Sugar-mediated ligand-receptor interactions in the immune system

Most molecules involved in the recognition and elimination of pathogens by the immune system are glycoproteins. Oligosaccharides attached to glycoproteins initiate biological functions through mechanisms that involve multiple interactions of the monosaccharide residues with receptors. For example, calreticulin, a quality-control lectin-like chaperone, interacts with glucosylated mannose glycans presented by empty major histocompatibility complex (MHC) class I molecules, retaining them in the endoplasmic reticulum (ER) until antigenic peptide is loaded. Clusters of specific IgG glycoforms, present in increased amounts in rheumatoid arthritis, bind mannose-binding lectin (MBL), providing a potential route to inflammation through activation of the complement pathway. Secretory IgA glycans bind gut bacteria, and an unusual cluster of mannose residues on gp120, the surface coat protein of the HIV virus, is recognized by the novel 'domain-swapped' IgG 2G12 serum antibody.     

Structural basis of cell-cell interactions in the immune system

During the past year, advances in our understanding of receptor-ligand interactions between opposing cell surfaces have occurred at a structural level. These include adhesion involving CD2-CD58, antigen-specific T-cell receptor interactions with peptides bound to major histocompatibility complex molecules (both pMHCI and pMHCII), the CD8alphaalpha co-receptor-pMHCI interaction and the binding of two distinct classes of natural killer receptors to self-MHC ligands.     

Highly glycosylated tumour antigens: interactions with the immune system

A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the potential role of CLRs (C-type lectin receptors), expressed by antigen-presenting cells of the immune system, in tumour recognition and immune modulation. Studies in recent years have provided significant insight into the immunomodulatory function of CLR during infections, but their role in cancer remains elusive; some strongly bind tumour cells and antigens, indicating participation in malignancy. The potential to use recombinant CLR as diagnostic tools will also be discussed.     

Structural basis of cell–cell interactions in the immune system

During the past year, advances in our understanding of receptor–ligand interactions between opposing cell surfaces have occurred at a structural level. These include adhesion involving CD2–CD58, antigen-specific T-cell receptor interactions with peptides bound to major histocompatibility complex molecules (both pMHCI and pMHCII), the CD8αα co-receptor–pMHCI interaction and the binding of two distinct classes of natural killer receptors to self-MHC ligands.     

鱼类肠道微生物与宿主免疫系统相互作用研究进展

鱼类肠道中存在大量微生物,对于维持宿主健康具有重要作用。鱼类免疫系统能够监视并调控肠道微生物组成,维持肠道菌群稳态。同时,鱼类肠道共生微生物调节鱼类免疫系统,抑制病原微生物的过度增殖,保证宿主的健康。本文回顾了鱼类肠道微生物与宿主免疫系统相互作用的研究进展,重点介绍了宿主免疫系统识别肠道微生物、塑造肠道菌群以及益生菌对宿主免疫和肠道菌群的调控等,提出了理想的益生菌应该来自动物自身胃肠道,生产中应谨慎选用非宿主来源的益生菌,以期为推动鱼类肠道功能微生物开发和应用提供理论支撑。     

Lymphocyte interactions and positioning: I. Adhesive interactions

We report on the effects of factors obtained from short-term cultures of mouse, rat, and human, B, peripheral T, and thymic lymphocytes on the adhesion of these cells and of a range of tissue cells. 1. Heterologous combinations of factor and cell in the mouse system lead to a diminution in lymphocyte to lymphocyte adhesion. Doseresponse curves are reported and a definition of activity is given. Homologous combinations do not affect adhesion. 2. Mouse B and peripheral T cells show no intrinsic specificity of adhesion but addition of one of the factors to a system of cells of both types leads to the appearance of specific aggregates. 3. The sera of normal mice contain both B and T factor activities, while sera from the B mouse contain only B factor activities. 4. The factors are not species specific in the group of organisms mouse, rat, man and also affect the cell to cell adhesion of various other cell types such as embryonic chick liver and neural retina. These cell types also produce factors that affect lymphocyte adhesion. Two CHO cell lines neither produce or are affected by factors. 5. The mouse B and T factors have molecular weights of approximately 3000 and 9000 daltons, respectively. They are heat sensitive molecules. 6. Injection of mouse T factor into a B mouse leads to extensive repositioning of the injected B lymphocytes. 7. The possible roles of such factors in lymphocyte ecotaxis, homing, and positioning are discussed.     

Adhesive interactions between fibroblasts and polymorphonuclear neutrophils in vitro

Although the in vivo interaction between polymorphonuclear neutrophils (PMN) and fibroblasts may be important, these pathways have not been well studied. We have investigated the adherence of PMN to monolayers of human fetal lung fibroblasts, using a microtiter plate assay based upon the uptake by cells of the vital stain Rose Bengal. Stimulation with phorbol myristate acetate (PMA) caused a significant increase of adherence over basal levels which was rapid in onset and plateaued at 5 min. Adhesion was dependent on the leucocyte integrin family of glycoproteins, notably on Mac-1, since monoclonal antibodies toward the beta chain (CD18) and alpha chain (CD11b) of Mac-1 almost completely suppressed PMA-induced PMN adhesion (88% and 77% inhibition, respectively). Adhesion was also inhibited by the peptides RGDS and GRGDS (24.2% and 26.6%, respectively using 1 mM peptide). Prestimulation of fibroblasts for longer time periods (5 and 24 h) with interleukin 1 alpha and tumor necrosis factor alpha, but not transforming growth factor beta, also resulted in a significant increase in adhesion of unstimulated PMN (after 24 h preincubation, 10 U/ml IL1 alpha stimulated adhesion by 179% of control, 500 U/ml TNF alpha by 157%). This indicated that there are both PMN- and fibroblast-dependent pathways for PMN adhesion. Components of the extracellular matrix of fibroblasts do not appear to play important roles in the adhesion process since addition of fibronectin and type IV collagen, or of purified antibodies to fibronectin and types I and IV collagen, did not affect PMA-induced PMN adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ubiquitin in the immune system

Ubiquitination is a post-translational modification process that has been implicated in the regulation of innate and adaptive immune responses. There is increasing evidence that both ubiquitination and its reversal, deubiquitination, play crucial roles not only during the development of the immune system but also in the orchestration of an immune response by ensuring the proper functioning of the different cell types that constitute the immune system. Here, we provide an overview of the latest discoveries in this field and discuss how they impact our understanding of the ubiquitin system in host defence mechanisms as well as self-tolerance.     

TOR in the immune system

The target of rapamycin (TOR) is a crucial intracellular regulator of the immune system. Recent studies have suggested that immunosuppression by TOR inhibition may be mediated by modulating differentiation of both effector and regulatory CD4 T cell subsets. However, it was paradoxically shown that inhibiting TOR signaling has immunostimulatory effects on the generation of long-lived memory CD8 T cells. Beneficial effects of TOR inhibition have also been observed with dendritic cells and hematopoietic stem cells. This immune modulation may contribute to lifespan extension seen in mice with mTOR inhibition. Here, we review recent findings on TOR modulation of innate and adaptive immune responses, and discuss potential applications of regulating TOR to provide longer and healthier immunity.     

Meaning-making in the immune system

Meaning-making is the process by which a system responds to an indeterminate signal. This article focuses on meaning-making in living systems. It proposes several guidelines for studying the process of meaning-making in living systems in general, and in the immune system in particular. Drawing on a general framework for studying meaning-making in living systems, I suggest three basic organizing concepts for studying meaning-making-variability of the signal, context markers, and transgradience. Those concepts present a radical alternative to the information-processing approach that governs biological research and may shed new light on biological processes.     

Tick-Theileria interactions in response to immune activation of the vector

Watt, D. M., Walker, A. R., Lamza, K. A., and Ambrose, N. C. 2001. Tick-Theileria interactions in response to immune activation of the vector. Experimental Parasitology 97, 89-94. Immune mechanisms towards the haemoprotozoan parasite Theileria parva were investigated in their tick vector, Rhipicephalus appendiculatus. The exoskeletons of adult ticks were initially pierced with bacteria-coated, saline-coated, or sterile dry glass needles. Haemolymph was extracted from the ticks at 6, 24, 48, and 72 h postinjection and applied to bacterial plates to measure the growth inhibition effects. The inhibition zones were larger with all the injected groups compared to uninjected controls. The largest inhibition zones were seen 24 h after injection with bacteria-coated needles. An experiment was carried out to investigate whether antibacterial immune responses were relevant to the parasite/tick relationship and, if so, which parasite form was most vulnerable. R. appendiculatus nymphs were infected with T. parva by feeding on an infected calf and were then injected with needles on days 7, 13, 15, and 17 throughout their moult in an attempt to induce tick immune responses at the same time as different lifecycle forms of T. parva would be present. Salivary glands from the moulted adult ticks in the control and different treatment groups were dissected out and examined for the presence of T. parva sporoblasts. No difference in infection levels was seen in any of the treatment groups compared with the controls, suggesting that immune responses in R. appendiculatus, induced by bacterial injection, do not affect T. parva infections. The fecundity of injected ticks was compared with that of uninjected controls to ensure that the injection procedure itself was not detrimental to the ticks. Injected females had higher engorgement masses than controls but reduced levels of egg hatching.     

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.