Changes in blood hormone levels during the immune response.

Injection of three different antigens into rats or mice led in the course of several days to about a threefold increase in serum corticosterone levels and concommitantly to a decrease in thyroxine (rats). In view of the known immuno-suppressive effect of the glucocorticoids the possibility is considered that the endocrine changes induced during the immune response could significantly modulate the subsequent character of the immune response, e.i. magnitude, duration and lymphoid cell proliferation, however, a more complete pattern of hormonal variations and their cause needs to be established. These findings while admittedly preliminary, suffice to provide an indication of a temporal pattern of hormonal change during the immune response which could be important in immunoregulation.     

Somatostatin and somatostatin receptors in the immune system: a review

Communication and reciprocal regulation between the nervous, endocrine and immune systems are essential for the stability of the organism. Among others, cytokines, hormones and neuropeptides have been identified as signalling molecules mediating the communication between the three systems. This review focuses on the role of the neuropeptide somatostatin as an intersystem signalling molecule, with emphasis on the immune system. Somatostatin down-modulates a number of immune functions, among others lymphocyte proliferation, immunoglobulin production and the release of proinflammatory cytokines such as IFN-g. Systemic or local treatment with somatostatin or somatostatin analogues has been shown to be beneficial in a number of in vivo models of autoimmune disease and chronic inflammation. In many of these models somatostatin appears to antagonise the effects of another neuropeptide, substance P. A somatostatin-substance P immunoregulatory circuit has been proposed to operate within murine Schistosoma mansoni-induced granulomas. In this review we extend the model of the somatostatin-substance P immunoregulatory circuit to include data derived from other biological systems, and those relying on human clinical situations. In addition, we present a hypothesis on the regulation of the default class of immune response within a tissue, based on the local balance of pro-and anti-inflammatory neuropeptides.     

Presence and functional regulation of cannabinoid receptors in immune cells.

In the last 30 years studies on drug-abusing humans and animals injected with cannabinoids, as well as in vitro models employing immune cell cultures, have demonstrated that marijuana and cannabinoids are immunomodulators. Both types of cannabinoid receptors, CB1 and CB2, have been found in immune cells, suggesting they are important in mediating the effects of cannabinoids on the immune system. This article reviews the data on the function and distribution of cannabinoid receptors in the immune system and their involvement in the immunomodulatory effect of these substances.     

The role of endogenous opioids and their receptors in the immune system.

Opioid peptides appear to be dynamic signaling molecules that are produced within the immune system and are active regulators of an immune response. Furthermore, the receptors for these peptides occurring on immunocyte membranes share characteristics with neuronal opioid receptors, including molecular size, immunogenicity, and the use of specific intracellular signaling pathways. Recent studies of the interaction of opioids with cytokines have indicated that opioid peptides are intimately involved within the immune system. Specifically, opioids, including 2-n-pentyloxy-2-phenyl-4-methyl-morpholine, naloxone, and beta-endorphin, have been shown to interact with IL-2 receptors (134) and regulate production of IL-1 and IL-2 (48-50, 135). Conversely, IL-1 has been shown to up-regulate opioid peptide binding in brain tissue (136). Furthermore, the induction of IL-1 by opioids has also been identified in the invertebrate Mytilus, indicating the evolutionary conservation of this relationship (137). These results seem to typify the intricate association between the immune and neuroendocrine systems through opioid pathways. It is predicted that future endeavors will use this relationship to diagnose and treat specific diseases that have at their basis neuroendocrine and immunologic imbalances.     

Divergent appearance of complement receptors and Fc receptors on T cells in a murine mammary tumor system.

The emergence of novel T cells during mammary tumorigenesis has been previously described. T cells with surface markers usually associated with B cells, i.e. complement receptors (CR), appear in the spleens from tumor bearing mice. We now report on the appearance of Fc receptor (FcR) positive T cells in the spleens from the same animals. The kinetics of appearance of the two kinds of cells are similar.Based on evidence from double and triple label assays, it was concluded that FcR and CR are not coexpressed on the same T cell and that the two kinds of T cells which emerge do so in an independent fashion. Furthermore, they appear to represent a branch in the differentiation process influenced by tumor growth. The development of CR⁺ T cells represents an irreversible process as evidenced by the lack of change in the cells' representation following surgical procedures. In contrast the development of FcR⁺ T cells appears to be quite flexible in nature since mere surgical trauma as well as tumor mass removal can effect a decrease in the proportion of such cells.     

Expression of P2X receptors on immune cells in the rat liver during postnatal development

Single and double-labeling immunofluorescence and RT-PCR expression of P2X receptor proteins and mRNAs were used in a study of the liver of postnatal rats. OX62 and ED1 were used as markers for dendritic and macrophage (Kupffer) cells respectively. The results showed that the P2X₆ receptor subunit was up-regulated by 15-fold on hepatic sinusoid cells during postnatal days P1 to P60. Subpopulations of Kupffer cells co-expressed P2X₄ and P2X₆ receptor subunits and dendritic cells co-expressed P2X₄ and P2X₇ receptor subunits. Lipopolysaccharide (endotoxin) injected into the peritoneal cavity led to increased expression of the P2X₆ receptor on Kupffer cells, suggesting that the P2X₆ receptor subunit may be up-regulated by endotoxin. This study presents the first evidence that P2X receptors are widely distributed in the rat liver immune system and that activation of Kupffer and dendritic cells in the rat liver might be regulated by extracellular ATP.     

Changes in integrin receptors on oncogenically transformed cells

Oncogenically transformed cells show reduced assembly of fibronectin-rich extracellular matrixes and diminished ability to adhere to fibronectin. The molecular bases of these phenotypic alteration are not fully understood. We report here alterations in the spectrum of integrins, including two fibronectin receptors, on oncogenic transformation of rodent cells. Transformation of rat1, NRK, and Nil8 cells by Rous sarcoma virus or by murine sarcoma viruses encoding ras oncogenes leads to reductions in the level of integrin alpha 5 beta 1, which is a well-defined fibronectin receptor, and of two other integrin receptors. In contrast, another receptor, alpha 3 beta 1, which is a polyspecific receptor for fibronectin, laminin, and collagen, is retained by transformed cells. These results provide explanations for earlier results concerning the interactions of extracellular matrix proteins with the surfaces of tumor cells and offer leads to further understanding of the altered adhesive and migratory behavior of malignant cells.     

Ca2+/calcineurin signalling in cells of the immune system

Calcineurin is a serine-threonine - phosphatase that is expressed in a wide variety of tissues and has particularly critical functions in neurons, cardiac and skeletal muscle cells, and lymphocytes. This review focuses on recent studies elucidating the role of Ca(2+)/calcineurin signalling of the immune system.     

The effects of dietary selenium on the immune system in healthy men

Eleven men were fed foods naturally high or low in selenium for 120 d. Selenium intake was stabilized at 47 μg/d for 21 d, then changed to either 13 or 297 μg/d for 99 d, leading to significantly different blood selenium and glutathione peroxidase concentrations. Serum immunoglobulins, complement components, and primary antibody responses to influenza vaccine were unchanged. Antibody titers against diphtheria vaccine were 2.5-fold greater after reinoculation in the high selenium group. White blood cell counts decreased in the high-selenium group and increased in the low-selenium group, resulting primarily from changes in granulocytes. Apparent increases in cytotoxic T-lymphocytes and activated T-cells in the high-selenium group only approached statistical significance. Lymphocyte counts increased on d 45 in the high-selenium group. In vitro proliferation of peripheral lymphocytes in autologous serum in response to pokeweed mitogen was stimulated in the high-selenium group by d 45 and remained elevated throughout the study, whereas proliferation in the low selenium group did not increase until d 100. This study indicates that the immune-enhancing properties of selenium in humans are the result, at least in part, of improved activation and proliferation of B-lymphocytes and perhaps enhanced T-cell function.     

Chemokines and lymphocytes: the role of chemokines and their receptors in the immune system.

In the last few years. chemokines have emerged as an important superfamily where importance extends far beyond their most famous function as inflammatory mediators. Indeed, they are important molecules not only in inflammatory responses but also as immunoregulators. Chemokines ensure the continuous recirculation of immune cells among the various anatomical microenvironments, and are essential for maintaining immunological homeostasis. In addition, chemokines also have critical functions in lymphocyte development. In this article, we review the role of chemokines and their receptors in lymphopoiesis, lymphocyte's migration and immune response.     

The role of scavenger receptors in the innate immune system

Akey aspect of the innate immune system is the ability to discriminate between self and infectious nonself. This is achieved through pattern recognition receptors which directly recognise molecular epitopes expressed by microbes. Scavenger receptors (SRs) have been studied primarily due to their ability to bind and internalise modified lipoproteins, suggesting an important role in foam cell formation and the pathogenesis of atherosclerosis. However, the ability of some SRs to function as pattern recognition receptors through their binding of a wide variety of pathogens indicates a potential role in host defence. This review will detail our current understanding of the function of SRs in innate immunity, and in the initiation of aquired immune responses.     

Dual function of C-type lectin-like receptors in the immune system

Carbohydrate-binding C-type lectin and lectin-like receptors play an important role in the immune system. The large family can be subdivided into subtypes according to their structural similarities and functional differences. The selectins are of major importance in mediating cell adhesion and migration, and the mannose receptor subfamily is specialised in the binding and uptake of pathogens. Recent advances show that some of the type II C-type lectin-like receptors, such as DC-SIGN, can function both as an adhesion receptor and as a phagocytic pathogen-recognition receptor, similar to the Toll-like receptors. Although major differences in the cytoplasmic domains of these receptors might predict their function, recent findings show that differences in glycosylation of ligands can dramatically alter C-type lectin-like receptor usage.     

Septate-like junctions between cells of the immune system in vivo.

Septate-like junctions between lymphocytes, lymphocytes and macrophages, and macrophages were observed in cellular capsules surrounding larvae of the tapeworm Taenia crassiceps after intraperitoneal inoculation into immunized mice. The morphology of the junctions found in vivo is similar to that reported for septate-like junctions between cells of the immune system in vitro. These findings support the possibility that septate-like junctions may be involved in functional interactions between cells of the immune system both in vivo and in vitro.     

Effect of wheat gluten hydrolysate on the immune system in healthy human subjects

Nine healthy volunteers were divided into a test group (n = 5) and a control group (n = 4). The test group consumed 3 grams per d of wheat gluten hydrolysate for 6 d, and their NK cell activity and hematological parameters were measured: The same assessments were performed in the control group, which did not receive wheat gluten hydrolysate. In the test group, NK cell activity increased significantly (P = 0.018) after wheat gluten hydrolysate intake. No adverse effects were observed in either group.     

Contribution of the innate immune system to autoimmune diabetes: a role for the CR1/CR2 complement receptors.

B lymphocytes are required for diabetogenesis in nonobese diabetic (NOD) mice. The complement component of the innate immune system regulates B cell activation and tolerance through complement receptors CR1/CR2. Thus, it is important to assess the contribution of complement receptors to autoimmune diabetes in NOD mice. Examination of the lymphoid compartments of NOD mice revealed striking expansion of a splenic B cell subset with high cell surface expression of CR1/CR2. This subset of B cells exhibited an enhanced C3 binding ability. Importantly, long-term in vivo blockade of C3 binding to CR1/CR2 prevented the emergence of the CR1/CR2(hi) B cells and afforded resistance to autoimmune diabetes in NOD mice. These findings implicate complement as an important regulatory element in controlling the T cell-mediated attack on islet beta cells of NOD mice.     

Canine blood groups. 2. Description of a new allele in the Tr blood group system

A previously unrecognized canine red cell antigen, tentatively named O, was found after absorption analysis of an alloimmune antiserum and absorption of several immune or naturally occurring cross-reacting heteroantibodies from man, cattle and swine. The serological results and genetic analysis of a limited number of complete dog families indicated that the new factor probably belongs to the Tr blood group system. No individual possessed both factors Tr and O, and a large proportion of animals was negative for both factors. The serological pattern for the new Tr system obtained was consistent with similar systems observed in sheep (A-O), pig (R-O) and man (Bombay) in which the gene for one factor was dominant over and masked the gene for the second factor in the system. The negative phenotype was accounted for by the actions of an epistatic gene.