Aspectos actuales de la organogénesis. Función e involución del timo / Present aspects of organogenesis. Function and thymic involution

El timo es un órgano linfoide central o primario localizado en la parte anterosuperior del tórax. Constituye el principal sitio de diferenciación y maduración de las células T. En esta revisión se detallan aspectos actuales de la embriología, la histología y la función tímica y en la generación de los diferentes subtipos de timocitos y su diferenciación a células T maduras efectoras, la inducción de las células T tímicas reguladoras involucradas en el mantenimiento de la tolerancia a lo propio y la involución que sufre este órgano durante el proceso de inmunosenescencia(AU)

Thymus is a primary organ located in the antesuperior area of the torax. It is the principal place of differentiation and maduration of T cells. In this review present aspects of the embriology, histology and thymic function are detailed, as well as its role in the generation of different kinds of thymic cells; its differentiation to mature cells and of regulator T cells has a crucial role in tolerance induction. Moreover, thymic involution during of immunosenescence process is shown(AU)

Aspectos actuales de la organogénesis. Función e involución del timo / Present aspects of organogenesis. Function and thymic involution

El timo es un órgano linfoide central o primario localizado en la parte anterosuperior del tórax. Constituye el principal sitio de diferenciación y maduración de las células T. En esta revisión se detallan aspectos actuales de la embriología, la histología y la función tímica y en la generación de los diferentes subtipos de timocitos y su diferenciación a células T maduras efectoras, la inducción de las células T tímicas reguladoras involucradas en el mantenimiento de la tolerancia a lo propio y la involución que sufre este órgano durante el proceso de inmunosenescencia

Thymus is a primary organ located in the antesuperior area of the torax. It is the principal place of differentiation and maduration of T cells. In this review present aspects of the embriology, histology and thymic function are detailed, as well as its role in the generation of different kinds of thymic cells; its differentiation to mature cells and of regulator T cells has a crucial role in tolerance induction. Moreover, thymic involution during of immunosenescence process is shown

Síndrome de DiGeorge (Aplasia o Hipoplasia tímica): presentación y revisión de la literatura / DiGeorge Syndrome (Aplasia or thymic hypoplasia). Presentation and revision of literature

Se presenta lactante femenina de 6 meses de edad, portadora de síndrome genético con aplasia tímica, a la cual se le realizaron estudios inmunológicos y cromosómicos. La patología se caracteriza por un espectro de malformaciones, ausencia o poco desarrollo del timo y las glándulas paratiroides, unido a defectos en el tracto eferente del corazón y anomalías craneofaciales (síndrome velocardiofacial). El término síndrome de deleción 22q11.2 describe el problema cromosómico subyacente o bien el término síndrome velocardiofacial (velo-cardio-facial syndrome, VCFS) refiere los principales sistemas del cuerpo. La paciente coincidía con un Síndrome de DiGeorge por infecciones a repetición, fenotípicamente fascie compatible a la de agenesia o aplasia tímica al compararse con la de otros pacientes según lo observado en la bibliografía, valores de calcio hacia los límites inferiores e imagen radiológica de timo disminuida de tamaño, contribuyendo al conocimiento y la experiencia para el tratamiento posterior de pacientes con similares patologías.(AU)

It is presented a female newborn at six months of age with a genetic syndrome of thymic aplasia and she was under immunologic and chromosomal analysis. The pathology was characterized by a spectrum of disorders, lack or poor development of the thymus and parathyroid glands with faults in the efferent tract of the heart and craniofacial anomalies (velo-cardio-facial syndrome VCFS). The term deletion syndrome describes the subjacent cromosomic problem and the term velo- cardio-facial syndrome refers to the main systems of the body. The patient coincided with the DiGeorge syndrome due to recurrent infections phenotypically compatible to the agenesia or thymic aplasia, and also compared to other patients according to the observed bibliography, the calcium values towards the inferior limits and the lower radiologic image of the thymus, favouring the knowledge and the experience to increase the treatments of similar pathologies in the future.(EU)

Present-day importance of the velocardiofacial syndrome. To commemorate the late prof. Eva sedlácková, MD, on the 50th anniversary of her original publication.

In the year 1955, Sedlácková described a syndrome of congenitally shortened velum accompanied by hypernasal speech, facial dysmorphisms and further anomalies, as well as mental retardation. In the following years, she also reported on cardiac malformations and submucous clefts. In 1978, Shprintzen's group published a very similar pattern apart from overt clefts, coined it as velocardiofacial syndrome (VCFS) and explained it in 1992 by microdeletion 22q11.2. Between 1996 and 2001, Vrticka and colleagues demonstrated del 22q11.2 in 16 of 20 cases classified as Sedlácková syndrome. Thus, the common etiology and the identity of Sedlácková syndrome with Shprintzen syndrome were proven. Our findings of frequent cardiovascular malformations, of prevailing mental retardation and of several late-onset psychoses emphasize the necessity of genetic testing in all individuals suspected of VCFS. In del 22q11.2-proven cases, we recommend genetic counseling because of the risk of more severe expression of the VCFS symptoms in subsequent generations. Recently, several authors repeatedly stressed the importance of VCFS by pointing out the associated cardiac and laryngeal malformations and by warning against the risk of innate carotid medialization in velopharyngeal surgery, by evoking linked otological problems, by elucidating the accompanying immune and hormonal dysfunctions, by summarizing the voice and resonance disorders as well as by discussing the difficulties in rehabilitation due to mental, language and speech retardation in VCFS subjects. Because of its multiple impact, the clinical pattern of VCFS due to del 22q11.2 remains a persistent and important present-day diagnostic and therapeutic challenge.

Cellular immunology in a historical perspective.

Bruton's XLA and DiGeorge syndrome patients show that two basic immune systems are distinct from each other in humans - thymus-dependent cell-mediated immunodeficiencies vs. antibody-based immunodeficiencies. The appendix-sacculus lymphoid organ of rabbits, like the bursa of Fabricius, represents a central lymphoid organ. Chronic granulomatous disease of childhood (CGD) revealed that phagocytosis killing of catalase-positive microorganisms employ oxidative burst. Bone marrow transplantation (BMT) proved life saving in severe combined immunodeficiency (SCID). The first BMT cured XSCID and the second BMT cured a complicating aplastic anemia launching BMT as a treatment of many diseases. Now 75 fatal diseases have been cured by myeloablative BMT. BMT also cured experimental autoimmune diseases. BMT alone did not cure lupus with polyarthritis in MRL/lpr mice or polyarthritis in NZB/KN mice, but BMT plus bone (stromal cell) transplants cured these diseases. Autoimmune diseases and lethal glomerulonephritis were prevented or cured in BXSB mice by mixed allogeneic plus syngeneic BMT. X-linked Hyper IgM syndrome (XHIM) was also cured by BMT from a 2-year-old MHC-matched sibling donor. Nonmyeloablative BMT plus mesenchymal stem cells (stromal cells) was effective treatment for a form of collagen-vascular disease and also a lethal form of hypophosphatasia. Mannan-binding lectin, an opsonin that activates the complement system when mutated and at low levels in blood, opens a door to frequent infections throughout childhood and adult life. This new immunodeficiency is based on genetic mutations that involve a native defense system.