Introduction: knowledge is survival-the mission of the immune system and its stochastic simulations

In this introduction the timeliness and interest of dedicating an issue of Autoimmunity to mostly "discrete" models is motivated by highlighting number of circumstances, observations encounters, that all have favored the rise of a family of agent based simulations of the Immune System. Franco Celada was among the first experimentalists to accept the challenge of interdisciplinarity and create a computational Immune System. He thinks that discrete models are especially useful in handling hypotheses: initiating them, representing their consequences, and revealing their plusses and minuses. He is sure that "looking at" the immune machinery as a cognitive system is useful both to the intuitive understanding and the creative development of models.     

Introduction: the immune response against dying cells

The innate immune system is charged with the daunting task to discriminate harmless cell death events, as they occur in normal tissue homeostasis, and potentially harmful cell deaths, as they are elicited by infectious microorganisms or as a byproduct of malignant transformation. The distinction between harmful and harmless cell death relies on subtle biochemical differences that precede or accompany cell death and that act on a series of receptors, including pattern recognition receptors that are present on cells of the innate immune system, particularly dendritic cells. The present series of articles provides an up-to-date compendium on the molecular crosstalk between cell death and immune cells.     

Genomics in the immune system

The analysis of gene expression in tissues, cells, and biologic systems has evolved in the last decade from the analysis of a selected set of genes to an efficient high throughput whole-genome screening approach of potentially all genes expressed in a tissue or cell sample. Development of sophisticated methodologies such as microarray technology allows an open-ended survey to identify comprehensively the fraction of genes that are differentially expressed between samples and define the samples' unique biology. This discovery-based research provides the opportunity to characterize either new genes with unknown function or genes not previously known to be involved in a biologic process. The latter category may hold surprises that sometimes urge us to redirect our thinking. Here, we review the impact of large-scale gene expression profiling by DNA-microarray technology on basic and clinical aspects of immunology.     

Oscillations in the immune system

Summary:  Oscillations are surprisingly common in the immune system, both in its healthy state and in disease. The most famous example is that of periodic fevers caused by the malaria parasite. A number of hereditary disorders, which also cause periodic fevers, have also been known for a long time. Various reports of oscillations in cytokine concentrations following antigen challenge have been published over at least the past three decades. Oscillations can also occur at the intracellular level. Calcium oscillations following T-cell activation are familiar to all immunologists, and metabolic and reactive oxygen species oscillations in neutrophils have been well documented. More recently, oscillations in nuclear factor κB activity following stimulation by tumor necrosis factor α have received considerable publicity. However, despite all of these examples, oscillations in the immune system still tend to be considered mainly as pathological aberrations, and their causes and significance remained largely unknown. This is partly because of a lack of awareness within the immunological community of the appropriate theoretical frameworks for describing and analyzing such behavior. We provide an introduction to these frameworks and give a survey of the currently known oscillations that occur within the immune system.     

Autophagy in the immune system

Autophagy is an intracellular homeostatic mechanism important for the degradation of waste components from the cytoplasm in acidic lysosomal compartments. Originally, surplus parts of the cytoplasm that acted as targets for autophagy were thought to comprise cellular organelles and proteins, but this has now extended to include a range of pathogens with particular emphasis on intracellular bacteria. The finding that autophagy can sequester intracellular bacteria and mediate their destruction has opened the door to a wider role for autophagy as an effector arm of the immune system. In innate immunity, autophagy works downstream of pattern recognition receptors where it facilitates a number of effector responses, including cytokine production and phagocytosis. Autophagy is also able to intersect pathways of innate and adaptive immunity through its potential to deliver antigens for antigen presentation. Autophagy provides a substantial source of antigens for loading onto MHC class II molecules and it may be important in dendritic cells for cross‐priming to CD8⁺ T cells. In lymphocytes, autophagy is essential for cell survival and homeostasis, particularly in T cells. In the thymus, autophagy can modulate the selection of certain CD4⁺ T‐cell clones while in the bone marrow autophagy is needed for B‐cell development at specific stages. However, large holes exist in our knowledge as to how autophagy regulates, and is regulated by, the immune system and it is important to now apply what we have gleaned from in vitro studies to how autophagy operates in vivo in the setting of natural infection.     

Immunosenescence: ageing of the immune system

Suboptimal function of an aged immune system may contribute significantly to morbidity and mortality in the elderly. At present, little is known of the biochemistry and molecular genetics of immunosenescence in humans. A recent meeting¹ brought together an interdisciplinary group to discuss whether current understanding of the molecular basis of ageing in other cells might be relevant to ageing of the immune system.     

Leptin: nourishment for the immune system

Leptin, a protein produced by adipocytes, exerts several functions, including modulation of the immune response. A report in this issue of the European Journal of Immunology describes for the first time the effect of either leptin receptor deficiency or blockade on murine dendritic cell (DC) maturation, survival and function. The study describes how leptin receptor deficiency/blockade delays DC maturation and promotes apoptosis, shifts the balance between pro- and anti-inflammatory cytokine production, and reduces the ability of DC to stimulate CD4(+) lymphocytes. These exciting novel data add an important piece of evidence to the picture of the role of leptin in immunity and inflammation and generate the possibility that many of the effects of leptin on T lymphocytes might be mediated through DC.     

RNA沉默:基因组的免疫系统

基因组是病毒入侵的敏感作用靶点。近年来发现的RNA沉默是普遍存在于真核生物的一种防御机制。RNA沉默作为基因组的免疫系统有几个特点 :特异的作用于外来核酸 ;扩增外来核酸并产生强大的效应。后一特性在分子水平正得以揭示。近来研究表明 ,哺乳动物细胞RNAi介导的抗病毒治疗表现出了良好的应用前景。本文综述了RNA沉默作为基因组免疫系统的特性及在抗病毒治疗方面的研究进展