Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Challenges with sensitized recipients in pediatric heart transplantation

The sensitization of patients to human leukocyte antigens prior to heart transplantation is increasingly being recognized as an important challenge both before and after the transplant, and the effects of sensitization on clinical outcomes are just beginning to be understood. Many patients are listed with the requirement of a negative prospective or virtual crossmatch prior to accepting a donor organ. This strategy has been associated with both longer waitlist times and higher waitlist mortality. An alternative approach is to transplant across a potentially positive crossmatch while utilizing strategies to decrease the significance of the human leukocyte antigen antibodies. This review will examine the challenges and the impact of sensitization on pediatric patients prior to and following heart transplantation.

Histocompatibility and Immunogenetics in Cord Blood Transplantation

This review of the immunogenetics of cord blood transplantation attempts to highlight the connections between classical studies and conclusions of the tissue transplantation field as a scholarly endeavor, exemplified by the work of Professor Hoecker, with the motivations and some recent and key results of clinical cord blood transplantation. The authors review the evolution of understanding of transplantation biology and find that the results of the application of cord blood stem cells to Transplantation Medicine are consistent with the careful experiments of the pioneers in the field, from the results of tumor and normal tissue transplants, histocompatibility immunogenetics, to cell and molecular biology. Recent results of the National Cord Blood Program of the New York Blood Center describe the functioning in cord blood transplantation of factors, well known in transplantation immunogenetics, like the Fl anti-parent effect and the tolerance-like status of donors produced by non-inherited maternal HLA antigens. Consideration of these factors in donor selection strategies can improve the prognosis of transplantation by characterizing "permissibility" in HLA-incompatible transplantation thereby increasing the probability of survival and reducing the likelihood of leukemic relapse.

Intervention with costimulatory pathways as a therapeutic approach for graft-versus-host disease

Graft-versus-host disease (GVHD) is mediated by mature donor T cells contained in the hematopoietic stem cell graft. During the development of GVHD, signaling through a variety of costimulatory receptors plays an important role in allogeneic T cell responses. Even though delivery of costimulatory signals is a prerequisite for full activation of donor T cells in the phase of their interactions with host APCs, their involvement with GVHD might occur over multiple stages. Like many other aspects of GVHD, promise of therapeutic interventions with costimulatory pathways has been gleaned from preclinical models. In this review, I summarize some of the advances in roles of costimulatory molecules in GVHD pathophysiology and discuss preclinical approaches that warrant further exploration in the clinic, focusing on novel strategies to delete pathogenic T cells.

Fundamentos de genética e inmunología para bancos de sangre y medicina transfusional: [revisión] / Fundamentals of genetics and immunology to blood banks and transfusion medicine: [review]

Más de 100 años han transcurrido desde el descubrimiento de los grupos sanguíneos A, B y O y hasta el presente se han reconocido 308 antígenos, de los cuales 270 están agrupados en 30 sistemas sanguíneos. Su importancia radica en la seguridad con la cual se transfunde la sangre de donantes a pacientes con pruebas tan sencillas en su elaboración, como la clasificación sanguínea ABO y Rh, las pruebas cruzadas y el rastreo de anticuerpos irregulares, con el fin de evitar la aloinmunización de los receptores...

Caracterização de subpopulações pró-inflamatórias e reguladoras, que reconhecem proteínas de choque térmico, no contexto do alotransplante murino / Characterization of different pro-inflammatory and regulatory heat shock proteins reactive T cell subsets in murine allografting

A reatividade imunológica a proteínas de choque térmico 60 (Hsp60), no transplante foi descrita por vários grupos, dentre eles o nosso grupo. Estudamos a reatividade celular à Hsp60 humana, fragmentos das diferentes regiões e peptídeos desta proteína, em diferentes de camundongos sadios e em modelos de transplante através de estudo de resposta proliferativa e produção de citocinas. Também avaliamos diferentes protocolos de indução de tolerância utilizando um peptídeo derivado desta proteína. Observou-se que existe reatividade celular a diferentes regiões desta proteína em animais sadios e no modelo de transplante, com produção de citocinas pró-inflamatórias e anti-inflamatórias. Desenvolvemos um esquema de inoculação intranasal que aumentou significativamente a sobrevida do aloenxerto cardíaco. Estes resultados sugerem a manipulação da reatividade à Hsp60 poderia inibir a resposta inflamatória do enxerto e aumentar sua sobrevida / Immune reactivity to heat shock protein 60 (Hsp60) has reported in different transplantation models by different groups including our group. We studied T cell reactivity induced by recombinant human Hsp60, recombinant fragments, and peptides from this protein in three different strains of naive mice and in different murine transplantation models, analyzing T cell proliferation and cytokine production. We also developed different protocols using Hsp-peptide for tolerance induction in transplantation. We showed that both naïve and transplanted mice have Hsp60 cell reactivity with pro-inflammatory and anti-inflammatory cytokines and developed an intranasal inoculation schedule that significantly increase graft survival. These results suggest that manipulation of Hsp60 reactivity may inhibit the inflammatory response in transplantation...

HLA and bone marrow transplant donor search strategies.

Searching for a family donor other than an HLA identical sibling can be successful. The chance of finding an identical or one antigen mismatched family donor can be calculated with a computer program, so this may help in the decision making whether to perform extended family typing or not. Extended family donors are often better matched rather than unrelated donors. The reason is that they have at least one haplotype genetically identical to the patient, and that there may be some higher match grade for the minor histocompatibility antigens. Sometimes extended family donor could be the only donor for the patient. Ethical considerations have to be taken into account and extended family donors should be volunteer donors.