Humoral and cell-mediated immune responses in fully allogeneic bone marrow chimera in mice

AKR mice were protected from lethal irradiation and established as long-lived chimeras by transplanting allogeneic C57BL/6 (B6) bone marrow that had been treated in vitro with anti-Thy-1 antiserum without complement. In these chimeras, which were designated [B6 {arrow} AKR], virtually all the thymus and spleen cells were shown to be derived from the B6 donor; several immune functions studied in these chimeras were as follows: (a) The chimeric mice were tolerant of histocompatibility antigens of both donor and recipient strain and nearly fully reactive to antigens of third party, as revealed by Simonsen's splenomegaly assay. The tolerance of these chimeras could not be attributed to suppressor cells but was compatible with clonal depletion. (b) Proliferative responses to concanavalin A, phytohemagglutinin, and lipopolysaccharide as well as natural killer and antibody-dependent cell- mediated cytotoxicity activity of the chimeric mice was normal. (c) Plaque- forming cell (PFC) assays of antibody responses to sheep erythrocytes (SRBC) showed gross deficiency in the primary response of the [B6 {arrow} AKR] and [AKR {arrow} B6] chimeras. By contrast, [B6-H-2(k)(E(k)) {arrow} AKR] H-2-compatible chimeras and [AKR {arrow} AKR] syngeneic marrow transplanted mice had normal primary PFC responses. PFC responses after secondary stimulation with SRBC, however, revealed vigorous direct plaque formation and substantial but somewhat smaller indirect plaque formation in the [B6 {arrow} AKR] chimeras. This observation favors operationally the concept of adaptive differentiation proposed by Katz et al. (44). (d) Analysis of ability of the chimeras to develop and express delayed-type hypersensitivity responses to contact sensitizer (2,4-dinitro-l-fluorobenzene [DNFB]) showed no apparent immunodeficiency of either chimeras to this form of immunization. Development of immunologic tolerance to DNFB, however, was grossly deficient in [B6 {arrow} AKR] chimeras but normal in [AKR {arrow} AKR], [B6 {arrow} B6], and [E(k) {arrow} AKR] chimeras. These findings indicate that full chimeras across major histocompatibility complex have considerable immunologic vigor even though primary immune responses that require histocompatibility between interacting cell types are initially defective

Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia

A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic μ chains without any evidence of light chain synthesis, and two produced primarily μ chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic μ chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out

Historic landmarks in clinical transplantation: Conclusions from the consensus conference at the University of California, Los Angeles

The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three-decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contribution of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here is six tables and annotated with references

T-helper 1 versus T-helper 2 lymphocyte immunodysregulation is the central factor in genesis of Burkitt lymphoma: hypothesis

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic has challenged our previous understanding of endemic Burkitt's lymphoma. Despite the strong association of Burkitt's lymphoma and HIV infection in the Developed world, and against previous postulations that the cancer is due to immunosupression among African children, the HIV epidemic in the Malaria belt has not been associated with a corresponding increase in incidence of childhood Burkitt's lymphoma. Even outside the context of HIV infection, there is substantial evidence for a strong but skewed immune response towards a TH2 response in genesis of Burkitt lymphoma.</p> <p>Presentation of the hypothesis</p> <p>Rather than a global and/or profound immunosupression, the final common pathway in genesis of Burkitt's lymphoma is the dysregulation of the immune response towards a TH2 response dominated by B-lymphocytes, and the concomitant suppression of the TH1 cell-mediated immune surveillance, driven by various viral/parasitic/bacterial infections.</p> <p>Testing the hypothesis</p> <p>Case control studies comparing TH2 and TH1 immune responses in Burkitt lymphoma of different etiological types (sporadic, HIV-related, endemic and post-transplant) to demonstrate significant dominance of TH2 immune response in presence of poor CMI response as a common factor. Immunological profiling to evaluate differences between immune states that are associated (such as recurrent Malaria infection) and those that are not associated (such as severe protein-energy malnutrition) with Burkitt lymphoma. Prospective cohorts profiling chronology of immunological events leading to Burkitt lymphoma in children with EBV infection.</p> <p>Implications of the hypothesis</p> <p>The dysregulation of the immune response may be the missing link in our understanding of Burkitt lymphomagenesis. This will provide possibilities for determination of risk and for control of development of malignancy in individuals/populations exposed to the relevant infections.</p

Critical review of the United Kingdom’s “gold standard” survey of public attitudes to science

Since 2000, the UK government has funded surveys aimed at understanding the UK public’s attitudes toward science, scientists, and science policy. Known as the Public Attitudes to Science series, these surveys and their predecessors have long been used in UK science communication policy, practice, and scholarship as a source of authoritative knowledge about science-related attitudes and behaviors. Given their importance and the significant public funding investment they represent, detailed academic scrutiny of the studies is needed. In this essay, we critically review the most recently published Public Attitudes to Science survey (2014), assessing the robustness of its methods and claims. The review casts doubt on the quality of key elements of the Public Attitudes to Science 2014 survey data and analysis while highlighting the importance of robust quantitative social research methodology. Our analysis comparing the main sample and booster sample for young people demonstrates that quota sampling cannot be assumed equivalent to probability-based sampling techniques

Large differences in regional precipitation change between a first and second 2 K of global warming

For adaptation and mitigation planning, stakeholders need reliable information about regional precipitation changes under different emissions scenarios and for different time periods. A significant amount of current planning effort assumes that each K of global warming produces roughly the same regional climate change. Here using 25 climate models, we compare precipitation responses with three 2 K intervals of global ensemble mean warming: a fast and a slower route to a first 2 K above pre-industrial levels, and the end-of-century difference between high-emission and mitigation scenarios. We show that, although the two routes to a first 2 K give very similar precipitation changes, a second 2 K produces quite a different response. In particular, the balance of physical mechanisms responsible for climate model uncertainty is different for a first and a second 2 K of warming. The results are consistent with a significant influence from nonlinear physical mechanisms, but aerosol and land-use effects may be important regionally

Changes in Gray Matter Induced by Learning—Revisited

BACKGROUND: Recently, activation-dependant structural brain plasticity in humans has been demonstrated in adults after three months of training a visio-motor skill. Learning three-ball cascade juggling was associated with a transient and highly selective increase in brain gray matter in the occipito-temporal cortex comprising the motion sensitive area hMT/V5 bilaterally. However, the exact time-scale of usage-dependant structural changes occur is still unknown. A better understanding of the temporal parameters may help to elucidate to what extent this type of cortical plasticity contributes to fast adapting cortical processes that may be relevant to learning. PRINCIPAL FINDINGS: Using a 3 Tesla scanner and monitoring whole brain structure we repeated and extended our original study in 20 healthy adult volunteers, focussing on the temporal aspects of the structural changes and investigated whether these changes are performance or exercise dependant. The data confirmed our earlier observation using a mean effects analysis and in addition showed that learning to juggle can alter gray matter in the occipito-temporal cortex as early as after 7 days of training. Neither performance nor exercise alone could explain these changes. CONCLUSION: We suggest that the qualitative change (i.e. learning of a new task) is more critical for the brain to change its structure than continued training of an already-learned task

Early warning signals of simulated Amazon rainforest dieback

Copyright © The Author(s) 2013. This article is published with open access at Springerlink.comWe test proposed generic tipping point early warning signals in a complex climate model (HadCM3) which simulates future dieback of the Amazon rainforest. The equation governing tree cover in the model suggests that zero and non-zero stable states of tree cover co-exist, and a transcritical bifurcation is approached as productivity declines. Forest dieback is a non-linear change in the non-zero tree cover state, as productivity declines, which should exhibit critical slowing down. We use an ensemble of versions of HadCM3 to test for the corresponding early warning signals. However, on approaching simulated Amazon dieback, expected early warning signals of critical slowing down are not seen in tree cover, vegetation carbon or net primary productivity. The lack of a convincing trend in autocorrelation appears to be a result of the system being forced rapidly and non-linearly. There is a robust rise in variance with time, but this can be explained by increases in inter-annual temperature and precipitation variability that force the forest. This failure of generic early warning indicators led us to seek more system-specific, observable indicators of changing forest stability in the model. The sensitivity of net ecosystem productivity to temperature anomalies (a negative correlation) generally increases as dieback approaches, which is attributable to a non-linear sensitivity of ecosystem respiration to temperature. As a result, the sensitivity of atmospheric CO2 anomalies to temperature anomalies (a positive correlation) increases as dieback approaches. This stability indicator has the benefit of being readily observable in the real world.NERCJoint DECC/Defra Met Office Hadley Centre Climate ProgrammeUniversity of Exete