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Critical Reviews in Immunology

Pal Boto, Tamas Imre Csuth, Istvan Szatmari
The transcription factor RUNX3 is a prominent regulator of multiple hematopoietic cell lineages. Gene loss of function studies demonstrated the unique and essential roles of this master regulator in differentiated lymphoid and myeloid cells. As a complementary approach, RUNX3 was upregulated in various leukocyte subsets to probe the instructive role of this 'multilineage'-specific transcription factor. In this report, we overview the immunomodulatory functions of RUNX3 within the hematopoietic compartment to gain insight into the consequences of Runx3 deletion or overexpression in committed immune cells...
2018: Critical Reviews in Immunology
Jasper Rip, Esmee K Van Der Ploeg, Rudi W Hendriks, Odilia B J Corneth
Bruton's tyrosine kinase (BTK) is an intracellular signaling molecule first identified as the molecule affected in X-linked agammaglobulinemia (XLA) patients, who almost completely lack peripheral B cells and serum immunoglobulins. BTK is crucial for B cell development and various B cell functions, including cytokine and natural antibody production. Importantly, it is also expressed in numerous other cells, including monocytes, macrophages, granulocytes, dendritic cells, and osteoclasts. A few rare cases of autoimmune disease in XLA patients have been described...
2018: Critical Reviews in Immunology
Luke S Uebelhoer, Christina L Lancioni
During the period of transition from intrauterine to extrauterine life, the neonatal immune system must learn to rapidly identify pathogens while balancing pro-inflammatory, antimicrobial responses with immune regulation that allows for resolution of inflammation and limits responses to commensal organisms and benign environmental antigens. However, the naive immune system of neonates is presented with several barriers that limit robust proinflammatory immune responses. Specifically, epigenetic modifications to neonatal naive CD4+ T cells, heightened neonatal regulatory T cell frequency and function, and limitations in the co-stimulatory potential of neonatal antigen presenting cells restrict development of CD4+ T cells with a T-helper 1 type functional profile...
2018: Critical Reviews in Immunology
Andrew C Lennard
The interleukin-1 receptor antagonist (IL-lra) is unusual in that it is the only known naturally occurring, cytokine receptor antagonist with no apparent agonist function. Over the last 5 years, since the cloning of the IL-lra cDNA sequence, there has been intensive research on the genetics, regulation, and potential therapeutic value of this protein. The later discovery of a second form of IL-lra in 1991 has complicated the picture. Whereas the originally described IL-lra is predominantly glycosylated and secreted (sIL-lra), the alternative isoform is unglycosylated and intracellular (icIL-lra)...
2017: Critical Reviews in Immunology
Denis P Snider
The bacterial enterotoxins, cholera toxin and the heat labile toxin of E. coli, are well known adjuvants for mucosal immune response. Their common A chain mediates the toxigenic mechanism by causing ADP ribosylation of G proteins and subsequent elevation of cAMP in target cells. A large IgA and IgG antibody response to admixed protein antigen (Ag) is the hallmark of these adjuvants and is clearly associated with the A chain activity. Expansion of Ag-specific B and T cells, alteration of T cell cytokine production, and changes in regulatory T cells have been reported as adjuvant mechanisms...
2017: Critical Reviews in Immunology
Elanchezhiyan Manickan, Kevin L Karem, Barry T Rouse
The reports in 1993 that naked DNA encoding viral genes conferred protective immunity came as a surprise to most vaccinologists. This review analyses the expanding number of examples where plasmid DNA induces immune responses. Issues such as the type of immunity induced, mechanisms of immune protection, and how DNA vaccines compare with other approaches are emphasized. Additional issues discussed include the likely means by which DNA vaccines induce CTL, how the potency and type of immunity induced can be modified, and whether DNA vaccines represent a practical means of manipulating unwanted immune response occurring during immunoinflammatory diseases...
2017: Critical Reviews in Immunology
Anette Gjorloff Wingren, Eduardo Parra, Mikael Varga, Terje Kalland, Hans-Olov Sjogren, Gunnar Hedlund, Mikael Dohlsten
Two signals are required for induction of cell proliferation and cytokine production in resting T cells. Occupancy of the T cell receptor by antigen/MHC complexes delivers the first signal to the T cell, while the second signal is provided by interaction with costimulatory ligands on APC. CD2, LFA-1, and CD28 are the major costimulatory and adhesive molecules on T cells and bind to the LFA-3, ICAM-1 and B7 ligands, respectively, on APC. LFA-3 plays a central role for naive and memory T helper cells during the early phase of an immune response...
2017: Critical Reviews in Immunology
Michael J Berridge
Lymphocytes employ a complex assembly of signaling elements that have been organized on a spatiotemporal map to define their role in stimulating both proliferation and apoptosis. The antigen/major histocompatibility complex (MHC) initiates the sequence by organizing the assembly of an active T-cell receptor (TCR) complex responsible for transmitting information down various signaling cassettes (e.g., the IP3/Ca2+, DAG/ PKC, ras/MAPK, and the PI 3-K pathways). It is proposed that CD28 may exert its costimulatory action by facilitating the assembly of an effective scaffold of signaling elements within the TCR complex...
2017: Critical Reviews in Immunology
Vasso Apostolopoulos, Ian F C McKenzie
Mucins are attracting great interest as potential targets for immunotherapy in the development of vaccines for cancers expressing Mucinl (MUC1) (e.g., breast, pancreas, ovary, and others) as there is (1) a 10-fold increase in the amount in adenocarcinomas; (2) an alteration in expression where they become ubiquitous, and (3) due to altered glycosylation, new epitopes appear on the cell surface that are absent in normal tissues. These new epitopes can be carbohydrate; others are peptide in nature. The cloning of the cDNAs from mucins, particularly MUC1, has led to rapid advances being made, and it is clear that a highly immunogenic peptide exists within the variable number of tandem repeats (VNTR) found in all mucins...
2017: Critical Reviews in Immunology
Jon D Laman, Eric Claassen, Randolph J Noelle
Initially, a role for the interaction between CD40, expressed on B cells, and gp39 (CD40L), expressed on activated T cells, has been defined in humoral immunity. CD40-CD40L interaction is an essential signal for B cell proliferation, expression of activation markers, immunoglobulin production, and isotype switching. CD40-CD40L interaction is also required for formation of B memory cells and germinal centers, and signaling through CD40 prevents apoptosis of germinal center B cells. Defective expression of CD40L in humans leads to an inability to produce isotypes other than IgM (hyper IgM syndrome), and to an absence of germinal centers...
2017: Critical Reviews in Immunology
Thierry Calandra, Richard Bucala
Originally described as a T lymphocyte-derived factor that inhibited the random migration of macrophages, the protein known as macrophage migration inhibitory factor (MIF) was an enigmatic cytokine for almost 3 decades. In recent years, the discovery of MIF as a product of the anterior pituitary gland and the cloning and expression of bioactive, recombinant MIF protein have led to the definition of its critical biological role in vivo. MIF has the unique property of being released from macrophages and T lymphocytes that have been stimulated by glucocorticoids...
2017: Critical Reviews in Immunology
Philippe Le Bouteiller
Among the various areas of recent investigation in the field of human MHC class I antigens, the following have been selected for discussion in this review: (1) classical HLA class I genes: are they ubiquitously expressed?, what are the special features of their polymorphism?, are HLA-C molecules functional?, (2) non-classical HLA class I gene products: how restricted is their tissue distribution?, do they exhibit a little polymorphism?, what is their function, if any? (3) non-HLA genes recently detected in the HLA class I chromosomal region: are some of them involved in immunological function and development?, (4) other novel coding sequences present, or possibly present, in the region: the hemochromatosis gene, grc region and associated tumor suppressor genes, housekeeping genes, human equivalent of the murine H-2M region and Ped gene; (5) transcriptional regulation: are there cis-regulatory elements, including locus control region(s)...
2017: Critical Reviews in Immunology
James M Krueger, Jeannine A Majde
Excessive sleepiness and fever are constitutional symptoms associated with systemic infection. Although fevers have been investigated for many years, sleep responses to infectious challenge have only recently been investigated. Inoculation of animals with bacterial, viral, protozoan and fungal organisms result in complex sleep responses dependent upon the microbial agent and route of administration. The general pattern is characterized by an initial robust increase in non-rapid eye movement sleep (NREMS) followed by a period of NREMS inhibition...
2017: Critical Reviews in Immunology
Michael Croft, Caroline Dubey
T cell activation is brought about by recognition of peptide/MHC complexes on an antigen-presenting cell (APC) by the T cell receptor (TCR). However, in general this appears to be insufficient for the full development of T cell responses and therefore additional signals are required, provided by ligation of counter-receptors on the T cell by APC accessory molecules. Although many studies have suggested that B7 molecules (CD80/CD86) binding to CD28 induce this second signal, it is now evident that any one of a number of molecules may provide accessory function and that efficient response is only generated following multiple interactions...
2017: Critical Reviews in Immunology
M H A Bemelmans, L J H van Tits, W A Buurman
Tumor Necrosis Factor (TNF) is a multifunctional cytokine. It plays an important role in the pathophysiology of several diseases. Recently, it has been discovered that TNF is circulating in two different forms, a bioactive form and an immunologically detectable form. These two forms of TNF show different clearance kinetics. The immunological form is supposed to be an inactivated TNF protein. For this inactivation, proteolytic degradation or TNF binding by inactivating proteins is necessary. In this review we have focused on TNF inactivation by TNF binding proteins...
2017: Critical Reviews in Immunology
George B Stefano, Berta Scharrer, Eric M Smith, Thomas K Hughes, Harold I Magazine, Thomas V Bilfinger, Alan R Hartman, Gregory L Fricchione, Yu Liu, Maynard H Makman
The discovery of the ability of the nervous system to communicate through "public" circuits with other systems of the body is attributed to Ernst and Berta Scharrer, who described the neurosecretory process in 1928. Indeed, the immune system has been identified as another important neuroendocrine target tissue. Opioid peptides are involved in this communication (i.e., neuroimmune) and with that of autoimmunoregulation (communication between immunocytes). The significance of opioid neuropeptide involvement with the immune system is ascertained from the presence of novel δ, μ...
2017: Critical Reviews in Immunology
Melissa A Brown, John Hural
IL-4 has been called the "prototypic immunoregulatory cytokine." Like many cytokines, it can affect a variety of target cells in multiple ways. IL-4 has an important role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-cell responses. It is produced only by a subset of activated hematopoietic cells, including T cells and FcεRl+ mast cells and basophils. Based on the different tissue distribution and access to distinct target cells, IL-4 derived from T and FcεRl+ cells may have quite different effects on these immunological processes...
2017: Critical Reviews in Immunology
Makoto Murakami, Yoshihito Nakatani, Gen-Ichi Atsumi, Keizo Inoue, Ichiro Kudo
Phospholipase A2 (PLA2) plays crucial roles in diverse cellular responses, including phospholipid digestion and metabolism, host defense and signal transduction. PLA2 provides precursors for generation of eicosanoids, such as prostaglandins (PGs) and leukotrienes (LTs), when the cleaved fatty acid is arachidonic acid, platelet-activating factor (PAF) when the sn-1 position of the phosphatidylcholine contains an alkyl ether linkage and some bioactive lysophospholipids, such as lysophosphatidic acid (lysoPA)...
2017: Critical Reviews in Immunology
Victor Apanius, Dustin Penn, Patricia R Slev, L Ramelle Ruff, Wayne K Potts
Only natural selection can account for the extreme genetic diversity of genes of the major histocompatibility complex (MHC). Although the structure and function of classic MHC genes is well understood at the molecular and cellular levels, there is controversy about how MHC diversity is selectively maintained. The diversifying selection can be driven by pathogen interactions and inbreeding avoidance mechanisms. Pathogen-driven selection can maintain MHC polymorphism based on heterozygote advantage or frequency-dependent selection due to pathogen evasion of MHC-dependent immune recognition...
2017: Critical Reviews in Immunology
Satoshi Watanabe, Masashi Arita, Miho Takahashi, Yu Saida, Toshiyuki Koya, Toshiaki Kikuchi
The effectiveness of lymphodepletion in antitumor immunity has been well established. Although recent studies have elucidated some of the broad mechanisms underlying the augmentation of antitumor immunity by lymphodepletion, such as increased availability of cytokines due to the elimination of cellular elements and improvement in tumor antigen presentation, the precise mechanisms remain unclear. Previous studies have focused on the enhancement of the functions of transferred antitumor CD8+ T cells after lymphodepletion...
2017: Critical Reviews in Immunology
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