Immunology's first priority dispute--an account of the 17th-century Rudbeck-Bartholin feud

Modern immunology has been notably free of public disputes over credit for major discoveries in this discipline. But the early recognition of the lymphatic system witnessed two examples of heated priority feuds. The first in the 17th-century concerned the greater anatomical organization of the system, while the second in the 18th-century concerned its function. This essay reviews the earlier of the two disputes, in which a Swedish medical student (Ole Rudbeck) charged a respected Danish Professor (T. Bartholin) with plagiarism and antedating his observations. Thus ethical issues in immunology predate modern times. How this discipline reached this point in its history is another focus of this essay and also an excuse to review briefly the anatomy of the lymphatic system. The influence of nationalistic pride on priority disputes is also discussed.     

Experimental immunotherapy for malignant glioma: lessons from two decades of research in the GL261 model

Nearly twenty years of experimental immunotherapy for malignant glioma yielded important insights in the mechanisms governing glioma immunology. Still considered promising, it is clear that immunotherapy does not on its own represent the magic bullet in glioma therapy. In this review, we summarize the major immunotherapeutic achievements in the mouse GL261 glioma model, which has emerged as the gold standard syngeneic model for experimental glioma therapy. Gene therapy, monoclonal antibody treatment, cytokine therapy, cell transfer strategies and dendritic cell therapy were hereby considered. Apart from the considerable progress made in understanding glioma immunology in this model, we also addressed its most pertinent issues and shortcomings. Despite these, the GL261 model will remain indispensable in glioma research since it is a fast, highly reproducible and easy-to-establish model system.     

Immune responses in multiple hosts to Nucleocapsid Protein (NP) of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

In 2019, the World Health Organization declared 3 billion to be at risk of developing Crimean Congo Hemorrhagic Fever (CCHF). The causative agent of this deadly infection is CCHFV. The data related to the biology and immunology of CCHFV are rather scarce. Due to its indispensable roles in the viral life cycle, NP becomes a logical target for detailed viral immunology studies. In this study, humoral immunity to NP was investigated in CCHF survivors, as well as in immunized mice and rabbits. Abundant antibody response against NP was demonstrated both during natural infection in humans and following experimental immunizations in mice and rabbits. Also, cellular immune responses to recombinant NP (rNP) was detected in multispecies. This study represents the most comprehensive investigation on NP as an inducer of both humoral and cellular immunity in multiple hosts and proves that rNP is an excellent candidate warranting further immunological studies specifically on vaccine investigations.     

Uncertainties about the self and the issue of the proper theoretical model in immunology

Theoretical immunology constitutes a critical basis of all medical discoveries. Immunology has been dominated since the 1940s by the self/nonself model. Here we try to shed light on the origins of this theoretical model and to show how and why this model has been called into question during the last thirty years. This paper has three aims. Firstly, we explore the sources of the immune self, going upstream from immunology to ecology-biology, psychology and eventually philosophy. Here the key questions : is the immune self really analogous with the philosophical and psychological selves in which it originates? What is the signification and adequacy of such a conceptual borrowing? We suggest that the < self > vocabulary in immunology is not clear and precise. Secondly, we present the experimental inadequacies of the self/non-self model. We show then how both the vagueness of the term < self > and these experimental flaws casted doubt on theories of immunology. Among the several models that have been proposed recently, none has attracted a consensus. Some immunologists have even suggested that immunology should rid itself of theorical concerns and concentrate on molecular aspects. This suggestion, however, is unacceptable\; hence it is still necessary to find a theoretical framework for immunology. Finally, we try to suggest a way to escape this uncomfortable situation of doubt. The immune < self > and the immune < system > (< network >) are rooted in strong metaphysical conceptions of identity, the main characteristic of which is to consider the organism as an enclosed and self-constructing entity. By contrast, based on experimental data about immune tolerance and host-pathogen interactions, we propose to consider organisms as open entities. To what theory does this conception lead? What would be the consequences of such a theory with regard to medical aspects?     

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for 60 years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity.     

Critical analysis of the immunological self/non-self model and of its implicit metaphysical foundations

An examination of the concepts used in immunology prompts us to wonder about the origins and the legitimacy of the notions of self and non-self, which constitute the core of the dominant theoretical model in this science. All theoretical reflection concerning immunology must aim at determining a criterion of immunogenicity, that is, an operational definition of the conditions in which an immune reaction occurs or does not occur. By criticizing both conceptually and experimentally the self/non-self vocabulary, we can demonstrate the inaccuracy and even the inadequacy of the dichotomy of self/non-self. Accordingly, the self/non-self model must be reexamined, or even rejected. On the basis of this critique, we can suggest an alternative theoretical hypothesis for immunology, based on the notion of continuity. The 'continuity hypothesis' developed here attempts to give a criterion of immunogenicity that avoids the reproaches leveled at the self model.     

Apoptosis: final control point in cell biology

The discovery of apoptosis, a widespread and morphologically distinct form of physiological cell death, has had an extraordinary impact on cell biology. The importance of apoptosis stems from its active nature and its potential for controlling biological systems. The growing appreciation of the significance of this process has stimulated intense investigation into the molecular mechanisms involved and into its fundamental implications for developmental biology, immunology and oncology.     

Towards an integrated network of coral immune mechanisms

Reef-building corals form bio-diverse marine ecosystems of high societal and economic value, but are in significant decline globally due, in part, to rapid climatic changes. As immunity is a predictor of coral disease and thermal stress susceptibility, a comprehensive understanding of this new field will likely provide a mechanistic explanation for ecological-scale trends in reef declines. Recently, several strides within coral immunology document defence mechanisms that are consistent with those of both invertebrates and vertebrates, and which span the recognition, signalling and effector response phases of innate immunity. However, many of these studies remain discrete and unincorporated into the wider fields of invertebrate immunology or coral biology. To encourage the rapid development of coral immunology, we comprehensively synthesize the current understanding of the field in the context of general invertebrate immunology, and highlight fundamental gaps in our knowledge. We propose a framework for future research that we hope will stimulate directional studies in this emerging field and lead to the elucidation of an integrated network of coral immune mechanisms. Once established, we are optimistic that coral immunology can be effectively applied to pertinent ecological questions, improve current prediction tools and aid conservation efforts.     

Schistosome immunology: more questions than answers

The past 30 years have seen research on the immunology of schistosomiasis move to encompass studies of responses in naturally exposed human populations, in addition to the studies in animal model systems. While animal systems still retain an important place in research on the immunology of schistosomiasis, recent debate has centred on aspects of human immunological responses that may or may not be associated with resistance or susceptibility to infection. In this article, Paul Hagan, Patricia Ndhlovu and David Dunne take stock of the present state of knowledge and offer their views on prospects for the future.     

Wild immunology

In wild populations, individuals are regularly exposed to a wide range of pathogens. In this context, organisms must elicit and regulate effective immune responses to protect their health while avoiding immunopathology. However, most of our knowledge about the function and dynamics of immune responses comes from laboratory studies performed on inbred mice in highly controlled environments with limited exposure to infection. Natural populations, on the other hand, exhibit wide genetic and environmental diversity. We argue that now is the time for immunology to be taken into the wild. The goal of 'wild immunology' is to link immune phenotype with host fitness in natural environments. To achieve this requires relevant measures of immune responsiveness that are both applicable to the host-parasite interaction under study and robustly associated with measures of host and parasite fitness. Bringing immunology to nonmodel organisms and linking that knowledge host fitness, and ultimately population dynamics, will face difficult challenges, both technical (lack of reagents and annotated genomes) and statistical (variation among individuals and populations). However, the affordability of new genomic technologies will help immunologists, ecologists and evolutionary biologists work together to translate and test our current knowledge of immune mechanisms in natural systems. From this approach, ecologists will gain new insight into mechanisms relevant to host health and fitness, while immunologists will be given a measure of the real-world health impacts of the immune factors they study. Thus, wild immunology can be the missing link between laboratory-based immunology and human, wildlife and domesticated animal health.     

Dismantling the immune system

During the past year, we have witnessed a veritable explosion in the number of mutant mouse strains produced by gene targeting in embryonic stem cells. Many of the informative targeted mutants have relevance to the field of immunology. At least one mutant mouse strain now exists for most of the important genes in immunology, and this collection of mutant mice has greatly expanded the experimental repertoire of immunologists. New targeting techniques have been developed that have often found their first application in immunology.     

Bioluminescence imaging: progress and applications

Application of bioluminescence imaging has increased tremendously in the past decade and has significantly contributed to core conceptual advances in biomedical research. This technology provides valuable means for monitoring of different biological processes in immunology, oncology, virology and neuroscience. In this review, we discuss current trends in bioluminescence and its application in different fields with an emphasis on cancer research.     

Special feature for the Olympics: effects of exercise on the immune system. Overview: exercise immunology

The review articles in this special feature reflect the current status of knowledge in the field of exercise immunology, with a focus on how exercise affects the human immune system and the health implications for resistance to infections and neoplastic diseases. In an Olympic year, the emphasis of exercise immunology research tends to be on elite athletes and the prevention of infections in the quest for optimum performance. However, research presented in this issue also covers recreational athletes, as well as highlighting the benefits of exercise for our ageing population.     

小鼠巨噬细胞RAW264.7 的培养技巧及经验总结

RAW264.7细胞具有很强的黏附和吞噬抗原的能力,是研究微生物学、免疫学的常用细胞株.很多研究者发现这种细胞形态极不稳定,细胞状态的评价也很困难.本文作者结合RAW264.7培养经历及文献资料探讨RAW264.7细胞培养的经验教训和评价细胞状态的方法,旨在为培养该细胞的科研工作者提供一定的借鉴.     

The dynamics of conceptual change in twentieth century immunology

I have attempted here to define three distinct eras in the 110-year history of the discipline of immunology. The first, extending from 1880 to about the First World War, centered around the new bacteriology and infectious diseases, and had a distinctly medical orientation. Several of the components of the original research program in immunology failed to maintain their original momentum or to fulfill their initial high promise, and went into decline. These include the development of new vaccines, serotherapeutic approaches, the study of cellular immunity, and the study of diseases that might be mediated by cytotoxic antibodies. Two other subprograms followed a somewhat different course; the study of anaphylaxis and related diseases passed primarily into the hands of clinical allergists, while the development and adaptation of serodiagnostic techniques passed into the hands of the new discipline of serology, both fields out of the mainstream of post-World War I immunology. As interest in the components of the old program was falling away, there developed a new area of interest in immunology. Leadership in the field devolved upon a new group of individuals with a predominantly chemical orientation to the study of antigens and antibodies, who pursued a research program and developed a theoretical base that reflected this orientation well. It may be interesting to examine more closely the forces responsible for this shift in emphasis. When interest in the old areas waned, the medically oriented practitioners did not switch to more immunochemical lines, but went in other directions. Karl Landsteiner was the only prominent "old-timer" who contributed significantly to the newer immunology, and it was his work that set the tone and attracted the new generation of immunochemists who became the reigning Denkkollektiv. A science does not change its precepts and approaches spontaneously; it is moved to the new position by those who explore fertile new areas. This is not to say, however, that there was no longer interesting and important work to be done along the old lines--it was just that such work was no longer "fashionable", as the reception of the work of Dienes, of Rich, of Rivers, and of the early Medawar illustrates. Whereas the earlier immunological program had interacted extensively with many different fields of biology and medicine, the immunochemical era was characterized by a relative introversion, as compared with the broad influence exerted by the earlier immunological program (92). We can date this second era from about the First World War until the late 1950s and early 1960s.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunology of placentation in eutherian mammals

The traditional way to study the immunology of pregnancy follows the classical transplantation model, which views the fetus as an allograft. A more recent approach, which is the subject of this Review, focuses on the unique, local uterine immune response to the implanting placenta. This approach requires knowledge of placental structure and its variations in different species, as this greatly affects the type of immune response that is generated by the mother. At the implantation site, cells from the mother and the fetus intermingle during pregnancy. Unravelling what happens here is crucial to our understanding of why some human pregnancies are successful whereas others are not.     

Mucosal immunology down under: Special Interest Group in Mucosal Immunology workshop, Australasian Society for Immunology, Sydney, Australia, 2 December 2007

The Mucosal Immunology Special Interest Group (SIG-MI) of the Australasian Society of Immunology was formed 14 years ago and has run regular symposia and workshops in conjunction with the Australasian Society of Immunology since that time. In December 2007 the Mucosal Immunology Special Interest Group held a 1-day satellite workshop in conjunction with the annual Australasian Society of Immunology scientific meeting in Sydney to celebrate the decade since hosting the 9th International Congress of Mucosal Immunology (9-ICMI) in 1997, which was also held in Sydney. The meeting that was attended by 65 delegates focussed on 4 session themes: reproductive immunology, respiratory immunology, mucosal immunology of the gastrointestinal tract and mucosal vaccines.     

Imagining 'reactivity': allergy within the history of immunology

An allergy is commonly understood to be an overreaction of the immune system to harmless substances that are misrecognised as foreign. This concept of allergy as an abnormal, misdirected immune response-a biological fault-stems from the idea that the immune system is an inherently defensive operation designed to protect the individual through an innate capacity to discriminate between the benign and toxic, or self and nonself. However, this definition of allergy represents a radical departure from its original formulation. Literally meaning 'altered reactivity', the term was coined in 1906 by Austrian paediatrician Clemens von Pirquet, to describe the fundamentally mutable nature of the immune response. This paper argues that the conventional interpretation of allergy-as-pathology derives from specific concepts of 'organism', 'response', and 'normal' immune function that have-for over a century-governed the perception and study of immune phenomena within immunology. Through an examination of Louis Pasteur's conceptualisation of the host body/microorganism relationship, I argue that immunology is founded on a view of the organism as a discrete, autonomous entity, and on a concomitant notion of the immune response as essentially reactive. Revisiting the concept of 'altered reactivity', this paper points to the fact that allergy was initially posited as a general theory of immune responsiveness and, importantly, one that poses a significant challenge to orthodox notions of immunopathology. It suggests that Pirquet's unique view of immune responsiveness presents an account of organismic or biological identity that encapsulates, rather than reduces, its ecological complexity.