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Major studies are still lacking on the impact of differing intensities of long-term donor plasmapheresis, not only on total serum protein, albumin and immunoglobulin G (IgG), but also on humoral and cellular immunity, red cell and iron metabolism, and biochemical cardiovascular risk markers. Three groups of donors, comprising 483 individuals undergoing differing intensities of long-term serial plasmapheresis, were entered into a cross-sectional study. A fourth control group consisted of 100 non-donors. In addition to measuring total protein, albumin and IgG levels, we determined parameters of humoral and cellular immunity, red cell and iron metabolism and recognized biochemical cardiovascular risk factors. The median annual net amount of plasma donated by the three donor groups was 37, 16 and 10 l, respectively ( P < 0·0001). Donors had significantly lower total serum protein, albumin and IgG levels than non-donors ( P < 0·0001), but the intensity of plasmapheresis had no influence on those parameters. Like non-donors, all plasma donors had normal humoral and cellular immunity. No increased rates of iron store depletion were observed in the three groups of plasma donors. Plasma donors were not at increased cardiovascular risk. Regular donor plasmapheresis of up to 45 l of plasma per year appears to be as safe as more moderate plasmapheresis programmes, with respect to the parameters analysed in this study. Individuals donating under these conditions did not develop impaired humoral and cellular immunity, iron store depletion, or increased cardiovascular risk with regard to established biochemical risk markers. Prospective studies are required to determine more exactly than in retrospective analyses the reasons why donors withdraw from plasmapheresis programmes. [ABSTRACT FROM AUTHOR]

Transferrin receptor 1 (TfR1) is a type II membrane protein that mediates cellular iron uptake. Transferrin receptor 2(TfR2), another receptor for transferrin (Tf), has recently been cloned. We examined expression levels of TfR1, TfR2-α (membrane form) and TfR2-β (non-membrane form) transcripts in cells from 67 patients with de novo acute myeloid leukaemia (AML) using reverse transcription-polymerase chain reaction (RT-PCR), and correlated the results with a variety of clinical features and disease outcomes of these patients. Significant correlations were noted between the levels of both TfR1 and TfR2-α ( r = 0·771, P < 0·001) and TfR1 and TfR2-β ( r = 0·534, P < 0·001). Unexpectedly, initial white blood cell (WBC) counts were inversely correlated with levels of expression of either TfR1( r = −0·357, P = 0·003), TfR2-α ( r = −0·486, P < 0·0001), or TfR2-β ( r = −0·435, P = 0·0003). Only TfR2 expression was significantly associated with either serum iron ( r = −0·270, P = 0·045) or serum ferritin ( r = −0·364, P = 0·008). Multivariate analyses using Cox's proportional hazard model showed that elevated TfR2-α, but not TfR1 or TfR2-β mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2-α and TfR2-β survived significantly longer than a group without high expression of both of them ( P < 0·01 by log-rank). The present study suggests that (i) TfRs-independent iron uptake might have an important role in in vivo proliferation of AML cells; (ii) expression of TfR2 (especially the α form) is a novel prognostic factor for patients with AML. [ABSTRACT FROM AUTHOR]

This article presents abstracts of various articles and research papers presented at the XXIIIrd Meeting of the Scandinavian Society for Immunology and the Vlllth Summer School, held during May 26-31, 1992, in Oslo, Norway. Abstract of the article "Cloning and Characterization of the 5'-transcriptional Regulators Region of Human α-2'6' Sialyltransferase," summarizes a study of the expression of the individual glycosyltransferases. It describes that cellular interactions such as homing, are processes which involve cell to cell adhesion and recognition. Some of these interactions are mediated by oligosaccharide epitopes on cell surface glycoproteins and glycolipids. Abstract of the paper, entitled "Production or Aleutian Disease Virus (ADV) Encoded Structural Proteins in a Baculovirus Expression System and Its Use in Vaccination Studies," presents results of various ongoing studies of recombinant baculovirus expression system and its uses in different vaccine trials. Abstract of another article, "Endotoxin and Staphylococcus aureus Enterotoxin A Induced Different Patterns of Cytokines," summarizes the study assessing effects of S. aureus enterotoxin A and lipopolysaccharide in cytokine production at the single cell level in cells obtained from healthy blood donors.

Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico‐amygdala circuit, lowers sensitivity to rewards in the cortico‐striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self‐medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress‐related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents. [ABSTRACT FROM AUTHOR]

The structural elucidation of lipopolysaccharides (LPSs) from Gram‐negative marine bacteria, along with the assessment of their immunological properties, is a fascinating and active research field. Such studies can aid understanding of adaptation phenomena that occur in the marine environment, but they can also open up new perspectives on the design and development of new immunoregulatory drugs. In this paper, we report the structural characterization of the lipid A component of the LPS isolated from the marine bacterium Cobetia pacifica KMM 3879T, which is characterized by a family of structures differing in their acylation patterns. The structural assignment was achieved through extensive chemical analysis and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. Moreover, cellular immunology studies on the LPS highlighted its low immunostimulatory impact, as well as a very interesting and promising inhibitory activity of the toxic effects of Escherichia coli LPS. [ABSTRACT FROM AUTHOR]

The article presents a list of forthcoming books about immunology. These include "IL-5 Target Genes Involved in B Cell Terminal Maturation," by Keisuke Horikawa and K. Takatsu, "The Riddle of the Dual Expression of IgM and IgD," by Roland Geisberger, Marinus Lamers and Gernot Achatz, and "Anti-Idiotype Antibody Induced Cellular Immunity in Mice Transgenic for Human Carcinoembryonic Antigen," by Asim Saha, Sunil Chaterjee, Kenneth Foon and Malaya Chatterjee.

The article presents instructions for the authors submitting manuscripts to be published in the periodical "Scandinavian Journal of Immunology." The periodical publishes papers within the various fields of cellular and molecular immunology. Manuscripts should be submitted either to one of the managing editors or to one of the editors, whose addresses are given on the second cover page of the periodical. Manuscripts must be typewritten, double-spaced throughout, on one side of the paper, with a 5 centimeters wide margin.

Our previous paper reported that it was difficult to induce tolerance using donor specific transfusion (DST) in Lewis rats, while in DA and PVG rats it was possible to induce tolerance using DST. In this paper we investigated the effects of DST in a local graft versus host reaction (GVHR) model using these rat strains. The following results were obtained: (i) DST suppressed the GVHR in the DA rat but not in the Lewis rat; (ii) DST did not suppress GVHR in PVG rat strain, but lymphocytes, prepared from the PVG rats that were tolerant of Lewis heart grafts induced by DST, could suppress the the GVHR; and (iii) in Lewis rats, intrathymic injection of whole blood suppressed the GVHR, suggesting this route of antigen delivery might be effective in prolonging allograft survival. Cardiac allograft survival in this strain was prolonged in some cases after pretreatment with intrathymic donor whole blood. These results suggest the value of the GVHR in the assessment of new protocols to induce allograft tolerance in rats. [ABSTRACT FROM AUTHOR]

The article discuses the golden anniversary of Macfarlane Burnet's preliminary account of clonal selection theory. The paper was published in the "Australian Journal of Science," which was the first clear outline of the clonal selection theory. This paved the way to the modern era of cellular and molecular immunology.

Parasite spillover from invasive aliens to native species increases the risk of disease emergence within native biota—either by direct harm to the new host or by indirect effects like increased risks of secondary infection.One example for such a detrimental effect is the parasitic copepod Mytilicola intestinalis that infected blue mussels Mytilus edulis after being introduced into the North Sea in the early 20th century. Since 1949, the parasite was blamed for multiple mass mortalities of infested blue mussels but evidence for a direct causal involvement of M. intestinalis remained circumstantial.Here, we now examine the potential effects of primary infections by the invasive parasite on the susceptibility to secondary infections with virulent bacteria (Vibrio spp.) in a full factorial infection experiment combining parasite infection (control vs. infected) with different Vibrio infection treatments (control, bath challenge, injection) in environmental conditions that either favoured the host (ambient temperature) or the bacterium (elevated temperature). The influence of primary and secondary infections on cellular immunity (phagocytosis) and Vibrio load in the haemolymph was used to correlate these results to host survival.Our results suggest that the rate of secondary Vibrio infection is increased due to lower efficiency of the cellular immune response. As a consequence, the failure of clearing Vibrio from the haemolymph might increase mortality of mussels infected by M. intestinalis.This demonstrates that indirect effects of parasite invasions can outweigh direct effects of the infection highlighting the need for a more integrative approach to understand and predict the consequences of parasite invasions. This paper demonstrates that indirect effects of immune modulation caused by infection with an invasive parasite can outweigh direct effects of the infection. This highlights the need for a more integrative approach to predict the consequences of parasite invasions and species invasions in general. [ABSTRACT FROM AUTHOR]

The goal of this paper is to investigate the dynamical behavior of a general nonlinear delayed viral infection model with cytotoxic T lymphocyte (CTL) immune response. The intrinsic growth rate of uninfected hepatocytes, incidence rate of infection, removal rate of infected hepatocytes and capsids, production and removal rate of viruses, activation rate of CTLs, and decay rate of CTLs are given by general nonlinear functions with a set of conditions on these general nonlinear functions, which make the analysis of the model more difficult. The global threshold dynamics with respect to the reproduction numbers for viral infection R0 and for CTL immune response R1 have been presented by constructing suitable Lyapunov functionals. Numerical simulations are carried out for a model with specific forms of the general functions to confirm the theoretical results and show that both the numerical and theoretical results are consistent. [ABSTRACT FROM AUTHOR]

In this paper, a humoral and cellular immunity virus dynamics model with the Beddington-DeAngelis incidence rate is set up. We derive the basic reproductive number R0, the cytotoxic T lymphocytes immune response reproductive number R1, the humoral immune response reproductive number R2, humoral immune response competitive reproductive number R3, and cytotoxic T lymphocytes immune response competitive reproductive number R4, and a full description of the relation between the existence of the equilibria and reproductive numbers is given. The global properties of the five equilibria are obtained by constructing Lyapunov functions. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We study a mathematical model of immune response by T cells where the regulatory T cells (Treg) inhibit interleukin 2 (IL‐2) secretion. We model the suppression of the autoimmune line of T cells after a different line of T cells responded to a pathogen infection. In this paper, we show that if the population of the pathogen responding line of T cells becomes large enough, the competition for IL‐2 and the increase in the death rates may lead to a depletion in the concentration of autoimmune T cells. Provided this lasts for a sufficiently long time, the concentration of autoimmune T cells can be brought down to values inside the basin of attraction of the controlled state, and autoimmunity can be suppressed. [ABSTRACT FROM AUTHOR]

Summary: The study of cellular and molecular immunology is almost completely dependent on monoclonal antibody technology. Despite the relatively long history of monoclonal antibodies, there is still huge potential for developing novel and transformative uses for this technology. In this issue of Immunology, we present two such papers, one focussing on anti‐complement (C5) antibodies, the other on anti‐CD6‐specific antibodies. Both manuscripts describe novel ways that monoclonal antibodies may be used for scientific and potentially for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Iran is the only country in the world currently with a legalized compensated kidney donation system, in which kidney sellers are matched with end‐stage renal disease patients through a regulated process. From a practical point of view, this model provides an abundance of kidneys for transplantation as opposed to the American model that relies on altruistic donation. The major concern about adopting the Iranian model is the possibility of exploitation. A large body of literature exists on this topic, but few have focused on its cultural aspects. This paper sheds light on the cultural implications of the Iranian model by providing empirical evidence on the social stigmas against kidney sale in Iran. We claim that these stigmas act as barriers to entry to the supply market of kidneys. Due to the conditions created by social stigmas, kidney sellers are forced to consider not only monetary rewards but also cultural factors. Thus, they tend to be more cautious and try to avoid impulsive decisions. Such social stigmas act as unofficial regulatory forces to keep kidney sale as the last resort for the poor, to diversify the supply market by age, and to stretch the decision‐making process in the absence of a mandatory waiting period for transplantation. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) present anti-inflammatory properties and are being used with great success as treatment for inflammatory and autoimmune diseases. In clinical applications MSCs are subjected to a strong pro-inflammatory environment, essential to their immunosuppressive action. Despite the wide clinical use of these cells, how MSCs exert their effect remains unclear. Several lipids are known to be involved in cell's signaling and modulation of cellular functions. The aim of this paper is to examine the variation in lipid profile of MSCs under pro-inflammatory environment, induced by the presence of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), using the most modern lipidomic approach. Major changes in lipid molecular profile of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), lysoPC (LPC), and sphingomyelin (SM) classes were found. No changes were observed in the phosphatidylinositol (PI) profile. The levels of PC species with shorter fatty acids (FAs), mainly C16:0, decreased under pro-inflammatory stimuli. The level of PC(40:6) also decreased, which may be correlated with enhanced levels of LPC(18:0), which is known to be an anti-inflammatory LPC, observed in MSCs subjected to TNF-α and IFN-γ. Simultaneously, the relative amounts of PC(36:1) and PC(38:4) increased. TNF-α and IFN-γ also enhanced the levels of PE(40:6) and decreased the levels of PE(O-38:6). Higher expression of PS(36:1) and SM(34:0) along with a decrease in PS(38:6) levels were observed. These results indicate that lipid metabolism and signaling are modulated during MSCs activation, which suggests that lipids may be involved in MSCs functional and anti-inflammatory activities. J. Cell. Physiol. 231: 1024-1032, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective Somatization is a symptom cluster characterized by 'psychosomatic' symptoms, that is, medically unexplained symptoms, and is a common component of other conditions, including depression and myalgic encephalomyelitis/chronic fatigue syndrome ( ME/ CFS). This article reviews the data regarding the pathophysiological foundations of 'psychosomatic' symptoms and the implications that this has for conceptualization of what may more appropriately be termed physio-somatic symptoms. Method This narrative review used papers published in PubMed, Scopus, and Google Scholar electronic databases using the keywords: depression and chronic fatigue, depression and somatization, somatization and chronic fatigue syndrome, each combined with inflammation, inflammatory, tryptophan, and cell-mediated immune ( CMI). Results The physio-somatic symptoms of depression, ME/ CFS, and somatization are associated with specific biomarkers of inflammation and CMI activation, which are correlated with, and causally linked to, changes in the tryptophan catabolite ( TRYCAT) pathway. Oxidative and nitrosative stress induces damage that increases neoepitopes and autoimmunity that contribute to the immuno-inflammatory processes. These pathways are all known to cause physio-somatic symptoms, including fatigue, malaise, autonomic symptoms, hyperalgesia, intestinal hypermotility, peripheral neuropathy, etc. Conclusion Biological underpinnings, such as immune-inflammatory pathways, may explain, at least in part, the occurrence of physio-somatic symptoms in depression, somatization, or myalgic encephalomyelitis/chronic fatigue syndrome and thus the clinical overlap among these disorders. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Nang et al. (2013) Live attenuated H5N1 vaccine with H9N2 internal genes protects chickens from infections by both Highly Pathogenic H5N1 and H9N2 Influenza Viruses. Influenza and Other Respiratory Viruses 7(2) 120-131. Background The highly pathogenic H5N1 and H9N2 influenza viruses are endemic in many countries around the world and have caused considerable economic loss to the poultry industry. Objectives We aimed to study whether a live attenuated H5N1 vaccine comprising internal genes from a cold-adapted H9N2 influenza virus could protect chickens from infection by both H5N1 and H9N2 viruses. Methods We developed a cold-adapted H9N2 vaccine virus expressing hemagglutinin and neuraminidase derived from the highly pathogenic H5N1 influenza virus using reverse genetics. Results and Conclusions Chickens immunized with the vaccine were protected from lethal infections with homologous and heterologous H5N1 or H9N2 influenza viruses. Specific antibody against H5N1 virus was detected up to 11 weeks after vaccination (the endpoint of this study). In vaccinated chickens, IgA and IgG antibody subtypes were induced in lung and intestinal tissue, and CD4+ and CD8+ T lymphocytes expressing interferon-gamma were induced in the splenocytes. These data suggest that a live attenuated H5N1 vaccine with cold-adapted H9N2 internal genes can protect chickens from infection with H5N1 and H9N2 influenza viruses by eliciting humoral and cellular immunity. [ABSTRACT FROM AUTHOR]

To cite this article: Benson AA, Toh JA, Vernon N, Jariwala SP. The role of vitamin D in the immunopathogenesis of allergic skin diseases. Allergy 2012; 67: 296-301. Abstract Vitamin D plays key roles in innate and adaptive immunity through the stimulation of Toll-like receptors, increasing pro-inflammatory cytokine production, and possibly enhancing T helper type 2 responses. These mechanisms may explain the growing body of evidence connecting vitamin D to allergic diseases, including asthma, food allergies, and allergic rhinitis. The data relating vitamin D to allergic skin diseases are equivocal with studies linking both high and low vitamin D levels to an increased risk of developing atopic dermatitis. In this paper, we describe the role of vitamin D in the immunopathogenesis of atopic dermatitis and other allergic skin diseases. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Witkin S, Linhares I, Bongiovanni A, Herway C, Skupski D. Unique alterations in infection-induced immune activation during pregnancy. BJOG 2011;118:145-153. Immune responses to infection are uniquely regulated during gestation to allow for antimicrobial defence and tissue repair, whilst preventing damage to developing fetal organs or the triggering of preterm labour. A review and analysis of studies delineating gestation-specific immune modulation and intra-amniotic regulation of pro-inflammatory immunity. Identification of the alterations between the fetus/neonate and adult with regard to the endogenous and infection-induced expression of molecules with immune regulatory properties, and the characterisation of intra-amniotic immune mediators that inhibit bacterial-induced pro-inflammatory cytokine production. English and non-English publications from 1985 to the present. An electronic literature search using MEDLINE, PubMed, articles cited in the primary sources, as well as pregnancy-related immunology research from our laboratory at Weill Medical College of Cornell University. During fetal development, interleukin (IL)-23, IL-10 and IL-6, as well as T-helper-17 (Th17)-mediated immune responses, are upregulated, whereas tumour necrosis factor-α (TNF-α) and IL-1β- and Th1-mediated immune responses are downregulated in the intrauterine environment (both the fetal compartment and the amniotic compartment). Infection-related immunity during gestation is preferentially directed towards combating extracellular microbial pathogens. Amniotic fluid and the neonatal circulation contain multiple components that improve the ability of the developing neonate to tolerate microbial-induced immune activation. The repertoire of immune mechanisms to control infection and inflammation differ between fetal and adult life. The dual mechanisms of resistance to infection and tolerance to infection-induced immune activation prevent damage to the developing fetus and the triggering of premature labour. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Taylor-Robinson D, Lamont R. Mycoplasmas in pregnancy. BJOG 2011;118:164-174. The genital mycoplasmas have been implicated in a number of adverse outcomes of pregnancy. Spontaneous preterm labour and preterm birth is an important contributor to perinatal mortality and morbidity. If Mycoplasma hominis plays an integral part in this problem, it is likely to contribute through its involvement with bacterial vaginosis. Ureaplasmas induce cytokines and inflammation, making a casual association compelling. The role of Mycoplasma genitalium and Mycoplasma fermentans is less clear, but M. genitalium is potentially pathogenic and should be treated if detected. There is considerable evidence for the role of M. hominis in post-partum and post-abortal sepsis, and for ureaplasmas causing chronic lung disease or death in very low birthweight infants. The role of the genital mycoplasmas in adverse outcomes of pregnancy is complicated by the presence or absence of bacterial vaginosis, and this association requires further research. [ABSTRACT FROM AUTHOR]

Many traditional Chinese medicines have been used as immunomodulators that act as either immunosuppressants or immunostimulators. Recently, our lab successfully isolated a monomer telocinobufagin (TCB) from the chloroform extract of Chan Su ( Venenum Bufonis). In the present paper, we evaluated the immunomodulatory effects of this compound in vitro. We found that TCB significantly stimulates splenocyte proliferation when administered alone or in combination with polyclonal T-cell mitogens concanavalin A (Con A) and lipopolysaccharide. Telocinobufagin markedly enhances natural killer cell and peritoneal macrophage activation. Telocinobufagin increases the percentage of CD4, CD8 positive cells within a population of splenocytes. Moreover, we found that the level of several Th1 cytokines, including interleukin-2 (IL-2), interleukin-12 (IL-12), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), are significantly increased after TCB treatment, while the level of the Th2 cytokine interleukin-4 (IL-4) is significantly decreased. As a result, the ratio of Th1/Th2 is significantly increased. Taken together, these results indicate that TCB has potential immune system regulatory effects and suggest that this compound could be developed as a novel immunotherapeutic agent to treat cancer and other immune-mediated diseases, and it may become a new immunomodulatory agent in many regions. [ABSTRACT FROM AUTHOR]

The ultimate outcome of T cell receptor recognition is determined by the context in which the antigen is encountered. In this fashion both antigen-presenting cells and T cells must integrate multiple environmental cues in the form of pathogen-associated molecular patterns, cytokines and accessory molecule signals. The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays a central role in integrating environmental signals critical to regulating metabolism and cell survival. In this paper we review the data demonstrating that mTOR integrates signals from the immune microenvironment and therefore facilitates the generation of the adaptive immune response. Specifically, we review the role of mTOR in promoting dendritic cell activation and maturation, in regulating full T cell activation versus anergy, and influencing the induction of regulatory T cells. [ABSTRACT FROM AUTHOR]

The pathogenesis of B-cell lymphoproliferative disorders in general and B-cell chronic lymphocytic leukaemia in particular appears to involve dysfunctional regulation of humoral and cellular immunity with the subsequent development of genetic aberrations in B cells. In theory, either component may arise de novo or may be influenced by environmental exposures including infectious agents, antigens, genotoxic chemicals, or radiation. As an intermediary within the exposure-disease continuum, monoclonal B-cell lymphocytosis may be a helpful biomarker for teasing out these various contributions to risk. This article introduces a series of papers that resulted from an International Workshop held in May 2007 entitled ‘Monoclonal B-cell Lymphocytosis and Chronic Lymphocytic Leukemia: Environmental and Genetic Risk Factors’. Research efforts, such as those described in this issue, should lead to improved interventions, more predictive biomarkers, more effective treatments, and a greater appreciation of how the immune system functions over the entire human lifespan. [ABSTRACT FROM AUTHOR]

This paper reviews the new biologic agents that selectively block the immunologic steps implicated in the pathogenesis of psoriasis. Four strategies have been targeted: reduction of the number of pathogenic T cells; inhibition of T-cell activation and migration; modulation of the immune system; and blockage of the activity of inflammatory cytokines. There are three classes: monoclonal antibodies, fusion proteins and recombinant cytokines or growth factors. The actions, efficacy and side-effect profile of the biologic agents, alefacept, efalizumab, etanercept and infliximab, are reviewed. [ABSTRACT FROM AUTHOR]

Aim: The pathophysiology of perinatal brain lesions is probably complex and multifactorial. The development and characterization of distinct yet complementary animal models should help to unravel the cellular and molecular mechanisms underlying perinatal brain lesions. This paper reviews experimental data obtained in animal models of neonatal excitotoxic brain lesions that closely mimic some of the lesions found in human cerebral palsy.Conclusion: Available data point to a key role for brain macrophages and oligodendrocytes in neonatal rodent excitotoxic brain lesions and underline the impact of cytokines on these lesions. [ABSTRACT FROM AUTHOR]

The role of cytokines in the accumulation of eosinophil granulocytes in inflamed tissue has been studied extensively during recent years, and these molecules have been found to participate throughout the whole process of eosinophil recruitment. Haematopoietic cytokines such as IL-3, IL-5 and GM-CSF stimulate the proliferation and differentiation of eosinophils in the bone marrow, and the release of mature eosinophils from the bone marrow into the blood is probably promoted by IL-5. Priming of eosinophils in the blood following, for example, allergen challenge is performed mainly by IL-3, IL-5 and GM-CSF. An important step in the extravasation of eosinophils is their adhesion to the vascular endothelium. Adhesion molecules are upregulated by, e.g. IL-1, IL-4, TNF- α and IFN- γ and the same cytokines may also increase the affinity of adhesion molecules both on eosinophils and endothelial cells. Finally, a number of cytokines have been shown to act as eosinophil chemotactic factors, attracting the cells to the inflammatory focus in the tissue. Some of the most important eosinophil chemoattractant cytokines are IL-5, IL-8, RANTES, eotaxin, eotaxin-2, eotaxin-3, MCP-3, MCP-4 and TNF- α. Th2 cells, mast cells and epithelial cells are important sources of proinflammatory cytokines, but in recent years, the eosinophils have also been recognized as cytokine-producing and thereby immunoregulatory cells. The aim of this paper is to review the role of cytokines in the process of eosinophil recruitment in asthma, allergy and ulcerative colitis. [ABSTRACT FROM AUTHOR]

Protein subunit vaccines have been used as prophylactic vaccines for a long time. The well‐established properties of these vaccines make them the first choice for the coronavirus disease 2019 (COVID‐19) outbreak. However, it is not easy to develop a protein vaccine that induces cytotoxic T lymphocyte responses and requires a longer time for manufacturing, which limits the usage of this vaccine type. Here, we report the combination of a recombinant spike (S)‐trimer protein with a DNA vaccine‐encoded S protein as a novel COVID‐19 vaccine. The recombinant S protein was formulated with different adjuvants and mixed with the DNA plasmid before injection. We found that the recombinant S protein formulated with the adjuvant aluminum hydroxide and mixed with the DNA plasmid could enhance antigen‐specific antibody titers, neutralizing antibody titers. We further evaluated the IgG2a/IgG1 isotype and cytokine profiles of the specific boosted T‐cell response, which indicated that the combined vaccine induced a T‐helper 1 cell‐biased immune response. Immunized hamsters were challenged with severe acute respiratory syndrome coronavirus 2, and the body weight of the hamsters that received the recombinant S protein with aluminum hydroxide and/or the DNA plasmid was not reduced. Alternatively, those that received control or only the DNA plasmid immunization were reduced. Interestingly, after the third day of the viral load in the lungs, the viral challenge could not be detected in hamsters immunized with the recombinant S protein in aluminum hydroxide mixed with DNA (tissue culture infectious dose < 10). The viral load in the lungs was 109, 106, and 107 for the phosphate‐buffered saline, protein in aluminum hydroxide, and DNA‐only immunizations, respectively. These results indicated that antiviral mechanisms neutralizing antibodies play important roles. Furthermore, we found that the combination of protein and DNA vaccination could induce relatively strong CD8+ T‐cell responses. In summary, the protein subunit vaccine combined with a DNA vaccine could induce strong CD8+ T‐cell responses to increase antiviral immunity for disease control. [ABSTRACT FROM AUTHOR]

T cell‐mediated antitumor immunity is modulated, in part, by N‐glycosylation. However, the interplay between N‐glycosylation and the loss of effector function in exhausted T cells has not yet been fully investigated. Here, we delineated the impact of N‐glycosylation on the exhaustion of tumor‐infiltrating lymphocytes in a murine colon adenocarcinoma model, focusing on the IFN‐γ‐mediated immune response. We found that exhausted CD8+ T cells downregulated the oligosaccharyltransferase complex, which is indispensable for N‐glycan transfer. Concordant N‐glycosylation deficiency in tumor‐infiltrating lymphocytes leads to loss of antitumor immunity. Complementing the oligosaccharyltransferase complex restored IFN‐γ production and alleviated CD8+ T cell exhaustion, resulting in reduced tumor growth. Thus, aberrant glycosylation induced in the tumor microenvironment incapacitates effector CD8+ T cells. Our findings provide insights into CD8+ T cell exhaustion by incorporating N‐glycosylation to understand the characteristic loss of IFN‐γ, opening new opportunities to amend the glycosylation status in cancer immunotherapies. [ABSTRACT FROM AUTHOR]

The structural elucidation of lipopolysaccharides (LPSs) from Gram‐negative marine bacteria, along with the assessment of their immunological properties, is a fascinating and active research field. Such studies can aid understanding of adaptation phenomena that occur in the marine environment, but they can also open up new perspectives on the design and development of new immunoregulatory drugs. In this paper, we report the structural characterization of the lipid A component of the LPS isolated from the marine bacterium Cobetia pacifica KMM 3879T, which is characterized by a family of structures differing in their acylation patterns. The structural assignment was achieved through extensive chemical analysis and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry. Moreover, cellular immunology studies on the LPS highlighted its low immunostimulatory impact, as well as a very interesting and promising inhibitory activity of the toxic effects of Escherichia coli LPS. [ABSTRACT FROM AUTHOR]

Background Selected cytokines produced by allergen specific CD4+ T cells from atopic individuals contribute to both the specific and non-specific effector mechanisms of the allergic immune response. The chemokine family of cytokines and tumour necrosis factor (TNF)-α are leucocyte regulatory and proinflammatory molecules. The chemokines include interleukin (IL)-8 and the RANTES/SIS cytokines. Objective There bas been no systematic survey of chemokine production in T-cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T-cell clones) these questions might be addressed. Methods Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked immunosorbent assay (ELISA) was used to quantitate soluble product. Results mRNA expression of the chemokines (IL-8. HuMIP-lα and HuMIP-lβ) and TNFα is upregulated in TH2-like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL-8 and TNFα, protein production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4+ /CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL-2, IL-4 and IL-5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison. Conclusion These data show that the induction of the anergic state coincides with post-transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization. [ABSTRACT FROM AUTHOR]

Highlights the papers with implications for allergy and respiratory cellular immunology that are presented during the 7th International Congress of Immunology in Berlin, Germany. Biology of the lower affinity Fc receptor for immunoglobulin E; Interactions between cytokines and endothelial cells; Role of T cell bearing gamm-delta antigen receptors.

This paper reports a case of malignant syphilis (man, 39 years old) in whom ultrastructural investigations of a typical nodule revealed an extremely low amount of bacteria with the characteristics of Treponema pallidum in poorly differentiated cells of the dermal infiltrate with plasma cells, stimulated lymphocytes, and neutrophils as predominating cell types. Most of the microorganisms bore signs of disintegration. Vascular changes and exocytosis were only demonstrable by light microscopy in a second nodule. Together with the high production rate of immunoglobulins and an excessive inflammatory reaction, these findings point to an aberrant biologic reaction pattern of those patients who develop malignant syphilis. Unfortunately, further investigations concerning a possible impairment of cellular immunity as supposed in the literature, had not been possible in the present case. [ABSTRACT FROM AUTHOR]

This paper describes the bacterial expression and purification of bioactive recombinant ovine interleukin-2 (rovIL-2), interleukin-l α (rovIL-1 α) and tumour necrosis factor α. These purified proteins had specific activities in appropriate bioassays of 1 × 107, 1 × 10 and 1 × 105 U/mg, respectively. Recombinant ovIL-1 α was assessed as an immunological adjuvant for the sheep response to the model protein avidin. When delivered either intradermally or intramuscularly in conjunction with avidin in aluminium hydroxide the rovIL-1 α significantly enhanced the secondary humoral response. Doses of 1, 10 or 100 μg per sheep enhanced the humoral response to a similar extent. Recombinant ovIL-1 β had similar adjuvant activity in that it was demonstrated to significantly enhance the sheep humoral response to an experimental H. contortus antigen. This increase in specific antibody, however, did not correlate with enhanced protection against infection with third stage H. contortus larvae. In addition incorporation of rovIL-1 β into the formulation was shown not to alter the isotype profile of H. contortus antigen specific antibody. [ABSTRACT FROM AUTHOR]

Cellular immune responses are important in the recovery from human cytomegalovirus (HCMV) infection. However, little is known about the CD4+ T cell response and the target antigens (Ag) recognized. In this paper, we have analysed the proliferative T cell response of healthy HCMV seropositive (HCMV+) blood donors to recombinant immediate-early proteins expressed in transfected astrocytoma cells and to total HCMV Ags expressed in infected astrocytoma cells. We found that CD4+ T cells were the major cell population that proliferated in the presence of IE or total HCMV Ags. Among healthy HCMV seropositive blood donors with anti-HCMV specific proliferative response, 33-44% also responded to IE Ags. Moreover, in high responders, the precursor frequencies of cells which proliferated in the presence of total HCMV, IE, or IE1 Ags were high (1/103 to 1/255, 1/2785 to 1/7744 and 1/5190 to 1/13531, respectively). In some donors, the anti-IE response was variable over time, whereas the anti-total HCMV Ags response remained constant, which suggests regulation of the anti-IE response in immunocompetent subjects. Our results suggest that the CD4+ anti-IE1 response represents a significant part of the anti-HCMV proliferative response, both at the population level, and within individual immune systems. [ABSTRACT FROM AUTHOR]

Thymocytes from mice with experimental Trypanosoma cruzi infection respond poorly to Con-A stimulation. However, the proliferative capacity of these cells is not impaired, as demonstrated by the fact that at high doses, exogenous rIL-2 restores thymidine uptake. This finding could be explained either by insufficient IL-2 production or by the appearance of inhibitory factors during T. cruzi infection. This paper shows that in response to Con A, IL-2 production is decreased in the model. Furthermore, the whole profile of cytokine production is modified, with a striking increase in IL-10, IFN-γ, IL-4, IL-5 and IL-6 production. The results indicate that IL-10 plus IFN-γ are responsible for the decrease in the Con A-induced proliferation since a normal proliferative response as well as normal IL-2 production can be restored if both cytokines are neutralized by adding their monoclonal antibodies (MoAbs). Evidence is provided also for an enhanced non-specific cytotoxicity of thymic cells from infected mice that might involve IL-4, IL-5 and IL-6. This is the first study demonstrating an alteration of thymic cell function by T. cruzi infection which results from overstimulation of IL-10 and IFN-γ production. [ABSTRACT FROM AUTHOR]

We have previously shown that two distinct mouse placental fractions (PF) are potent immunomodulators in vivo. A 40 kDa PF induces a marked decrease of plaque forming cell (PFC) responses, while a 60 kDa PF increases them. Both effects are specific for the priming antigen. In the present study, these two PF are assayed on a cell-mediated response to allogeneic cells, i.e. in a local graft-versus-host reaction (LGVHR). Mice were primed with allogeneic cells in the presence of various amounts of the 40 kDa or 60 kDa PF, or liver extract (LE) as control. Six days later, their spleen cells were injected into the footpads of F1 recipients. Precise dose-response curves were established and the kinetics of the GVH response were carefully followed. Parallel with the modulation of PFC responses, the 40 kDa PF caused a potent inhibition of the LGVHR, while the 60 kDa PF greatly enhanced it. Both effects were specific for the alloantigens injected with the PF. Furthermore, we showed that these modulations were observed whatever the intensity of the GVH reaction, which varied according to the number of primed spleen cells transferred. This report also demonstrates that these PF can be greatly enriched by package over affinity columns made of insolubilized lectins. The 40 kDa PF is retained on and can be eluted from columns of insolubilized concanavalin A (Con A) or wheat germ agglutinin (WGA), which indicates that it is a glycoprotein. Conversely, the 60 kDa PF does not bind to any of the above lectins and is probably not a glycoprotein. This biochemical purification step is also a good procedure for obtaining an even cleaner separation of the two fractions from each other. Thus, this paper demonstrates that both PF have important regulatory, properties on specific cellular immune responses. [ABSTRACT FROM AUTHOR]

We demonstrated the efficacy of a long- term cultured cytotoxic T-lymphocyte line, CTLL-D4, on tumour growth inhibition using athymic nude mice as recipients. CTLL-D4, specific for a unique surface determinant on a radiation-induced leukaemia RL♂1 of BALB/c origin, was obtained from the limiting dilution culture of MLTC cells performed between spleen cells of a CS6F1-nu/ + mouse immunized in vivo and RL♂1 stimulator cells, and cultured for several months in the absence of added TCGF as described in our preceding paper (Kuribayashi, 1985). The specific inhibition of tumour growth by CTLL-D4 was demonstrated both in Winn-type neutralization assay and in systemic transfer experiments. A subcutaneous inoculation of the mixture of CTLL-D4 and RL♂1 cells resulted in the complete inhibition of tumour growth, even at the effector to tumour cell ratio of 1 : 1, whereas non-cytolytic D4f, which was self-Ia antigen(s)-reactive, composed entirely of Lyt-l + 23- T cells and derived originally from CTLL-D4 but completely lost its cytotoxic activity during culture with the irradiated syngeneic feeder cells alone, had no inhibitory effect at all. In the adoptive transfer studies, the subcutaneously established tumours were rejected by the single i.v. transfer of 2 × 107 CTLL-D4 cells into CB6F1-nu/nu mice. However, D4f was ineffective again in this systemic transfer system. When the effect of CTLL-D4 cells on tumour rejection in vivo was compared to that of non-cultured spleen cells hyperimmunized with RL♂1 cells, the former exhibited more rapid rejection in nude mice after i.v. transfer than the latter did, suggesting that CTLL-D4 cells also attack the tumour cells much more effectively as effectors in vivo. Thus, it is conceivable that CTLs are mainly involved in tumour rejection in this adoptive transfer system using RL♂ 1 tumour cells and athymic nude mice. [ABSTRACT FROM AUTHOR]

Pretreatment of mice by intravenous injection with killed Listeria provided neither delayed-type hypersensitivity to Listeria protoplasm nor protection against Listeria infection. Assuming that this suppression is due to suppressor cells, we attempted to clarify their induction and characterization. Pretreatment with killed BCG instead of killed Listeria suppressed the induction of DTH and protection in subsequent Listeria-immunized mice. Conversely, pretreatment with killed Listeria suppressed subsequent induction of DTH to PPD or protection from tuberculosis. Thus, these suppressions were. induced antigen non- specifically. Transfer of splenic non-adherent cells from killed Listeria-injected mice which had been treated with anti-BAθ serum plus complement, or had been passed through Sephadex G-10 columns, resulted in both afferent and efferent DTH suppression, suggesting that the DTH suppression is closely associated with suppressor T cells. Moreover, the splenic non-adherent cells from killed Listeria-injected mice showed suppression in vitro of listericidal activity of PEC from Listeria-immune mice in the presence of Listeria protoplasm. [ABSTRACT FROM AUTHOR]

This paper describes the effect of altering liposomal membrane composition on humoral and cellular immunogenicity of haptenated liposomes in mice. Antibody formation was determined by enumeration of direct, plaque-forming cells in the spleen and delayed-type hypersensitivity (DH) was measured with a footpad swelling test. Humoral immunogenicity of haptenated liposomes was strongly influenced by membrane phospholipid, cholesterol and charged amphiphile composition. Haptenated liposomes prepared from phospholipids with a low (diolcoyl- and dilauroyl-phosphatidylcho- line) or high (distearoyl phosphatidylcholine) phase- transition temperature were less immunogenic than those prepared from phospholipids with an intermediate phase-transition temperature (dipalmitoyl phosphatidylcholine and sphingomyelin). In general, increasing the amount of liposomal membrane cholesterol induced a higher humoral response. These results are discussed in relation to liposomal membrane fluidity. Induction of an optimal DH with haptenated liposomes did not occur in the absence of the adjuvant dimethyl dioctadecyl ammonium bromide (DDA). When DDA was used, alterations in membrane composition did not influence cellular immunogenicity. From these results it was concluded that ‘intermediate’ liposomal membrane fluidity is the most important requirement for induction of optimal antibody formation with haptenated liposomes and that a certain physicochemical configuration of the antigen, provided by the adjuvant DDA, is a prerequisite for induction of DH. [ABSTRACT FROM AUTHOR]

This paper describes the induction of delayed-type hypersensitivity (DH) in the mouse and guinea-pig to haptenated liposomes. The tripeptide- enlarged hapten 3-(p-azobenzenearsonate)-N-acetyl- L-tyrosylglycylglycine (A) was coupled to phosphatidylethanolamine (PE) and incorporated into liposomal membranes (A PE-liposomes). In mice DH was measured as footpad swelling and in guinea pigs by skin testing. To induce hapten A-specific DH in mice with A-PE- liposomes the application of the cationic, surface- active lipid, dimethyl dioctadecyl ammonium bromide (DDA) was necessary. The use of Freund's complete adjuvant (FCA) did not result in the induction of DH to hapten A. In guinea-pigs, however, FCA and DDA had equally good adjuvant properties in the induction of DH. The time course of the DH and the optimal time interval between immunization and elicitation were determined for the mouse system. Also, the effect of dose and epitope density was studied in that system. Cyclophosphamide treatment, before immunizing mice with A-PE-liposomes and DDA, resulted in greatly impaired DH, probably caused by the short lifetime of the integrity of liposomes after intracutaneous administration to mice. The results make it very likely that presentation of hapten A in a liposomal or micellar structure is required to induce a cellular immune response to this hapten in mice. [ABSTRACT FROM AUTHOR]

This paper describes a technique utilizing rosette formation with sheep red blood cells as a human T lymphocyte marker, and separation of T cells by rosette sedimentation. [ABSTRACT FROM AUTHOR]

The paper describes the use of mitogens for the functional characterization of human lymphocyte subpopulations with special reference to the activation of human B lymphocytes by antibodies to β2microglobulin. [ABSTRACT FROM AUTHOR]

This paper gives a review of the field of virus-lymphocyte interactions and virus receptors on lymphocytes as well as the use of viruses as markers for various lymphocyte populations. [ABSTRACT FROM AUTHOR]

This paper describes the assay system for two different types of lymphocyte complement receptors, the immune adherence receptor (C3b receptor) and the C3d receptor. [ABSTRACT FROM AUTHOR]

This paper describes the generation, detection and characterization of cytotoxic T lymphocyte activity in vitro and the application of this assay system to various immunological problems. [ABSTRACT FROM AUTHOR]

This paper describes lymphocyte binding of aggregated immunoglobulin, which appears to bind to B lymphocytes and the third lymphocyte-like cell population. The applications of aggregated Ig binding are also discussed, and the relation to Fc receptors and Ia-like antigens. [ABSTRACT FROM AUTHOR]

This paper deals with recent developments in the fractionation of immunocornpetent cells with different physical properties, using preparative free flow cell electrophoresis, fractionation of cells according to their size and density. [ABSTRACT FROM AUTHOR]

Immune responsiveness to the streptotoccal group polysaccharides at the clonal level can conveniently be monitored by analytical isoelectric focusing combined witb autoradiography. The parameters investigated in this paper can be summarized as follows: [l] Within the first week after injection antistreptococcal polysaccbaride responses art characterized by IgM antibodies, followed by subclass restriction in Balb/c mice to IgG2a antihodies. [2] The clonal pattern of specific IgG2a antibodies established in the second week after inimunization does not change within the following 6 weeks. [3] Persistence of a specific response pattern established within a primary immunization course holds for Balb/c mice and rabbits for as long as 12 to 13 months. [4] Repeated immunization courses in mice and rabbits maintain established clonal antibody patterns in toto. Temporal variations of clonal expression are generally quantitative rather than qualitative. B-cell memory within this system is therefore stable and long-lived. [ABSTRACT FROM AUTHOR]