Biomedical subjects

S Ehl

Publications and source records attributed to S Ehl.

22 records · Page 2Linked to original sources

PubMed1997

Antigen localisation regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity.

This review summarises experimental evidence to illustrate that induction of immune reactivity depends upon antigen reaching and being available in lymphoid organs in a dose- and time-dependent manner. If antigen reaches lymph organs in a localised staggered manner and with a concentration gradient, a response is induced in the draining lymph node. Antigen-presenting cells are of critical importance to transport antigen from the periphery to local organised lymphoid tissue. If antigen is all over the lymphoid system, then it deletes all specific cells in the thymus or induces them within a few days; because of their limited life-span they then die off, leaving the repertoire depleted of this specificity. If antigen does not reach lymphoid organs it is ignored by immune cells. Once a response is induced, activated but not resting T cells will reach antigen outside lymphoid organs, whereas activated B cells differentiate into plasma cells in an inducing environment, mostly in lymphoid tissue including bone marrow, but also in chronic lymphoid-like infiltrations in peripheral organs. In immunopathology (when the infectious agent is known) or in autoimmunity (when the triggering infectious agent is not known or not recognised) lymphoid tissue may become organised close to the antigen (e.g. in organ-specific autoimmune diseases) and may thereby maintain an autoantigen-driven disease-causing immune response for a long time. The notion that native T cells get induced or silenced in the periphery may be questioned because induction can only occur in lymphoid organs providing anatomical structures where critical cell-cell interactions are properly guided and where, therefore, cells are likely to meet sufficiently frequently and in a critical milieu. Since overall immune reactivity critically depends upon the localisation of antigens in a dose- and time-dependent manner, it seems more likely-but this remains to be shown-that activated T cells may get exhausted in non-lymphoid peripheral tissues, whereas they are usually maintained in lymphoid organs. The critical role of antigen in regulating immune responses also has relevance for our understanding of immunological defence against epithelial and mesenchymal tumours, against many infectious diseases and for understanding autoimmunity and immunological memory. Collectively the data indicate that antigen, dependent upon localisation, dose and time, seems to be the simplest regulator of immune responses.

Adjuvants, Immunologic↗

PubMed1997

C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection.

OBJECTIVE: To determine whether C-reactive protein (CRP) can be used as a parameter to identify the time point when antibiotic treatment can safely be discontinued in a defined major subgroup of neonates treated for suspected bacterial infection. PATIENTS: One hundred seventy-six newborns with birth weights of greater than 1500 g and without central lines and mechanical ventilation who had suspected bacterial infection were enrolled in a prospective study. SETTING: Tertiary care neonatal reference center. DESIGN: Serum concentrations of CRP were determined 24 to 48 hours after the first dose of antibiotics. If CRP levels were less than 10 mg/L, infants were considered unlikely to be infected, and the antibiotic treatment was stopped using CRP as the single decision criterion in 84 of 94 newborns (group 1). Infants with CRP levels of 10 mg/L or greater were considered likely to be infected and randomized to two study groups. In 38 of 39 neonates (group 2a), CRP was determined daily, and antibiotic therapy was discontinued as soon as CRP returned to less than 10 mg/L. Forty-three neonates with likely infection (group 2b) were treated for at least 5 days, and relapse rates of bacterial infections were compared between groups 2a and 2b. OUTCOME MEASURES: The primary outcome variable of the study was the number of infectious relapses of the primary infection. This was assessed by the need for a second course of antibiotics within 4 weeks of the first one. The value of CRP for guiding treatment duration was determined by calculating the negative predictive value of CRP with respect to further treatment in study groups 1 and 2a. Treatment durations and relapse incidence in the two groups of neonates with likely infection (groups 2a and 2b) were compared. RESULTS: Within the 4-week follow-up period, one infant in group 1 and no infant in group 2a received a second course of antibiotics for bacterial infection. CRP levels of less than 10 mg/L determined later than 24 hours after beginning the antibiotic treatment thus correctly identified 120 of 121 infants as not needing further antibiotics. This corresponds to a negative predictive value with respect to further treatment of 99% (95% confidence interval, 95.4% to 99.9%). The mean treatment duration was 3.7 (median, 4; range, 3 to 6) days in the CRP-guided group and 5.5 (median, 5; range, 5 to 7) days in the at least 5-day study group. In the latter group, one infant was treated for a potential relapse, and one infant was treated for a likely relapse. The low relapse rates in both treatment groups are a preliminary indication that relapses may not occur more frequently if patients are treated until CRP is negative rather than for a 5-day or longer treatment period. CONCLUSIONS: We conclude that CRP could be a key parameter for individually guiding the duration of antibiotic treatment in a major subgroup of newborns with suspected bacterial infection. This approach would allow considerably shorter courses of antibiotic therapy.

Anti-Bacterial Agents↗

PubMed1996

A comparison of efficacy and specificity of three NK depleting antibodies.

This study compares in vivo efficacy and specificity of the three NK cell depleting antibodies anti-asialo GM1, anti-NK 1.1 and the recently described TM beta 1, which is directed against the interleukin-2 receptor beta chain. All three antibodies are equally efficacious as assessed by abolishing NK mediated cytolytic activity induced by a high dose virus infection or Poly IC against YAC-1 targets. Similarly, the generation of virus-specific cytotoxic T cells (CTL) was unimpaired after NK depletion in two different virus infections. However, if mice are treated with the antibodies several days after virus infection, when strong CTL responses have already been generated, anti-asialo GM1 and-to a lesser extent-also TM beta 1 have a significant effect on CTL activity. Only after treatment with anti-NK 1.1 antibody, CTL activity was not significantly impaired. We conclude, that of the NK depleting antibodies currently available, anti-NK 1.1 allows the best differentiation of activated CTL and NK cells in vivo.

Animals↗

PubMed1996

Different susceptibility of cytotoxic T cells to CD95 (Fas/Apo-1) ligand-mediated cell death after activation in vitro versus in vivo.

To address the question of whether cytotoxic CD8+ T cells (CTL) activated in vivo are susceptible to cell death mediated by CD95 (Fas/Apo-1) ligand, a recombinant vaccinia virus expressing murine CD95L (vacc CD95L) was constructed, which drives CD95L expression to infected cells. T cells contacting virus-infected cells during priming, killing, or restimulation therefore encounter CD95L on the same cells. CD95L expression in vivo after infection with the vaccinia recombinant was sufficient to induce extensive necrosis in the liver of normal but not of CD95 mutant lpr mice. Fibroblast cell lines infected with this virus specifically killed CD95-transfected target cells and in vitro activated T cells. In contrast, when T cells were activated by a viral infection in vivo, they were not susceptible to CD95L-mediated cell death during the induction, effector, or memory phase in vitro or in vivo. These results suggest no direct role for CD95L in regulating CTL responses in vivo.

Animals↗