Two Different Manifestations of Locked-InSyndrome

Locked-in syndrome (LIS) is an entity that usually occur a consequence of the lesion of ventral part of pons. Etiology of locked-in syndrome can be vascular and nonvascular origin. Locked-in syndrome usually occurs as a consequence of thrombosis of intermedial segment of basilar artery that induces bilateral infaction of the ventrobasal part of the pons. Additionally, LIS can be caused by trauma which often leads to posttraumatic thrombosis of basilar artery. The incidence of locked-in syndrome is still unknown. The basic clinical features of locked-in syndrome are: quadriplegia (a consequence of disruption of corticospinal pathways located in ventral part of pons), different stages of paralysis of mimic musculature, paralysis of pharynx, tongue and palate with mutism and anarthria. The patient can not move, but is conscious and can communicate only by eye movements. Two patients with locked-in syndrome were present in this article. In the first case, the patient had classic locked-in syndrome that was first described by Plum and Posner1. Other patient had incomplete form of locket-in syndrome which was first described by Bauer2. In these two patients locked-in syndrome occurred as a consequence of trauma. In the first patient locked-in syndrome was caused by direct contusion of ventral part of pons while in other patient locked-in syndrome was a consequence of posttraumatic thrombosis of vertebrobasilar artery. The introduction of anticoagulant therapy, besides the other measures of intensive therapy, has shown complete justification in the second patient. The gradual partial recovery of neurologic deficit has developed in the second patient without any additional complications

Perforin Is Required for Innate and Adaptive Immunity Induced by Heat Shock Protein Gp96

Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejection. In vivo secreted gp96-Ig and gp96-myc cause NK activation and clonal expansion of specific CD8+ CTL in wild-type and in Fas-ligand-deficient (gld) mice but not in perforin- (PKO) or IFN-γ-deficient (GKO) mice. Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig. The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes. Crosspresentation of antigens by heat shock proteins seems to require a perforin-dependent positive feedback loop between NK and DC for both sustained NK activation and clonal CTL expansion. The studies also explain how depressed NK activity in patients with tumors or after viral infections could diminish CTL responses

Traumatic brain injury and peripheral immune suppression: primer and prospectus

Nosocomial infections are a common occurrence in patients following traumatic brain injury (TBI) and are associated with an increased risk of mortality, longer length of hospital stay and poor neurological outcome. Systemic immune suppression arising as a direct result of injury to the central nervous system (CNS) is considered to be primarily responsible for this increased incidence of infection, a view strengthened by recent studies that have reported novel changes in the composition and function of the innate and adaptive arms of the immune system post TBI. However, our knowledge of the mechanisms that underlie TBI-induced immune suppression is equivocal at best. Here, after summarising our current understanding of the impact of TBI on peripheral immunity and discussing CNS-mediated regulation of immune function, we propose roles for a series of novel mechanisms in driving the immune suppression that is observed post TBI. These mechanisms, which have never been considered before in the context of TBI-induced immune paresis include the CNS-driven emergence into the circulation of myeloid derived suppressor cells and suppressive neutrophil subsets, and the release from injured tissue of nuclear and mitochondria-derived damage associated molecular patterns. Moreover, in an effort to further our understanding of the mechanisms that underlie TBI-induced changes in immunity, we pose throughout the review a series of questions, which if answered would address a number of key issues such as establishing whether manipulating peripheral immune function has potential as a future therapeutic strategy by which to treat and/or prevent infections in the hospitalised TBI patient

Early pregnancy decidual lymphocytes beside perforin use Fas ligand (FasL) mediated cytotoxicity

Decidual natural killer (NK) cells are the predominant lymphocytes at the maternal–fetal interface. They are involved in defense against virally infected, parasitized and transformed cells and may contribute to the control of trophoblast invasion. The presence of perforin and other possible cytolytic mediators suggests these functions. Cytolytic mechanisms of unstimulated and Th1 cytokine stimulated decidual lymphocytes (DL), as well as purified decidual CD56+ cells, were analyzed against NK sensitive and resistant targets. DL were isolated from decidual mononuclear cells (DMC) cultured in the medium only or in the presence of Th1 cytokines: IL-2, IL-12, IL-15, IL-18 and their combinations (IL-12/IL-18 or IL-15/IL-18). Fas ligand (FasL), perforin and granzyme B mRNAs expression and cytotoxicity were analyzed by flow cytometry and/or RT-PCR. DL (containing 72.19±7.53% of CD56+ cells), obtained from 18h-cultured DMC in the medium only, expressed perforin, FasL and granzyme B mRNAs and lysed the NK-sensitive K-562 cell line, and also the NK-resistant P815 and P815-Fas transfected cell lines. Concanamycin A, a blocker of granule exocytosis, decreased significantly K-562 lysis, but not P815 lysis. However, the addition of anti-FasL antibody diminished significantly P815 lysis as well. IL-2 and IL-15, known inducers of perforin and FasL mRNAs and protein expression, could not additionally increase P 815 cell lysis by DL cultured within DMC. These results suggest that DL cultured in DMC for 18h, have the characteristics of lymphokine-activated killer (LAK) cells and are able to use efficiently both the perforin and the FasL cytolytic pathways

The presence of functional mannose receptor on macrophages at the maternal–fetal interface

BACKGROUND: The mannose receptor (MR) is involved in the initiation of the immune response and regulation of homeostasis during inflammation and tissue remodeling. METHODS: Distribution, endocytosis and possible natural ligand tumor associated glycoprotein-72 (TAG-72) for the MR have been examined by immunohistology, immunocytochemistry and flow cytometry at the maternal–fetal interface, characterized by extensive tissue remodeling. RESULTS: Contrary to disseminated distribution of the MR positive (MR+) cells in term placenta, the MR+ cells of early pregnancy decidua intimately surrounded glands and followed tissue distribution of CD14 positive cells. The mannose receptor was present on freshly isolated first trimester decidual mononuclear cells and distributed mostly on macrophages (77.08 ± 10.55%, mean ± SD). The expression of the MR on CD14 positive cells decreased following 18 h culture (P<0.01) and was accompanied by the reduction of fluorescein isothiocyanate (FITC)–dextran uptake. PAM-1 anti-MR antibody, mannan and TAG-72 reduced FITC–dextran uptake by decidual macrophages. CONCLUSIONS: These data indicate that the MR+ macrophages, surrounding early decidual glands, are able to internalize ligands for carbohydrate recognition domain of the receptor, including decidual secretory phase mucin TAG-72