A question of self-preservation : immunopathology in influenza virus infection

Influenza A viruses that circulate normally in the human population cause a debilitating, though generally transient, illness that is sometimes fatal, particularly in the elderly. Severe complications arising from pandemic influenza or the highly pathogenic avian H5N1 viruses are often associated with rapid, massive inflammatory cell infiltration, acute respiratory distress, reactive hemophagocytosis and multiple organ involvement. Histological and pathological indicators strongly suggest a key role for an excessive host response in mediating at least some of this pathology. Here, we review the current literature on how various effector arms of the immune system can act deleteriously to initiate or exacerbate pathological damage in this viral pneumonia. Generally, the same immunological factors mediating tissue damage during the anti-influenza immune response are also critical for efficient elimination of virus, thereby posing a significant challenge in the design of harmless yet effective therapeutic strategies for tackling influenza virus.

An in vivo cytotoxicity threshold for influenza A virus-specific effector and memory CD8+ T cells

Influenza A virus infection of C57BL/6 (B6) mice is characterized by prominent CD8 T cell responses to H2Db complexed with peptides from the viral nucleoprotein (NP366, ASNENMETM) and acid polymerase (PA224, SSLENFRAYV). An in vivo cytotoxicity assay that depends on the adoptive transfer of peptide-pulsed, syngeneic targets was used in this study to quantitate the cytotoxic potential of DbNP366- and DbPA224-specific acute and memory CD8 T cells following primary or secondary virus challenge. Both T cell populations displayed equivalent levels of in vivo effector function when comparable numbers were transferred into naive B6 hosts. Cytotoxic activity following primary infection clearly correlated with the frequency of tetramer-stained CD8 T cells. This relationship looked, however, to be less direct following secondary exposure, partly because the numbers of CD8DbNP366 T cells were greatly in excess. However, calculating the in vivo E:T ratios indicated that in vivo lysis, like many other biological functions, is threshold dependent. Furthermore, the capacity to eliminate peptide-pulsed targets was independent of the differentiation state (i.e., primary or secondary effectors) and was comparable for the two T cell specificities that were analyzed. These experiments provide insights that may be of value for adoptive immunotherapy, where careful consideration of both the activation state and the number of effector cells is required.

Finding multiple needles in one immune haystack

An approach using multiple fluorochrome combinations allows the simultaneous detection of many T-cell populations within a single blood sample.

John Martyn Harlow: 'obscure country physician?'

If John Martyn Harlow is known at all in the neurosciences, it is because he was the physician who attended Phineas Gage and followed up his case. Although Harlow's brief but insightful accounts of the changes in Gage's personality are fairly well recognized, and his skill in treating Gage often acknowledged, Harlow himself is, for the most part, the shadowy figure caught by the self-depreciatory characterization of the subtitle of this paper. Although his contribution to the neurosciences was singular, literally and figuratively, he deserves a place in the history of the subject. Harlow's training in antiphlogistic therapy can be seen in his treatment of Gage and in his evaluation of its results. As a medical student, he was also exposed to phrenological doctrine, the influence of which can also be seen in his  appreciation and explanation of some aspects of Gage's behaviour.  Manuscript materials, newspaper reports, and other little known material are used here to evaluate Harlow's contributions to medicine and to the medical, political, and civic life of Cavendish, Woburn, and the Commonwealth of Massachusetts.

Misunderstanding John Stuart Mill on science: Paul Feyerabend`s bad influence

Feyerabend, 1975; Feyerabend, 1981 and Feyerabend, 1987 takes J. S. Mill’s On Liberty to support the proliferation of theories in science and to emphasize the fallibility of scientific knowledge. On Liberty, according to Feyerabend, contradicts and overthrows Mill’s major study of science, A System of Logic. Staley (1999) reads the 2 works of Mill as giving complementary accounts of science. The present author rejects these interpretations of Mill, arguing that A System of Logic and On Liberty are mutually compatible since On Liberty concerns the nature of non-scientific knowledge and the methods that Mill believes are appropriate to expanding and assessing that knowledge.

Western maps/Yanyuwa meaning: an interview with John Bradley

In July 2003 an important one-volume text, Forget about Flinders: A Yanyuwa atlas of the south west gulf of Carpentaria produced in a limited edition of 14 copies, returned to Yanyuwa country and to the families who collaborated with John Bradley and artist Nona Cameron on the project. Subsequently, a second edition of 20 copies has been released, mainly to institutions. It is the most comprehensive attempt yet to restore Yanyuwa names to country and to produce a multilayered, dynamic, history-rich, and bilingual representation of how country is known in this community, and how the central song cycle texts intersect with Yanyuwa tradition. What follows is a condensed and edited interview with Frances Devlin-Glass, in which John Bradley discusses the motivations, the hybridised methodologies employed, the innovations of this new genre, and the pedagogical ends served by this latest iteration of Yanyuwa song cycles.

From crystals to pixels: new technology in the documentary work of John Hughes

Film technology, in the broadest sense, embraces a vast array of knowledge, skills, tools, and systems. These include the codes and conventions of screen representation at the centre of much screen scholarship. The electro-mechanical tools of filmmaking are less often the focus of academic study than these codes and conventions, but they are central to them and to the daily work of artists and educators in the field of screen production. This paper traces the scope and significance of technical change, for independent film making, over the past four decades. Melbourne documentary filmmaker John Hughes provides a varied and expansive oeuvre through which to arrange an historical equipment list.