la concentración óptima para provocar blastogénesis linfocitaria. Además, en el plasma de las mujeres gestantes existirían sustancias que potencian la acción del extracto in vitro, permitiendo TBL > 0,5 con la adición de sólo 5 por ciento de MCPH