[Nursing Care of the First Neonatal Patient with Veno-arterial ECMO plus venting in Peru]. / Cuidado de Enfermería del Primer Paciente Neonato con ECMO Central Veno-arterial más Venting en Perú.

We report the nursing care of the first newborn patient in Peru who used central veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) - plus left atrial decompression cannula (VENT). We standardized specialized nursing care by identifying 15 diagnoses according to taxonomy II nursing diagnoses (NANDA) and 3 that could be incorporated into it for newborn care in ECMO.

Proteolytic enzymes involved in MHC class I antigen processing: A guerrilla army that partners with the proteasome.

Major histocompatibility complex class I proteins (MHC-I) load short peptides derived from proteolytic cleavage of endogenous proteins in any cell of the body, in a process termed antigen processing and presentation. When the source proteins are altered self or encoded by a pathogen, recognition of peptide/MHC-I complexes at the plasma membrane leads to CD8(+) T-lymphocyte responses that clear infections and probably underlie tumor immune surveillance. On the other hand, presentation of self peptides may cause some types of autoimmunity. The peptides that are presented determine the specificity and efficiency of pathogen clearance or, conversely, of immunopathology. In this review we highlight the growing number of peptidases which, as a by-product of their regular activity, can generate peptide epitopes for immune surveillance. These ∼20 peptidases collectively behave as a guerrilla army partnering with the regular proteasome army in generating a variety of peptides for presentation by MHC-I and thus optimally signaling infection.

N-ras couples antigen receptor signaling to Eomesodermin and to functional CD8+ T cell memory but not to effector differentiation.

Signals from the TCR that specifically contribute to effector versus memory CD8⁺ T cell differentiation are poorly understood. Using mice and adoptively transferred T lymphocytes lacking the small GTPase N-ras, we found that N-ras-deficient CD8⁺ T cells differentiate efficiently into antiviral primary effectors but have a severe defect in generating protective memory cells. This defect was rescued, although only partly, by rapamycin-mediated inhibition of mammalian target of rapamycin (mTOR) in vivo. The memory defect correlated with a marked impairment in vitro and in vivo of the antigen-mediated early induction of T-box transcription factor Eomesodermin (Eomes), whereas T-bet was unaffected. Besides N-ras, early Eomes induction in vitro required phosphoinositide 3-kinase (PI3K)-AKT but not extracellular signal-regulated kinase (ERK) activation, and it was largely insensitive to rapamycin. Consistent with N-ras coupling Eomes to T cell memory, retrovirally enforced expression of Eomes in N-ras-deficient CD8⁺ T cells effectively rescued their memory differentiation. Thus, our study identifies a critical role for N-ras as a TCR-proximal regulator of Eomes for early determination of the CD8⁺ T cell memory fate.

Are membrane proteins favored over cytosolic proteins in TAP-independent processing pathways?

Recognition of infected or altered cells by CD8(+) cytotoxic T lymphocytes is mediated by direct interaction of their T-cell receptor with peptides presented by MHC class I molecules. Peptides are transferred for assembly with newly synthesized MHC molecules by the transporters associated with antigen processing (TAP). Yet, a fraction of described epitopes are presented independently of TAP. Current belief is that most of them derive from membrane proteins, mostly from their signal sequences, and are processed by vesicular proteases. A thorough review of the published data may challenge some of these views.

Generation of MHC class I ligands in the secretory and vesicular pathways.

CD8(+) T lymphocytes screen the surface of all cells in the body to detect pathogen infection or oncogenic transformation. They recognize peptides derived from cellular proteins displayed at the plasma membrane by major histocompatibility complex (MHC) class I molecules. Peptides are mostly by-products of cytosolic proteolytic enzymes. Peptidic ligands of MHC class I molecules are also generated in the secretory and vesicular pathways. Features of protein substrates, of proteases and of available MHC class I molecules for loading peptides in these compartments shape a singular collection of ligands that also contain different, longer, and lower affinity peptides than ligands produced in the cytosol. Especially in individuals who lack the transporters associated with antigen processing, TAP, and in infected and tumor cells where TAP is blocked, which thus have no supply of peptides derived from the cytosol, MHC class I ligands generated in the secretory and vesicular pathways contribute to shaping the CD8(+) T lymphocyte response.