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Sample records for human immunology autoimmunity

  1. Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes

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    Podder Soumita

    2012-01-01

    Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.

  2. Experimental autoimmune orchitis as a model of immunological male infertility.

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    Naito, Munekazu; Terayama, Hayato; Hirai, Shuichi; Qu, Ning; Lustig, Livia; Itoh, Masahiro

    2012-12-01

    Clinically, 60-75% of male infertility cases are categorized as idiopathic spermatogenic disturbance. In previous studies of this condition, lymphocytic infiltration and immune deposits were present in several testis biopsy specimens, indicating that inflammatory or immunological factors contribute to the occurrence of the lesions. However, there is currently little evidence regarding immunological infertility in men. Previously, we established an immunological infertility model, experimental autoimmune orchitis (EAO), that can be induced in mice by two subcutaneous injections of viable syngeneic testicular germ cells without the use of any adjuvant. In this EAO model, lymphocytes surround the tubuli recti and then induce spermatogenic disturbance. In addition, after the active inflammation stage of this model, the seminiferous epithelium is damaged irreversibly, resembling the histopathology of human male idiopathic spermatogenic disturbance. In the majority of patients with testicular autoimmunity, there is a chronic and asymptomatic development of the inflammatory reaction. Therefore, this disease is very difficult to diagnose at the ongoing stage, and it is possible that the histopathology of idiopathic spermatogenic disturbance in the clinic is reported at the post-active inflammation stage of autoimmune orchitis. In this review, the histopathology of EAO before and after inflammation is discussed, comparing it with human orchitis.

  3. Autoimmune diseases and fungal infections: immunological mechanisms and therapeutic approaches

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    ZHANG Jian-zhong

    2009-01-01

    @@ Autoimmune disease represents a breakdown of natural tolerance to autoreactive antigens.Pemphigus and lupus erythematosus are common autoimmune diseases either skin-specific or with predominant skin involvement. During the past decades,much progress has been made in understanding the mechanism of autoimmune diseases and the immunological mechanism in some infectious diseases such as fungal infections. Various novel approaches have been developed in the treatment of these diseases.

  4. Clinical immunology - Autoimmunity in the Netherlands

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    Tervaert, Jan Willem Cohen; Kallenberg, Cees G. M.

    2014-01-01

    Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking ca

  5. Clinical immunology - Autoimmunity in the Netherlands

    NARCIS (Netherlands)

    Tervaert, Jan Willem Cohen; Kallenberg, Cees G. M.

    2014-01-01

    Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking

  6. Autoimmune disease: Conceptual history and contributions of ocular immunology.

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    Margo, Curtis E; Harman, Lynn E

    2016-01-01

    Medical historians identify the mid-20th century as the time when the scientific and medical communities acknowledged the existence of autoimmune disease. Several conditions including sympathetic ophthalmia and endophthalmitis phacoanaphylactica, however, were proposed as autoimmune disorders much earlier. During the first half of the century, autoimmune disease was viewed as biologically implausible. Paul Ehrlich coined the term horror autotoxicus to emphasize that autoimmunity would contradict nature's aversion to self-injury. The discoveries of allergy and anaphylaxis were the first clues that the immune system was capable of self-harm. A major obstacle to comprehending the pathogenesis of autoimmunity was how the immune system distinguishes foreign from self, a process eventually understood in the context of immune tolerance. Investigators of sympathetic ophthalmia and endophthalmitis phacoanaphylactica were positioned to invalidate horror autotoxicus but lacked sufficiently convincing experimental and clinical evidence to accomplish the task. Seminal studies of chronic thyroiditis and a series of clinical laboratory breakthroughs led to the general acceptance of autoimmune disease in the 1950s. The travails encountered by ophthalmic investigators offer insights into the how medical ideas take shape. We review the contributions of ocular immunology to the conceptual development of autoimmune disease and explore the reasons why the concept caught on slowly.

  7. [Nozological Heterogeneity, Molecular Genetics and Immunology of Autoimmune Diabetes Mellitus].

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    Dedov, I I; Shestakova, M V; Kuraeva, T L; Titovich, E V; Nikonova, T V

    2015-01-01

    Article is devoted to the review of literature data, and also the analysis of results of own researches concerning genetics, molecular genetics and immunological violations at various forms of the autoimmune diabetes (DM) including classical T1DM, LADA type and an autoimmune polyglandular syndrome of 1 type (APS1). In case of T1DM more than 80% of patients are carriers of one or two strongest predisposing haplotypes: DRB1*04-DQA1*0301-DQB1*0302 and DRB1*03-DQA1*0501-DQB1*0201 designated as DQ2 and DQ8. HLA genes can model a clinical features of disease. In Russian population, the children with diabetes manifestation up to 5-year age has significantly often high risk genotypes (DQ2/ DQ8) and significantly less the low risk genotypes in comparison with children, who had manifestation of T1DMin 10 years and later. The long-term 16-yearsfamily studies showed the maximum frequency of TJDMin high risk group, constantly accruing in process of increase in term of supervision, and in groups of an average and low risk lower and invariable. The highest risk of T1DM manifestation, reaching 90% at 10 years of supervision is defined by existence of HLA high risk genotypes and many antibodies, revealedfrom early age. LADA - the hybridform of autoimmune DM having signs of T1DM and T2DM in the basis. The development of autoimmune process against β-cells can be caused by only gene mutation (APS1). The part of T1DM cases which doesn't have the contributing HLA genes and autoimmune markers in process of studying of the importance of various genes and their biological value can be attributed to new, yet unknown forms of DM.

  8. [Immunological Techniques that Support the Diagnosis of the Autoimmune Diseases].

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    Hernández Ramírez, Diego F; Cabiedes, Javier

    2010-01-01

    During the past few years technological advance have been allowed the developing of techniques that help to the diagnosis of multiple diseases. In the case of the autoimmune diseases, immunological techniques are helpful since they allow the detection of multiple autoantibodies at the same time with small volumes of sample. Together with the development of the new techniques, sensitivity and specificity in the detection of the antibodies specificities' also have been increased, in such a way that the clinicians can count with tests that allow them to make early diagnoses with greater certainty and also to follow the course of the disease based on the variation of the antibodies presents in the patient's samples. It is important to emphasize that the new techniques of laboratory that are used for the support of the diagnosis of autoimmune diseases, no longer are exclusive for research laboratories but by their facility of standardization, quality control and reproducibility they can be used in clinical laboratory of medium and small sizes. In the present paper we describe those techniques with greater application in the clinical laboratory of autoimmune diseases.

  9. Immunology & Human Health.

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    Dawson, Jeffrey R.; And Others

    This monograph was designed for the high school biology curriculum. The first section reviews the major areas of importance in immunology. Section three contains six instructional activities for the high school classroom and the second section contains teacher's materials for those activities. The activities address for students some of the major…

  10. Autoimmune Hepatitis as a Unique Form of an Autoimmune Liver Disease: Immunological Aspects and Clinical Overview

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    Hind I. Fallatah

    2012-01-01

    Full Text Available Autoimmune hepatitis (AIH is a unique form of immune-mediated disease that attacks the liver through a variety of immune mechanisms. The outcomes of AIH are either acute liver disease, which can be fatal, or, more commonly, chronic progressive liver disease, which can lead to decompensated liver cirrhosis if left untreated. AIH has characteristic immunological, and pathological, features that are important for the establishment of the diagnosis. More importantly, most patients with AIH have a favorable response to treatment with prednisolone and azathioprine, although some patients with refractory AIH or more aggressive disease require more potent immune-suppressant agents, such as cyclosporine or Mycophenolate Mofetil. In this paper, we discuss the immunological, pathological and clinical features of AIH, as well as the standard and alternative treatments for AIH.

  11. Immunological GABAergic interactions and therapeutic applications in autoimmune diseases.

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    Prud'homme, Gérald J; Glinka, Yelena; Wang, Qinghua

    2015-11-01

    medicine, and include benzodiazepines, barbiturates, anticonvulsants, and anesthetic drugs such as propofol. Native GABA can be administered orally to humans as a drug, and has few adverse effects. However, the immune effects of GABAergic drugs in patients are not well documented. GABAergic immunobiology is a recent area of research, which shows potential for the development of new therapies for autoimmune diseases.

  12. [Aspects of molecular immunology and immunogenetics in autoimmune uveitis].

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    Istrate, Bogdan

    2012-01-01

    Generally speaking, the uveitis comprises a relative complex group of autoimmune diseases or other autoimmune associated illness. Until now, a little from molecular and cellular mechanisms are known in the autoimmunity of uveitis. The uveitis may cause a visual handicap as well, leading even to blindness. This paper tries to bring into focus some of the molecular mechanisms and immunogenetic features of the disease.

  13. Autoimmune pancreatocholangitis, non-autoimmune pancreatitis and primary sclerosing cholangitis: a comparative morphological and immunological analysis.

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    Irene Esposito

    Full Text Available BACKGROUND: Autoimmune pancreatocholangitis (AIPC is an emerging, not completely characterized disease. Aim of this study was the comprehensive evaluation of a series of AIPC patients, who were diagnosed and treated in a European institution between January 2003 and July 2006. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-three patients with histologically confirmed AIPC were analyzed and compared to 20 patients with non-autoimmune chronic pancreatitis (CP and 14 patients with primary sclerosing cholangitis (PSC. Clinical features and conventional histopathology were taken into account. Immunohistochemistry and real-time quantitative PCR were used for the characterization of the inflammatory infiltrate and the stromal reaction. AIPC was localized in the pancreatic head in 94% of the patients. Intra- and/or extrapancreatic biliary tract involvement was present in 64% of the cases. The number of infiltrating T-lymphocytes, macrophages and total plasma cells was significantly higher in AIPC than in CP (3-, 4- and 8-fold increase, respectively. The absolute number of IgG4-positive plasma cells was higher in AIPC than in CP and PSC (7-fold and 35-fold increase, respectively, but significance was only reached in comparison with PSC. CXCR5- and CXCL13-positive cells were almost exclusively detected in AIPC. CONCLUSIONS/SIGNIFICANCE: AIPC is mainly a disease of the pancreatic head with possible extension into the periphery of the gland and/or into the biliary tract/gallbladder. The morphology of AIPC, as well as the immune- and stromal reaction is characteristic and comparable between cases with and without biliary tract involvement. Immunological markers (IgG4, CXCR5, CXCL13 can be of diagnostic relevance in specific settings.

  14. Human Cytomegalovirus and Autoimmune Disease

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    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  15. Humanized in vivo Model for Autoimmune Diabetes

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    2009-02-01

    AWARD NUMBER: W81XWH-07-1-0121 TITLE: Humanized in vivo Model for Autoimmune Diabetes PRINCIPAL INVESTIGATOR: Gerald T Nepom, M.D., Ph.D...4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Humanized in vivo Model for Autoimmune Diabetes Sb. GRANT NUMBER W81XWH-07-1-0121 Sc. PROGRAM ELEMENT...therapies. This research study entails using humanized mice manifesting type 1 diabetes (T1 D)-associated human HLA molecules to address the fate and

  16. Genetic and immunologic aspects of autoimmune poliendocrine syndrome type I: review

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    Alice Rachel Bandeira de Araújo

    2016-10-01

    Full Text Available The autoimmune polyendocrinopathy syndrome type 1 (APS-1, also known as candidiasis ectodermal-autoimmune polyendocrinopathy-dystrophy (APECED, it is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE. Therefore, it is immunologically characterized by cell attack and / or antibodymediated generating the destruction of target organs. Furthermore, it is characterized by the pathognomonic triad chronic candidiasis, hypoparathyroidism and Addison's disease with many other endocrine and non-endocrine events. Soon, the diagnosis is made based on the presence of two of the three classic features and treatment aims to control the numerous deficiencies that patients may present. This literature review was aimed at understanding the involvement of AIRE gene in relation to immunological aspects present and, consequently, clinical manifestations of this disease. Thus, evidence of the need to broaden the discussion about this disease, in order to improve the quality of life of patients by early diagnosis and treatment and are in accordance with the clinical manifestations of each patient. Thereby, qualitative research involved scientific articles from electronic journals LILACS (Latin American and Caribbean, SCIELO (Scientific Electronic Library Online and NCBI (National Center for Biotechnology Information, between the years 2009 and 2016. Pursuant to, there is the relevance of this review, it is noted that, although the authors converge on views on this syndrome, there are still many unclear matters with regard to the mechanisms of the disease. This highlights the need to promote more discussion on this topic.

  17. Synthetic immunology: modulating the human immune system.

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    Geering, Barbara; Fussenegger, Martin

    2015-02-01

    Humans have manipulated the immune system to dampen or boost the immune response for thousands of years. As our understanding of fundamental immunology and biotechnological methodology accumulates, we can capitalize on this combined knowledge to engineer biological devices with the aim of rationally manipulating the immune response. We address therapeutic approaches based on the principles of synthetic immunology that either ameliorate disorders of the immune system by interfering with the immune response, or improve diverse pathogenic conditions by exploiting immune cell effector functions. We specifically highlight synthetic proteins investigated in preclinical and clinical trials, summarize studies that have used engineered immune cells, and finish with a discussion of possible future therapeutic concepts.

  18. Immunological effects of ayahuasca in humans.

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    dos Santos, Rafael Guimarães

    2014-01-01

    Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

  19. Perspectives on autoimmunity

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    Cohen, I.R.

    1987-01-01

    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  20. Natural killer cells in human autoimmune disorders

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    2013-01-01

    Natural killer (NK) cells are innate lymphocytes that play a critical role in early host defense against viruses. Through their cytolytic capacity and generation of cytokines and chemokines, NK cells modulate the activity of other components of the innate and adaptive immune systems and have been implicated in the initiation or maintenance of autoimmune responses. This review focuses on recent research elucidating a potential immunoregulatory role for NK cells in T-cell and B-cell-mediated autoimmune disorders in humans, with a particular focus on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A better understanding of the contributions of NK cells to the development of autoimmunity may lead to novel therapeutic targets in these diseases. PMID:23856014

  1. Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

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    Jordana Grazziela Alves Coelho-dos-Reis

    Full Text Available In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+HLA-DR(+, CD8(+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

  2. Melanocyte antigen triggers autoimmunity in human psoriasis.

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    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus; Prinz, Jörg C

    2015-12-14

    Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02-restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes HLA-C*06:02-positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway.

  3. IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    5.1 Autoimmune disease2003029 A linkage study of cytotoxic T lymphocyte-associated antigen 4 gene and Graves’ disease in northern Chinese Han ethnic. JIN Ying ( 金迎 ), et al. Dept Endocrinol, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Intern Med 2002; 41 (12): 809-812. Objective: To determine if the cytotoxic T lympho-

  4. IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    3.1 Autoimmune disease2004022 BL-2, IL-6 and their receptors in patients with systemic lupus erythematosus. QIAN Qihong (钱齐宏), et al. Dept Dermatol & Venereol, 1st Affili Hosp, Suzhou Univ, Suzhou 215006. Chin J Dermatol 2003; 36 (12): 696-698.

  5. IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    5.1 Autoimmune disease2004189 Serum levels of matrix metallopro-teinases-9 in patients with systemic lupus erythemato-sus. YIN Wenhao (殷文浩), et al. Dept Dermatol 2nd Affili Hosp, Med Sch Zhejiang Univ, Hangzhou 310009. Chin J Dermatol 2004;37(2):77-79.Objective: To determine the serum levels of matrix

  6. Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

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    Vatanen, Tommi; Kostic, Aleksandar D.; d’Hennezel, Eva; Siljander, Heli; Franzosa, Eric A.; Yassour, Moran; Kolde, Raivo; Vlamakis, Hera; Arthur, Timothy D.; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Uibo, Raivo; Mokurov, Sergei; Dorshakova, Natalya; Ilonen, Jorma; Virtanen, Suvi M.; Szabo, Susanne J.; Porter, Jeffrey A.; Lähdesmäki, Harri; Huttenhower, Curtis; Gevers, Dirk; Cullen, Thomas W.; Knip, Mikael; Xavier, Ramnik J.

    2016-01-01

    Summary According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore their Lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education. PMID:27133167

  7. IMMUNOLOGICAL AND METABOLIC FACTORS INTERACTION IN THE DEVELOPMENT AND PROGRESSION OF MICROVASCULAR COMPLICATIONS IN LATENT AUTOIMMUNE DIABETES OF ADULTS (LADA

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    T. V. Saprina

    2014-01-01

    Full Text Available Some researchers found that the development of microvascular complications (nephropathy, retinopathy with latent autoimmune diabetes adults (LADA occurs much earlier than in type 1 diabetes mellitus. The research devoted to the study of the spectrum and the time of development of microangiopathy in patients with latent autoimmune diabetes of adults, compared to patients with type 1 and 2 diabetes mellitus. Also studied immunological factors (cytokine secretion of mononuclear leukocytes as one of the possible mechanisms of diabetic angiopathy progression. It has been shown that in LADA, as in patients with type 2 diabetes mellitus, the development of microvascular complications (nephropathy, retinopathy occurs much earlier than in type 1 diabetes mellitus (after a 4-year course of the disease due to a sharp decline in the serum concentration of C peptide. Thus in patients with LADA, having microvascular complications in the supernatants of cell cultures of mononuclear leukocytes determined a significant increase in the concentrations of cytokines IL-2, IL-4, TNFα.

  8. The human microbiome in rheumatic autoimmune diseases: A comprehensive review.

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    Coit, Patrick; Sawalha, Amr H

    2016-09-01

    The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression.

  9. [Immunology in medical practice. XIV. Central nervous system complications in systemic autoimmune diseases].

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    Markusse, H M; van den Bent, M J; Vecht, C J

    1998-03-07

    Complications of the central nervous system (CNS) are common in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. Specific diagnostic tests are lacking and early intervention with immunosuppressive therapy is frequently necessary. Therefore knowledge of these CNS complications is essential for early diagnosis and treatment. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.

  10. Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

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    Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

    2016-06-01

    Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers

  11. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

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    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  12. The immunology of human and animal cysticercosis: a review

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    Flisser, A.; Pérez-Montfort, R.; Larralde, C.

    1979-01-01

    In this review of the literature concerning the immunology of animal and human cysticercosis, emphasis is placed on whether previous exposure to the antigen confers protection to the host. Statistical analysis of the published data indicates that immunized animals have a lower risk than non-immunized animals of contracting cysticercosis, there being large variations within and between different host—cysticercus relationships. There is no indication as to which antigen is best for immunization but, although live parasites in all stages of development, or extracts, appear to give protection, embryos, eggs, and excretions are most frequently used. Antibodies appear to be the principal mediators of resistance, but the action seems to be only upon very young larvae, while fully grown cysticerci are unharmed. Several immunological methods are valuable in the diagnosis of cysticercosis, the choice depending more on the purpose of the study than on differences in their ability to discriminate between healthy and sick. The presence of anticysticercus antibodies in the serum of up to 50% of human patients indicates that human vaccination may be possible in high-risk areas; the remaining patients pose an interesting problem open to speculation and research on immunological evasion, immunodepression, and the existence of serotypes. ImagesFig. 3Fig. 4Fig. 4(Contd.) PMID:396058

  13. Relationship between Clinical and Immunological Features of Thyroid Autoimmunity and Ophthalmopathy during Pregnancy

    Directory of Open Access Journals (Sweden)

    Jack R. Wall

    2015-01-01

    Full Text Available Problem. Clinical features of Graves’ hyperthyroidism (GH generally improve during pregnancy and rebound in the postpartum period. It is unclear whether the ophthalmopathy that is associated with GH and, less often, Hashimoto’s thyroiditis (HT changes in parallel with the thyroid associated antibody reactions and clinical features or runs a different course. Method of Study. We retrospectively studied 19 patients with autoimmune thyroid disease over 22 pregnancies: 9 pregnancies with GH and 13 with HT. Ophthalmopathy was defined by NOSPECS class. Results. Thyroid peroxidase (TPO and thyroglobulin (Tg antibody titres decreased during pregnancy and rose in the postpartum period. During pregnancy, 5 patients with GH and 4 patients with HT developed mild ophthalmopathy and two patients with GH and HT developed new upper eyelid retraction (UER. In the postpartum period, eye scores improved in 3 patients with GH and 3 with HT, remained stable in two and 5 patients, respectively, and worsened in 2 patients with GH and one with HT. Conclusions. In patients with mild to moderate eye signs associated with GH and HT, the orbital and thyroid reactions ran different courses during pregnancy. Since no patient had severe ophthalmopathy, we cannot draw definitive conclusions from this preliminary study.

  14. Immunology of Taenia solium taeniasis and human cysticercosis.

    Science.gov (United States)

    Garcia, H H; Rodriguez, S; Friedland, J S

    2014-08-01

    The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by faecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data are limited by the relative lack of animal models. This manuscript revises the available information on the immunology of human taeniasis and cysticercosis.

  15. CRALBP is a Highly Prevalent Autoantigen for Human Autoimmune Uveitis

    Directory of Open Access Journals (Sweden)

    Cornelia A. Deeg

    2007-01-01

    uveitis patient's sera was first evaluated in two-dimensional (2D Western blot analysis. Subsequent identification of the immunoreactive proteins by mass spectrometry resulted in the identification of CRALBP as a putative autoantigen. Additionally, sera from human uveitis and control patients were by Western blot using purified human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently (P<.01 in human uveitis patients than in normal controls. Thirty out of 56 tested uveitis patient's sera contained autoantibodies reactive against CRALBP, compared to only four out of 23 normal control subjects. The presence of CRALBP autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible autoantigen in human autoimmune uveitis.

  16. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte...

  17. Immunologic endocrine disorders.

    Science.gov (United States)

    Michels, Aaron W; Eisenbarth, George S

    2010-02-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA-like molecules determining tissue-specific targeting that, with the loss of tolerance, leads to organ-specific autoimmunity. Disorders such as type 1A diabetes, Graves disease, Hashimoto thyroiditis, Addison disease, and many others result from autoimmune-mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in patients with type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. Although therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  18. Update on immunologic and molecular diagnosis of human strongyloidiasis.

    Science.gov (United States)

    Levenhagen, Marcelo A; Costa-Cruz, Julia M

    2014-07-01

    Human strongyloidiasis is an intestinal parasitosis that may affect 100 million individuals. However, the prevalence rates of this infection may represent smaller values than the actual data, mainly due to difficulties in its diagnosis. The aim of this study was to update the immunological and molecular methods applied to the diagnosis of human strongyloidiasis. There is a great diversity of techniques used in the diagnosis of this parasitosis, such as immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), immunoblotting, luciferase immunoprecipitation system (LIPS), dispstick and polymerase chain reaction (PCR), all with advantages and disadvantages, and with unique features for specific purposes. Considering the magnitude of strongyloidiasis and the importance of early diagnosis, due to the possibility of chronicity and hyperinfection, this study analyzes the different methods currently employed, and demonstrates the necessity of developing innovative methodologies, which also maintain diagnostic accuracy, particularly for regions with limited technological resources.

  19. Immunological reaction of the demyelinating Semliki Forest virus with immune serum to glycolipids and its possible importance to central nervous system viral auto-immune disease.

    Science.gov (United States)

    Webb, H E; Mehta, S; Gregson, N A; Leibowitz, S

    1984-01-01

    The avirulent demyelinating strain A7(74) of Semliki Forest virus after passage through mouse brain in vivo and mouse brain cell cultures has been shown to react immunologically with immune sera against galactocerebroside, glucocerebroside, total ganglioside and GT1b ganglioside but not against myelin or sulphatide . Semliki Forest virus is known to take host membrane glycolipid into its coat. The importance of the findings is discussed in relation to the production of a possible anti-brain cell auto-immune phenomenon and its implication in a disease such as multiple sclerosis.

  20. Transient Expression of Transgenic IL-12 in Mouse Liver Triggers Unremitting Inflammation Mimicking Human Autoimmune Hepatitis.

    Science.gov (United States)

    Gil-Farina, Irene; Di Scala, Marianna; Salido, Eduardo; López-Franco, Esperanza; Rodríguez-García, Estefania; Blasi, Mercedes; Merino, Juana; Aldabe, Rafael; Prieto, Jesús; Gonzalez-Aseguinolaza, Gloria

    2016-09-15

    The etiopathogenesis of autoimmune hepatitis (AIH) remains poorly understood. In this study, we sought to develop an animal model of human AIH to gain insight into the immunological mechanisms driving this condition. C57BL/6 mice were i.v. injected with adeno-associated viral vectors encoding murine IL-12 or luciferase under the control of a liver-specific promoter. Organ histology, response to immunosuppressive therapy, and biochemical and immunological parameters, including Ag-specific humoral and cellular response, were analyzed. Mechanistic studies were carried out using genetically modified mice and depletion of lymphocyte subpopulations. Adeno-associated virus IL-12-treated mice developed histological, biochemical, and immunological changes resembling type 1 AIH, including marked and persistent liver mononuclear cell infiltration, hepatic fibrosis, hypergammaglobulinemia, anti-nuclear and anti-smooth muscle actin Abs, and disease remission with immunosuppressive drugs. Interestingly, transgenic IL-12 was short-lived, but endogenous IL-12 expression was induced, and both IL-12 and IFN-γ remained elevated during the entire study period. IFN-γ was identified as an essential mediator of liver damage, and CD4 and CD8 T cells but not NK, NKT, or B cells were essential executors of hepatic injury. Furthermore, both MHC class I and MHC class II expression was upregulated at the hepatocellular membrane, and induction of autoreactive liver-specific T cells was detected. Remarkably, although immunoregulatory mechanisms were activated, they only partially mitigated liver damage. Thus, low and transient expression of transgenic IL-12 in hepatocytes causes loss of tolerance to hepatocellular Ags, leading to chronic hepatitis resembling human AIH type 1. This model provides a practical tool to explore AIH pathogenesis and novel therapies.

  1. Autoimmune hepatitis in patients with human immunodeficiency virus (HIV)

    Science.gov (United States)

    Kia, Leila; Beattie, Adam; Green, Richard M.

    2017-01-01

    Abstract Rationale: Chronic liver disease is a major cause of morbidity and mortality in patients with HIV. However, autoimmune hepatitis (AIH) in patients with HIV has rarely been reported. Our aim was to evaluate a cohort of patients with HIV and AIH and identify clinical presentations and outcomes. Patient Concerns: Management of autoimmune hepatitis in context of human immunodeficiency virus, long-term outcomes, and safety in setting of underlying immunocompromised state. Diagnoses: Autoimmune Hepatitis, Human Immunodeficiency Virus, Hepatotoxicity, Liver Injury, Liver Transplantation. Interventions: We retrospectively reviewed the charts of patients with HIV and AIH based on histological, serologic, biochemical demographic, and clinical data. Outcomes: Five patients were identified with autoimmune hepatitis; 4 of 5 were women, and all were African or African-American. The age at the time of AIH diagnosis was 46.6 ± 13.4 years. All patients acquired HIV sexually and all had CD4 counts >250 cells/uL (456–1011 cells/uL) and undetectable HIV viral loads at the time of AIH diagnosis. One patient presented with acute liver failure necessitating liver transplantation and developed AIH posttransplantation. At the time of diagnosis, the AST were 350 ± 448 U/L, ALT 247 ± 190 U/L, bilirubin 7 ± 12 mg/dL, and alkaline phosphatase 126 ± 53 U/L. All patients had histologic evidence of AIH on liver biopsies. Patients were successfully treated with prednisone and azathioprine, without a decrease in CD4 <250 cells/uL, infectious complications or significant side effects. Lessons: AIH occurs in patients with well-controlled HIV. In our patient cohort, immunosuppressive therapy with prednisone and azathioprine was safe and effective in inducing remission, without significant complications or development of opportunistic infections. PMID:28207511

  2. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.

    Science.gov (United States)

    Alvaro-Benito, Miguel; Morrison, Eliot; Wieczorek, Marek; Sticht, Jana; Freund, Christian

    2016-08-01

    Classical MHC class II (MHCII) proteins present peptides for CD4(+) T-cell surveillance and are by far the most prominent risk factor for a number of autoimmune disorders. To date, many studies have shown that this link between particular MHCII alleles and disease depends on the MHCII's particular ability to bind and present certain peptides in specific physiological contexts. However, less attention has been paid to the non-classical MHCII molecule human leucocyte antigen-DM, which catalyses peptide exchange on classical MHCII proteins acting as a peptide editor. DM function impacts the presentation of both antigenic peptides in the periphery and key self-peptides during T-cell development in the thymus. In this way, DM activity directly influences the response to pathogens, as well as mechanisms of self-tolerance acquisition. While decreased DM editing of particular MHCII proteins has been proposed to be related to autoimmune disorders, no experimental evidence for different DM catalytic properties had been reported until recently. Biochemical and structural investigations, together with new animal models of loss of DM activity, have provided an attractive foundation for identifying different catalytic efficiencies for DM allotypes. Here, we revisit the current knowledge of DM function and discuss how DM function may impart autoimmunity at the organism level.

  3. Evaluation of a Rat Model of Experimental Autoimmune Encephalomyelitis with Human MBP as Antigen

    Institute of Scientific and Technical Information of China (English)

    Lin Guo; Yuehua Li; Hongyi Lin; Xiaohui Ji; Jing Li; Lingli Que; Yingdong Zhang; Yushan Rong; Jianwen Wang

    2004-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a good model for human multiple sclerosis (MS)research. However, there are some defects in the traditional models. Here, we improved the model by using the human myelin basic protein (MBP) as antigen. EAE was induced by immunization of female Wistar rats with human MBP. Compared with the traditional models, the new model was evaluated by clinical signs to pathological changes. The immune state of the model was assessed by the lymphocyte infiltrative response and levels of TNF-α,IFN-γ, IL-10. It was found that most of rats exhibited tail tone loss and hind-limb paralysis,also there were demyelination, infiltrative lymphocyte foci, "Neuronophagia" in the cortex of cerebra and the white matter of spinal cords. PBMC and spleen lymphocytes were strongly response to the stimulation of MBP and PHA. The levels of TNF-α,IFN-γ were altered with the severity of EAE. In the remitting phase, IL-10 was increased significantly. This study demonstrate that the animal model of EAE induced by human MBP bears resemblance to the features of human multiple sclerosis and promises to be a better model than ever before for the study of MS. Cellular & Molecular Immunology. 2004;1(5):387-391.

  4. Evaluation of a Rat Model of Experimental Autoimmune Encephalomyelitis with Human MBP as Antigen

    Institute of Scientific and Technical Information of China (English)

    LinGuo; YuehuaLi; HongyiLin; XiaohuiJi; JingLi; LingliQue; YingdongZhang; YushanRong; JianwenWang

    2004-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a good model for human multiple sclerosis (MS)research. However, there are some defects in the traditional models. Here, we improved the model by using the human myelin basic protein (MBP) as antigen. EAE was induced by immunization of female Wistar rats with human MBP. Compared with the traditional models, the new model was evaluated by clinical signs topathological changes. The immune state of the model was assessed by the lymphocyte infiltrative response and levels of TNF-α, IFN-γ, IL-10. It was found that most of rats exhibited tail tone loss and hind-limb paralysis,also there were demyelination, infiltrative lymphocyte foci, “Neuronophagia” in the cortex of cerebra and the white matter of spinal cords. PBMC and spleen lymphocytes were strongly response to the stimulation of MBP and PHA. The levels of TNF-α, IFN-γ were altered with the severity of EAE. In the remitting phase, IL-10 wasincreased significantly. This study demonstrate that the animal model of EAE induced by human MBP bears resemblance to the features of human multiple sclerosis and promises to be a better model than ever before for the study of MS. Cellular & Molecular Immunology. 2004;1(5):387-391.

  5. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  6. Vaccines for the future: learning from human immunology

    Science.gov (United States)

    De Gregorio, Ennio; Rappuoli, Rino

    2012-01-01

    Summary Conventional vaccines have been extremely successful in preventing infections by pathogens expressing relatively conserved antigens through antibody‐mediated effector mechanisms. Thanks to vaccination some diseases have been eradicated and mortality due to infectious diseases has been significantly reduced. However, there are still many infections that are not preventable with vaccination, which represent a major cause of mortality worldwide. Some of these infections are caused by pathogens with a high degree of antigen variability that cannot be controlled only by antibodies, but require a mix of humoral and cellular immune responses. Novel technologies for antigen discovery, expression and formulation allow now for the development of vaccines that can better cope with pathogen diversity and trigger multifunctional immune responses. In addition, the application of new genomic assays and systems biology approaches in human immunology can help to better identify vaccine correlates of protection. The availability of novel vaccine technologies, together with the knowledge of the distinct human immune responses that are required to prevent different types of infection, should help to rationally design effective vaccines where conventional approaches have failed. PMID:21880117

  7. Adeno-associated virus-mediated human IL-10 gene transfer suppresses the development of experimental autoimmune orchitis.

    Science.gov (United States)

    Watanabe, M; Kashiwakura, Y; Kusumi, N; Tamayose, K; Nasu, Y; Nagai, A; Shimada, T; Daida, H; Kumon, H

    2005-07-01

    Testicular germ cell-induced autoimmune orchitis is characterized by inflammatory cell infiltration followed by disturbance of spermatogenesis. Experimental autoimmune orchitis (EAO) is an animal model for human immunological male infertility; delayed-type hypersensitivity (DTH) response plays a key role in its induction. Interleukin-10 (IL-10) is a regulatory cytokine that is critical in preventing organ-specific autoimmune inflammation. To determine the effects on EAO of human IL-10 (hIL-10) gene transfer, C3H/He mice immunized by unilateral testicular injury were administered intramuscular (i.m.) injections of adeno-associated viral (AAV) vector-encoding hIL-10 on the day of immunization. Serum hIL-10 was detected beginning at 1 week postinjection, and peaked at 3 weeks. Histological examinations showed a significantly low incidence of orchitis and disturbance of spermatogenesis in AAV hIL-10-treated mice, and the DTH response to autologous testicular cells was significantly suppressed. Immunohistochemical analysis of IFN- and IL-2, T-cell-associated cytokines, in the spleen and testes revealed significantly fewer cytokine-expressing cells after treatment. We conclude that a single i.m. administration of AAV hIL-10 significantly suppresses EAO and hypospermatogenesis by regulating cell-mediated immunity in the testes.

  8. Vaccines and autoimmunity.

    Science.gov (United States)

    De Martino, M; Chiappini, E; Galli, L

    2013-01-01

    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  9. Program in Functional Genomics of Autoimmunity and Immunology of yhe University of Kentucky and the University of Alabama

    Energy Technology Data Exchange (ETDEWEB)

    Alan M Kaplan

    2012-10-12

    This grant will be used to augment the equipment infrastructure and core support at the University of Kentucky and the University of Alabama particularly in the areas of genomics/informatics, molecular analysis and cell separation. In addition, we will promote collaborative research interactions through scientific workshops and exchange of scientists, as well as joint exploration of the role of immune receptors as targets in autoimmunity and host defense, innate and adaptive immune responses, and mucosal immunity in host defense.

  10. Current humanized mouse models for studying human immunology and HIV-1 immuno-pathogenesis

    Institute of Scientific and Technical Information of China (English)

    MEISSNER; Eric

    2010-01-01

    A robust animal model for "hypothesis-testing/mechanistic" research in human immunology and immuno-pathology should meet the following criteria.First,it has well-studied hemato-lymphoid organs and target cells similar to those of humans.Second,the human pathogens establish infection and lead to relevant diseases.Third,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological means.Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle.The mouse with a reconstituted human immune system and other human target organs is a good candidate.A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years,but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv mouse.This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models.It also reviews the recent progress in the development of humanized mouse models with a functional human immune system,especially the recent progress in the immunodeficient mice that carry a defective gammaC gene.NOD/SCID/gammaC-/(NOG or NSG) or the Rag2-/-/gammaC-/double knockout (DKO) mice,which lack NK as well as T and B cells (NTB-null mice),have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34+ HSC.These NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic interventions.Such models,with further improvements,will contribute to study human immunology,human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo.

  11. Neo-epitopes on methylglyoxal modified human serum albumin lead to aggressive autoimmune response in diabetes.

    Science.gov (United States)

    Jyoti; Mir, Abdul Rouf; Habib, Safia; Siddiqui, Sheelu Shafiq; Ali, Asif; Moinuddin

    2016-05-01

    Glyco-oxidation of proteins has implications in the progression of diabetes type 2. Human serum albumin is prone to glyco-oxidative attack by sugars and methylglyoxal being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. This study has probed the methylglyoxal mediated modifications of HSA, the alterations in its immunological characteristics and possible role in autoantibody induction. We observed an exposure of chromophoric groups, loss in the fluorescence intensity, generation of AGEs, formation of cross-linked products, decrease in α-helical content, increase in hydrophobic clusters, FTIR band shift, attachment of methylglyoxal to HSA and the formation of N(ε)-(carboxyethyl) lysine in the modified HSA, when compared to the native albumin. MG-HSA was found to be highly immunogenic with additional immunogenicity invoking a highly specific immune response than its native counterpart. The binding characteristics of circulating autoantibodies in type 2 diabetes mellitus (DM) patients showed the generation of anti-MG-HSA auto-antibodies in the these patients, that are preferentially recognized by the modified albumin. We propose that MG induced structural perturbations in HSA, result in the generation of neo-epitopes leading to an aggressive auto-immune response and may contribute to the immunopathogenesis of diabetes type 2 associated complications.

  12. Basic and clinical immunology

    Science.gov (United States)

    Chinen, Javier; Shearer, William T.

    2003-01-01

    Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

  13. Immunological characterization of plasminogen activator activities in human tissues and body fluids

    NARCIS (Netherlands)

    Rijken, D.C.; Wijngaards, G.; Welbergen, J.

    1981-01-01

    Human plasminogen activators were compared immunologically in both a double-diffusion technique and quenching experiments on the fibrinolytic activities of the activators. Antisera against HMW and LMW urokinase and an antiserum against highly purified tissue plasminogen activator from human uterus

  14. Immunologic effects of emdogain in humans: one-year results.

    Science.gov (United States)

    Nikolopoulos, Symeon; Peteinaki, Efthymia; Castanas, Elias

    2002-06-01

    Tissue regeneration after therapeutic manipulations is essential in periodontology, oral surgery, and trauma of the periodontal tissues. Local inflammation because of poor oral hygiene also plays a crucial role in the above situations. Local inflammatory reaction, accompanied by the local production of cytokines, profoundly influences bone turnover and regeneration. Several products of low immunogenicity for augmenting tissue regeneration have been recently proposed as boosters of soft and mineralized tissue regeneration. Among them, Emdogain, an amelogenin derivative of porcine origin, has recently been introduced. Clinical results indicate that this product might be a good additive, producing fast tissue regeneration with no apparent clinical side effects. In contrast, very little is known about its in vivo immunologic effects. A previous study showed that Emdogain does not modify the cellular or humoral immune response in vitro. In the present work, performed in 10 patients, only a slight, nonsignificant activation of the immune system occurred during the first year following Emdogain application. Neither cellular immunity nor humoral immune response was significantly modified. In addition, the in vitro response of the patients' lymphocytes to Emdogain was assayed 2 and 12 months postoperative. We did not find any significant specific lymphocyte transformation in the presence of Emdogain, although lymphocytes could be stimulated by nonselective mitogens. These results indicate the immunologic safety of the agent in vivo, at least after 1 year.

  15. Single-gene association between GATA-2 and autoimmune hepatitis: A novel genetic insight highlighting immunologic pathways to disease.

    Science.gov (United States)

    Webb, Gwilym; Chen, Yung-Yi; Li, Ka-Kit; Neil, Desley; Oo, Ye Htun; Richter, Alex; Bigley, Venetia; Collin, Matthew; Adams, David H; Hirschfield, Gideon M

    2016-05-01

    Background & Aims Autoimmune hepatitis (AIH), an immune-mediated liver disease, originates as a consequence of interacting genetic and environmental risk factors. Treatment remains non-specific and prone to side effects. Deficiencies in regulatory T cell (Treg) function are hypothesized to contribute to the pathogenesis of AIH. Methods We describe an adult patient who presented with AIH in the context of monocytopenia. The patient was characterized by GATA2 gene sequencing, flow cytometry of peripheral blood for leucocyte subsets, ELISA for serum Flt-3 ligand, and immunohistochemistry of liver biopsy tissue. Results Sequencing confirmed a GATA2 mutation. Peripheral Treg were absent in the context of a preserved total T cell count. Immunostaining for the Treg transcription factor FOXP3 was reduced in liver tissue as compared to a control AIH specimen. There were marked deficiencies in multiple antigen-presenting cell subsets and Flt-3 ligand was elevated. These findings are consistent with previous reports of GATA2 dysfunction. Conclusions The association of a GATA2 mutation with AIH is previously unrecognized. GATA2 encodes a hematopoietic cell transcription factor, and mutations may manifest as monocytopenia, dendritic and B cell deficiencies, myelodysplasia, and immunodeficiency. Tregs may be depleted as in this case. Our findings provide support for the role of Tregs in AIH, complement reports of other deficiencies in T cell regulation causing AIH-like syndromes, and support the rationale of attempting to modulate the Treg axis for the therapeutic benefit of AIH patients.

  16. Immunological Responses against SARS-Coronavirus Infection in Humans

    Institute of Scientific and Technical Information of China (English)

    XiaojunXu; Xiao-MingGao

    2004-01-01

    Since the outbreak of a SARS epidemic last year, significant advances have been made on our understanding of the mechanisms of interaction between the SARS coronavirus (CoV) and the immune system. Strong humoral responses have been found in most patients following SARS-CoV infection, with high titers of neutralizing Abs present in their convalescent sera. The nucleocapsid (N) and spike (S) proteins of SARS-CoV appear to be the dominant antigens recognized by serum Abs. CD4+ T cell responses against the N protein have been observed in SARS patients and an HLA-A2-restricted cytotoxic T lymphocyte epitope in the S protein has been identified. It is likely that the immune responses induced by SARS-CoV infection could also cause pathological damage to the host, especially in the case of proinflammatory cytokines. There is also evidence suggesting that SARS-CoV might be able to directly invade cells of the immune system. Our understanding on the interaction between SARS-CoV, the immune system and local tissues is essential to future diagnosis, control and treatment of this very contagious disease. Cellular & Molecular Immunology. 2004;1(2):119-122.

  17. Human neurocysticercosis: immunological features involved in the host's susceptibility to become infected and to develop disease.

    Science.gov (United States)

    Sciutto, Edda; Cárdenas, Graciela; Adalid-Peralta, Laura; Fragoso, Gladis; Larralde, Carlos; Fleury, Agnes

    2013-06-01

    Human neurocysticercosis (NC) is a clinically and radiologically heterogeneous disease caused by the establishment of Taenia solium larvae in the central nervous system. Herein, the immunological and endocrinological features involved in resistance to infection and severe forms of the disease are reviewed, and their clinical relevance is discussed.

  18. Investigating the Effectiveness of an Educational Card Game for Learning How Human Immunology Is Regulated

    Science.gov (United States)

    Su, TzuFen; Cheng, Meng-Tzu; Lin, Shu-Hua

    2014-01-01

    This study was conducted in an attempt to investigate the effectiveness of an educational card game we developed for learning human immunology. Two semesters of evaluation were included to examine the impact of the game on students' understanding and perceptions of the game-based instruction. Ninety-nine senior high school students (11th graders)…

  19. Gene expression demonstrates an immunological capacity of the human endolymphatic sac

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2015-01-01

    OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the innate immune system in the human endolymphatic sac. It is hypothesized that the endolymphatic sac has a significant immunological function in the human inner ear....... STUDY DESIGN: DNA microarrays and immunohistochemistry were used for analyses of fresh human endolymphatic-sac tissue samples. METHODS: Twelve tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery for vestibular schwannoma. Microarray technology was used...... was obtained. Multiple key elements of both the cellular and humoral innate immune system were expressed, including Toll-like receptors 4 and 7, as well as beta-defensin and lactoferrin. CONCLUSIONS: The present data provides the first direct evidence of an immunological capacity of the human endolymphatic sac...

  20. [Proteins of human milk involved in immunological processes].

    Science.gov (United States)

    Lis, Jolanta; Orczyk-Pawiłowicz, Magdalena; Kątnik-Prastowska, Iwona

    2013-05-31

    Human milk contains a lot of components (i.e. proteins, carbohydrates, lipids, inorganic elements) which provide basic nutrients for infants during the first period of their lives. Qualitative composition of milk components of healthy mothers is similar, but their levels change during lactation stages. Colostrum is the fluid secreted during the first days postpartum by mammary epithelial cells. Colostrum is replaced by transitional milk during 5-15 days postpartum and from 15 days postpartum mature milk is produced. Human milk, apart from nutritional components, is a source of biologically active molecules, i.e. immunoglobulins, growth factors, cytokines, acute phase proteins, antiviral and antibacterial proteins. Such components of human milk are responsible for specific biological activities of human milk. This secretion plays an important role in growth and development of newborns. Bioactive molecules present in the milk support the immature immune system of the newborn and also protect against the development of infection. In this article we describe the pathways involved in the production and secretion of human milk, the state of knowledge on the proteome of human milk, and the contents of components of milk during lactation. Moreover, some growth factors and proteins involved in innate and specific immunity, intercellular communication, immunomodulation, and inflammatory processes have been characterized.

  1. Proteins of human milk involved in immunological processes 

    Directory of Open Access Journals (Sweden)

    Jolanta Lis

    2013-05-01

    Full Text Available Human milk contains a lot of components (i.e. proteins, carbohydrates, lipids, inorganic elements which provide basic nutrients for infants during the first period of their lives. Qualitative composition of milk components of healthy mothers is similar, but their levels change during lactation stages. Colostrum is the fluid secreted during the first days postpartum by mammary epithelial cells. Colostrum is replaced by transitional milk during 5-15 days postpartum and from 15 days postpartum mature milk is produced. Human milk, apart from nutritional components, is a source of biologically active molecules, i.e. immunoglobulins, growth factors, cytokines, acute phase proteins, antiviral and antibacterial proteins. Such components of human milk are responsible for specific biological activities of human milk. This secretion plays an important role in growth and development of newborns. Bioactive molecules present in the milk support the immature immune system of the newborn and also protect against the development of infection. In this article we describe the pathways involved in the production and secretion of human milk, the state of knowledge on the proteome of human milk, and the contents of components of milk during lactation. Moreover, some growth factors and proteins involved in innate and specific immunity, intercellular communication, immunomodulation, and inflammatory processes have been characterized.

  2. Incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease after quadrivalent human papillomavirus vaccination: a cohort study.

    Science.gov (United States)

    Grönlund, O; Herweijer, E; Sundström, K; Arnheim-Dahlström, L

    2016-12-01

    To assess whether quadrivalent human papillomavirus (qHPV) vaccination is associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. This register-based open cohort study included all girls and women between 10 and 30 years of age in Sweden in 2006-2012 diagnosed with at least one of 49 prespecified autoimmune diseases (n = 70 265). Incidence rate ratios were estimated for new-onset autoimmune disease within 180 days of qHPV vaccination using Poisson regression adjusting for, country of birth, parental country of birth, parental income and parental education. A total of 70 265 girls and women had at least one of the 49 predefined autoimmune diseases; 16% of these individuals received at least one dose of qHPV vaccine. In unvaccinated girls and women, 5428 new-onset autoimmune diseases were observed during 245 807 person-years at a rate of 22.1 (95% CI 21.5-22.7) new events per 1000 person-years. In vaccinated girls and women, there were 124 new events during 7848 person-years at a rate of 15.8 (95% CI 13.2-18.8) per 1000 person-years. There was no increase in the incidence of new-onset autoimmune disease associated with qHPV vaccination during the risk period; on the contrary, we found a slightly reduced risk (incidence rate ratio 0.77, 95% CI 0.65-0.93). In this nationwide study, qHPV vaccination was not associated with increased incidence of new-onset autoimmune disease in girls and women with pre-existing autoimmune disease. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  3. Preparation of human hepatocellular carcinoma-targeted liposome microbubbles and their immunological properties

    Institute of Scientific and Technical Information of China (English)

    Ai-Na Bian; Yun-Hua Gao; Kai-Bin Tan; Ping Liu; Gong-Jun Zeng; Xin Zhang; Zheng Liu

    2004-01-01

    AIM: To prepare the human hepatocellular carcinoma.(HCC)-targeted liposome microbubbles and to investigate their immunological properties.METHODS: Human hepatocarcinoma specific monoclonal antibody HAb18 was attached to the surface of home-made liposome microbubbles by static attraction to prepare the targeted liposome microbubbles. The combination of HAb18 with liposome microbubbles was confirmed by the slide agglutination test and immunofluorescent assay. Their immunological activity was measured by ELISA. Rosette formation test, rosette formation blocking test and immunofluorescent assay were used to identify the specific binding of targeted liposome microbubbles to SMMC-7721 hepatoma cells, and cytotoxicity assay was used to detect their effect on human hepatocytes.RESULTS: The targeted liposome microbubbles were positive in the slide agglutination test and immunofluorescent assay. ELISA indicated that the immunological activity of HAb18 on the liposome microbubbles was similar to that of free HAb18. SMMC-7721 cells were surrounded by the targeting liposome microbubbles to form rosettes, while the control SGC-7901 gastric cancer cells were not. Proliferation of SMMC-7721 cells and normal human hepatocytes was not influenced by the targeted liposome microbubbles.CONCLUSION: The targeted liposome microbubbles with a high specific biological activity have been successfully prepared, which specifically bind to human hepatocarcinoma cells, and are non-cytotoxic to hepatocytes. These results indicate that the liposome microbubbles can be used as a HCC-targeted ultrasound contrast agent that may enhance ultrasound images and thus improve the diagnosis of HCC,especially at the early stage.

  4. Immunological diagnosis of human hydatid cyst using Western immunoblotting technique

    Science.gov (United States)

    Hadipour, Mahboubeh; Nazari, Mohammad; Sanei, Behnam; Ghayour, Zahra; Sharafi, Seyedeh Maryam; Yazdani, Hajar; Darani, Hossein Yousofi

    2016-01-01

    Background: Echinococcosis is a parasitic disease with worldwide distribution which is caused by the tapeworms Echinococcus granulosus. Diagnosis of the disease relies on imaging techniques, but the techniques are not able to differentiate the cyst from benign or malignant tumors; hence, appropriate serologic methods are required for the differential diagnosis of the infection. Materials and Methods: In this investigation, different sheep hydatid cyst antigens probed with thirty sera of patients with hydatid cyst and also thirty human normal sera using Western immunoblotting technique. Considering results of surgery as gold standard, sensitivity and specificity of Western blotting was estimated. Results: Sera of 29, 26, and 16 patients with hydatid cyst reacted with specific bands of hydatid cyst fluid (HCF), protoscolex crude antigen, and cyst wall crude antigen, respectively. However, none of the normal human sera reacted with those specific bands. Conclusion: A 20 kDa band of sheep HCF is an appropriate antigen for serodiagnosis of hydatid cyst infection. PMID:28331516

  5. Immunological diagnosis of human hydatid cyst using Western immunoblotting technique

    Directory of Open Access Journals (Sweden)

    Mahboubeh Hadipour

    2016-01-01

    Full Text Available Background: Echinococcosis is a parasitic disease with worldwide distribution which is caused by the tapeworms Echinococcus granulosus. Diagnosis of the disease relies on imaging techniques, but the techniques are not able to differentiate the cyst from benign or malignant tumors; hence, appropriate serologic methods are required for the differential diagnosis of the infection. Materials and Methods: In this investigation, different sheep hydatid cyst antigens probed with thirty sera of patients with hydatid cyst and also thirty human normal sera using Western immunoblotting technique. Considering results of surgery as gold standard, sensitivity and specificity of Western blotting was estimated. Results: Sera of 29, 26, and 16 patients with hydatid cyst reacted with specific bands of hydatid cyst fluid (HCF, protoscolex crude antigen, and cyst wall crude antigen, respectively. However, none of the normal human sera reacted with those specific bands. Conclusion: A 20 kDa band of sheep HCF is an appropriate antigen for serodiagnosis of hydatid cyst infection.

  6. A Novel Immunological Assay for Hepcidin Quantification in Human Serum

    OpenAIRE

    Vasiliki Koliaraki; Martha Marinou; Vassilakopoulos, Theodoros P.; Eustathios Vavourakis; Emmanuel Tsochatzis; Pangalis, Gerassimos A.; George Papatheodoridis; Alexandra Stamoulakatou; Dorine W Swinkels; George Papanikolaou; Avgi Mamalaki

    2009-01-01

    BACKGROUND: Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a v...

  7. Immunometabolism of human autoimmune diseases: from metabolites to extracellular vesicles.

    Science.gov (United States)

    de Candia, Paola; De Rosa, Veronica; Gigantino, Vincenzo; Botti, Gerardo; Ceriello, Antonio; Matarese, Giuseppe

    2017-06-26

    Immunometabolism focuses on the mechanisms regulating the impact of metabolism on lymphocyte activity and autoimmunity outbreak. The adipose tissue is long known to release adipokines, either pro- or anti-inflammatory factors bridging nutrition and immune function. More recently, adipocytes were discovered to also release extracellular vesicles (EVs) containing a plethora of biological molecules, including metabolites and microRNAs, which can regulate cell function/metabolism in distant tissues, suggesting that immune regulatory function by the adipose tissue may be far more complex than originally thought. Moreover, EVs were also identified as important mediators of immune cell-to-cell communication, adding a further microenvironmental mechanism of plasticity to fine-tune specific lymphocyte responses. This Review will first focus on the known mechanisms by which metabolism impacts immune function, presenting a systemic (nutrition and long-ranged adipokines) and a cellular point of view (metabolic pathway derangement in autoimmunity). It will then discuss the new discoveries concerning how EVs may act as nanometric vehicles integrating immune/metabolic responses at the level of the extracellular environment and affecting pathological processes. © 2017 Federation of European Biochemical Societies.

  8. Are humans prone to autoimmunity? Implications from evolutionary changes in hominin sialic acid biology.

    Science.gov (United States)

    Varki, Ajit

    2017-09-01

    Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity. We have explored multiple genomic changes in sialic acid biology that occurred in human ancestors (hominins), some with implications for enhanced immunoreactivity, and hence for autoimmunity. Human ancestors lost the enzyme synthesizing the common mammalian sialic acid Neu5Gc, with an accumulation of the precursor sialic acid Neu5Ac. Resulting changes include an enhanced reactivity by some immune cells and increased ability of macrophages to kill bacteria, at the cost of increased endotoxin sensitivity. There are also multiple human-specific evolutionary changes in inhibitory and activating Siglecs, immune cell receptors that recognize sialic acids as "self-associated molecular patterns" (SAMPs) to modulate immunity, but can also be hijacked by pathogen molecular mimicry of SAMPs. Altered expression patterns and fixed or polymorphic SIGLEC pseudogenization in humans has modulated both innate and adaptive immunity, sometimes favoring over-reactivity. Meanwhile, dietary intake of Neu5Gc (derived primarily from red meats) allows metabolic incorporation of this non-human molecule into human cells--apparently the first example of "xeno-autoimmunity" involving "xeno-autoantigen" interactions with circulating "xeno-autoantibodies". Taken together, some of these factors may contribute to the apparent human propensity for autoimmunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Immunology of membranous nephropathy: from animal models to humans.

    Science.gov (United States)

    Sinico, R A; Mezzina, N; Trezzi, B; Ghiggeri, G M; Radice, A

    2016-02-01

    Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement-mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome-wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.

  10. A novel immunological assay for hepcidin quantification in human serum.

    Directory of Open Access Journals (Sweden)

    Vasiliki Koliaraki

    Full Text Available BACKGROUND: Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes a specific and non-operator demanding immunoassay for hepcidin quantification in human sera. METHODS AND FINDINGS: An ELISA assay was developed for measuring hepcidin serum concentration using a recombinant hepcidin25-His peptide and a polyclonal antibody against this peptide, which was able to identify native hepcidin. The ELISA assay had a detection range of 10-1500 microg/L and a detection limit of 5.4 microg/L. The intra- and interassay coefficients of variance ranged from 8-15% and 5-16%, respectively. Mean linearity and recovery were 101% and 107%, respectively. Mean hepcidin levels were significantly lower in 7 patients with juvenile hemochromatosis (12.8 microg/L and 10 patients with iron deficiency anemia (15.7 microg/L and higher in 7 patients with Hodgkin lymphoma (116.7 microg/L compared to 32 age-matched healthy controls (42.7 microg/L. CONCLUSIONS: We describe a new simple ELISA assay for measuring hepcidin in human serum with sufficient accuracy and reproducibility.

  11. Immunology in the Clinic Review Series; focus on metabolic diseases: development of islet autoimmune disease in type 2 diabetes patients: potential sequelae of chronic inflammation.

    Science.gov (United States)

    Brooks-Worrell, B; Palmer, J P

    2012-01-01

    Historically, the development of type 2 diabetes has been considered not to have an autoimmune component, in contrast to the autoimmune pathogenesis of type 1 diabetes. In this review we will discuss the accumulating data supporting the concept that islet autoreactivity and inflammation is present in type 2 diabetes pathogenesis, and the islet autoimmunity appears to be one of the factors associated with the progressive nature of the type 2 diabetes disease process.

  12. Immunological Effects of Probiotics and their Significance to Human Health

    Science.gov (United States)

    Gill, Harsharn S.; Grover, Sunita; Batish, Virender K.; Gill, Preet

    Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit upon the host (FAO/WHO, 2001). Lactic acid bacteria, particularly Lactobacillus and Bifidobacterium species are commonly used as probiotics. Other less commonly used probiotics include the yeast Sacchromyces cerevisiae and some non-pathogenic Escherichia coli and Bacillus species. Studies over the past 20 years have demonstrated that probiotic intake is able to confer a range of health benefits including modulation of the immune system, protection against gastrointestinal and respiratory tract infections, lowering of blood cholesterol levels, attenuation of overt immuno-inflammatory disorders (such as inflammatory bowel disease, allergies) and anti-cancer effects. However, the strongest clinical evidence for probiotics relates to their effectiveness in improving gut health and modulating (via stimulation or regulation) the host immune system. This chapter provides an overview of the current status of our knowledge regarding the immunostimulatory and immunoregulatory effects of probiotics on the immune system and their significance to human health.

  13. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment

    NARCIS (Netherlands)

    Nistala, Kiran; Adams, Stuart; Cambrook, Helen; Ursu, Simona; Olivito, Biagio; de Jager, Wilco; Evans, Jamie G.; Cimaz, Rolando; Bajaj-Elliott, Mona; Wedderburn, Lucy R.

    2010-01-01

    In several murine models of autoimmune arthritis, Th17 cells are the dominant initiators of inflammation. In human arthritis the majority of IL-17-secreting cells within the joint express a cytokine phenotype intermediate between Th17 and Th1. Here we show that Th17/1 cells from the joints of childr

  14. Prevention of murine experimental autoimmune orchitis by recombinant human interleukin-6

    DEFF Research Database (Denmark)

    Li, Lu; Itoh, Masahiro; Ablake, Maila;

    2002-01-01

    We studied the effect of exogenously administered recombinant human interleukin (IL)-6 on the development of experimental autoimmune orchitis (EAO) in C3H/Hej mice. IL-6 significantly reduced histological signs of EAO and appearance of delayed type hypersensitivity against the immunizing testicul...

  15. Integration of immunological aspects in the European Human Embryonic Stem Cell Registry.

    Science.gov (United States)

    Borstlap, Joeri; Kurtz, Andreas

    2008-05-01

    The immunological properties of stem cells are of increasing importance in regenerative medicine. Immunomodulatory mechanisms seem to play an important role not only with respect to the understanding of underlying mechanisms of autologous versus allogenic therapeutic approaches, but also for endogeneous tissue regeneration. The newly established European human embryonic stem cell registry (hESCreg) offers an international database for the registration, documentation and characterisation of human embryonic stem cells (hESC) and their use. By doing so, hESCreg aims to develop a model procedure for further standardisation efforts in the field of stem cell research and regenerative medicine, and eventually the registry may lead to a repository of therapy-related information. Currently the stem cell characterisation data acquired by the registry are divided into several categories such as cell derivation, culture conditions, genetic constitution, stem cell marker expression and degree of modification. This article describes immunological aspects of stem cell characterisation and explores the layout and relevance of a possible additional section to the hESCreg repository to include immunological characteristics of human embryonic stem cells.

  16. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

    Science.gov (United States)

    Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

    2015-04-09

    Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.

  17. An interactive web application for the dissemination of human systems immunology data.

    Science.gov (United States)

    Speake, Cate; Presnell, Scott; Domico, Kelly; Zeitner, Brad; Bjork, Anna; Anderson, David; Mason, Michael J; Whalen, Elizabeth; Vargas, Olivia; Popov, Dimitry; Rinchai, Darawan; Jourde-Chiche, Noemie; Chiche, Laurent; Quinn, Charlie; Chaussabel, Damien

    2015-06-19

    Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

  18. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Neven, Bénédicte; Stolzenberg, Marie-Claude; Daussy, Cécile; Arkwright, Peter D; Lanzarotti, Nina; Schaffner, Catherine; Cluet-Dennetiere, Sophie; Haerynck, Filomeen; Michel, Gérard; Bole-Feysot, Christine; Zarhrate, Mohammed; Radford-Weiss, Isabelle; Romana, Serge P; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2011-01-01

    Autoimmune diseases develop in approximately 5% of humans. They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved in lymphocyte activation, survival, or death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects in self-tolerance checkpoints as a consequence of mutations in the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as FAS). However, some mutation carriers remain asymptomatic throughout life. We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele. Analysis of the patients' CD4(-)CD8(-) (double negative) T cells--accumulation of which is a hallmark of ALPS--revealed that in these cells, 3 patients had somatic mutations in their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10. This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases.

  19. Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis.

    Science.gov (United States)

    Palioura, Sotiria; Herkel, Johannes; Simonović, Miljan; Lohse, Ansgar W; Söll, Dieter

    2010-07-01

    Selenocysteine, the 21st genetically encoded amino acid, is the major form of the antioxidant trace element selenium in the human body. In eukaryotes and archaea its synthesis proceeds through a phosphorylated intermediate in a tRNA-dependent fashion. The final step of selenocysteine formation is catalyzed by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) that converts phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec). The human SepSecS protein is also known as soluble liver antigen/liver pancreas (SLA/LP), which represents one of the antigens of autoimmune hepatitis. Here we review the discovery of human SepSecS and the current understanding of the immunogenicity of SLA/LP in autoimmune hepatitis.

  20. Mechanical compliance and immunological compatibility of fixative-free decellularized/cryopreserved human pericardium.

    Science.gov (United States)

    Vinci, Maria Cristina; Tessitore, Giulio; Castiglioni, Laura; Prandi, Francesca; Soncini, Monica; Santoro, Rosaria; Consolo, Filippo; Colazzo, Francesca; Micheli, Barbara; Sironi, Luigi; Polvani, Gianluca; Pesce, Maurizio

    2013-01-01

    The pericardial tissue is commonly used to produce bio-prosthetic cardiac valves and patches in cardiac surgery. The procedures adopted to prepare this tissue consist in treatment with aldehydes, which do not prevent post-graft tissue calcification due to incomplete xeno-antigens removal. The adoption of fixative-free decellularization protocols has been therefore suggested to overcome this limitation. Although promising, the decellularized pericardium has not yet used in clinics, due to the absence of proofs indicating that the decellularization and cryopreservation procedures can effectively preserve the mechanical properties and the immunologic compatibility of the tissue. The aim of the present work was to validate a procedure to prepare decellularized/cryopreserved human pericardium which may be implemented into cardiovascular homograft tissue Banks. The method employed to decellularize the tissue completely removed the cells without affecting ECM structure; furthermore, uniaxial tensile loading tests revealed an equivalent resistance of the decellularized tissue to strain, before and after the cryopreservation, in comparison with the fresh tissue. Finally, immunological compatibility, showed a minimized host immune cells invasion and low levels of systemic inflammation, as assessed by tissue transplantation into immune-competent mice. Our results indicate, for the first time, that fixative-free decellularized pericardium from cadaveric tissue donors can be banked according to Tissue Repository-approved procedures without compromising its mechanical properties and immunological tolerance. This tissue can be therefore treated as a safe homograft for cardiac surgery.

  1. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    JingwuZhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cellrepertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactionsof a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble thein vivo situation where the immune system is challenged by clonal activation and expansion of given T cellpopulations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting naturalreactions of the immune system in response to clonal expansion of T cells, which can used as a therapeuticapproach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinicaltrials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun toreveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing aunique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004; 1(5):321-327.

  2. Possible Role of Human Herpesvirus 6 as a Trigger of Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Francesco Broccolo

    2013-01-01

    Full Text Available Human herpesvirus 6 (HHV-6 infection is common and has a worldwide distribution. Recently, HHV-6A and HHV-6B have been reclassified into two distinct species based on different biological features (genetic, antigenic, and cell tropism and disease associations. A role for HHV-6A/B has been proposed in several autoimmune disorders (AD, including multiple sclerosis (MS, autoimmune connective tissue diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the above-mentioned AD associated with HHV-6 and the mechanisms proposed for HHV-6A/B-induced autoimmunity. HHV-6A/B could trigger autoimmunity by exposing high amounts of normally sequestered cell antigens, through lysis of infected cells. Another potential trigger is represented by molecular mimicry, with the synthesis of viral proteins that resemble cellular molecules, as a mechanism of immune escape. The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of autoantigens. CD46-HHV-6A/B interaction is a new attractive mechanism proposed: HHV-6A/B (especially HHV-6A could participate in neuroinflammation in the context of MS by promoting inflammatory processes through CD46 binding. Although HHV-6A/B has the ability to trigger all the above-mentioned mechanisms, more studies are required to fully elucidate the possible role of HHV-6A/B as a trigger of AD.

  3. Immunological Identification of Trypanosoma cruzi Lineages in Human Infection Along the Endemic Area

    OpenAIRE

    2011-01-01

    Genotyping studies show a polarized geographic distribution of Trypanosoma cruzi lineages in humans. Here, we assessed their distribution along Latin America through an immunological approach we designated Western blot (WB) assay with Trypomastigote small-surface antigen (TSSA) I and TSSA II (TSSA-WB). These antigens are expressed by T. cruzi I (TCI; now TcI) and T. cruzi II (TCII; reclassified as TcII to TcVI) parasites. TSSA-WB showed good concordance with genotyping tests. An unexpected fr...

  4. Interferon triggers experimental synovitis and may potentiate auto-immune disease in humans.

    Science.gov (United States)

    Rosenbach, T O; Moshonov, S; Zor, U; Yaron, M

    1984-09-01

    From these data it appears that IFN is capable of stimulating prostaglandin E and hyaluronic acid production by human synovial fibroblasts in vitro and of initiating an inflammatory reaction in animal joints. In chronic arthritis its production may result from persisting viral or other antigenic stimulation. IFN may enhance the immune response and mediate the inflammatory process in the joint. Its role in the pathogenesis of rheumatic and various other autoimmune diseases is undergoing further study.

  5. Immunological findings in autism.

    Science.gov (United States)

    Cohly, Hari Har Parshad; Panja, Asit

    2005-01-01

    The immunopathogenesis of autism is presented schematically in Fig. 1. Two main immune dysfunctions in autism are immune regulation involving pro-inflammatory cytokines and autoimmunity. Mercury and an infectious agent like the measles virus are currently two main candidate environmental triggers for immune dysfunction in autism. Genetically immune dysfunction in autism involves the MHC region, as this is an immunologic gene cluster whose gene products are Class I, II, and III molecules. Class I and II molecules are associated with antigen presentation. The antigen in virus infection initiated by the virus particle itself while the cytokine production and inflammatory mediators are due to the response to the putative antigen in question. The cell-mediated immunity is impaired as evidenced by low numbers of CD4 cells and a concomitant T-cell polarity with an imbalance of Th1/Th2 subsets toward Th2. Impaired humoral immunity on the other hand is evidenced by decreased IgA causing poor gut protection. Studies showing elevated brain specific antibodies in autism support an autoimmune mechanism. Viruses may initiate the process but the subsequent activation of cytokines is the damaging factor associated with autism. Virus specific antibodies associated with measles virus have been demonstrated in autistic subjects. Environmental exposure to mercury is believed to harm human health possibly through modulation of immune homeostasis. A mercury link with the immune system has been postulated due to the involvement of postnatal exposure to thimerosal, a preservative added in the MMR vaccines. The occupational hazard exposure to mercury causes edema in astrocytes and, at the molecular level, the CD95/Fas apoptotic signaling pathway is disrupted by Hg2+. Inflammatory mediators in autism usually involve activation of astrocytes and microglial cells. Proinflammatory chemokines (MCP-1 and TARC), and an anti-inflammatory and modulatory cytokine, TGF-beta1, are consistently

  6. Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans

    Directory of Open Access Journals (Sweden)

    Kazuhisa Iwabuchi

    2015-01-01

    Full Text Available Glycosphingolipids (GSLs are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17 is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Src family tyrosine kinase Lyn and the Gαi subunit of heterotrimeric G proteins. The very long fatty acids C24:0 and C24:1 are the main ceramide components of LacCer in neutrophil plasma membranes and are directly connected with the fatty acids of Lyn and Gαi. These observations suggest that the very long fatty acid chains of ceramide are critical for GSL-mediated outside-in signaling. Sphingosine is another component of ceramide, with the hydrolysis of ceramide by ceramidase producing sphingosine and fatty acids. Sphingosine is phosphorylated by sphingosine kinase to sphingosine-1-phosphate, which is involved in a wide range of cellular functions, including growth, differentiation, survival, chemotaxis, angiogenesis, and embryogenesis, in various types of cells. This review describes the role of ceramide moiety of GSLs and its metabolites in immunological and inflammatory reactions in human.

  7. Preparation, Characterization, and Determination of Immunological Activities of Transfer Factor Specific to Human Sperm Antigen

    Directory of Open Access Journals (Sweden)

    Jianwei Zhou

    2013-01-01

    Full Text Available Objective. The objective of this study was to prepare, characterize, and determine immunological activities of specific transfer factor (STF specific to human sperm antigen (HSA for the preparation of antisperm contraceptive vaccine that can be used as an immunocontraceptive. Methods. HSA-STF was prepared using the spleens of rabbits vaccinated with HSA. The specific immunological activities were examined by lymphocyte proliferation test (LPT, leukocyte adhesion inhibition test (LAIT, and by determining the concentrations of IL-4, γ-IFN, and IL-21. HSA-STF was a helveolous substance, having a pH value of 7.0±0.4 and UV absorption maxima at 258 ± 6 nm. It contained seventeen amino acids; glycine and glutamic acids were the highest in terms of concentrations (38.8 μg/mL and 36.3 μg/mL, resp.. Results. The concentration of polypeptide was 2.34±0.31 mg/mL, and ribose was 0.717±0.043 mg/mL. The stimulation index for lymphocyte proliferation test was 1.84, and the leukocyte adhesion inhibition rate was 37.7%. There was a statistically significant difference between the cultural lymphocytes with HSA-STF and non-HSA-STF for γ-IFN and IL-21 (P0.05. Conclusion. HSA-STF was prepared and characterized successfully. It had immunological activity which could transfer the immune response specific to HSA and prove to be a potential candidate for the development of male immunocontraceptive agents.

  8. Investigating the effectiveness of an educational card game for learning how human immunology is regulated.

    Science.gov (United States)

    Su, TzuFen; Cheng, Meng-Tzu; Lin, Shu-Hua

    2014-01-01

    This study was conducted in an attempt to investigate the effectiveness of an educational card game we developed for learning human immunology. Two semesters of evaluation were included to examine the impact of the game on students' understanding and perceptions of the game-based instruction. Ninety-nine senior high school students (11th graders) were recruited for the first evaluation, and the second-semester group consisted of 72 students (also 11th graders). The results obtained indicate that students did learn from the educational card game. Moreover, students who learned from playing the game significantly outperformed their counterparts in terms of their understanding of the processes and connections among different lines of immunological defense (first semester: t = 2.92, p game-based instruction and its learning efficiency, and they felt the game-based instruction was much more interesting than traditional didactic lectures (first semester: t = 2.79, p game has potential to facilitate students' learning of how the immune system works. The implications and suggestions for future work are further discussed. © 2014 T. Su et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  9. Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

    Science.gov (United States)

    Reinert-Hartwall, Linnea; Honkanen, Jarno; Salo, Harri M.; Nieminen, Janne K.; Luopajärvi, Kristiina; Härkönen, Taina; Veijola, Riitta; Simell, Olli; Ilonen, Jorma; Peet, Aleksandr; Tillmann, Vallo; Knip, Mikael; Knip, Mikael; Koski, Katriina; Koski, Matti; Härkönen, Taina; Ryhänen, Samppa; Hämäläinen, Anu-Maaria; Ormisson, Anne; Peet, Aleksandr; Tillmann, Vallo; Ulich, Valentina; Kuzmicheva, Elena; Mokurov, Sergei; Markova, Svetlana; Pylova, Svetlana; Isakova, Marina; Shakurova, Elena; Petrov, Vladimir; Dorshakova, Natalya V.; Karapetyan, Tatyana; Varlamova, Tatyana; Ilonen, Jorma; Kiviniemi, Minna; Alnek, Kristi; Janson, Helis; Uibo, Raivo; Salum, Tiit; von Mutius, Erika; Weber, Juliane; Ahlfors, Helena; Kallionpää, Henna; Laajala, Essi; Lahesmaa, Riitta; Lähdesmäki, Harri; Moulder, Robert; Nieminen, Janne; Ruohtula, Terhi; Vaarala, Outi; Honkanen, Hanna; Hyöty, Heikki; Kondrashova, Anita; Oikarinen, Sami; Harmsen, Hermie J. M.; De Goffau, Marcus C.; Welling, Gjalt; Alahuhta, Kirsi; Virtanen, Suvi M.

    2015-01-01

    Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions. PMID:25480564

  10. Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

    OpenAIRE

    Aira, Lazaro E.; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A.; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima

    2015-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical ...

  11. Effect of extended exposure of low-dose radiation on autoimmune diseases of immunologically depressed MRL/MpJ-gld/gld mice

    Energy Technology Data Exchange (ETDEWEB)

    Ootsuyama, A.; Okazaki, R.; Norimura, T. [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    2000-05-01

    We analyzed alterations of splenic T cell subpopulations and amelioration of autoimmune disease of MRL/MpJ-gld/gld mice (MRL/gld mice) after the extended exposure to low-dose radiation (LDR). Four-month old MRL/gld mice were exposed to 0.05, 0.2 and 0.5 Gy/day for 4 weeks (5 days/week) with a total dose of 1, 4 and 10 Gy, respectively. The mice irradiated with 0.2 and 0.5 Gy/day showed an obvious decrease in the proportions of splenic CD4{sup -}CD8{sup -} T cells and remission of their autoimmune disease. In the mice irradiated with 0.2 Gy/day, apoptotic cells were found in the white pulp of the spleen after the last irradiation, but not in that of the treated MRL/MpJ-+/+ mice (MRL/wild type mice). It seems that the accumulated CD4{sup -}CD8{sup -} T cells are more sensitive to radiation than other T cell subpopulations and prone to apoptosis, and efficient elimination of abnormal CD4{sup -}CD8{sup -} T cells by radiation-induced apoptosis may lead to the amelioration of autoimmune disease. (author)

  12. Towards human exploration of space: The THESEUS review series on immunology research priorities

    DEFF Research Database (Denmark)

    Jean-Pol, Frippiat; Crucian, Brian E; de Quervain, Dominique

    2016-01-01

    to maintain immune homeostasis under such challenges. In the framework of the THESEUS project whose aim was to develop an integrated life sciences research roadmap regarding human space exploration, experts working in the field of space immunology, and related disciplines, established a questionnaire sent......Dysregulation of the immune system occurs during spaceflight and may represent a crew health risk during exploration missions because astronauts are challenged by many stressors. Therefore, it is crucial to understand the biology of immune modulation under spaceflight conditions in order to be able...... to scientists around the world. From the review of collected answers, they deduced a list of key issues and provided several recommendations such as a maximal exploitation of currently available resources on Earth and in space, and to increase increments duration for some ISS crew members to 12 months or longer...

  13. Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells*

    Science.gov (United States)

    Sparks, Avis E.; Chen, Chiachen; Breslin, Mary B.; Lan, Michael S.

    2016-01-01

    INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity. PMID:27048654

  14. Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells.

    Science.gov (United States)

    Sparks, Avis E; Chen, Chiachen; Breslin, Mary B; Lan, Michael S

    2016-05-20

    INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity.

  15. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment

    OpenAIRE

    Nistala, Kiran; Adams, Stuart; Cambrook, Helen; Ursu, Simona; Olivito, Biagio; de Jager, Wilco; Evans, Jamie G.; Cimaz, Rolando; Bajaj-Elliott, Mona; Wedderburn, Lucy R.

    2010-01-01

    In several murine models of autoimmune arthritis, Th17 cells are the dominant initiators of inflammation. In human arthritis the majority of IL-17–secreting cells within the joint express a cytokine phenotype intermediate between Th17 and Th1. Here we show that Th17/1 cells from the joints of children with inflammatory arthritis express high levels of both Th17 and Th1 lineage-specific transcription factors, RORC2 and T-bet. Modeling the generation of Th17/1 in vitro, we show that Th17 cells ...

  16. Human innate B cells: a link between host defense and autoimmunity?

    Science.gov (United States)

    Milner, Eric C B; Anolik, Jennifer; Cappione, Amedeo; Sanz, Iñaki

    2005-03-01

    B cells play a variety of immunoregulatory roles through their antigen-presentation ability and through cytokine and chemokine production. Innate immune activation of B cells may play a beneficial role through the generation of natural cross-reactive antibodies, by maintaining B cell memory and by exercising immunomodulatory functions that may provide protection against autoimmunity. In this article, we review human B cell populations and their functional properties, with a particular focus on a population of inherently autoreactive B cells, which seem to play an important physiological role in innate immunity, but which, if selected into adaptive immune responses, appear to become pathogenic agents in systemic lupus erythematosus.

  17. Coinfection with Hymenolepis nana, Hymenolepis diminuta, Giardia intestinalis, and Human Immunodeficiency Virus: A Case Report with Complex Immunologic Interactions.

    Science.gov (United States)

    Pérez-Chacón, Gladymar; Pocaterra, Leonor A; Rojas, Elsy; Hernán, Aurora; Jiménez, Juan Carlos; Núñez, Luz

    2017-02-20

    We describe the case of a 43-year-old human immunodeficiency virus-infected man receiving combined antiretroviral therapy and coinfected with Hymenolepis nana, Hymenolepis diminuta, and Giardia intestinalis, presenting as chronic diarrhea and critical weight loss. Immunological aspects of these interactions are reviewed.

  18. Immunological changes in human immunodeficiency virus (HIV)-infected individuals during HIV-specific protease inhibitor treatment

    DEFF Research Database (Denmark)

    Ullum, H; Katzenstein, T; Aladdin, H

    1999-01-01

    The present study examines the influence of effective anti-retroviral treatment on immune function, evaluated by a broad array of immunological tests. We followed 12 individuals infected with human immunodeficiency virus (HIV) for 6 months after initiation of combination anti-retroviral treatment...

  19. Neuropathology of autoimmune encephalitides.

    Science.gov (United States)

    Bauer, Jan; Bien, Christian G

    2016-01-01

    In recent years a large number of antibody-associated or antibody-defined encephalitides have been discovered. These conditions are often referred to as autoimmune encephalitides. The clinical features include prominent epileptic seizures, cognitive and psychiatric disturbance. These encephalitides can be divided in those with antibodies against intracellular antigens and those with antibodies against surface antigens. The discovery of new antibodies against targets on the surface of neurons is especially interesting since patients with such antibodies can be successfully treated immunologically. This chapter focuses on the pathology and the pathogenetic mechanisms involved in these encephalitides and discusses some of the questions that are raised in this exciting new field. It is important to realise, however, that because of the use of antibodies to diagnose the patients, and their improvement with treatment, there are relatively few biopsy or postmortem reports, limiting the neuropathological data and conclusions that can be drawn. For this reason we especially focus on the most frequent autoimmune encephalitides, those with antibodies to the NMDA receptor and with antibodies to the known protein components of the VGKC complex. Analysis of these encephalitides show completely different pathogenic mechanisms. In VGKC complex encephalitis, antibodies seem to bind to their target and activate complement, leading to destruction and loss of neurons. On the other hand, in NMDAR encephalitis, complement activation and neuronal degeneration seems to be largely absent. Instead, binding of antibodies leads to a decrease of NMDA receptors resulting in a hypofunction. This hypofunction offers an explanation for some of the clinical features such as psychosis and episodic memory impairment, but not for the frequent seizures. Thus, additional analysis of the few human brain specimens present and the use of specific animal models are needed to further understand the effects

  20. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    Science.gov (United States)

    Ha, Tai-You

    2011-10-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

  1. Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Katherine eLintner

    2016-02-01

    Full Text Available The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP, has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE. Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy number variation, and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low gene copy numbers of total C4, heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein alterations for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases.

  2. Influence of exposure history on the immunology and development of resistance to human Schistosomiasis mansoni.

    Directory of Open Access Journals (Sweden)

    Carla L Black

    2010-03-01

    Full Text Available Previous studies suggest that humans can acquire immunity to reinfection with schistosomes, most probably due to immunologic mechanisms acquired after exposure to dying schistosome worms.We followed longitudinally two cohorts of adult males occupationally exposed to Schistosoma mansoni by washing cars (120 men or harvesting sand (53 men in Lake Victoria. Men were treated with praziquantel each time S. mansoni infection was detected. In car washers, a significant increase in resistance to reinfection, as measured by the number of cars washed between cure and reinfection, was observed after the car washers had experienced, on average, seven cures. In the car washers who developed resistance, the level of schistosome-specific IgE increased between baseline and the time at which development of resistance was first evidenced. In the sand harvesters, a significant increase in resistance, as measured by the number of days worked in the lake between cure and reinfection, was observed after only two cures. History of exposure to S. mansoni differed between the two cohorts, with the majority of sand harvesters being lifelong residents of a village endemic for S. mansoni and the majority of car washers having little exposure to the lake before they began washing cars. Immune responses at study entry were indicative of more recent infections in car washers and more chronic infections in sand harvesters.Resistance to reinfection with S. mansoni can be acquired or augmented by adults after multiple rounds of reinfection and cure, but the rate at which resistance is acquired by this means depends on immunologic status and history of exposure to S. mansoni infection.

  3. Th1/Th17 plasticity is a marker of advanced β cell autoimmunity and impaired glucose tolerance in humans

    NARCIS (Netherlands)

    Reinert-Hartwall, Linnea; Honkanen, Jarno; Salo, Harri M; Nieminen, Janne K; Luopajärvi, Kristiina; Härkönen, Taina; Veijola, Riitta; Simell, Olli; Ilonen, Jorma; Peet, Aleksandr; Tillmann, Vallo; Knip, Mikael; Vaarala, Outi; Harmsen, Hermanus

    2015-01-01

    Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pa

  4. Autoimmunity in 2015.

    Science.gov (United States)

    Selmi, Carlo

    2016-08-01

    Compared to the clear trend observed in previous years, the number of peer-reviewed articles published during 2015 and retrieved using the "autoimmunity" key word declined by 4 %, while remaining 5 % of immunology articles. On the other hand, a more detailed analysis of the published articles in leading immunology and autoimmunity journals revealed exciting scenarios, with fascinating lines of evidence being supported by convincing data and likely followed by rapid translational or clinical developments. As examples, the study of the microbiome, the development of new serum or other tissue biomarkers, and a more solid understanding of disease pathogenesis and tolerance breakdown mechanisms have been central issues in the past year. Furthermore and similar to the oncology field, progress in the understanding of single autoimmune condition is becoming most specific with psoriatic and rheumatoid arthritis being ideal paradigms with treatment options diverging after decades of common therapies, as illustrated by IL17-targeting approaches. The ultimate result of these advances is towards personalized medicine with an ideal approach being tailored on a single patient, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers. Finally, experimental reports suggest that cancer-associated immune mechanisms or the role of T and B cell subpopulations should be better understood in autoimmune diseases. While we hailed the 2014 literature in the autoimmunity world as part of an annus mirabilis, we should not be mistaken in the strong stimulus of research in autoimmunity represented by the 2015 articles that will be summarized in this article.

  5. Autoimmune hepatitis

    Directory of Open Access Journals (Sweden)

    F Motamed

    2014-04-01

    Full Text Available Autoimmune hepatitis is (AIH is a chronic hepatitis that occurs in children and adults of all ages. It is characterized by immunologic and autoimmune features, including circulating auto antibodies and high serum globulin concentrations. It was first described in the 1950s by term of chronic active hepatitis. It has 2 types with different auto antibodies. Diagnosis is based upon serologic and histologic findings and exclusion of other forms of chronic liver disease.   A scoring system should be used in assessment based upon: 1 Auto anti bodie titer 2 Serum IgG level  3 Liver histology 4 Absence of viral and other causes of hepatitis. Clear indications for treatment: 1   rise of aminotrasferases 2   clinical symptoms of liver disease 3   histological features in liver biopsy 4   Children with AIH initial treatment involve glucocorticoid with or without azathioprine. For patients with fulminant hepatitis liver transplantation, should be kept in mind.   Remission is defined by: 1   Resolution of symptoms 2   Normalization of serum trasaminases 3   Normalization of serum bilirubin and gamma globuline levels. 4   Improvement in liver histology 5   Treatment is continued for at least 2-5 years, glucocorticoids are with drawn first, by tapering over six weeks. Azathioprine will be with drawn.  

  6. Autoimmune thyroid disease and other non-endocrine autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Todorović-Đilas Ljiljana

    2011-01-01

    Full Text Available Introduction, Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. Autoimmune thyroid disease and other organ specific non-endocrine autoimmune diseases. This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. Autoimmune thyroid disease and other organ non-specific non-endocrine autoimmune diseases. Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Conclusions. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Other­wise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  7. Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.

    Science.gov (United States)

    Knudsen, Niels Peter H; Olsen, Anja; Buonsanti, Cecilia; Follmann, Frank; Zhang, Yuan; Coler, Rhea N; Fox, Christopher B; Meinke, Andreas; D'Oro, Ugo; Casini, Daniele; Bonci, Alessandra; Billeskov, Rolf; De Gregorio, Ennio; Rappuoli, Rino; Harandi, Ali M; Andersen, Peter; Agger, Else Marie

    2016-01-21

    The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvants to enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvants in licensed human vaccines. A vast number of adjuvants have been tested pre-clinically using different experimental conditions, rendering it impossible to directly compare their activity. We performed a head-to-head comparison of five different adjuvants Alum, MF59®, GLA-SE, IC31® and CAF01 in mice and combined these with antigens from M. tuberculosis, influenza, and chlamydia to test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvant had a unique immunological signature suggesting that the adjuvants have potential for different disease targets. Alum increased antibody titers; MF59® induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31® induced strong Th1 responses. MF59® and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31® enhanced protection to TB and chlamydia. Importantly, this is the first extensive attempt to categorize clinical-grade adjuvants based on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.

  8. Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

    Science.gov (United States)

    Olivry, T; Chan, L S; Xu, L; Chace, P; Dunston, S M; Fahey, M; Marinkovich, M P

    1999-07-01

    In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

  9. Eye findings and immunological markers in probands and their euthyroid relatives from a single family with multiple cases of thyroid autoimmunity

    Directory of Open Access Journals (Sweden)

    Ardley Melissa

    2012-06-01

    Full Text Available Abstract Background Ophthalmopathy is a common manifestation of Graves’ disease (GD occurring in up to 50% of patients. Mild eye signs are also common in patients with Hashimoto’s thyroiditis. Whilst a genetic predisposition to GD has been demonstrated this is not the case for the ophthalmopathy which often runs a separate course. Objective We determined the prevalences of eye and eyelid signs and positive thyroid and orbital antibody tests in first and second degree relatives from a single family with multiple cases of Graves’ disease, ophthalmopathy and Hashimoto’s thyroiditis. Design The study cohort comprised 16 subjects from the same family, 4 probands namely, 3 with GD and one with Hashimoto’s thyroiditis and hypothyroidism and 12 of their euthyroid first or second degree relatives. We measured antibodies against calsequestrin (CASQ1 and collagen XIII in an enzyme-linked-immunosorbent assays and TSH-Receptor (TSH-R antibodies as i TSH-R binding inhibiting immunoglobulin (TBII and ii thyroid stimulating immunoglobulin (TSI. Eye signs were classified and quantified using the clinical activity score (CAS, NOSPECS classes, Nunery types 1 and 2 and the margin-reflex-distance (MRD as a measure of upper eyelid retraction (UER. Main outcomes Whilst significant ophthalmopathy was uncommon in the relatives, mild eye signs, in particular UER, were demonstrated in about a third of them. The presence of eye signs was moderately, but not significantly, associated with the detection of CASQ1 and collagen XIII antibodies, but not TSH-R antibodies. Conclusion Our study demonstrates a significant prevalence of positive orbital antibody tests and ophthalmopathy in probands with thyroid autoimmunity and their euthyroid relatives, favouring a role of genetic factors in the development of ophthalmopathy in patients with thyroid autoimmunity.

  10. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  11. Vitamin D in systemic and organ-specific autoimmune diseases.

    Science.gov (United States)

    Agmon-Levin, Nancy; Theodor, Emanuel; Segal, Ramit Maoz; Shoenfeld, Yehuda

    2013-10-01

    Lately, vitamin D has been linked with metabolic and immunological processes, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and upon activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. Epidemiological data underline a strong correlation between poor vitamin D status and higher risk for chronic inflammatory illnesses of various etiologies, including autoimmune diseases. Epidemiological, genetic, and basic studies indicated a potential role of vitamin D in the pathogenesis of certain systemic and organ-specific autoimmune diseases. These studies demonstrate correlation between low vitamin D and prevalence of diseases. In addition, VDRs' polymorphisms observed in some of these autoimmune diseases may further support a plausible pathogenic link. Notably, for some autoimmune disease, no correlation with vitamin D levels could be confirmed. Thus, in the current review we present the body of evidence regarding the plausible roles of vitamin D and VDR's polymorphism in the pathogenesis of autoimmunity. We summarize the data regarding systemic (i.e., systemic lupus erythematosus, rheumatoid arthritis, etc.) and organ-specific (i.e., multiple sclerosis, diabetes mellitus, primary biliary cirrhosis, etc.) autoimmune diseases, in which low level of vitamin D was found comparing to healthy subjects. In addition, we discuss the correlations between vitamin D levels and clinical manifestations and/or activity of diseases. In this context, we address the rational for vitamin D supplementation in patients suffering from autoimmune diseases. Further studies addressing the mechanisms by which vitamin D affects autoimmunity and the proper supplementation required are needed.

  12. National incidence of autoimmune liver diseases and its relationship with the human development index.

    Science.gov (United States)

    Pan, Hong-Ying; Dai, Yi-Ning; Zheng, Ji-Na; Shi, Ke-Qing; Van Poucke, Sven; Zou, Hai; Zheng, Ming-Hua

    2016-07-19

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) and immunoglobulin G4 related cholangitis represent the major autoimmune liver diseases (AILD). However, the relationship between AILD incidence and socioeconomic development levels is yet to be explored. A total of 43 studies were included. There was a positive but not significant correlation between the PBC incidence and HDI on a global level (r=0.348, P=0.082). However, in Europe, a significantly positive correlation existed between the PBC incidence and HDI (r=0.455, P=0.044). No statistical correlation between PSC incidence and HDI was observed (r=0.116, P=0.706). The incidence of AIH revealed a positive correlation with the national HDI both globally (r=0.638, P=0.014) and in Europe (r=0.644, P=0.045). Moreover, the PBC incidence demonstrated a positive correlation with the health index (r=0.422, P=0.036), but a negative correlation with the education index (r= -0.650, Phuman development index (HDI) was applied as an indicator for socioeconomic development. HDI data were obtained and calculated based on the 2014 Human Development Report. Pearson coefficient and linear regression analysis were conducted to estimate the correlation between incidence and HDI. There is positive association between the national incidence of AILD and the socioeconomic status, as measured by HDI. In less-developed countries, the incidence of AILD, especially PBC and AIH, might be less common.

  13. Serum PEDF levels are decreased in a spontaneous animal model for human autoimmune uveitis.

    Science.gov (United States)

    Zipplies, Johanna K; Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Ueffing, Marius; Deeg, Cornelia A

    2009-02-01

    Identification of biomarkers is of critical relevance toward improving diagnosis and therapy of autoimmune disorders. Serum markers are a desirable choice as sera are easily accessible and the development of assays for routine clinical detection prompts feasible. Autoimmune uveitis, a recurrent disease affecting the eye, is characterized by returning inflammatory attacks of the inner eye followed by variable periods of quiescent stages. Spontaneous equine recurrent uveitis (ERU) is the equine equivalent and serves as a model for the human disease. To identify potential biomarker candidates, we first systematically compared the proteomes of individual ERU cases with healthy controls by proteomic profiling using 2-D difference-gel-electrophoresis (2-D DIGE) followed by tandem mass spectrometry. A total of seven differentially expressed proteins were identified. Besides the upregulation of IgG and the significant lower expression of albumin, Antithrombin III, and Vitamin D binding protein, we found complement components C1q and C4, to be downregulated in uveitic state. Interestingly, Pigment epithelium-derived factor (PEDF), a marker already detected by 2DE differential proteome analysis in ERU target tissues, vitreous and retina, was found to be also significantly downregulated in sera. The lower expression of PEDF in sera of horses with uveitis could be verified in a cohort of 116 ERU cases and 115 healthy controls. Our findings of a significant lower PEDF expression in ERU cases also in the periphery of the eye proves PEDF as a promising uveitis biomarker.

  14. Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.

    Science.gov (United States)

    Kanatsuna, Norio; Taneera, Jalal; Vaziri-Sani, Fariba; Wierup, Nils; Larsson, Helena Elding; Delli, Ahmed; Skärstrand, Hanna; Balhuizen, Alexander; Bennet, Hedvig; Steiner, Donald F; Törn, Carina; Fex, Malin; Lernmark, Åke

    2013-10-04

    Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain, and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine the expression of INS-IGF2 in human pancreatic islets and autoantibodies in newly diagnosed children with type 1 diabetes and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared with donors with either type 2 diabetes (p = 0.006) or high HbA1c levels (p INS-IGF2 autoantibody levels were increased in newly diagnosed patients with type 1 diabetes (n = 304) compared with healthy controls (n = 355; p INS-IGF2 revealed that more patients than controls had doubly reactive insulin-INS-IGF2 autoantibodies. These data suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain, and eight amino acids of the C-peptide may be an autoantigen in type 1 diabetes. INS-IGF2 and insulin may share autoantibody-binding sites, thus complicating the notion that insulin is the primary autoantigen in type 1 diabetes.

  15. Autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Pietro Invernizzi; Ian R Mackay

    2008-01-01

    The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

  16. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  17. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  18. A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis.

    Science.gov (United States)

    Barbaud, A; Tréchot, P; Granel, F; Lonchamp, P; Faure, G; Schmutz, J L; Béné, M C

    1999-01-01

    Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.

  19. Changes in Serological Immunology Measures in UK and Kenyan Adults Post-Controlled Human Malaria Infection

    Directory of Open Access Journals (Sweden)

    Susanne Helena Hodgson

    2016-10-01

    Full Text Available Background: The timing of infection is closely determined in controlled human malaria infection (CHMI studies, and as such they provide a unique opportunity to dissect changes in immunological responses before and after a single infection. The first Kenyan Challenge Study (KCS (Pan African Clinical Trial Registry: PACTR20121100033272 was performed in 2013 with the aim of establishing the CHMI model in Kenya. This study used aseptic, cryopreserved, attenuated Plasmodium falciparum sporozoites administered by needle and syringe and was the first to evaluate parasite dynamics post-CHMI in individuals with varying degrees of prior exposure to malaria. Methods: We describe detailed serological and functional immunological responses pre- and post-CHMI for participants in the KCS and compare these with those from malaria-naïve UK volunteers who also underwent CHMI (VAC049 (ClinicalTrials.gov NCT01465048 using PfSPZ Challenge. We assessed antibody responses to three key blood-stage merozoite antigens (merozoite surface protein 1 (MSP1, apical membrane protein 1 (AMA1 and reticulocyte-binding protein homolog 5 (RH5 and functional activity using two candidate measures of anti-merozoite immunity; the growth inhibition activity (GIA assay and the antibody-dependent respiratory burst activity (ADRB assay. Results: Clear serological differences were observed pre- and post-CHMI by ELISA between malaria-naïve UK volunteers in VAC049, and Kenyan volunteers who had prior malaria exposure. Antibodies to AMA1 and schizont extract correlated with parasite multiplication rate (PMR post-CHMI in KCS. Serum from volunteer 110 in KCS, who demonstrated a dramatically reduced PMR in vivo, had no in vitro GIA prior to CHMI but the highest level of ADRB activity. A significant difference in ADRB activity was seen between KCS volunteers with minimal and definite prior exposure to malaria and significant increases were seen in ADRB activity post-CHMI in Kenyan volunteers

  20. Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

    Science.gov (United States)

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

  1. Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity.

    Science.gov (United States)

    Shaw, C A; Tomljenovic, L

    2013-07-01

    We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer's and has been linked to this disease and to the Guamanian variant, ALS-PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.

  2. [Application of the gel test using and anti-IgA antiglobulin for the immunologic diagnosis of autoimmune hemolytic anemia with a negative direct Coombs test].

    Science.gov (United States)

    Meyer, F; Garin, L; Smati, C; Gaspard, M; Giannoli, C; Rigal, D

    1999-07-01

    Autoimmune hemolytic anemias (AIHA) are characterized by hyperhemolysis associated with the presence of the immunoglobulins IgG, IgM or IgA on the red cell membrane. These immunoglobulins react as auto-antibodies against the red cell auto-antigens of the patient. The diagnosis is supported by clinical and biological signs of hemolysis, and by the identification of the auto-antibodies using the direct antiglobulin test (DAT). Here we report 14 cases of patients who showed the clinical and biological profile of AIHA, but who gave a negative DAT. We therefore tried to determine the presence of IgA on the red cell membrane with a method more sensitive than the DAT: the gel test using anti-IgA. With such a gel test, we demonstrated that there were IgA auto-antibodies on the red cell membrane in the 14 cases, therefore confirming the diagnosis of AIHA. We discuss the interest of performing a gel test with anti-IgA in each case where AIHA is suspected, but in which a negative DAT has been observed.

  3. Analysis of genetic regulation of chicken spontaneous autoimmune thyroiditis, an animal model of human Hashimoto's thyroiditis.

    Science.gov (United States)

    Vasícek, D; Vasícková, K; Kaiser, P; Drozenová, R; Cítek, J; Hala, K

    2001-12-01

    We analyzed the genetic regulation of spontaneous autoimmune thyroiditis (SAT) by means of crosses between Obese strain (OS) chickens with the disease, and healthy inbred chicken of line CB. Mononuclear cell infiltration of the thyroid was used as a criterion for the disease. We confirmed the existence of one recessive gene, regulating the susceptibility of the thyroid gland to autoimmune attack. From the frequency of progeny with the thyroid infiltration in backcross and F2 generations, we presume the existence of one or two additional dominant genes coding for abnormal reactivity of the immune system. The total number of genes regulating SAT is therefore a maximum of three. We attempted to identify disease-specific transcripts responsible for the initiation of the disease using suppression subtractive hybridization of RNA prepared from OS and CB thyroid lobes, obtained from 3-day-old chicks. From forward and reverse subtractions, we recovered a fragment mixture in the range of 300 bp to 1.5 kb. In total, 768 clones were screened and 9 were sequenced. Four of them represent unknown sequences. Two, specific for OS thyroid, correspond to envelope genes of avian endogenous viruses (ev)-1, -3 and -6. The expressed product of an env gene could be iodinated in the thyroid gland and become involved in thyroglobulin metabolism. This may be another possible mechanism driving SAT, as iodine modulates SAT in the chicken. Further experiments will be required to prove this hypothesis. Two thyroid-specific clones had significant alignment to human thyroglobulin, and one clone to human coatomer protein. We analyzed, by RFLP and RNA dot blots, cosegregation between clones for the env gene of endogenous viruses as the most promising candidate for involvement in driving SAT; we did not find differences at the DNA and RNA levels. We can possibly therefore rule out a simple involvement of env genes with the initiation of disease.

  4. Purification of full-length human Pregnane and Xenobiotic Receptor: polyclonal antibody preparation for immunological characterization

    Institute of Scientific and Technical Information of China (English)

    Mallampati SARADHI; Biji KRISHNA; Gauranga MUKHOPADHYAY; Rakesh K TYAGI

    2005-01-01

    Pregnane and Xenobiotic Receptor (PXR; or Steroid and Xenobiotic Receptor, SXR), a new member of the nuclear receptor superfamily, is thought to modulate a network of genes that are involved in xenobiotic metabolism and elimination. To further explore the role of PXR in body's homeostatic mechanisms, we for the first time, report successful prokaryotic expression and purification of full-length PXR and preparation of polyclonal antibody against the whole protein. Thefull-length cDNA encoding a 434 amino acids protein was sub-cloned into prokaryotic expression vector, pET-30b and transformed into E. coli BL21 (DE3) cells for efficient over expression. The inclusion body fraction, containing the expressed recombinant protein, was purified first by solubilizing in sarcosine extraction buffer and then by affinity column chromatography using Ni-NTA His-Bind matrix. The efficacy of anti-PXR antibody was confirmed by immunocytology, Western blot analysis, EMSA and immunohistochemistry. The antibody obtained was capable of detecting human and mouse PXR with high specificity and sensitivity. Immunofluorescence staining of COS-1 cells transfected with human or mouse PXR showed a clear nuclear localization. Results from immunohistochemistry showed that level of PXR in liver sections is immunologically detectable in the nuclei. Similar to exogenously transfected PXR, Western blot analysis of cell extract from HepG2 and COLO320DM cells revealed a major protein band for endogenous PXR having the expected molecular weight of 50 kDa. Relevance of other immunodetectable bands with reference to PXR isoforms and current testimony are evaluated. Advantages of antibody raised against full-length PXR protein for functional characterization of receptor is discussed and its application for clinical purposes is envisaged.

  5. Autoimmune autonomic disorders.

    Science.gov (United States)

    Mckeon, Andrew; Benarroch, Eduardo E

    2016-01-01

    Autoimmune autonomic disorders occur because of an immune response directed against sympathetic, parasympathetic, and enteric ganglia, autonomic nerves, or central autonomic pathways. In general, peripheral autoimmune disorders manifest with either generalized or restricted autonomic failure, whereas central autoimmune disorders manifest primarily with autonomic hyperactivity. Some autonomic disorders are generalized, and others are limited in their anatomic extent, e.g., isolated gastrointestinal dysmotility. Historically, these disorders were poorly recognized, and thought to be neurodegenerative. Over the last 20 years a number of autoantibody biomarkers have been discovered that have enabled the identification of certain patients as having an autoimmune basis for either autonomic failure or hyperactivity. Peripheral autoimmune autonomic disorders include autoimmune autonomic ganglionopathy (AAG), paraneoplastic autonomic neuropathy, and acute autonomic and sensory neuropathy. AAG manifests with acute or subacute onset of generalized or selective autonomic failure. Antibody targeting the α3 subunit of the ganglionic-type nicotinic acetylcholine receptor (α3gAChR) is detected in approximately 50% of cases of AAG. Some other disorders are characterized immunologically by paraneoplastic antibodies with a high positive predictive value for cancer, such as antineuronal nuclear antibody, type 1 (ANNA-1: anti-Hu); others still are seronegative. Recognition of an autoimmune basis for autonomic disorders is important, as their manifestations are disabling, may reflect an underlying neoplasm, and have the potential to improve with a combination of symptomatic and immune therapies.

  6. Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering.

    Science.gov (United States)

    Holzapfel, Boris Michael; Wagner, Ferdinand; Thibaudeau, Laure; Levesque, Jean-Pierre; Hutmacher, Dietmar Werner

    2015-06-01

    Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to "make the model organism mouse more human." To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.

  7. Immunological aspects of Graves' disease

    NARCIS (Netherlands)

    B.M. van Ouwerkerk (Marcel)

    1986-01-01

    textabstractAssuming an autoimmune interested to know whether apart from restoring the immunologic parameters. Freshly diagnosed hyperthyroid patients with Graves' disease were all similarly treated with MMI 10 mg t.i.d. and when euthyroidism was achieved, with substitution of thyroid hormone. At

  8. Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Brett Eugene Phillips

    2017-10-01

    Full Text Available Tolerogenic dendritic cell (tDC-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS, and Crohn’s disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells are, for the most part, increased in frequency in the circulation. Other than this observation, there are significant differences in the major phenotypes of the tDC. These differences may affect the outcome in efficacy of recently launched and impending phase II trials. Recent efforts to establish a catalog listing where tDC converge and diverge in phenotype and functional outcome are an important first step toward understanding core mechanisms of action and critical “musts” for tDC to be therapeutically successful. In our view, the most critical parameter to efficacy is in vivo stability of the tolerogenic activity over phenotype. As such, methods that generate tDC that can induce and stably maintain immune hyporesponsiveness to allo- or disease-specific autoantigens in the presence of powerful pro-inflammatory signals are those that will fare better in primary endpoints in phase II clinical trials (e.g., disease improvement, preservation of autoimmunity-targeted tissue, allograft survival. We propose that pre-treatment phenotypes of tDC in the absence of functional stability are of secondary value especially as such phenotypes can dramatically change following administration, especially under dynamic changes in the inflammatory state of the patient. Furthermore, understanding the outcomes of different methods of cell delivery and sites

  9. Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b.

    Science.gov (United States)

    Matsuo, Tomohito; Noguchi, Yukiko; Shindo, Mieko; Morita, Yoshifumi; Oda, Yoshie; Yoshida, Eiko; Hamada, Hiroko; Harada, Mine; Shiokawa, Yuichi; Nishida, Takahiro; Tominaga, Ryuji; Kikushige, Yoshikane; Akashi, Koichi; Kudoh, Jun; Shimizu, Nobuyoshi; Tanaka, Yuka; Umemura, Tsukuru; Taniguchi, Taketoshi; Yoshimura, Akihiko; Kobayashi, Takashi; Mitsuyama, Masao; Kurisaki, Hironori; Katsuta, Hitoshi; Nagafuchi, Seiho

    2013-11-01

    Although mutations of autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), presenting a wide spectrum of many characteristic and non-characteristic clinical features, some patients lack AIRE gene mutations. Therefore, something other than a mutation, such as dysregulation of AIRE gene, may be a causal factor for APECED or its related diseases. However, regulatory mechanisms for AIRE gene expression and/or translation have still remained elusive. We found that IL-2-stimulated CD4(+) T (IL-2T) cells showed a high expression of AIRE gene, but very low AIRE protein production, while Epstein-Barr virus-transformed B (EBV-B) cells express both AIRE gene and AIRE protein. By using microarray analysis, we could identify miR-220b as a possible regulatory mechanism for AIRE gene translation in IL-2T cells. Here we report that miR-220b significantly reduced the expression of AIRE protein in AIRE gene with 3'UTR region transfected 293T cells, whereas no alteration of AIRE protein production was observed in the open reading frame of AIRE gene alone transfected cells. In addition, anti-miR-220b reversed the inhibitory function of miR-220b for the expression of AIRE protein in AIRE gene with 3'UTR region transfected cells. Moreover, when AIRE gene transfected cells with mutated 3'UTR were transfected with miR-220b, no reduction of AIRE protein production was observed. Taken together, it was concluded that miR-220b inhibited the AIRE gene translation through the 3'UTR region of AIRE gene, indicating that miR-220b could serve as a regulator for human AIRE gene translation. © 2013.

  10. Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

    Science.gov (United States)

    Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

    2017-04-01

    Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ε-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

  11. A novel human STAT3 mutation presents with autoimmunity involving Th17 hyperactivation

    NARCIS (Netherlands)

    Wienke, Judith; Janssen, Willemijn; Scholman, Rianne; Spits, Hilde; Gijn, Marielle van; Boes, Marianne; van Montfrans, Joris; Moes, Nicolette; de Roock, Sytze

    2015-01-01

    Mutations in STAT3 have recently been shown to cause autoimmune diseases through increased lymphoproliferation. We describe a novel Pro471Arg STAT3 mutation in a patient with multiple autoimmune diseases, causing hyperactivation of the Th17 pathway. We show that IL-17 production by primary T cells w

  12. Immunodeficiency and autoimmune enterocolopathy linked to NFAT5 haploinsufficiency.

    Science.gov (United States)

    Boland, Brigid S; Widjaja, Christella E; Banno, Asoka; Zhang, Bing; Kim, Stephanie H; Stoven, Samantha; Peterson, Michael R; Jones, Marilyn C; Su, H Irene; Crowe, Sheila E; Bui, Jack D; Ho, Samuel B; Okugawa, Yoshinaga; Goel, Ajay; Marietta, Eric V; Khosroheidari, Mahdieh; Jepsen, Kristen; Aramburu, Jose; López-Rodríguez, Cristina; Sandborn, William J; Murray, Joseph A; Harismendy, Olivier; Chang, John T

    2015-03-15

    The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.

  13. The influence of iodine on the immunological properties of thyroglobulin and its immunological complexes.

    Science.gov (United States)

    Gardas, A

    1991-01-01

    Several papers described different immunological properties of thyroglobulin (Tg) after iodination. The influence of iodine-iodide solution on the immunological properties of hTg and its immunological complexes with autoantibodies (aAbs) were studied. Human Tg coated to polystyrene plates, incubated for 30 min with iodine-iodide solution at concentration from 1 to 200 microM at pH 9.0 lost its ability to bind aAbs. Preincubation with iodine (2 microM), decreased aAbs binding by 50%. Tg epitope inactivation induced by iodine depended on the buffer pH and the presence of carbonate ions. The binding of rabbit Tg-antibodies to iodine pretreated Tg was only slightly changed. Thyroglobulin preincubation with iodine solutions decreased aAbs binding from all tested sera (67) of patients with autoimmune thyroid disease (AITD). Excess of iodide (0.2 M KJ) or equimolar concentration of diiodotyrosine protects the Tg molecule from iodine induced inactivation. Immunological complexes of Tg with aAbs dissociate at low iodine concentrations. The results suggest that a product of iodine disproportionation reaction induces changes in the Tg molecule and Tg-aAb's complexes leading to complex dissociation or epitope inactivation.

  14. Autoimmunity in 2013.

    Science.gov (United States)

    Selmi, Carlo

    2014-08-01

    The peer-reviewed publications in the field of autoimmunity published in 2013 represented a significant proportion of immunology articles and grew since the previous year to indicate that more immune-mediated phenomena may recognize an autoimmune mechanism and illustrated by osteoarthritis and atherosclerosis. As a result, our understanding of the mechanisms of autoimmunity is becoming the paradigm for translational research in which the progress in disease pathogenesis for both tolerance breakdown and inflammation perpetuation is rapidly followed by new treatment approaches and clinical management changes. The similarities across the autoimmune disease spectrum outnumber differences, particularly when treatments are compared. Indeed, the therapeutics of autoimmune diseases are based on a growing armamentarium that currently includes monoclonal antibodies and small molecules which act by targeting molecular markers or intracellular mediators with high specificity. Among the over 100 conditions considered as autoimmune, the common grounds are well illustrated by the data reported for systemic lupus erythematosus and rheumatoid arthritis or by the plethora of studies on Th17 cells and biomarkers, particularly serum autoantibodies. Further, we are particularly intrigued by studies on the genomics, epigenetics, and microRNA at different stages of disease development or on the safe and effective use of abatacept acting on the costimulation of T and B cells in rheumatoid arthritis. We are convinced that the data published in 2013 represent a promising background for future developments that will exponentially impact the work of laboratory and clinical scientists over the next years.

  15. Redefining strategies to introduce tolerance inducing cellular therapy in humans to combat autoimmunity and transplantation reactions

    Directory of Open Access Journals (Sweden)

    Anja eTen Brinke

    2014-08-01

    Full Text Available Clinical translation of tolerance-inducing cell therapies requires a novel approach focused on innovative networks, patient involvement and, foremost, a fundamental paradigm shift in thinking from both Academia, Industry and Regulatory Agencies. Tolerance-inducing cell products differ essentially from conventional drugs. They are personalized and target interactive immunological networks to shift the balance towards tolerance. The human cell products are often absent or fundamentally different in animals. This creates important limitations of pre-clinical animal testing for safety and efficacy of these products and calls for novel translational approaches, which require the combined efforts of the different parties involved. Dedicated international and multidisciplinary consortia that focus on clinical translation are of utmost importance. They can help inform and educate regulatory policy makers on the unique requirements for these cell products, ranging from preclinical studies in animals to in vitro human studies. In addition, they can promote reliable immunomonitoring tools. The development of tolerance-inducing cell products requires not only bench-to-bedside but also reverse translation, from bedside back to the bench.

  16. Immunologic Endocrine Disorders

    Science.gov (United States)

    Michels, Aaron W.; Eisenbarth, George S.

    2010-01-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

  17. Understanding immunology: fun at an intersection of the physical, life, and clinical sciences

    Science.gov (United States)

    Chakraborty, Arup K.

    2014-10-01

    Understanding how the immune system works is a grand challenge in science with myriad direct implications for improving human health. The immune system protects us from infectious pathogens and cancer, and maintains a harmonious steady state with essential microbiota in our gut. Vaccination, the medical procedure that has saved more lives than any other, involves manipulating the immune system. Unfortunately, the immune system can also go awry to cause autoimmune diseases. Immune responses are the product of stochastic collective dynamic processes involving many interacting components. These processes span multiple scales of length and time. Thus, statistical mechanics has much to contribute to immunology, and the oeuvre of biological physics will be further enriched if the number of physical scientists interested in immunology continues to increase. I describe how I got interested in immunology and provide a glimpse of my experiences working on immunology using approaches from statistical mechanics and collaborating closely with immunologists.

  18. Environmental factors and human health: fibrous and particulate substance-induced immunological disorders and construction of a health-promoting living environment.

    Science.gov (United States)

    Otsuki, Takemi; Matsuzaki, Hidenori; Lee, Suni; Kumagai-Takei, Naoko; Yamamoto, Shoko; Hatayama, Tamayo; Yoshitome, Kei; Nishimura, Yasumitsu

    2016-03-01

    Among the various scientific fields covered in the area of hygiene such as environmental medicine, epidemiology, public health and preventive medicine, we are investigating the immunological effects of fibrous and particulate substances in the environment and work surroundings, such as asbestos fibers and silica particles. In addition to these studies, we have attempted to construct health-promoting living conditions. Thus, in this review we will summarize our investigations regarding the (1) immunological effects of asbestos fibers, (2) immunological effects of silica particles, and (3) construction of a health-promoting living environment. This review article summarizes the 2014 Japanese Society for Hygiene (JSH) Award Lecture of the 85th Annual Meeting of the JSH entitled "Environmental health effects: immunological effects of fibrous and particulate matter and establishment of health-promoting environments" presented by the first author of this manuscript, Prof. Otsuki, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan, the recipient of the 2014 JSH award. The results of our experiments can be summarized as follows: (1) asbestos fibers reduce anti-tumor immunity, (2) silica particles chronically activate responder and regulatory T cells causing an unbalance of these two populations of T helper cells, which may contribute to the development of autoimmune disorders frequently complicating silicosis, and (3) living conditions to enhance natural killer cell activity were developed, which may promote the prevention of cancers and diminish symptoms of virus infections.

  19. Immunohistochemistry of human Hsp60 in health and disease: from autoimmunity to cancer.

    Science.gov (United States)

    Cappello, Francesco; de Macario, Everly Conway; Zummo, Giovanni; Macario, Alberto J L

    2011-01-01

    Hsp60 (also called Cpn60) is a chaperonin with essential functions for cell physiology and survival. Additionally, its involvement in the pathogenesis of a number of diseases (e.g., some autoimmune disorders and cancer) is becoming evident with new research. For example, the distribution and levels of Hsp60 in cells and tissues have been found altered in many pathologic conditions, and the significance of these alterations is being investigated in a number of laboratories. The aim of this ongoing research is to determine the meaning of these Hsp60 alterations with regard to pathogenetic mechanisms, diagnosis, classification of lesions, and assessing of prognosis and response to treatment. Hsp60 occurs in the mitochondria, i.e., its typical residence according to classic knowledge, and also in other locales, such as the cytosol, the cell membrane, the intercellular space, and biological fluids (e.g., blood and cerebrospinal fluid). Detection and quantitative determinations in all these locations are becoming essential components of laboratory pathology in clinics and research. Consequently, immunohistochemistry targeting Hsp60 is also becoming essential for pathologists and researchers interested in disorders involving this chaperonin. In this chapter, we briefly summarize some recent discoveries on the participation of Hsp60 in the pathogenesis of human diseases and describe in detail how to perform immunohistochemical reactions for detecting the chaperonin, determining its location, and measuring its levels of expression.

  20. Multiple autoimmune syndrome with celiac disease.

    Science.gov (United States)

    Harpreet, Singh; Deepak, Jain; Kiran, B

    2016-01-01

    Multiple autoimmune syndrome (MAS) is a condition characterised by three or more autoimmune disorders in a same individual. Familial, immunologic and infectious factors are implicated in the development of MAS. Here we report a case of a 32-year-old woman with co-existence of four auto-immune diseases, namely autoimmune hypothyroidism, Sjögren's syndrome, systemic lupus erythematosus (SLE) and celiac disease which leads to the final diagnosis of multiple autoimmune syndrome type 3 with celiac disease. Patients with single autoimmune disorder are at 25% risk of developing other autoimmune disorders. The present case emphasises to clinicians that there is a need for continued surveillance for the development of new autoimmune disease in predisposed patients.

  1. Autoimmunity in 2014.

    Science.gov (United States)

    Selmi, Carlo

    2015-10-01

    Our PubMed search for peer-reviewed articles published in the 2014 solar year retrieved a significantly higher number of hits compared to 2013 with a net 28 % increase. Importantly, full articles related to autoimmunity constitute approximately 5 % of immunology articles. We confirm that our understanding of autoimmunity is becoming a translational paradigm with pathogenetic elements rapidly followed by new treatment options. Furthermore, numerous clinical and pathogenetic elements and features are shared among autoimmune diseases, and this is well illustrated in the recent literature. More specifically, the past year witnessed critical revisions of our understanding and management of antiphospholipid syndrome with new exciting data on the pathogenicity of the serum anti-beta2 glycoprotein autoantibody, a better understanding of the current and new treatments for rheumatoid arthritis, and new position papers on important clinical questions such as vaccinations in patients with autoimmune disease, comorbidities, or new classification criteria. Furthermore, data confirming the important connections between innate immunity and autoimmunity via toll-like receptors or the critical role of T regulatory cells in tolerance breakdown and autoimmunity perpetuation were also reported. Lastly, genetic and epigenetic data were provided to confirm that the mosaic of autoimmunity warrants a susceptible individual background which may be geographically determined and contribute to the geoepidemiology of diseases. The 2014 literature in the autoimmunity world should be cumulatively regarded as part of an annus mirabilis in which, on a different level, the 2014 Annual Meeting of the American College of Rheumatology in Boston was attended by over 16,000 participants with over selected 3000 abstracts.

  2. Immunological relationship between acetylcholine receptor and thymus: a possible significance in myasthenia gravis.

    Science.gov (United States)

    Aharonov, A; Tarrab-Hazdai, R; Abramsky, O; Fuchs, S

    1975-01-01

    A defined immunological cross-reaction was observed between acetylcholine receptor fraction from the electric eel, Electrophorus electricus, and two calf thymus fractions. The cross-reaction was demonstrated on the cellular level by means of the lymphocyte transformation technique, and on the humoral level, by means of the microcomplement fixation assay. In the human disease myasthenia gravis both acetylcholine receptor at the neuromuscular junction and the thymus are affected, probably by an autoimmune mechanism. The immunological cross-reaction between acetylcholine receptor and thymic components may explain the association between endplate and thymus disorders in myasthenia gravis. PMID:1055418

  3. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    Science.gov (United States)

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-09

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations.

  4. Immunological changes in human immunodeficiency virus (HIV)-infected individuals during HIV-specific protease inhibitor treatment

    DEFF Research Database (Denmark)

    Ullum, H; Katzenstein, T; Aladdin, H;

    1999-01-01

    The present study examines the influence of effective anti-retroviral treatment on immune function, evaluated by a broad array of immunological tests. We followed 12 individuals infected with human immunodeficiency virus (HIV) for 6 months after initiation of combination anti-retroviral treatment...... Vaccinia virus was increased after 3-6 months, whereas the specific HIV-directed CTL activity and the concentration and lytic activity of natural killer (NK) cells were unchanged during follow-up. These results demonstrate that the initiation of a treatment including an HIV protease inhibitor is followed...

  5. The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases.

    Science.gov (United States)

    Chardès, Thierry; Chapal, Nicolas; Bresson, Damien; Bès, Cédric; Giudicelli, Véronique; Lefranc, Marie-Paule; Péraldi-Roux, Sylvie

    2002-06-01

    Human anti-thyroid peroxidase (TPO) autoantibodies (aAb) are generated during autoimmune thyroid diseases (AITD). Within recent years, increasing knowledge of the TPO-specific aAb repertoire, gained mainly by the use of combinatorial library methodology, has led to the cloning and sequencing of around 180 human anti-TPO aAb. Analysis of the immunoglobulin (Ig) variable (V) genes encoding the TPO aAb in the ImMunoGeneTics database (IMGT) (http://imgt.cines.fr) reveals major features of the TPO-directed aAb repertoire during AITD. Heavy chain VH domains of TPO-specific aAb from Graves' disease patients preferentially use D proximal IGHV1 genes, whereas those from Hashimoto's thyroiditis are characterized more frequently by IGHV3 genes, mainly located in the middle of the IGH locus. A large proportion of the anti-TPO heavy chain VH domains is obtained following a VDJ recombination process that uses inverted D genes. J distal IGKV1 and IGLV1 genes are predominantly used in TPO aAb. In contrast to the numerous somatic hypermutations in the TPO-specific heavy chains, there is only limited amino acid replacement in most of the TPO-specific light chains, particularly in those encoded by J proximal IGLV or IGKV genes, suggesting that a defect in receptor editing can occur during aAb generation in AITD. Among the predominant IGHV1 or IGKV1 TPO aAb, conserved somatic mutations are the hallmark of the TPO aAb repertoire. The aim of this review is to provide new insights into aAb generation against TPO, a major autoantigen involved in AITD.

  6. 2015 Russell Ross Memorial Lecture in Vascular Biology: Protective Autoimmunity in Atherosclerosis.

    Science.gov (United States)

    Ley, Klaus

    2016-03-01

    Atherosclerosis is an inflammatory disease of the arterial wall. It is accompanied by an autoimmune response against apolipoprotein B-100, the core protein of low-density lipoprotein, which manifests as CD4 T cell and antibody responses. To assess the role of the autoimmune response in atherosclerosis, the nature of the CD4 T cell response against apolipoprotein B-100 was studied with and without vaccination with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides. The immunologic basis of autoimmunity in atherosclerosis is discussed in the framework of theories of adaptive immunity. Older vaccination approaches are also discussed. Vaccinating Apoe(-/-) mice with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides reduces atheroma burden in the aorta by ≈40%. The protective mechanism likely includes secretion of interleukin-10. Protective autoimmunity limits atherosclerosis in mice and suggests potential for developing preventative and therapeutic vaccines for humans.

  7. Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

    Directory of Open Access Journals (Sweden)

    Oliver W Gramlich

    Full Text Available BACKGROUND: There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. METHODS AND RESULTS: Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group. A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007. Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004. CD27(+ cells and CD27(+/IgG(+ plasma cells were observed in all glaucomatous subjects, but not in controls. CONCLUSION: This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an

  8. HPVdb: a data mining system for knowledge discovery in human papillomavirus with applications in T cell immunology and vaccinology.

    Science.gov (United States)

    Zhang, Guang Lan; Riemer, Angelika B; Keskin, Derin B; Chitkushev, Lou; Reinherz, Ellis L; Brusic, Vladimir

    2014-01-01

    High-risk human papillomaviruses (HPVs) are the causes of many cancers, including cervical, anal, vulvar, vaginal, penile and oropharyngeal. To facilitate diagnosis, prognosis and characterization of these cancers, it is necessary to make full use of the immunological data on HPV available through publications, technical reports and databases. These data vary in granularity, quality and complexity. The extraction of knowledge from the vast amount of immunological data using data mining techniques remains a challenging task. To support integration of data and knowledge in virology and vaccinology, we developed a framework called KB-builder to streamline the development and deployment of web-accessible immunological knowledge systems. The framework consists of seven major functional modules, each facilitating a specific aspect of the knowledgebase construction process. Using KB-builder, we constructed the Human Papillomavirus T cell Antigen Database (HPVdb). It contains 2781 curated antigen entries of antigenic proteins derived from 18 genotypes of high-risk HPV and 18 genotypes of low-risk HPV. The HPVdb also catalogs 191 verified T cell epitopes and 45 verified human leukocyte antigen (HLA) ligands. Primary amino acid sequences of HPV antigens were collected and annotated from the UniProtKB. T cell epitopes and HLA ligands were collected from data mining of scientific literature and databases. The data were subject to extensive quality control (redundancy elimination, error detection and vocabulary consolidation). A set of computational tools for an in-depth analysis, such as sequence comparison using BLAST search, multiple alignments of antigens, classification of HPV types based on cancer risk, T cell epitope/HLA ligand visualization, T cell epitope/HLA ligand conservation analysis and sequence variability analysis, has been integrated within the HPVdb. Predicted Class I and Class II HLA binding peptides for 15 common HLA alleles are included in this database as

  9. The new immunology.

    Science.gov (United States)

    Siminovitch, K A

    1992-03-01

    Among the biomedical sciences, immunology stands out as a discipline in which knowledge emanating from fundamental research has rapidly been transferred to the clinical paradigm, with consequent improvement in human health. Virtually all medical subspecialties have benefitted from diagnostic reagents and technologies provided by basic immunology. In terms of numbers of lives saved, immunologic-based therapeutic strategies, most notably vaccination, rank among the most effective measures ever achieved by medical intervention. Yet, despite immunology's profound impact on medicine and the longstanding recognition of many of the general principles and cellular components involved in immunity, until relatively recently, the operational workings of the immune system eluded precise definition. The abstract nature of the immune system rendered the field intangible or, at the very least, confusing, to the nonimmunologic medical community. However, in recent years, this situation has changed radically, as cell cloning, hybridoma, and recombinant DNA technologies have provided the means to delineate the precise immunologic cellular structures and interactions. The purpose of this review is to highlight a few of the most significant advances in immunology during the past decade, and to show how they have made possible the translation of abstract concepts of classical immunology into tangible, structural information. Striking gains in the understanding of antigen recognition, one of the most fundamental aspects of immunity, are described as an illustrative case.

  10. Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).

    Science.gov (United States)

    Nishijima, Hitoshi; Kajimoto, Tatsuya; Matsuoka, Yoshiki; Mouri, Yasuhiro; Morimoto, Junko; Matsumoto, Minoru; Kawano, Hiroshi; Nishioka, Yasuhiko; Uehara, Hisanori; Izumi, Keisuke; Tsuneyama, Koichi; Okazaki, Il-Mi; Okazaki, Taku; Hosomichi, Kazuyoshi; Shiraki, Ayako; Shibutani, Makoto; Mitsumori, Kunitoshi; Matsumoto, Mitsuru

    2017-09-17

    Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Autoimmune hepatitis in patients with human immunodeficiency virus (HIV): Case reports of a rare, but important diagnosis with therapeutic implications.

    Science.gov (United States)

    Kia, Leila; Beattie, Adam; Green, Richard M

    2017-02-01

    Chronic liver disease is a major cause of morbidity and mortality in patients with HIV. However, autoimmune hepatitis (AIH) in patients with HIV has rarely been reported. Our aim was to evaluate a cohort of patients with HIV and AIH and identify clinical presentations and outcomes. Management of autoimmune hepatitis in context of human immunodeficiency virus, long-term outcomes, and safety in setting of underlying immunocompromised state. Autoimmune Hepatitis, Human Immunodeficiency Virus, Hepatotoxicity, Liver Injury, Liver Transplantation. We retrospectively reviewed the charts of patients with HIV and AIH based on histological, serologic, biochemical demographic, and clinical data. Five patients were identified with autoimmune hepatitis; 4 of 5 were women, and all were African or African-American. The age at the time of AIH diagnosis was 46.6 ± 13.4 years. All patients acquired HIV sexually and all had CD4 counts >250 cells/uL (456-1011 cells/uL) and undetectable HIV viral loads at the time of AIH diagnosis. One patient presented with acute liver failure necessitating liver transplantation and developed AIH posttransplantation. At the time of diagnosis, the AST were 350 ± 448 U/L, ALT 247 ± 190 U/L, bilirubin 7 ± 12 mg/dL, and alkaline phosphatase 126 ± 53 U/L. All patients had histologic evidence of AIH on liver biopsies. Patients were successfully treated with prednisone and azathioprine, without a decrease in CD4 <250 cells/uL, infectious complications or significant side effects. AIH occurs in patients with well-controlled HIV. In our patient cohort, immunosuppressive therapy with prednisone and azathioprine was safe and effective in inducing remission, without significant complications or development of opportunistic infections.

  12. Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Markus W(o)rns; Arndt Weinmann; Catherine Centner; Anja Piendl; Ansgar W Lohse; Peter R Galle; Stephan Kanzler

    2006-01-01

    AIM: To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1.METHODS: Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases.Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP)autoantibodies either with or without ANA or SMA autoantibodies.RESULTS: Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compared to the Italian and North American patients, we found fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2human leucocyte antigen (HLA) was also less prominent compared to the North American patients. However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the Italian and North American patients. Furthermore, we report on an additional subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION: Although HLA subtypes were comparable between these three collectives, the German patients were distinct from the Italian and North American patients with respect to DQ2 and from the North American patients with respect to B8-DR3-DQ2HLA. A clinical correlation, e.g. difference in severity or treatability of AIH type 1, has yet to be determined.

  13. Lack of immunological analogy between the beta-subunits of cholera toxin and human choriogonadotropin.

    Science.gov (United States)

    Acevedo, H F; Kellen, J A

    1986-01-01

    A chemical relatedness has been described between the beta-subunit of cholera toxin and that of the four dimeric glycoprotein hormones (hCG, hLH, hFSH and hTSH). However, antibodies induced by cholera toxin did not crossreact, when tested by labeled hCG binding and immunocytochemistry, with the beta-subunit of hCG. It appears that differences in the tertiary structures, as shown in this study, account for distinct epitopes. Similarities in biological activity between these two compounds, such as induction of adenyl cyclase or a protective effect against some tumors, are not based on immunological mechanisms.

  14. Monoclonal antibodies in human organ transplantation and auto-immune diseases.

    Science.gov (United States)

    Wijdenes, J; Roy, C; Morel-Fourrier, B; Racadot, E

    1992-01-01

    The usefulness of monoclonal antibodies (mAbs) in the transplantation field has become evident over the last couple of years. Different mAbs have been used as a prophylactic treatment after transplantation, in a therapeutic way against acute organ rejection and new diagnostic tools to predict clinical rejection immerge. One can even hope that with humanised mAbs or human mAbs obtained by repertoire cloning the formation of human anti-mouse antibodies will be solved although on the one hand this appeared not to be a big problem and on the other hand anti-idiotypic antibodies can still be expected. However, the most puzzling question is how the mAbs modulates the immuno-response and this not only in organ rejection but also in auto-immune diseases. Only one out of many CD25 mAbs with seemingly similar epitope recognition can be used in therapeutical treatment of acute Graft versus Host Disease. The same mAb is not, however, very efficient in the prophylactic treatment of kidney transplantation without association of suboptimal doses of cyclosporin A. Another example is a CD4 mAb which is efficient in the treatment of polyarthritis with no side effects but which provokes transient but clear side effects when used in psoriasis or multiple sclerosis patients. A second CD4 mAb with high inhibitory activity in several bioassays compared to the first CD4 mAb has no beneficial effect at all on polyarthritis. Also the question why there is a percentage of "no response" patients among apparently identical "good response" patients remains unanswered. However it becomes clear from these experiences that: 1) mAbs recognizing a similar epitope and being of the same isotype will not automatically have the same effect in therapy. 2) side effects may be depending of the disease treated. 3) the activities of mAbs in bioassays and even animal models very often do not reflect the in vivo situation in human. 4) efficiency of the treatment with mAbs can be increased by a better

  15. The critical role of epigenetics in systemic lupus erythematosus and autoimmunity.

    Science.gov (United States)

    Long, Hai; Yin, Heng; Wang, Ling; Gershwin, M Eric; Lu, Qianjin

    2016-11-01

    One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary

  16. Immunological alterations in hepatitis C virus infection.

    Science.gov (United States)

    Calvaruso, Vincenza; Craxì, Antonio

    2013-12-21

    A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

  17. Immunological responses to envelope glycoprotein 120 from subtypes of human immunodeficiency virus type 1.

    Science.gov (United States)

    Gilljam, G; Svensson, A; Ekström, A; Wahren, B

    1999-07-01

    The outer envelope glycoprotein (gp120) from subtypes A-E of HIV-1 was purified using a specific high mannose-binding lectin, Galanthus nivalis agglutinin. All isolates were grown in peripheral blood lymphocyte cells in order to avoid selection in cell lines. A comparison of the reactivities of the envelope proteins was made using sera from patients infected with the different subtypes. In this study, the B and C subtype envelope glycoproteins showed the strongest immunological reactivity, when reacted with sera from patients infected with the same subtype of virus. On the other hand, sera of patients infected with subtype A or C virus had the strongest and broadest reactivities, to envelope glycoproteins of many subtypes. The purified gp120 proteins from all five subtypes stimulated mononuclear cells from HIV-1 (subtype B)-infected patients, indicating conserved T cell-activating epitopes. The immunological reactivities indicate that strong antigenicity does not always predict the broadest immunogenicity of an envelope glycoprotein. Glycoprotein 120 from foreign subtypes may serve to induce strong cross-reactive immune responses.

  18. Autoimmune Addison's disease.

    Science.gov (United States)

    Napier, Catherine; Pearce, Simon H S

    2012-12-01

    Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

  19. Comparison of cytotoxicity, genotoxicity and immunological inflammatory biomarker activity of several endodontic sealers against immortalized human pulp cells.

    Science.gov (United States)

    Martinho, F C; Camargo, S E A; Fernandes, A M M; Campos, M S; Prado, R F; Camargo, C H R; Valera, M C

    2017-04-25

    To establish an SV40 T-Ag-transfected cell line of human pulp-derived cells in order to compare the cytotoxicity, genotoxicity and to investigate the activities of immunological biomarkers of several endodontic sealers. Primary human pulp cells and transfected cells were cultured. Cell morphology and proliferation were analysed, and the expression of cell-specific gene transcripts and proteins was detected by RT-PCR and immunohistochemistry. Transfection of human pulp-derived cells resulted in an immortalized cell line retaining phenotypic characteristics from the primarily cells tested. The SV40 T-Ag-transfected cells were cultured and stimulated by sealers (Apexit Plus, Real Seal, AH Plus, and EndoREZ) to evaluate the cytotoxicity and genotoxicity by MTT and MTN assays, respectively. Immunological inflammatory biomarkers (IL6, IL8 and TNF-α) were determined by ELISA assay. The differences between median values were statistically analysed using Kruskal-Wallis and Dunn's tests at 5% significance level. The cytotoxicity assay revealed that multimethacrylate (Real Seal) was the most cytotoxic sealer (P root canal sealers tested were able to stimulate the immortalized pulp cells to produce IL-6, IL-8 and TNF-α, with differences in relation to the control group (P sealers tested (P epoxy resin-based sealer (AHPlus), single-methacrylate sealer (EndoREZ) and calcium hydroxide-based sealer (Apexit Plus), regardless of the cytokine investigated (all P > 0.05). A SV40 T-Ag-transfected cell line of human pulp-derived cells was established. The methacrylate resin-based sealer (Real Seal) exhibited the greatest cytoxicity and inflammatory potential against immortalized pulp cells compared to an epoxy resin-based sealer (AH Plus), a methacrylate-based sealer (EndoRez) and a calcium hydroxide-based sealer (Apexit). © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  20. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  1. AIRE-mutations and autoimmune disease.

    Science.gov (United States)

    Bruserud, Øyvind; Oftedal, Bergithe E; Wolff, Anette B; Husebye, Eystein S

    2016-12-01

    The gene causing the severe organ-specific autoimmune disease autoimmune polyendocrine syndrome type-1 (APS-1) was identified in 1997 and named autoimmune regulator (AIRE). AIRE plays a key role in shaping central immunological tolerance by facilitating negative selection of T cells in the thymus, building the thymic microarchitecture, and inducing a specific subset of regulatory T cells. So far, about 100 mutations have been identified. Recent advances suggest that certain mutations located in the SAND and PHD1 domains exert a dominant negative effect on wild type AIRE resulting in milder seemingly common forms of autoimmune diseases, including pernicious anemia, vitiligo and autoimmune thyroid disease. These findings indicate that AIRE also contribute to autoimmunity in more common organ-specific autoimmune disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

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    Dae-Kwon Bae

    2016-01-01

    Full Text Available Since multiple sclerosis (MS is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG- induced experimental autoimmune encephalomyelitis (EAE model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP. The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, ciliary neurotrophic factor (CNTF, and leukemia inhibitory factor (LIF. In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

  3. T Cell Vaccination as an Immunotherapy for Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    Jingwu Zhang

    2004-01-01

    Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual's own T cell repertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactions of a variety of related surface molecules (1). It induces regulatory immune responses that closely resemble the in vivo situation where the immune system is challenged by clonal activation and expansion of given T cell populations in various autoimmune diseases. T cell vaccination provides a powerful means of eliciting natural reactions of the immune system in response to clonal expansion of T cells, which can used as a therapeutic approach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinical trials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun to reveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing a unique opportunity to test the autoimmune theories in a clinical setting. Cellular & Molecular Immunology.2004;1(5):321-327.

  4. The experimental autoimmune encephalomyelitis model for proteomic biomarker studies : From rat to human

    NARCIS (Netherlands)

    Rosenling, Therese; Attali, Amos; Luider, Theo M.; Bischoff, Rainer

    2011-01-01

    Multiple sclerosis (MScl) is defined by central nervous system (CNS) inflammation, demyelination and axonal damage. Some of the disease mechanisms are known but the cause of this complex disorder stays an enigma. Experimental autoimmune encephalomyelitis (EAE) is an animal model mimicking many aspec

  5. CD8+ T cells in human autoimmune arthritis : The unusual suspects

    NARCIS (Netherlands)

    Petrelli, Alessandra; Van Wijk, Femke

    2016-01-01

    CD8+ T cells are key players in the body's defence against viral infections and cancer. To date, data on the role of CD8+ T cells in autoimmune diseases have been scarce, especially when compared with the wealth of research on CD4+ T cells. However, growing evidence suggests that CD8+ T-cell homeost

  6. Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors

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    Targoni Oleg S

    2005-06-01

    Full Text Available Abstract Background One means of treating osteoarthritis is with autologous or allogeneic osteochondral grafts. The purpose of this study was to evaluate the innate immunological response in humans toward xeno-derived osteochondral grafts that have been partially or entirely treated by the photooxidation process. Methods The antigens tested included bovine, porcine, ovine and equine osteochondral samples that have been treated in successive steps of photooxidation. ELISPOT assays were used to evaluate the production of IL-1, IL-4, IL-6, IL-10, IL-12 and TNF-α by human monocytes in response to the antigens. Results Results indicated vigorous production of IL-1, IL-6, IL-10 and TNF-α in response to untreated bovine, porcine and equine specimens. This indicates that these samples are perceived as foreign, or stimulatory, by the human monocytes. There was no induction of IL-4 or IL-12, which is required for Th2 and Th1 immunity, respectively. In contrast, the processed bovine, porcine and equine samples did not induce significant activation of cells of the innate immune system. This occurred after the first step in processing (after cleaning in increasing strengths of ethanol. This suggests that the processing steps dramatically, if not completely, negated the immunostimulatory properties of the test sample. The results for the ovine samples indicate a reverse response. Conclusion The findings of the study suggest that photooxidized bovine, porcine or equine samples have the potential to be used as an osteochondral graft. Although the first step in processing reduced the immunological response, photooxidation is still necessary to retain the structure and mechanical integrity of the cartilage, which would allow for immediate joint resurfacing.

  7. Plasmacytoid Dendritic Cell Activation and IFN-α Production Are Prominent Features of Murine Autoimmune Pancreatitis and Human IgG4-Related Autoimmune Pancreatitis.

    Science.gov (United States)

    Arai, Yasuyuki; Yamashita, Kouhei; Kuriyama, Katsutoshi; Shiokawa, Masahiro; Kodama, Yuzo; Sakurai, Toshiharu; Mizugishi, Kiyomi; Uchida, Kazushige; Kadowaki, Norimitsu; Takaori-Kondo, Akifumi; Kudo, Masatoshi; Okazaki, Kazuichi; Strober, Warren; Chiba, Tsutomu; Watanabe, Tomohiro

    2015-10-01

    The abnormal immune response accompanying IgG4-related autoimmune pancreatitis (AIP) is presently unclear. In this study, we examined the role of plasmacytoid dendritic cell (pDC) activation and IFN-α production in this disease as well as in a murine model of AIP (MRL/Mp mice treated with polyinosinic-polycytidylic acid). We found that the development of AIP in treated MRL/Mp mice occurred in parallel with pancreatic accumulation of pDCs producing IFN-α, and with pDC depletion and IFN-α-blocking studies, we showed that such accumulation was necessary for AIP induction. In addition, we found that the pancreas of treated MRL/Mp mice contained neutrophil extracellular traps (NETs) shown previously to stimulate pDCs to produce IFN-α. Consistent with these findings, we found that patients with IgG4-related AIP also exhibited pancreatic tissue localization of IFN-α-expressing pDCs and had significantly higher serum IFN-α levels than healthy controls. In addition, the inflamed pancreas of these patients but not controls also contained NETs that were shown to be capable of pDC activation. More importantly, patient pDCs cultured in the presence of NETs produced greatly increased levels of IFN-α and induced control B cells to produce IgG4 (but not IgG1) as compared with control pDCs. These data suggest that pDC activation and production of IFN-α is a major cause of murine AIP; in addition, the increased pDC production of IFN-α and its relation to IgG4 production observed in IgG4-related AIP suggest that this mechanism also plays a role in the human disease.

  8. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

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    Ana M. C. Faria

    2006-01-01

    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  9. Autoimmune epilepsy.

    Science.gov (United States)

    Greco, Antonio; Rizzo, Maria Ida; De Virgilio, Armando; Conte, Michela; Gallo, Andrea; Attanasio, Giuseppe; Ruoppolo, Giovanni; de Vincentiis, Marco

    2016-03-01

    Despite the fact that epilepsy is the third most common chronic brain disorder, relatively little is known about the processes leading to the generation of seizures. Accumulating data support an autoimmune basis in patients with antiepileptic drug-resistant seizures. Besides, recent studies show that epilepsy and autoimmune disease frequently co-occur. Autoimmune epilepsy is increasingly recognized in the spectrum of neurological disorders characterized by detection of neural autoantibodies in serum or spinal fluid and responsiveness to immunotherapy. An autoimmune cause is suspected based on frequent or medically intractable seizures and the presence of at least one neural antibody, inflammatory changes indicated in serum or spinal fluid or on MRI, or a personal or family history of autoimmunity. It is essential that an autoimmune etiology be considered in the initial differential diagnosis of new onset epilepsy, because early immunotherapy assures an optimal outcome for the patient.

  10. The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases

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    Rodney Dietert

    2012-10-01

    Full Text Available In this review, we discuss an immunological-driven sign termed the Completed Self, which is related to a holistic determination of health vs. disease. This sign (human plus commensal microbiota forms the human superorganism. The worldwide emergence of an epidemic of chronic diseases has caused increased healthcare costs, increased premature mortality and reduced quality of life for a majority of the world’s population. In addition, it has raised questions concerning the interactions between humans and their environment and potential imbalances. Misregulated inflammation, a host defense-homeostasis disorder, appears to be a key biomarker connecting a majority of chronic diseases. We consider the apparent contributors to this disorder that promote a web of interlinked comorbid conditions. Three key events are suggested to play a role: (1 altered epigenetic programming (AEP that may span multiple generations, (2 developmental immunotoxicity (DIT, and (3 failure to adequately incorporate commensal microbes as a newborn (i.e., the incomplete self. We discuss how these three events can combine to determine whether the human superorganism is able to adequately and completely form during early childhood. We also discuss how corruption of this event can affect the risk of later-life diseases.

  11. Immunogenetics and genetic susceptibility in the pathogenesis of autoimmune hepatitis

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    Das Anup K

    2014-11-01

    Full Text Available vAutoimmune hepatitis is a progressive liver disease. Its pathogenesis is unclear, but needs a ‘trigger’ to initiate the disease in a genetically susceptible person. The susceptibility is partly related to MHCII class genes, and more so with human leukocyte antigen (HLA. Several mechanisms have been proposed which, however, cannot fully explain the immunologic findings in autoimmune hepatitis. The susceptibility to any autoimmune disease is determined by several factors where genetic and immunological alterations, along with, environmental factor are active. MHCII antigens as a marker for AIH, or a predictor of treatment response and prognosis has been investigated. Since MHCII antigens show significant ethnic heterogeneity, mutations in MHCII may merely act as only precursors of the surface markers of immune cells, which can be of significance, because the changes in HLA and MHC are missing in certain populations. One such marker is the CTLA-4 (CD152 gene mutation, reported in the phenotypes representing susceptibility to AIH. Other candidate genes of cytokines, TNF, TGF-beta1 etc, have also been investigated but with unvalidated results. Paediatric AIH show differences in genetic susceptibility. Genetic susceptibility or resistance to AIH may be associated with polypeptides in DRB1 with certain amino-acid sequences. Understanding which genes are implicated in genesis and/or disease progression will obviously help to identify key pathways in AIH and provide better insights into its pathogenesis. But studies to identify responsible genes are complex because of the complex trait of AIH.

  12. [Autoimmune hepatitis].

    Science.gov (United States)

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  13. Autoimmune hepatitis

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2010:chap 88. Read More Autoimmune disorders Chronic thyroiditis (Hashimoto disease) Cirrhosis Glomerulonephritis Hemolytic anemia Liver cancer - hepatocellular carcinoma Mesenteric venous thrombosis Type ...

  14. The genetics of human autoimmune disease: A perspective on progress in the field and future directions.

    Science.gov (United States)

    Seldin, Michael F

    2015-11-01

    Progress in defining the genetics of autoimmune disease has been dramatically enhanced by large scale genetic studies. Genome-wide approaches, examining hundreds or for some diseases thousands of cases and controls, have been implemented using high throughput genotyping and appropriate algorithms to provide a wealth of data over the last decade. These studies have identified hundreds of non-HLA loci as well as further defining HLA variations that predispose to different autoimmune diseases. These studies to identify genetic risk loci are also complemented by progress in gene expression studies including definition of expression quantitative trait loci (eQTL), various alterations in chromatin structure including histone marks, DNase I sensitivity, repressed chromatin regions as well as transcript factor binding sites. Integration of this information can partially explain why particular variations can alter proclivity to autoimmune phenotypes. Despite our incomplete knowledge base with only partial definition of hereditary factors and possible functional connections, this progress has and will continue to facilitate a better understanding of critical pathways and critical changes in immunoregulation. Advances in defining and understanding functional variants potentially can lead to both novel therapeutics and personalized medicine in which therapeutic approaches are chosen based on particular molecular phenotypes and genomic alterations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Psoriasis and autoimmunity.

    Science.gov (United States)

    Sticherling, Michael

    2016-12-01

    Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.

  16. Target Proteins in Human Autoimmunity: Cytochromes P450 and Udp-Glycoronosyltransferases

    Directory of Open Access Journals (Sweden)

    Petra Obermayer-Straub

    2000-01-01

    Full Text Available Cytochromes P450 (CYPs and UDP-glucuronosyltransferases (UGTs are targets of autoantibodies in several hepatic and extrahepatic autoimmune diseases. Autoantibodies directed against hepatic CYPs and UGTs were first detected by indirect immunofluorescence as antiliver and/or kidney microsomal antibodies. In autoimmune hepatitis (AIH type 2, liver and/or kidney microsomal (LKM type 1 autoantibodies are detected and are directed against CYP2D6. About 10% of AIH-2 sera further contain LKM-3 autoantibodies directed against family 1 UGTs. Chronic infections by hepatitis C virus and hepatitis delta virus may induce several autoimmune phenomena, and multiple autoantibodies are detected. Anti-CYP2D6 autoantibodies are detected in up to 4% of patients with chronic hepatitis C, and anti-CYP2A6 autoantibodies are detected in about 2% of these patients. In contrast, 14% of patients with chronic hepatitis delta virus infections generate anti-UGT autoantibodies. In a small minority of patients, certain drugs are known to induce immune-mediated, idiosyncratic drug reactions, also known as ’drug-induced hepatitis’. Drug-induced hepatitis is often associated with autoantibodies directed against hepatic CYPs or other hepatic proteins. Typical examples are tienilic acid-induced hepatitis with anti-CYP2C9, dihydralazine hepatitis with anti-CYP1A2, halothane hepatitis with anti-CYP2E1 and anticonvulsant hepatitis with anti-CYP3A. Recent data suggest that alcoholic liver disease may be induced by mechanisms similar to those that are active in drug-induced hepatitis. Autoantibodies directed against several CYPs are further detected in sera from patients with the autoimmune polyglandular syndrome type 1. Patients with autoimmune polyglandular syndrome type 1 with hepatitis often develop anti-CYP1A2; patients with adrenal failure develop anti-CYP21, anti- CYP11A1 or CYP17; and patients with gonadal failure develop anti-CYP11A1 or CYP17. In idiopathic Addison disease

  17. RADIOECOLOGY AND ECOLOGICAL IMMUNOLOGY

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    V. M. Shubik

    2009-01-01

    Full Text Available The author's investigations results are presented in comparing with literary materials concerning the application of principles and methods of ecological immunology for solving radioecological questions. The data on characteristic of immunity and health of human population affected with radiation factors of the environment is given as well as animals' population state as the links offood ecological chains.

  18. Persistent human papillomavirus infection in the etiology of cervical carcinoma: The role of immunological, genetic, viral and cellular factors

    Directory of Open Access Journals (Sweden)

    Živadinović Radomir

    2014-01-01

    Full Text Available The aim of this paper was to present the role of human papillomavirus (HPV in cervical carcinogenesis from several aspects. By explaining the HPV virus lifecycle and structure, its effect on cervical cell cycle and subversion of immune response can be better understood. Early E region of the viral genome encodes proteins that are directly involved in carcinogenesis. The E6 protein binds to p53 protein (product of tumor-suppressor gene blocking and degrading it, which in turn prevents cell cycle arrest and apoptosis induction. E6 is also capable of telomerase activation, which leads to cell immortalization; it also reacts with host proto-oncogene c-jun, responsible for transcription, shortens G1 phase and speeds up the transition from G1 to S phase of the cells infected by HPV. E7 forms bonds with retinoblastoma protein (product of tumor-suppressor gene and inactivates it. It can inactivate cyclin inhibitors p21, p27, and abrogate the mitotic spindle checkpoint with the loss of protective effect of pRB and p53. The immune system cannot initiate early immunological reaction since the virus is non-lytic, while the concentration of viral proteins - antigens is low and has a basal intracellular position. Presentation through Langerhans cells (LC is weak, because the number of these cells is low due to the effect of HPV. E7 HPV reduces the expression of E-cadherin, which is responsible for LC adhesion to HPVtransformed keratinocytes. Based on these considerations, it may be concluded that the process of cervical carcinogenesis includes viral, genetic, cellular, molecular-biological, endocrine, exocrine and immunological factors.

  19. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

    Science.gov (United States)

    Piketty, C; Weiss, L; Thomas, F; Mohamed, A S; Belec, L; Kazatchkine, M D

    2001-05-01

    Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

  20. Autoimmunity against laminins.

    Science.gov (United States)

    Florea, Florina; Koch, Manuel; Hashimoto, Takashi; Sitaru, Cassian

    2016-09-01

    Laminins are ubiquitous constituents of the basement membranes with major architectural and functional role as supported by the fact that absence or mutations of laminins lead to either lethal or severely impairing phenotypes. Besides genetic defects, laminins are involved in a wide range of human diseases including cancer, infections, and inflammatory diseases, as well as autoimmune disorders. A growing body of evidence implicates several laminin chains as autoantigens in blistering skin diseases, collagenoses, vasculitis, or post-infectious autoimmunity. The current paper reviews the existing knowledge on autoimmunity against laminins referring to both experimental and clinical data, and on therapeutic implications of anti-laminin antibodies. Further investigation of relevant laminin epitopes in pathogenic autoimmunity would facilitate the development of appropriate diagnostic tools for thorough characterization of patients' antibody specificities and should decisively contribute to designing more specific therapeutic interventions.

  1. [Autoimmune syndrome in the tropical spastic paraparesis/myelopathy associated with human T-lymphotropic virus infections].

    Science.gov (United States)

    Domínguez, Martha C; Torres, Miyerlandi; Tamayo, Oscar; Criollo, William; Quintana, Milton; Sánchez, Adalberto; García, Felipe

    2008-12-01

    Previous reports have given evidence that in tropical spastic paraparesis (TSP)/human T-lymphotrophic virus (HTLV-I)-associated myelopathy (HAM), an autoimmune process occurs as part of its pathogenesis. The roles of autoimmunity and the molecular mimicry was evaluated in TSP/HAM patients. Plasma samples were characterized from patients in the Pacific coastal region of Colombia. Thirty-seven were identified as TSP/HAM, 10 were diagnosed with adult T-cell leukemia virus, 22 were asymptomatic carriers but seropositive for HTLV-I and 20 were seronegative and served as negative controls. Plasmatic levels of the following were determined: antinuclear antibody (ANA) levels, anticardiolipine-2 (ACL-2), interferon- (IFN-gamma) and interleukin-4 (IL-4). Using Western blot, the crossreactivity of the seropositive and seronegative samples was evaluated against proteins extracted from several central nervous system components of non infected Wistar rats. The HTLV-I seropositive plasmas were crossreacted with a monoclonal tax (LT4 anti-taxp40) from spinal cord neurons of non infected Wistar rats. Of the TSP/HAM patients, 70.2% were reactive against ANA and 83.8% against ACL-2, in contrast with those ATL and asymptomatic seropositives subjects that were not reactive (P<0.001). Moreover, 70.3% had detectable levels of IFN and 43.2% had detectable IL-4. LT4 anti-taxp40 and plasma of TSP/HAM exhibited cross reactivity with a MW 33-35 kDa protein from the rat spinal cord nuclei. Support was provided for the existence of an autoimmune syndrome mediated by molecular mimicry; the syndrome was responsible for some of the axonal degeneration observed in TSP/HAM patients.

  2. Autoimmune myelopathies.

    Science.gov (United States)

    Flanagan, Eoin P

    2016-01-01

    Autoimmune myelopathies are a heterogeneous group of immune-mediated spinal cord disorders with a broad differential diagnosis. They encompass myelopathies with an immune attack on the spinal cord (e.g., aquaporin-4-IgG (AQP4-IgG) seropositive neuromyelitis optica (NMO) and its spectrum disorders (NMOSD)), myelopathies occurring with systemic autoimmune disorders (which may also be due to coexisting NMO/NMOSD), paraneoplastic autoimmune myelopathies, postinfectious autoimmune myelopathies (e.g., acute disseminated encephalomyelitis), and myelopathies thought to be immune-related (e.g., multiple sclerosis and spinal cord sarcoidosis). Spine magnetic resonance imaging is extremely useful in the evaluation of autoimmune myelopathies as the location of signal change, length of the lesion, gadolinium enhancement pattern, and evolution over time narrow the differential diagnosis considerably. The recent discovery of multiple novel neural-specific autoantibodies accompanying autoimmune myelopathies has improved their classification. These autoantibodies may be pathogenic (e.g., AQP4-IgG) or nonpathogenic and more reflective of a cytotoxic T-cell-mediated autoimmune response (collapsin response mediator protein-5(CRMP5)-IgG). The presence of an autoantibody may help guide cancer search, assist treatment decisions, and predict outcome/relapse. With paraneoplastic myelopathies the initial goal is detection and treatment of the underlying cancer. The aim of immunotherapy in all autoimmune myelopathies is to maximize reversibility, maintain benefits (while preventing relapse), and minimize side effects.

  3. The Biological Significance of Evolution in Autoimmune Phenomena

    Directory of Open Access Journals (Sweden)

    Carlos A. Cañas

    2012-01-01

    Full Text Available It is an inherent part of living to be in constant modification, which are due to answers resulting from environmental changes. The different systems make adaptations based on natural selection. With respect to the immune system of mammals, these changes have a lot to do with the interactions that occur continuously with other living species, especially microorganisms. The immune system is primarily designed to defend from germs and this response triggers inflammatory reactions which must be regulated in order not to generate damage to healthy tissue. The regulatory processes were added over time to prevent such damage. Through evolution the species have stored “an immunological experience,” which provides information that is important for developing effective responses in the future. The human species, which is at a high level of evolutionary immunological accumulation, have multiple immune defense strategies which, in turn, are highly regulated. Imbalances in these can result in autoimmunity.

  4. Circular Dichroism and Fluorescence Spectroscopic Study of RNA-protein Folding Patterns in Human hnRNP A3 and Their Implications in Human Autoimmune Diseases

    Institute of Scientific and Technical Information of China (English)

    E.SüLEYMANO(G)LU

    2004-01-01

    In human cells, the heterogeneous nuclear ribonucleoproteins (hnRNP) are represented by a group of polypeptides, with various molecular properties, comprizing the most abundant constituents of the cell nucleus. Autoantibodies to hnRNPs have been reported in patients suffering from different rheumatic dieseases since 1980s. Experimental evidence indicates that hnRNP complexes undergo substantial structural changes during mRNA formation and export. However, how this contributes to disease development still has to be elucidated. Here some preliminary physicochemical features of RNA-protein folding and stability patterns of newly characterized hnRNP A3 with further functional implications in development of systemic human autoimmune states are reported.

  5. Human endogenous retroviral genetic element with immune suppressive activity in both human autoimmune diseases and experimental arthritis

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Troldborg, Anne; Hauge, Ellen-Margrethe

    2016-01-01

    HERV locus was identified as a potential modulator of autoimmunity in this way. The env gene encoded by this HERV locus was cloned and examined for the ability to express a functional protein with immune suppressive potential. RESULTS: We show that the expression of the Env59 gene is negatively...

  6. cDNA immunization of mice with human thyroglobulin generates both humoral and T cell responses: a novel model of thyroid autoimmunity.

    Directory of Open Access Journals (Sweden)

    Eric M Jacobson

    Full Text Available Thyroglobulin (Tg represents one of the largest known self-antigens involved in autoimmunity. Numerous studies have implicated it in triggering and perpetuating the autoimmune response in autoimmune thyroid diseases (AITD. Indeed, traditional models of autoimmune thyroid disease, experimental autoimmune thyroiditis (EAT, are generated by immunizing mice with thyroglobulin protein in conjunction with an adjuvant, or by high repeated doses of Tg alone, without adjuvant. These extant models are limited in their experimental flexibility, i.e. the ability to make modifications to the Tg used in immunizations. In this study, we have immunized mice with a plasmid cDNA encoding the full-length human Tg (hTG protein, in order to generate a model of Hashimoto's thyroiditis which is closer to the human disease and does not require adjuvants to breakdown tolerance. Human thyroglobulin cDNA was injected and subsequently electroporated into skeletal muscle using a square wave generator. Following hTg cDNA immunizations, the mice developed both B and T cell responses to Tg, albeit with no evidence of lymphocytic infiltration of the thyroid. This novel model will afford investigators the means to test various hypotheses which were unavailable with the previous EAT models, specifically the effects of hTg sequence variations on the induction of thyroiditis.

  7. Immunological Effects of Silica and Asbestos

    Institute of Scientific and Technical Information of China (English)

    Takemi Otsuki; Fuminori Hyodoh; Ayako Ueki; Yasumitsu Nishimura; Megumi Maeda; Shuko Murakami; Hiroaki Hayashi; Yoshie Miura; Masayasu Kusaka; Takashi Nakano; Kazuya Fukuoka; Takumi Kishimoto

    2007-01-01

    Silicosis patients (SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis (known as Caplan syndrome), and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occurr in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition,immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cellmediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestosrelated malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.

  8. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss.

    Science.gov (United States)

    Yoo, T J; Du, Xiaoping; Zhou, Bin

    2015-12-01

    The aim of this study was to examine the activities of hASCs (Human Adipose tissue Derived Stem Cells) on experimental autoimmune hearing loss (EAHL) and how human stem cells regenerated mouse cochlea cells. We have restored hearing in 19 years old white female with autoimmune hearing loss with autologous adipose tissue derived stem cells and we wish to understand the mechanism of restoration of hearing in animal model. BALB/c mice underwent to develop EAHL; mice with EAHL were given hASCs intraperitoneally once a week for 6 consecutive weeks. ABR were examined over time. The helper type 1 autoreactive responses and T-reg cells were examined. H&E staining or immunostaining with APC conjugated anti-HLA-ABC antibody were conducted. The organ of Corti, stria vascularis, spira ligament and spiral ganglion in stem cell group are normal. In control group, without receiving stem cells, the organ of Corti is replaced by a single layer of cells, atrophy of stria vascularis. Systemic infusion of hASCs significantly improved hearing function and protected hair cells in established EAHL. The hASCs decreased the proliferation of antigen specific Th1/Th17 cells and induced the production of anti-inflammatory cytokine interleukin10 in splenocytes. They also induced the generation of antigen specific CD4(+)CD25(+)Foxp3(+)T-reg cells. The experiment showed the restoration is due to the paracrine activities of human stem cells, since there are newly regenerated mice spiral ganglion cells, not human mesenchymal stem cells derived tissue given by intraperitoneally.

  9. Novel mutations in TNFRSF7/CD27 : Clinical, immunologic, and genetic characterization of human CD27 deficiency

    NARCIS (Netherlands)

    Alkhairy, Omar K.; Perez-Becker, Ruy; Driessen, Gertjan J.; Abolhassani, Hassan; van Montfrans, JM; Borte, Stephan; Choo, Sharon; Wang, Ning; Tesselaar, Kiki; Fang, Mingyan; Bienemann, Kirsten; Boztug, Kaan; Daneva, Ana; Mechinaud, Francoise; Wiesel, Thomas; Becker, Christian; Duckers, Gregor; Siepermann, Kathrin; van Zelm, Menno C.; Rezaei, Nima; van der Burg, Mirjam; Aghamohammadi, Asghar; Seidel, Markus G.; Niehues, Tim; Hammarstrom, Lennart

    Background: The clinical and immunologic features of CD27 deficiency remain obscure because only a few patients have been identified to date. Objective: We sought to identify novel mutations in TNFRSF7/CD27 and to provide an overview of clinical, immunologic, and laboratory phenotypes in patients

  10. Growth potential of human hepatocarcinoma cells in the liver of neonatal immunocompetent mice and its relation to immunological tolerance

    Institute of Scientific and Technical Information of China (English)

    Ze Wang; Zengliang Bai; Hui Zhang; Tianxiao Huan; Juan Li; Xiumin Du; Jingping Zhang

    2009-01-01

    To determine the pathological behavior of human hepatocarcinoma cells in the liver microenvironment of neonatal non-immunode-ficient mice, three human hepatocarcinoma cell lines (Be7402, HepG2, and SK-Hep-1), traced by Dil, were transplanted into the intrahepatic or subcutaneous tissue of neonatal and adult Kunming mice. Histopathological observations showed that cells in the adult liver induced a severe immune response as early as the second day after the implantation, while the subcutaneous neoplasm underwent extensive necrosis by the end of the study. Only the cells injected into the neonatal liver underwent a delayed immunologic rejection in the organ mieroenvironment. These cells retained recognizable tumor features over the first seven days, and displayed an intrahepatic inva-sive pattern. The expression of tumor markers including alpha-fetoprotein and survivin was maintained. The quantitative ELISA for the expression patterns of IL-2 and IL-10 also confirmed that the intrahepatic immunity was non-susceptive during this period. The high serum alpha-fetoprotein level was inversely correlated with the change in immune response. Our study provided a bio-system for the research of immune responses to xenografts in the liver.

  11. From autoimmunity to autoimmune disease

    NARCIS (Netherlands)

    Franco Salinas, G.

    2012-01-01

    This thesis describes several mechanisms in which T and B lymphocytes, together with the costimulatory molecules and cytokines that influence their behavior, are fundamental in the progression of autoimmunity to autoimmune disease. If these mechanisms can be understood in greater detail, more

  12. Novel marmoset (Callithrix jacchus model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization.

    Directory of Open Access Journals (Sweden)

    Emily Leibovitch

    2013-01-01

    Full Text Available Human Herpesvirus 6 (HHV-6 is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders.

  13. Novel marmoset (Callithrix jacchus) model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization.

    Science.gov (United States)

    Leibovitch, Emily; Wohler, Jillian E; Cummings Macri, Sheila M; Motanic, Kelsey; Harberts, Erin; Gaitán, María I; Maggi, Pietro; Ellis, Mary; Westmoreland, Susan; Silva, Afonso; Reich, Daniel S; Jacobson, Steven

    2013-01-01

    Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders.

  14. Autoimmune gastritis.

    Science.gov (United States)

    Kulnigg-Dabsch, Stefanie

    2016-10-01

    Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

  15. Autoimmune paediatric liver disease

    Institute of Scientific and Technical Information of China (English)

    Giorgina Mieli-Vergani; Diego Vergani

    2008-01-01

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of

  16. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Hashimoto's Thyroiditis and Autoimmune Gastritis.

    Science.gov (United States)

    Cellini, Miriam; Santaguida, Maria Giulia; Virili, Camilla; Capriello, Silvia; Brusca, Nunzia; Gargano, Lucilla; Centanni, Marco

    2017-01-01

    The term "thyrogastric syndrome" defines the association between autoimmune thyroid disease and chronic autoimmune gastritis (CAG), and it was first described in the early 1960s. More recently, this association has been included in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis represents the pivotal disorder. Hashimoto's thyroiditis (HT) is the most frequent autoimmune disease, and it has been reported to be associated with gastric disorders in 10-40% of patients while about 40% of patients with autoimmune gastritis also present HT. Some intriguing similarities have been described about the pathogenic mechanism of these two disorders, involving a complex interaction among genetic, embryological, immunologic, and environmental factors. CAG is characterized by a partial or total disappearance of parietal cells implying the impairment of both hydrochloric acid and intrinsic factor production. The clinical outcome of this gastric damage is the occurrence of a hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia concomitant with the progression to a severe gastric atrophy. Malabsorption of levothyroxine may occur as well. We have briefly summarized in this minireview the most recent achievements on this peculiar association of diseases that, in the last years, have been increasingly diagnosed.

  18. Autoimmune Hemolytic Anemia Triggered by Infection with Human Parvovirus B19 after Total Abdominal Colectomy for Ulcerative Colitis.

    Science.gov (United States)

    Iida, Tomoya; Satoh, Shuji; Nakagaki, Suguru; Shimizu, Haruo; Kaneto, Hiroyuki

    2016-01-01

    A 50-year-old man was admitted to our hospital for an adhesive ileus 14 years after total abdominal colectomy for ulcerative colitis (UC). The ileus decreased with conservative treatment, however, autoimmune hemolytic anemia (AIHA) was diagnosed due to worsening anemia, a positive direct Coombs test, low haptoglobin, high lactase dehydrogenase, reticulocytosis, and an increase in the erythroblastic series in a bone-marrow examination. Human parvovirus B19 (PV-B19) IgM and PV-B19 DNA were present, indicating the development of AIHA triggered by an infection with PV-B19. The patient is currently being monitored after spontaneous remission. This is the first report of UC after total abdominal colectomy complicated by AIHA triggered by PV-B19 infection.

  19. Utilizing population variation, vaccination, and systems biology to study human immunology.

    Science.gov (United States)

    Tsang, John S

    2015-08-01

    The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis.

  20. Autoimmune hypophysitis.

    Science.gov (United States)

    Ezzat, S; Josse, R G

    1997-03-01

    Autoimmune (lymphocytic) hypophysitis has emerged as a distinct and specific clinical and pathological disease entity. Although relatively rare compared with other autoimmune endocrine diseases, nearly a hundred cases have been described. The condition is much more common in females (9:1) and appears to have a particular predilection for the pregnant and postpartum states. The anterior pituitary, and less often the neurohypophysis, appear to be the target for inflammatory autoimmune destruction. During the evolution of the disease process, pituitary hyperfunction (usually hyperprolactinemia) has been noted. This disease should now be included in the differential diagnosis of pituitary disorders, especially in females presenting with pituitary enlargement, particularly if symptoms occur in temporal relationship to pregnancy. The disease may form part of the spectrum of the polyglandular autoimmune endocrine disorders. (Trends Endocrinol Metab 1997;8:74-80). (c) 1997, Elsevier Science Inc.

  1. Autoimmune hepatitis.

    Science.gov (United States)

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  2. Autoimmune disorders

    Science.gov (United States)

    ... as azathioprine, cyclophosphamide, mycophenolate, sirolimus, or tacrolimus. Targeted drugs called tumor necrosis factor (TFN) blockers can be used for some diseases. Outlook (Prognosis) The outcome depends on the disease. Most autoimmune diseases are chronic , but many can be controlled ...

  3. Autoimmune Hepatitis

    Science.gov (United States)

    ... the digestive tract Graves' disease, the most common cause of hyperthyroidism in the United States Hashimoto's disease, also called chronic lymphocytic thyroiditis or autoimmune thyroiditis, a form of chronic inflammation ... which causes irritation, scarring, and narrowing of the bile ducts ...

  4. Experimental mouse tumour models: what can be learnt about human cancer immunology?

    Science.gov (United States)

    Dranoff, Glenn

    2011-12-02

    The recent demonstration that cancer immunotherapy extends patient survival has reinvigorated interest in elucidating the role of immunity in tumour pathogenesis. Experimental mouse tumour models have provided key mechanistic insights into host antitumour immune responses, and these have guided the development of novel treatment strategies. To accelerate the translation of these findings into clinical benefits, investigators need to gain a better understanding of the strengths and limitations of mouse model systems as tools for deciphering human antitumour immune responses.

  5. Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases.

    Directory of Open Access Journals (Sweden)

    Jiunn-Diann Lin

    Full Text Available The B-lymphocyte-activating factor (BAFF is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs. In this study, we explored possible associations of two BAFF single-nucleotide polymorphisms (SNPs, rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs in an ethnic Chinese population.In total, 319 Graves' disease (GD, 83 Hashimoto's thyroiditis (HT patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569.There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR = 0.76, and p = 0.017, OR = 0.68, respectively and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively. The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb (p = 0.015 in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb (TSHRAb and Hashimoto's autoantibody (anti-thyroglobulin or anti-microsomal antibody in females and with that of one type in males.rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.

  6. Immunological characterization of recombinantWuchereria bancrofti cuticular collagen (COL-4) as putative vaccine candidate for human lymphatic filariasis

    Institute of Scientific and Technical Information of China (English)

    Chakkaravarthy Arunkumar; Pandurangan Pandiaraja; P. R. Prince; Perumal Kaliraj

    2014-01-01

    Objective:To elucidate immunoprophylactic potential of recombinantWuchereria bancrofti(W. bancrofti) cuticular collagen(COL-4) inBALB/c mice and filarial clinical samples.Methods:col-4 gene wasPCR amplified fromW. bancroftiL3 cDNA library and cloned in pRSETB vector. RecombinantCOL-4 was over expressed in salt inducible system and was purified by nickel affinity chromatography.Humoral and cellular responses were measured byELISA and peripheral blood mononuclear cells(PBMC) of various filarial clinical samples respectively using purified recombinantCOL-4 antigen.Then the protective immune responses ofCOL-4 immunizedBALB/c mice were characterized.Results:Sequence analysis ofCOL-4 with human host proteins reveals lack of homology.The recombinantCOL-4 was found to be at15 kDa fusion protein.The affinity purifiedCOL-4 showed significant reactivity with putatively immune sera and in a similar fashion it demonstrated marked proliferation inPBMC samples.Immunization studies in experimental filarial host(mice) elicited significant titers with protective antibody isotype profile(IgM and IgG).Cellular immune responses were also significant in terms of splenocytes proliferation assay on mice samples.Conclusions:Our immunological findings in experimental host suggestTh2 mediated immune response.Hence, we propose thatW. bancroftiCOL-4 could be an efficacious vaccine candidate against lymphatic filariasis.

  7. Serum Cytokine Responses over the Entire Clinical-Immunological Spectrum of Human Leishmania (L. infantum chagasi Infection

    Directory of Open Access Journals (Sweden)

    Patrícia Karla Ramos

    2016-01-01

    Full Text Available The clinical-immunological spectrum of human Leishmania (L. infantum chagasi infection in Amazonian Brazil was recently reviewed based on clinical, DTH, and IFAT (IgG evaluations that identified five profiles: three asymptomatic (asymptomatic infection, AI; subclinical resistant infection, SRI; and indeterminate initial infection, III and two symptomatic (symptomatic infection, SI; American visceral leishmaniasis, AVL; and subclinical oligosymptomatic infection, SOI. TNF-α, IL-4, IL-6, and IL-10 serum cytokines were analyzed using multiplexed Cytometric Bead Array in 161 samples from endemic areas in the Brazilian Amazon: SI [AVL] (21 cases, III (49, SRI (19, SOI (12, AI (36, and a control group [CG] (24. The highest IL-6 serum levels were observed in the SI profile (AVL; higher IL-10 serum levels were observed in SI than in SOI or CG and in AI and III than in SOI; higher TNF-α serum levels were seen in SI than in CG. Positive correlations were found between IL-6 and IL-10 serum levels in the SI and III profiles and between IL-6 and TNF-α and between IL-4 and TNF-α in the III profile. These results provide strong evidence for associating IL-6 and IL-10 with the immunopathogenesis of AVL and help clarify the role of these cytokines in the infection spectrum.

  8. Autoimmune pancreatitis

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    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  9. Autoimmune hepatitis.

    Science.gov (United States)

    Strassburg, Christian P

    2010-10-01

    Autoimmune hepatitis is a chronic inflammatory disease of the liver with a dismal prognosis when left untreated. Key for the improvement of prognosis is a timely diagnosis before cirrhosis has developed. This is reached by the exclusion of other causes of hepatitis, elevated immunoglobulin G, autoantibody profile and histological assessment. Treatment achieves remission rates in 80% of individuals and consists of immunosuppression with corticosteroids and azathioprine. A recent randomised controlled multicenter trial has added budesonide to the effective treatment options in non-cirrhotic patients and leads to a reduction of unwanted steroid side effects. Autoimmune hepatitis is an autoimmune disease of unknown aetiology. Association studies of major histocompatibility complex and other genes demonstrate an influence of immunogenetics. However, apart from the autoimmune polyglandular syndrome type 1, in which 10% of patients suffer from an autoantibody-positive autoimmune hepatitis linked to mutations of the autoimmune regulator gene, there is no clear evidence for a hereditary aetiology of this disease. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

    Directory of Open Access Journals (Sweden)

    Shigeru Kotake

    2016-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

  11. Aspects of gastrointestinal immunology and nutrition in human immunodeficiency virus-1 infection in Brazil

    Directory of Open Access Journals (Sweden)

    Castello-Branco Luiz RR

    2000-01-01

    Full Text Available Mucosal surfaces have a fundamental participation in many aspects of the human immunodeficiency virus (HIV infection pathogenesis. In Brazilian HIV-1 infected subjects, loss of weight and appetite are among the most debilitating symptoms. In this review we describe a defined mucosal immunogen that has profound but transient effects on HIV viral load, and we suggest that gut associated lymphoid tissue under constant immunostimulation is likely to provide a major contribution to the total levels of HIV. We also show that hypermetabolism appears to play a role in the wasting process in Brazilian patients coinfected with HIV and tuberculosis.

  12. Modulation of autoimmune rheumatic diseases by oestrogen and progesterone.

    Science.gov (United States)

    Hughes, Grant C; Choubey, Divaker

    2014-12-01

    Sexual dimorphism is evident in the risk and expression of several human autoimmune diseases. Differences in disease manifestations observed between sexes are likely to involve immunomodulation by sex steroids, nonhormonal factors encoded by genes on the X and Y chromosomes, and immunological phenomena unique to pregnancy. In systemic lupus erythematosus (SLE), and perhaps other autoantibody-mediated diseases, oestrogen seems to increase the risk of disease in genetically predisposed women by targeting key immune pathways, including the type 1 interferon (IFN) response, differentiation of CD4(+) T helper cells and survival of autoreactive B cells. By contrast, progesterone seems to reduce the risk of SLE by counteracting the effects of oestrogen on some of these same pathways, which suggests that the balance between oestrogen and progesterone can determine disease expression. In this Review we focus on the roles of the sex steroid hormones oestrogen and progesterone in modulating the risk and expression of SLE and rheumatoid arthritis. Intensive research in this area promises to identify novel therapeutic strategies and improve understanding of the immunological requirements and complications of pregnancy, and is expected to define the mechanisms behind sexual dimorphism in autoimmunity, immunity and other aspects of human health--a newly announced directive of the NIH.

  13. Computer immunology.

    Science.gov (United States)

    Forrest, Stephanie; Beauchemin, Catherine

    2007-04-01

    This review describes a body of work on computational immune systems that behave analogously to the natural immune system. These artificial immune systems (AIS) simulate the behavior of the natural immune system and in some cases have been used to solve practical engineering problems such as computer security. AIS have several strengths that can complement wet lab immunology. It is easier to conduct simulation experiments and to vary experimental conditions, for example, to rule out hypotheses; it is easier to isolate a single mechanism to test hypotheses about how it functions; agent-based models of the immune system can integrate data from several different experiments into a single in silico experimental system.

  14. Long-term immunologically competent human peripheral lymphoid tissue cultures in a 3D bioreactor

    Science.gov (United States)

    Kuzin, Igor; Sun, Hongliang; Moshkani, Safiekhatoon; Feng, Changyong; Mantalaris, Athanasios; Wu, JH David; Bottaro, Andrea

    2011-01-01

    Peripheral lymphoid organs (PLOs), the primary sites of development of adaptive immune responses, display a complex structural organization reflecting separation of cellular subsets (e.g. T and B lymphocytes) and functional compartments which is critical for immune function. The generation of in vitro culture systems capable of recapitulating salient features of PLOs for experimental, biotechnological and clinical applications would be highly desirable, but has been hampered so far by the complexity of these systems. We have previously developed a three-dimensional bioreactor system for long-term, functional culture of human bone marrow cells on macroporous microspheres in a packed-bed bioreactor with frequent medium change. Here we adapt the same system for culture of human primary cells from PLOs (tonsil) in the absence of specific exogenous growth factors or activators. Cells in this system displayed higher viability over several weeks, and maintain population diversity and cell surface markers largely comparable to primary cells. Light microscopy showed cells organizing in large diverse clusters within the scaffold pores and presence of B cell-enriched areas. Strikingly, these cultures generated a significant number of antibody-producing B cells when challenged with a panel of diverse antigens, as expected from a lymphoid tissue. Thus the three-dimensional tonsil bioreactor culture system may serve as a useful model of PLOs by recapitulating their structural organization and function ex vivo. PMID:21309085

  15. Premature delivery influences the immunological composition of colostrum and transitional and mature human milk.

    Science.gov (United States)

    Castellote, Cristina; Casillas, Rosario; Ramírez-Santana, Carolina; Pérez-Cano, Francisco J; Castell, Margarida; Moretones, M Glòria; López-Sabater, M Carmen; Franch, Angels

    2011-06-01

    Human breast milk is the ideal nutrition for the newborn, and in addition to its nutritional contribution, necessary for infant growth and development, it contains various immune bioactive factors that confer some of the numerous beneficial effects of breastfeeding. The current study analyzed the concentrations of IgA, growth factors such as epidermal growth factor (EGF), TGFβ1, and TGFβ2, cytokines IL-6, IL-8, IL-10, IL-13, and TNFα, and TNF-receptor I (TNF-RI) in colostrum and transitional and mature milk from mothers with mature, premature, and very premature infants. Human milk samples were collected from mothers delivering at term (T), preterm (PT), and very preterm (VPT). Milk from all the mothers was collected at 3 different time points after delivery corresponding to colostrum and transitional and mature milk. After obtaining milk whey, IgA, EGF, TGFβ1, and TGFβ2 were determined by ELISA and IL-6, IL-8, IL-10, IL-13, TNFα and TNF-RI by cytometric bead array immunoassay. The colostrum of the PT group was extremely rich in most of the factors studied, but higher concentrations than in the T group were only found for IL-6 (P = 0.051), TGFβ1, and TGFβ2 (P IgA, IL-8, IL-10, and TNFα than those in the T group (P < 0.05). Results suggest that maternal lactogenic compensatory mechanisms accelerating the development of immature breast-fed preterm infants may take effect only after wk 30 of gestation.

  16. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  17. Autoimmune polyglandular syndrome type 2 manifested as Hashimoto's thyroiditis and adrenocortical insufficiency, in Turner syndrome woman, with onset following introduction of treatment with recombinant human growth hormone.

    Science.gov (United States)

    Cyniak-Magierska, Anna; Lasoń, Agnieszka; Smyczyńska, Joanna; Lewiński, Andrzej

    2015-01-01

    Autoimmune polyglandular syndrome is a constellation of signs and symptoms of simultaneous insufficiencies of several endocrine glands. Autoimmune polyglandular syndrome type 2 (APS 2) may be diagnosed when the adrenocortical insufficiency is associated with an autoimmune thyroid disease (Hashimoto's thyroiditis or Graves' disease), and/or insulin-dependent diabetes mellitus. Turner syndrome is the most common chromosomal disorder in females, caused by complete or partial X chromosome monosomy. We present the case of a 20-year-old woman with Turner syndrome, in whom APS 2 (Hashimoto's thyroiditis and adrenocortical insufficiency) has been diagnosed after introduction of recombinant human growth hormone (rhGH) therapy. In Turner syndrome, examination of the patient must regularly be conducted in order to diagnose a possible onset of autoimmune diseases; respective treatment must be applied as soon as the diagnosis is established. In particular, therapy of rhGH, used for short stature treatment, may be a trigger factor of adrenal insufficiency. The cortisol level in blood should be assessed before rhGH administration and carefully monitored during the therapy, especially in case of autoimmune thyroid disease coexistence.

  18. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  19. Immunology for the toxicologic pathologist.

    Science.gov (United States)

    Snyder, Paul W

    2012-01-01

    The immune system functions primarily as a defense mechanism to provide protective immunity against microbial pathogens and cancer. The resulting protective responses occur through the complex interaction of tissues, cells, proteins, and molecular pathways that act in concert with other systems (e.g., nervous and endocrine) to provide the host with immunologic responses that cause pathologic processes seen primarily as inflammatory reactions. The pathologic responses can be attributed to either normal responses to infectious organisms and cancer cells, misdirected responses as in the case of hypersensitivity or autoimmune diseases, or deficient responses attributable to deficiencies or defects in components of the immune system. Pathologists need to have a basic understanding of the immune system to not only interpret findings as to their likely pathogenesis, but also to predict when the immune system may be a potential target. This review will be limited to a general overview of the basic immunologic responses and primary components involved.

  20. Genital-tract infection and disease in nude and immunologically competent mice after inoculation of a human strain of Chlamydia trachomatis.

    OpenAIRE

    1982-01-01

    A fast, human strain of Chlamydia trachomatis was introduced into the uterus of progesterone-treated CBA mice and congenic CBA nude mice through the uterine wall or via the cervical canal. The numbers of inclusions produced by samples taken from the vagina of the nude mice were significantly greater (P less than 0.05) than those produced by samples from immunologically competent normal mice. However, the infection was self-limited, lasting about 60 days, and there was no statistical differenc...

  1. The immunology and inflammatory responses of human melanocytes in infectious diseases.

    Science.gov (United States)

    Gasque, Philippe; Jaffar-Bandjee, Marie Christine

    2015-10-01

    Melanin is a canonical and major defense molecule in invertebrates but its role in mammalian immunity remains unexplored. In contrast, several recent studies have highlighted the emerging innate immune activities of human melanin-producing cells which can sense and respond to bacterial and viral infections. Indeed, the skin is a major portal of entry for pathogens such as arboviruses (Chikungunya, Dengue) and bacteria (mycobacterium leprae, Leptospira spirochetes). Melanocytes of the epidermis could contribute to the phagocytosis of these invading pathogens and to present antigens to competent immune cells. Melanocytes are known to produce key cytokines such as IL-1β, IL6 and TNF-α as well as chemokines. These molecules will subsequently alert macrophages, neutrophils, fibroblasts and keratinocytes through unique crosstalk mechanisms. The infection and the inflammatory responses will control melanocyte's immune and metabolic functions and could contribute to skin manifestations (rash, hyper or de-pigmentation, epidermolysis and psoriasis-like lesions). This review will address the potential role of melanocytes in immunity, inflammation and infection of the skin in health and diseases.

  2. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease.

    Science.gov (United States)

    Lurain, Nell S; Hanson, Barbara A; Martinson, Jeffrey; Leurgans, Sue E; Landay, Alan L; Bennett, David A; Schneider, Julie A

    2013-08-15

    Serum, cerebrospinal fluid (CSF), and cryopreserved lymphocytes from subjects in the Rush Alzheimer's Disease Center Religious Orders Study were analyzed for associations between cytomegalovirus (CMV) infection and clinical and pathological markers of Alzheimer disease. CMV antibody levels were associated with neurofibrillary tangles (NFTs). CSF interferon γ was only detected in seropositive subjects and was significantly associated with NFTs. The percentage of senescent T cells (CD4+ or CD8+CD28-CD57+) was significantly higher for CMV-seropositive as compared to CMV-seronegative subjects and was marginally associated with the pathologic diagnosis of Alzheimer disease (CD4+) or amyloid-β (CD8+). Immunocytochemical analysis showed induction of amyloid-β in human foreskin fibroblasts (HFFs) infected with each of 3 clinical CMV strains. In the same subjects, there was no association of herpes simplex virus type 1 (HSV-1) antibody levels with CMV antibody levels or clinical or pathological markers of Alzheimer disease. HSV-1 infection of HFFs did not induce amyloid-β. These data support an association between CMV and the development of Alzheimer disease.

  3. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop.

    Science.gov (United States)

    Miller, Frederick W; Alfredsson, Lars; Costenbader, Karen H; Kamen, Diane L; Nelson, Lorene M; Norris, Jill M; De Roos, Anneclaire J

    2012-12-01

    Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.

  4. Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

    Directory of Open Access Journals (Sweden)

    Rafael Fenutría

    Full Text Available CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg, expressing a circulating soluble form of human CD5 (shCD5 as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE, as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma. This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+, and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens.

  5. 60 kD Ro and nRNP A frequently initiate human lupus autoimmunity.

    Science.gov (United States)

    Heinlen, Latisha D; McClain, Micah T; Ritterhouse, Lauren L; Bruner, Benjamin F; Edgerton, Colin C; Keith, Michael P; James, Judith A; Harley, John B

    2010-03-10

    Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns.

  6. Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts.

    Science.gov (United States)

    Swijnenburg, Rutger-Jan; Schrepfer, Sonja; Govaert, Johannes A; Cao, Feng; Ransohoff, Katie; Sheikh, Ahmad Y; Haddad, Munif; Connolly, Andrew J; Davis, Mark M; Robbins, Robert C; Wu, Joseph C

    2008-09-02

    Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not well characterized. In fact, controversy remains as to whether hESCs have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging to track the fate of transplanted hESCs stably transduced with a double-fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show that survival after transplant is significantly limited in immunocompetent as opposed to immunodeficient mice. Repeated transplantation of hESCs into immunocompetent hosts results in accelerated hESC death, suggesting an adaptive donor-specific immune response. Our data demonstrate that transplanted hESCs trigger robust cellular and humoral immune responses, resulting in intragraft infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we have found CD4(+) T cells to be an important modulator of hESC immune-mediated rejection. Finally, we show that immunosuppressive drug regimens can mitigate the anti-hESC immune response and that a regimen of combined tacrolimus and sirolimus therapies significantly prolongs survival of hESCs for up to 28 days. Taken together, these data suggest that hESCs are immunogenic, trigger both cellular and humoral-mediated pathways, and, as a result, are rapidly rejected in xenogeneic hosts. This process can be mitigated by a combined immunosuppressive regimen as assessed by molecular imaging approaches.

  7. Ocular diseases: immunological and molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Jing Song

    2016-05-01

    Full Text Available Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

  8. Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity.

    Science.gov (United States)

    Lejon, Veerle; Mumba Ngoyi, Dieudonné; Kestens, Luc; Boel, Luc; Barbé, Barbara; Kande Betu, Victor; van Griensven, Johan; Bottieau, Emmanuel; Muyembe Tamfum, Jean-Jacques; Jacobs, Jan; Büscher, Philippe

    2014-03-01

    In mice, experimental infection with Trypanosoma brucei causes decreased bone marrow B-cell development, abolished splenic B-cell maturation and loss of antibody mediated protection including vaccine induced memory responses. Nothing is known about this phenomenon in human African trypanosomiasis (HAT), but if occurring, it would imply the need of revaccination of HAT patients after therapy and abolish hope for a HAT vaccine. The effect of gambiense HAT on peripheral blood memory T- and B-cells and on innate and vaccine induced antibody levels was examined. The percentage of memory B- and T-cells was quantified in peripheral blood, prospectively collected in DR Congo from 117 Trypanosoma brucei gambiense infected HAT patients before and six months after treatment and 117 controls at the same time points. Antibodies against carbohydrate antigens on red blood cells and against measles were quantified. Before treatment, significantly higher percentages of memory B-cells, mainly T-independent memory B-cells, were observed in HAT patients compared to controls (CD20+CD27+IgM+, 13.0% versus 2.0%, p<0.001). The percentage of memory T-cells, mainly early effector/memory T-cells, was higher in HAT (CD3+CD45RO+CD27+, 19.4% versus 16.7%, p = 0.003). After treatment, the percentage of memory T-cells normalized, the percentage of memory B-cells did not. The median anti-red blood cell carbohydrate IgM level was one titer lower in HAT patients than in controls (p<0.004), and partially normalized after treatment. Anti-measles antibody concentrations were lower in HAT patients than in controls (medians of 1500 versus 2250 mIU/ml, p = 0.02), and remained so after treatment, but were above the cut-off level assumed to provide protection in 94.8% of HAT patients, before and after treatment (versus 98.3% of controls, p = 0.3). Although functionality of the B-cells was not verified, the results suggest that immunity was conserved in T.b. gambiense infected HAT patients and

  9. Antitumor vaccines, immunotherapy and the immunological constant of rejection.

    Science.gov (United States)

    Wang, Ena; Monaco, Alessandro; Monsurró, Vladia; Sabatino, Marianna; Pos, Zoltan; Uccellini, Lorenzo; Wang, Jeanne; Worschech, Andrea; Stroncek, David F; Marincola, Francesco M

    2009-05-01

    Anticancer vaccines have not matched the clinical expectations projected from their ability to induce consistently systemic anticancer T-cell responses. Thus, a dichotomy is observed between the immunological and clinical endpoints of anticancer immunization. Anticancer vaccines have clearly demonstrated that highly specific T-cell responses can be induced that can recognize autologous cancer antigens in patients with cancer. This ability is an outstanding achievement of modern biotechnology, yielding one of the most specific types of potential anticancer reagents. However, systemic, vaccine-induced anticancer responses exemplify a broader immunological paradox: cytotoxic T-cells can coexist within the same organism with their target cells not only in the context of cancer, but also in the context of chronic infections, well-controlled allo-transplant reactions and autoimmunity. According to this view, anticancer immune responses are a facet of a tissue-specific autoimmune phenomenon specific for cancer tissue that may or may not result in the successful immune-destruction of target cells, depending on an assortment of genetic factors related to the background of the host or evolving phenotypes of a heterogeneous cancer environment. This feature article summarizes the current understanding of the mechanisms leading to tumor rejection in humans as well as in experimental models, in the context of the broader immunological phenomenon leading to tissue-specific destruction. Anticancer vaccines that may not induce clinically significant anticancer responses independently could function as a unique tool to enhance the specificity of the response of the host against cancer, provided that strategies are implemented to amplify the immune reaction initiated by vaccine-induced antibodies and/or T-cells.

  10. Social and immunological differences among uninfected Brazilians exposed or unexposed to human immunodeficiency virus-infected partners

    Science.gov (United States)

    Silva, Maria Luiza; Melo, Victor Hugo; Aleixo, Agdemir Waléria; Aleixo, Lúcia Fernandes; Pascoal-Xavier, Marcelo Antônio; Silva, Rafaela Oliveira; Ferreira, Laís Alves; Domingos, Willian Cunha; Greco, Dirceu Bartolomeu

    2014-01-01

    Understanding the social conditions and immunological characteristics that allow some human immunodeficiency virus (HIV)-exposed patients to remain uninfected represents an on-going challenge. In this study, the socio-demographic and sexual behaviour characteristics and immune activation profiles of uninfected individuals exposed to HIV-infected partners were investigated. A confidential and detailed questionnaire was administered and venous blood was tested using HIV-1/enzyme immunoassays, plasma HIV-1 RNA levels/bDNA and immunophenotyping/flow cytometry to determine the frequencies of CD4 and CD8 T cells expressing activation markers. The data analysis showed significant differences (p < 0.05) for immune parameters in individuals who were uninfected, albeit exposed to HIV-infected partners, compared with unexposed individuals. In particular, the exposed, uninfected individuals had a higher frequency (median, minimum-maximum) of CD4+HLA-DR+ (4.2, 1.8-6.1), CD8+HLA-DR+ (4.6, 0.9-13.7), CD4+CD45RO+ (27.5, 14.2-46.6), CD4+CD45RO+CD62L+ (46.7, 33.9-67.1), CD8+CD45RA+HLA-DR+ (12.1, 3.4-35.8) and CD8+CD45RO+HLA-DR+ (9.0, 3.2-14.8) cells, a decreased percentage of CD8+CD28+ cells (11.7, 4.5-24.0) and a lower cell-surface expression of Fcγ-R/CD16 on monocytes (56.5, 22.0-130.0). The plasma HIV-1 RNA levels demonstrated detectable RNA virus loads in 57% of the HIV-1+ female partners. These findings demonstrate an activation profile in both CD4 and CD8 peripheral T cells from HIV-1 exposed seronegative individuals of serodiscordant couples from a referral centre in Belo Horizonte, state of Minas Gerais. PMID:25317705

  11. Social and immunological differences among uninfected Brazilians exposed or unexposed to human immunodeficiency virus-infected partners

    Directory of Open Access Journals (Sweden)

    Maria Luiza Silva

    2014-09-01

    Full Text Available Understanding the social conditions and immunological characteristics that allow some human immunodeficiency virus (HIV-exposed patients to remain uninfected represents an on-going challenge. In this study, the socio-demographic and sexual behaviour characteristics and immune activation profiles of uninfected individuals exposed to HIV-infected partners were investigated. A confidential and detailed questionnaire was administered and venous blood was tested using HIV-1/enzyme immunoassays, plasma HIV-1 RNA levels/bDNA and immunophenotyping/flow cytometry to determine the frequencies of CD4 and CD8 T cells expressing activation markers. The data analysis showed significant differences (p < 0.05 for immune parameters in individuals who were uninfected, albeit exposed to HIV-infected partners, compared with unexposed individuals. In particular, the exposed, uninfected individuals had a higher frequency (median, minimum-maximum of CD4+HLA-DR+ (4.2, 1.8-6.1, CD8+HLA-DR+ (4.6, 0.9-13.7, CD4+CD45RO+ (27.5, 14.2-46.6, CD4+CD45RO+CD62L+ (46.7, 33.9-67.1, CD8+CD45RA+HLA-DR+ (12.1, 3.4-35.8 and CD8+CD45RO+HLA-DR+ (9.0, 3.2-14.8 cells, a decreased percentage of CD8+CD28+ cells (11.7, 4.5-24.0 and a lower cell-surface expression of Fcγ-R/CD16 on monocytes (56.5, 22.0-130.0. The plasma HIV-1 RNA levels demonstrated detectable RNA virus loads in 57% of the HIV-1+ female partners. These findings demonstrate an activation profile in both CD4 and CD8 peripheral T cells from HIV-1 exposed seronegative individuals of serodiscordant couples from a referral centre in Belo Horizonte, state of Minas Gerais.

  12. Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses.

    Directory of Open Access Journals (Sweden)

    Emiley A Eloe-Fadrosh

    Full Text Available The resident microbial consortia of the human gastrointestinal tract play an integral role in modulating immune responses both locally and systemically. However, detailed information regarding the effector immune responses after vaccine administration in relation to the gastrointestinal microbiota is absent. In this study, the licensed oral live-attenuated typhoid vaccine Ty21a was administered in a clinical study to investigate whether oral immunization resulted in alterations of the microbiota and to identify whether a given microbiota composition, or subsets of the community, are associated with defined S. Typhi-specific immunological responses. The fecal microbiota composition and temporal dynamics were characterized using bacterial 16S rRNA pyrosequencing from individuals who were either immunized with the Ty21a typhoid vaccine (n = 13 or served as unvaccinated controls (n = 4. The analysis revealed considerable inter- and intra-individual variability, yet no discernible perturbations of the bacterial assemblage related to vaccine administration were observed. S. Typhi-specific cell mediated immune (CMI responses were evaluated by measurement of intracellular cytokine production using multiparametric flow cytometry, and humoral responses were evaluated by measurement of serum anti-LPS IgA and IgG titers. Volunteers were categorized according to the kinetics and magnitude of their responses. While differences in microbial composition, diversity, or temporal stability were not observed among individuals able to mount a positive humoral response, individuals displaying multiphasic CMI responses harbored more diverse, complex communities. In line with this preliminary observation, over two hundred operational taxonomic units (OTUs were found to differentiate multiphasic and late CMI responders, the vast majority of which classified within the order Clostridiales. These results provide an unprecedented view into the dramatic temporal

  13. Complement and autoimmunity.

    Science.gov (United States)

    Ballanti, Eleonora; Perricone, Carlo; Greco, Elisabetta; Ballanti, Marta; Di Muzio, Gioia; Chimenti, Maria Sole; Perricone, Roberto

    2013-07-01

    The complement system is a component of the innate immune system. Its main function was initially believed to be limited to the recognition and elimination of pathogens through direct killing or stimulation of phagocytosis. However, in recent years, the immunoregulatory functions of the complement system were demonstrated and it was determined that the complement proteins play an important role in modulating adaptive immunity and in bridging innate and adaptive responses. When the delicate mechanisms that regulate this sophisticated enzymatic system are unbalanced, the complement system may cause damage, mediating tissue inflammation. Dysregulation of the complement system has been involved in the pathogenesis and clinical manifestations of several autoimmune diseases, such as systemic lupus erythematosus, vasculitides, Sjögren's syndrome, antiphospholipid syndrome, systemic sclerosis, dermatomyositis, and rheumatoid arthritis. Complement deficiencies have been associated with an increased risk to develop autoimmune disorders. Because of its functions, the complement system is an attractive therapeutic target for a wide range of diseases. Up to date, several compounds interfering with the complement cascade have been studied in experimental models for autoimmune diseases. The main therapeutic strategies are inhibition of complement activation components, inhibition of complement receptors, and inhibition of membrane attack complex. At present, none of the available agents was proven to be both safe and effective for treatment of autoimmune diseases in humans. Nonetheless, data from preclinical studies and initial clinical trials suggest that the modulation of the complement system could constitute a viable strategy for the treatment of autoimmune conditions in the decades to come.

  14. Unwanted Immunology

    Directory of Open Access Journals (Sweden)

    M.V. Supotnytskyi

    2016-07-01

    Full Text Available The paper considers the role of antigenic imprin­ting phenomena and antibody-dependent enhancement of infection in epidemic, infectious and postvaccinal processes. Based on published experimental data, it is shown that both phenomena are directly related to the laws of development and course of epide­mics, the pathogenesis of infectious diseases and safe use of vaccines. Their ignoring by researchers has led to failures in the design of vaccines against HIV/AIDS, dengue fever, influenza, malaria, hemorrhagic fever and encephalitis. These data show that, without taking into account the two phenomena, the further development of immunology and epidemiology in the direction of breakthrough discoveries in there areas of science are impossible.

  15. Autoimmune prostatitis: state of the art.

    Science.gov (United States)

    Motrich, R D; Maccioni, M; Riera, C M; Rivero, V E

    2007-01-01

    The prostate is one of the main male sex accessory glands and the target of many pathological conditions affecting men of all ages. Pathological conditions of the prostate gland range from infections, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown aetiology to benign hyperplasia and cancer. CP/CPPS is one of the most prevalent diseases in the urologic clinic and affects men younger than 50 years old. A significant advance in the understanding of CP/CPPS was made when an autoimmune response against prostate antigens was revealed in a considerable number of patients. During the last 30 years, extensive work has been done regarding the development and characterization of different rodent models of experimental autoimmune prostatitis (EAP). It has been demonstrated that tolerance to prostate antigens can be disrupted in some strains of rats and mice and cellular and humoral responses to prostate antigens are elicited. A Th1 pattern has been described and the cellular response seems to be the major pathogenic mechanism involved. Immune cells infiltrate the gland and induce prostate lesions. The genetic background and hormonal imbalance are factors that could contribute to the onset of the disease in susceptible young males. Moreover, spontaneous autoimmune prostatitis could also occur with advanced age in susceptible strains. In this review, we summarize the current knowledge regarding rodent models of EAP and the immunological alterations present in CP/CPPS patients. We also discuss the reliability of these experimental approaches as genuine tools for the study of human disease.

  16. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women...... during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...

  17. Autoimmune disease

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005164 Optimal cut-point of glutamic acid decar-boxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (LADA). LI Xia(李霞), et al. Dept Endocrinol, 2nd Xiangya Hosp, Central South Univ, Changsha, 410011. Chin J Diabetes, 2005;13(1) :34-38. Objective: To investigate the optimal cut-point of glutamate decarboxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (I. ADA). Methods: The frequency

  18. Cosmos-1989 immunology studies

    Science.gov (United States)

    Sonnenfeld, Gerald

    1991-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.

  19. Birth of the science of immunology.

    Science.gov (United States)

    Schmalstieg, Frank C; Goldman, Armond S

    2010-05-01

    The science of immunology emerged in the last of the 19th and the first of the 20th century. Substantial progress in physics, chemistry and microbiology was essential for its development. Indeed, microorganisms became one of the principal investigative tools of the major founders of that science - Louis Pasteur, Robert Koch, Ilya Ilich Metchnikoff, Paul Ehrlich and Jules Bordet. It is pertinent that these pioneering scientists were born when questioning and exploration were encouraged because of the legacies of the previous century of enlightenment. Mentors greatly aided their development. Their discoveries were shaped by their individual personalities. In turn they developed other contributors to the nascent field. Their discoveries included the types of leukocytes, the roles of neutrophils in inflammation and defence, cellular lysis due to complement, the principles of humoral and cellular immunology, passive and active immunization, tissue antigens, anaphylaxis, anaphylactoid reactions and autoimmunity. Their work formed the basis of modern immunology that developed many decades later. Immunology has enormously impacted our understanding of the pathogenesis, diagnosis and treatment of infections, immune-mediated disorders and inflammation. Burgeoning advances forecast further important clinical applications of immunology. Yet, their applications will be problematic because few physicians sufficiently understand the science. We propose that understanding modern immunology requires a grasp of how that science developed - who made the discoveries, how they were made, their successes and failures, their interactions and debates all reveal the foundation of modern immunology.

  20. Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis.

    Science.gov (United States)

    Sandal, Indra; Karydis, Anastasios; Luo, Jiwen; Prislovsky, Amanda; Whittington, Karen B; Rosloniec, Edward F; Dong, Chen; Novack, Deborah V; Mydel, Piotr; Zheng, Song Guo; Radic, Marko Z; Brand, David D

    2016-10-26

    The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease

  1. Autoimmune sialadenitis

    NARCIS (Netherlands)

    Guntinas-Lichius, O.; Vissink, A.; Ihrler, S.

    2010-01-01

    Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjogren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT lymphomas

  2. The autoimmune regulator (AIRE), which is defective in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients, is expressed in human epidermal and follicular keratinocytes and associates with the intermediate filament protein cytokeratin 17.

    Science.gov (United States)

    Kumar, Vipul; Pedroza, Luis A; Mace, Emily M; Seeholzer, Steven; Cotsarelis, George; Condino-Neto, Antonio; Payne, Aimee S; Orange, Jordan S

    2011-03-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is caused by mutation of the autoimmune regulator (AIRE) gene, is a highly variable disease characterized by multiple endocrine failure, chronic mucocutaneous candidiasis, and various ectodermal defects. AIRE is a transcriptional regulator classically expressed in medullary thymic epithelial cells, monocytes, macrophages, and dendritic cells. Previous studies have suggested that AIRE can shuttle between the nucleus and cytoplasm of cells, although its cytoplasmic functions are poorly characterized. Through mass spectrometry analysis of proteins co-immunoprecipitating with cytoplasmic AIRE, we identified a novel association of AIRE with the intermediate filament protein cytokeratin 17 (K17) in the THP-1 monocyte cell line. We confirmed AIRE expression in HaCaT epidermal keratinocytes, as well as its interaction with K17. Confocal microscopy of human fetal and adult scalp hair follicles demonstrated a cytoplasmic pattern of AIRE staining that moderately colocalized with K17. The cytoplasmic association of AIRE with the intermediate filament network in human epidermal and follicular keratinocytes may provide a new path to understanding the ectodermal abnormalities associated with the APECED syndrome. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Islet transplantation: immunological perspectives.

    Science.gov (United States)

    Inverardi, Luca; Kenyon, Norma S; Ricordi, Camillo

    2003-10-01

    Clinical trials of islet transplantation are showing remarkable success, but they require administration of chronic immunosuppression, and are underscoring the large gap that exists between the number of human donors available and the number of patients that could benefit from the procedure. Recent progress has been made in the definition of key immunological mechanisms that are involved in determining islet transplant outcome. Clinical and preclinical studies, and studies in small animal model systems, will all eventually contribute to the definition of efficient and safe protocols for islet transplantation. If the use of xenografts is successful, it might represent a solution to the shortage of human organs.

  4. Is Graves' disease a primary immunodeficiency? New immunological perspectives on an endocrine disease.

    Science.gov (United States)

    Struja, Tristan; Kutz, Alexander; Fischli, Stefan; Meier, Christian; Mueller, Beat; Recher, Mike; Schuetz, Philipp

    2017-09-25

    Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.

  5. Autoimmunity in Chagas' heart disease

    Directory of Open Access Journals (Sweden)

    Edécio Cunha-Neto

    Full Text Available The time scale dissociation between high parasitemia and tissue pathology, allied to the absence of parasites in the heart lesions of chronic Chagas' disease cardiopathy, casted doubt on the direct participation of Trypanosoma cruzi in tissue lesions. Moreover, the heart tissue lesions in chronic Chagas' disease cardiopathy are associated to an inflammatory mononuclear cell infiltrate, presumably the ultimate effectors of tissue damage. It has been hypothesized that the inflammatory cell infiltrate could mediate a delayed hypersensitivity process directed to the heart tissue components, an autoimmune response triggered by immunological cross-reactivity in the course of a protective immune response against some T.cruzi antigen homologous to heart proteins. However, little is known about the efector role of the T cells in the infiltrate, or about the nature of the antigen that lead to their accumulation in tissue. In this paper, we will review the published evidence on autoimmunity and immunological cross-reactivity between T. cruzi and the mammalian host, along with data generated in our laboratory. The definition of the precise role played by autoimmunity in the pathogenesis of Chagas' disease cardiopathy may have important consequences both for immunoprophylaxis and for the therapeutic approach of chronic Chagas' disease.

  6. Successful clinical treatment and functional immunological normalization of human MALT1 deficiency following hematopoietic stem cell transplantation.

    Science.gov (United States)

    Rozmus, Jacob; McDonald, Rachel; Fung, Shan-Yu; Del Bel, Kate L; Roden, Juliana; Senger, Christof; Schultz, Kirk R; McKinnon, Margaret L; Davis, Jeffrey; Turvey, Stuart E

    2016-07-01

    MALT1 mutations impair normal NF-κB activation and paracaspase activity to cause a novel combined immunodeficiency. The clinical and immunological phenotype of MALT1 deficiency can be successfully treated with hematopoietic stem cell transplantation following reduced intensity conditioning.

  7. Thrombin Cleavage of Osteopontin Modulates Its Activities in Human Cells In Vitro and Mouse Experimental Autoimmune Encephalomyelitis In Vivo.

    Science.gov (United States)

    Boggio, Elena; Dianzani, Chiara; Gigliotti, Casimiro Luca; Soluri, Maria Felicia; Clemente, Nausicaa; Cappellano, Giuseppe; Toth, Erika; Raineri, Davide; Ferrara, Benedetta; Comi, Cristoforo; Dianzani, Umberto; Chiocchetti, Annalisa

    2016-01-01

    Osteopontin is a proinflammatory cytokine and plays a pathogenetic role in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), by recruiting autoreactive T cells into the central nervous system. Osteopontin functions are modulated by thrombin cleavage generating N- and C-terminal fragment, whose individual roles are only partly known. Published data are difficult to compare since they have been obtained with heterogeneous approaches. Interestingly, thrombin cleavage of osteopontin unmasks a cryptic domain of interaction with α 4 β 1 integrin that is the main adhesion molecule involved in lymphocyte transmigration to the brain and is the target for natalizumab, the most potent drug preventing relapses. We produced recombinant osteopontin and its N- and C-terminal fragments in an eukaryotic system in order to allow their posttranslational modifications. We investigated, in vitro, their effect on human cells and in vivo in EAE. We found that the osteopontin cleavage plays a key role in the function of this cytokine and that the two fragments exert distinct effects both in vitro and in vivo. These findings suggest that drugs targeting each fragment may be used to fine-tune the pathological effects of osteopontin in several diseases.

  8. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.

    Directory of Open Access Journals (Sweden)

    Gordan Lauc

    Full Text Available Glycosylation of immunoglobulin G (IgG influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS results identified 9 genome-wide significant loci (P<2.27 × 10(-9 in the discovery analysis and two of the same loci (B4GALT1 and MGAT3 in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3, while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3. However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma. Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842. Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein

  9. Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis.

    Science.gov (United States)

    de la Hera, Belén; Varadé, Jezabel; García-Montojo, Marta; Lamas, José Ramón; de la Encarnación, Ana; Arroyo, Rafael; Fernández-Gutiérrez, Benjamín; Alvarez-Lafuente, Roberto; Urcelay, Elena

    2013-01-01

    Human endogenous retroviruses (HERVs) are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS). The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS) performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility. Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions) conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942), rheumatoid arthritis (n = 462) and ethnically matched controls (n = 601). Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls. Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI) = 1.5 (1.04-2.17) and 154W/Stop: p = 0.001; OR (95% CI) = 1.6 (1.19-2.16)]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H) = 0.0008; OR(M-H) (95% CI) = 1.22 (1.09-1.38)]. Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

  10. [Autoimmune channelopathies].

    Science.gov (United States)

    Michaud, M; Delrieu, J; Astudillo, L

    2011-12-01

    Autoimmune channelopathies are rare neuromuscular diseases that have been characterized clinically for several decades but for which the evidence of associated antibodies has only been recently demonstrated. Ion channels have an important role of activation, inhibition and regulation in neuromuscular transmission. Myasthenia gravis, generally associated with the presence of anti-acetylcholine receptor antibody, is the best-known channelopathy. Other anti-channel antibodies, including voltage-dependent, are associated with several neurological diseases, as illustrated by anti-voltage-gated calcium channels found in Lambert-Eaton myasthenic syndrome and paraneoplastic cerebellar ataxia, and anti-voltage-gated potassium channels found in neuromyotonia, Morvan's syndrome and limbic encephalitis. The treatment of autoimmune channelopathies is logically based on corticosteroids, immunosuppressant drugs, intravenous immunoglobulins and plasmapheresis. Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  11. Autoimmun pankreatitis

    DEFF Research Database (Denmark)

    Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad;

    2015-01-01

    Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...... are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer....

  12. Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity.

    Science.gov (United States)

    Parry, Christian S; Gorski, Jack; Stern, Lawrence J

    2007-08-10

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin alphaII(B)betaIII glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the alphaII(B)betaIII 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 A. There are two alphabeta heterodimers to the asymmetric unit in space group P4(1)2(1)2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive "1-4-9" peptide binding motif. A beta57 Asp-->Val substitution abrogates the salt-bridge to alpha76 Arg and along with a hydrophobic beta37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  13. Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Respone and Autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Parry,C.; Gorski, J.; Stern, L.

    2007-01-01

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  14. Lymphopenia-induced proliferation in aire-deficient mice helps to explain their autoimmunity and differences from human patients.

    Science.gov (United States)

    Kisand, Kai; Peterson, Pärt; Laan, Martti

    2014-01-01

    Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) and its mouse model - both caused by mutant AIRE - have greatly advanced the understanding of thymic processes that generate a self-tolerant T-cell repertoire. Much is now known about the molecular mechanisms by which AIRE induces tissue-specific antigen expression in thymic epithelium, and how this leads to negative selection of auto-reactive thymocytes. However, we still do not understand the processes that lead to the activation of any infrequent naïve auto-reactive T-cells exported by AIRE-deficient thymi. Also, the striking phenotypic differences between APECED and its mouse models have puzzled researchers for years. The aim of this review is to suggest explanations for some of these unanswered questions, based on a fresh view of published experiments. We review evidence that auto-reactive T-cells can be activated by the prolonged neonatal lymphopenia that naturally develops in young Aire-deficient mice due to delayed export of mature thymocytes. Lymphopenia-induced proliferation (LIP) helps to fill the empty space; by favoring auto-reactive T-cells, it also leads to lymphocyte infiltration in the same tissues as in day 3 thymectomized animals. The LIP becomes uncontrolled when loss of Aire is combined with defects in genes responsible for anergy induction and Treg responsiveness, or in signaling from the T-cell receptor and homeostatic cytokines. In APECED patients, LIP is much less likely to be involved in activation of naïve auto-reactive T-cells, as humans are born with a more mature immune system than in neonatal mice. We suggest that human AIRE-deficiency presents with different phenotypes because of additional precipitating factors that compound the defective negative selection of potentially autoaggressive tissue-specific thymocytes.

  15. Skin as a Psychoneuroendocrine Immunology Microcosm: The New Frontier of Low Dose Therapy With Cytokines and Growth Factors in the Systemic Treatment of Chronic Autoimmune Inflammatory Diseases in Dermatology

    Directory of Open Access Journals (Sweden)

    Lotti

    2016-04-01

    Full Text Available In recent years, the central role of signaling molecules, such as hormones, cytokines and growth factors, has become evident in both physiological and pathological processes; these signaling molecules are the main regulating effectors of whole body biological functions, in accordance with the guiding principle of psychoneuroendocrine immunology (PNEI. Low dose medicine (LDM represents an innovative medical approach in which the latest evidence in the fields of molecular biology, PNEI and nano-concentration pharmacology are merged. LDM suggests the use of low-doses of activated biological molecules in order to manage PNEI homeostasis, and this approach represents a new opportunity for the development of therapeutic strategies based on immune balancing interventions. Scientific evidence regarding the efficacy and safety of the LDM approach in the treatment of psoriasis vulgaris, and positive preliminary data regarding the oral administration of low dose activated cytokines for vitiligo and atopic dermatitis treatment, support the LDM-based therapeutic approach for many dermatological diseases.

  16. Homing of GAD65 specific autoimmunity and development of insulitis requires expression of both DQ8 and human GAD65 in transgenic mice

    Science.gov (United States)

    Elagin, Raya B.; Balijepalli, Sadguna; Diacovo, Maria J.; Baekkeskov, Steinunn; Jaume, Juan C.

    2009-01-01

    MHC-class II genes determine susceptibility in human type-1 diabetes. In their context, presentation of target antigen(s) results in autoimmunity and β-cell destruction. An animal model, in which human β-cell autoantigen(s) are presented to effector-cells in the context of human MHC-class II diabetes susceptibility genes, would be desirable for studying molecular mechanisms of disease and developing antigen-specific immune-interventions. We report the development of antigen-specific insulitis in double-transgenic mice carrying the HLA-DQ8 diabetes susceptibility haplotype and expressing the human autoantigen GAD65 in pancreatic β-cells. Immunization with human GAD65 cDNA resulted in severe insulitis and low antibody levels in double-transgenic mice while control mice were mostly insulitis free. CFA/protein immunization resulted in high antibody levels and modest insulitis. Pancreatic lymphocytic infiltration progressed through stages (exocrine pancreas followed by peri and intra-insulitis). Adoptive transfer of splenocytes from DNA-immunized mice resulted in development of insulitis in recipient transgenics. Our results show that immunization with a clinically relevant, type-1 diabetes human autoantigen, in a humanized genetic setting, results in the development of an immune response that homes to islets of Langerhans. This animal model will facilitate studies of autoimmunity to GAD65 in the context of HLA-DQ8, and development of methods to induce tolerance and prevent insulitis. PMID:19289270

  17. Preface to the Publication of Cellular & Molecular Immunology

    Institute of Scientific and Technical Information of China (English)

    Wei-Feng Chen; Kuang-Yen Chou

    2004-01-01

    @@ Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and provided insights into creating a better environment for contemporary human existence.

  18. Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease.

    Directory of Open Access Journals (Sweden)

    Renato Sathler-Avelar

    2016-01-01

    Full Text Available Cynomolgus macaques (Macaca fascicularis represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI. Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications.Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease.

  19. DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis

    Science.gov (United States)

    Elisia, Ingrid; Nakamura, Hisae; Lam, Vivian; Hofs, Elyse; Cederberg, Rachel; Cait, Jessica; Hughes, Michael R.; Lee, Leora; Jia, William; Adomat, Hans H.; Guns, Emma S.; McNagny, Kelly M.; Samudio, Ismael; Krystal, Gerald

    2016-01-01

    Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for various inflammatory conditions as well as for cancer. Despite its widespread use, there is a paucity of data regarding its safety and efficacy as well as its mechanism of action in human cells. Herein, we demonstrate that DMSO has ex-vivo anti-inflammatory activity using Escherichia coli- (E. coli) and herpes simplex virus-1 (HSV-1)-stimulated whole human blood. Specifically, we found that between 0.5%– 2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E2 (PGE2). However, a significant reduction in monocyte viability was also observed at 2% DMSO, suggesting a narrow window of efficacy. Anti-inflammatory concentrations of DMSO suppressed E. coli-induced ERK1/2, p38, JNK and Akt phosphorylation, suggesting DMSO acts on these signaling pathways to suppress inflammatory cytokine/chemokine production. Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth. Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood. Thus, while we cannot confirm the efficacy of DMSO as an anti-cancer agent, the use of DMSO in arthritis warrants further investigation to ascertain its therapeutic potential. PMID:27031833

  20. Complete remission of multiple myeloma after autoimmune hemolytic anemia: possible association with interferon-alpha.

    Science.gov (United States)

    Gesundheit, Benjamin; Zelig, Orly; Shapira, Michael Y; Ackerstein, Aliza; Avgil, Meytal; Or, Reuven

    2007-06-01

    A patient with multiple myeloma (MM) was being maintained on human recombinant interferon-alpha (INF-alpha) after VAD and autologous bone marrow transplantation (pretreated with melphalan). An episode of immune thrombocytopenia and (Coombs positive) autoimmune hemolytic anemia (AIHA) was noted while on maintenance INF-alpha, which remitted when it was withdrawn. Following this event, he achieved a state of stable disease that persists (more than 3 years) with no specific myeloma treatment. This sequence of events suggests a relationship between an immunological reaction induced by INF-alpha and the prolonged phase of stable disease.

  1. How pregnancy can affect autoimmune diseases progression?

    Science.gov (United States)

    Piccinni, Marie-Pierre; Lombardelli, Letizia; Logiodice, Federica; Kullolli, Ornela; Parronchi, Paola; Romagnani, Sergio

    2016-01-01

    Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother's circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases.

  2. Cancer immunology

    Energy Technology Data Exchange (ETDEWEB)

    Herberman, R.B. (Univ. of Pittsburgh, Pittsburgh, PA (US))

    1986-01-01

    This book contains seven chapters. They are: Immunlogy of human T-cell leukemia/lymphonma (lymphotropic) viruses (the HTLV 'family'); Tumor specific antigens induced by mutagens and DNA hypomethylating agents: implications for the immunobiology of neoplasia; Destruction of tumor cells by macrophages: mechanisms of recognition and lysis and their regulation; Mechanisms of NK-cell mediated cytotoxicity; Role of natural killer (NK) cells in the control of tumor growth and metastatic spread; Monoclonal antibody therapy of cancer; preclinical models and investigations in humans; and Abnormalities in interleukin 2 production and response in cancer and possible therapeutic approaches.

  3. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  4. Pregnancy after azathioprine therapy for ulcerative colitis in a woman with autoimmune premature ovarian failure and Addison's disease: HLA haplotype characterization.

    Science.gov (United States)

    Ferraù, Francesco; Gangemi, Sebastiano; Vita, Giuseppe; Trimarchi, Francesco; Cannavò, Salvatore

    2011-06-01

    To present a case of fertility restored by azathioprine treatment in a woman with autoimmune premature ovarian failure, Addison's disease, and ulcerative colitis, and to study the genetic background of the three autoimmune diseases. Case report. Endocrinology and Immunology Units of an university hospital. A 30-year-old woman with autoimmune premature ovarian failure, Addison's disease, and ulcerative colitis. Azathioprine has been administered as immunosuppressive treatment. We performed analysis of human leukocyte antigens expression on lymphocytes and genomic haplotype of the patient. The human leukocyte antigen haplotype of the patient was consistent with the haplotypes predisposing for the three autoimmune diseases, as reported in the literature. The administration of azathioprine restored regular menses and allowed uneventful pregnancy. This is the first clinical evidence of association of immunosuppressive azathioprine treatment and restored ovarian function and fertility in a woman with autoimmune premature ovarian failure. In this patient, the haplotype was associated with susceptibility to autoimmune premature ovarian failure, Addison's disease, and ulcerative colitis. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Helicobacter pylori and autoimmune disease: Cause or bystander

    Science.gov (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  6. Autoimmunity, Not a Developmental Defect, is the Cause for Subfertility of Autoimmune Regulator (Aire) Deficient Mice.

    Science.gov (United States)

    Kekäläinen, E; Pöntynen, N; Meri, S; Arstila, T P; Jarva, H

    2015-05-01

    Autoimmune regulator's (AIRE) best characterized role is in the generation immunological tolerance, but it is also involved in many other processes such as spermatogenesis. Loss-of-function mutations in AIRE cause a disease called autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED; also called autoimmune polyendocrinopathy syndrome type 1, APS-1) that is dominated by various autoimmune manifestations, mainly endocrinopathies. Both patients with APECED and Aire(-/-) mice suffer from varying levels of infertility, but it is not clear if it is a result of an autoimmune tissue damage or more of a developmental defect. In this study, we wanted to resolve whether or not the reduced fertility of Aire(-/-) mice is dependent on the adaptive immune system and therefore a manifestation of autoimmunity in these mice. We generated lymphopenic mice without Aire expression that were devoid of the autoimmune manifestations previously reported in immunocompetent Aire(-/-) mice. These Aire(-/-) Rag1(-/-) mice regained full fertility. This confirms that the development of infertility in Aire(-/-) mice requires a functional adaptive immune system. We also show that only the male Aire(-/-) mice are subfertile, whereas Aire(-/-) females produce litters normally. Moreover, the male subfertility can be adoptively transferred with lymphocytes from Aire(-/-) donor mice to previously fertile lymphopenic Aire(-/-) recipients. Our data show that subfertility in Aire(-/-) mice is dependent on a functional adaptive immune system thus confirming its autoimmune aetiology. © 2015 John Wiley & Sons Ltd.

  7. [Autoimmune pancreatitis].

    Science.gov (United States)

    Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J

    2013-11-01

    Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50 % of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease.

  8. Virtual Immunology: Software for Teaching Basic Immunology

    Science.gov (United States)

    Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

    2013-01-01

    As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…

  9. Familial clustering of juvenile thyroid autoimmunity: higher risk is conferred by human leukocyte antigen DR3-DQ2 and thyroid peroxidase antibody status in fathers.

    Science.gov (United States)

    Segni, Maria; Pani, Michael A; Pasquino, Anna Maria; Badenhoop, Klaus

    2002-08-01

    Thyroid autoimmunity is one of the most common immune disorders in females, and its polygenic background remains to be elucidated. The human leukocyte antigen (HLA) DQ region of chromosome 6 has been shown to confer susceptibility to thyroid autoimmune disease. The aim of our present investigation was to determine whether the transmission of high risk HLA DQ to patients with thyroid autoimmunity differs when transmission is from fathers as opposed to when transmission is from mothers. We studied 91 juvenile patients with chronic lymphocytic thyroiditis (68 females and 23 males; mean age, 10.5 +/- 3.9 yr), 12 patients with Graves' disease (all females; mean age, 8.8 +/- 4.0 yr), 53 healthy siblings, and their parents for thyroid function, antibodies, ultrasound, and DNA typing for HLA DQ susceptibility alleles. We observed an increased rate of transmission for the DQA1*0501-DQB1*0201 (DQ2) haplotype [35 of 53 transmitted (66%); P = 0.02]. This allele was preferentially transmitted by fathers [21 of 27 (78%); P < 0.004], whereas the maternal DQ2 haplotypes were not transmitted more often than expected. Subsequently, families were stratified as follows according to the parental thyroid peroxidase antibody (TPOAb) status: no parent, only mothers, only fathers, and both parents positive. There was no significant maternal transmission disequilibrium in any subset, but the paternal HLA DQ2 was preferentially transmitted [11 of 14 cases (79%); P = 0.03] in the group of TPOAb-positive mothers, and we observed a similar trend in the group of TPOAb- positive fathers (P = 0.08). Also, the portion of offspring affected by Graves' disease was significantly higher in TPOAb-positive than in TPOAb-negative fathers (P < 0.02). In conclusion, our findings demonstrate a significant effect of paternal HLA DQ alleles as well as antibody status on susceptibility to thyroid autoimmune disease in juvenile patients.

  10. Pathophysiology of autoimmune polyneuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2013-06-01

    The most common autoimmune neuropathies include the acute inflammatory polyneuropathy [the Guillain-Barré Syndrome(s)]; chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN) and IgM anti-MAG-antibody mediated paraproteinemic neuropathy. These neuropathies occur when immunologic tolerance to peripheral nerve components (myelin, Schwann cell, axon, and motor or ganglionic neurons) is lost. Based on the immunopathologic similarities with experimental allergic neuritis induced after immunization with nerve proteins, disease transfer experiments with the patients' serum or with intraneural injections, and immunocytochemical studies on the patients' nerves, it appears that both cellular and humoral factors, either independently or in concert with each other, play a role in the cause of these neuropathies. Although in some of them there is direct evidence for autoimmune reactivity mediated by specific antibodies or autoreactive T lymphocytes, in others the underlying immune-mediated mechanisms have not been fully elucidated, in spite of good response to immunotherapies. The review highlights the factors associated with breaking the T-cell tolerance, the T-cell activation and costimulatory molecules, the immunoregulatory T-cells and relevant cytokines and the antibodies against peripheral nerve glycolipids or glycoproteins that seem to be of pathogenic relevance. Antigens in the nodal, paranodal and juxtaparanodal regions are discussed as potentially critical targets in explaining conduction failure and rapid recovery. Based on the immunopathologic network believed to play a fundamental role in the pathogenesis of these neuropathies, future therapeutic directions are highlighted using new biological agents against T-cells, cytokines, B-cells, transmigration and transduction molecules.

  11. Amplification of autoimmune disease by infection

    OpenAIRE

    Posnett, David N; Yarilin, Dmitry

    2005-01-01

    Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even ...

  12. 21 CFR 866.5660 - Multiple autoantibodies immunological test system.

    Science.gov (United States)

    2010-04-01

    .... Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  13. Pediatric allergy and immunology in Israel.

    Science.gov (United States)

    Geller-Bernstein, Carmi; Etzioni, Amos

    2013-03-01

    After the geographic and sociodemographic settings as well as the health care in Israel are briefly described, the scope of pediatric allergy and immunology in Israel is presented. This includes specific disorders commonly encountered, the environment that induces symptoms, the specialists who treat them, and the common challenges of patients, parents, doctors, and allied health personnel who collaborate to manage the maladies and patient care. Allergies usually affect some overall 15-20% of the pediatric population. The main allergens are inhaled, ingested, or injected (insects stings). Generally, the incidence of the various allergens affecting children in Israel, is similar to other parts of the Western world. Owing to the high consanguinity rate in the Israeli population, the prevalence of the various immunodeficiency conditions (in the adaptive as well as the innate system) is higher than that reported worldwide. Pediatric allergists/immunologists also treat autoimmune disorders affecting the pediatric group. Pediatric allergy and clinical immunology are not separate specialties. The 25 specialists who treat children with allergic/immunologic diseases have undergone a basic training in Pediatrics. They also received an additional 2-yr training in allergy and clinical immunology and then have to pass the board examinations. They work mainly in pediatric allergy units, in several hospitals that are affiliated to the five medical schools in the country. Aside from clinical work, most of the centers are also heavily involved in clinical and basic research in allergy and immunology.

  14. Immunology of breast milk

    Directory of Open Access Journals (Sweden)

    Patricia Palmeira

    Full Text Available Summary In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk’s immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant’s ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant’s secretory IgA production is insignificant.

  15. Preface to the Publication of Cellular & Molecular Immunology

    Institute of Scientific and Technical Information of China (English)

    Wei-FengChen; Kuang-YenChou

    2004-01-01

    Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and

  16. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

    Science.gov (United States)

    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

  17. Introduction: characterization and functions of human T regulatory cells.

    Science.gov (United States)

    Romagnani, Sergio

    2005-06-01

    The field of human T regulatory (Treg) cells is a rapidly progressing, but still confused field of immunology. The effects of dendritic cell (DC) manipulation in Treg generation and the main features of human "natural" Treg cells, as well as of different populations of adaptive Treg subsets, are still partially unclear. However, it is clear that Treg cells play an important role in human diseases, such as autoimmune disorders, allergy, HIV infection, tumors and graft-versus-host disease.

  18. A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison's Disease in Humans.

    Science.gov (United States)

    Pazderska, Agnieszka; Oftedal, Bergithe E; Napier, Catherine M; Ainsworth, Holly F; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S; Mitchell, Anna L

    2016-11-01

    Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs3757247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls. The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 × 10(-4); odds ratio [OR], 1.68; 95% confidence interval [CI], 1.29-2.18; WTCCC2 controls, P = 1.4 × 10(-6); OR, 1.44; 95% CI, 1.23-1.69). This finding was replicated in the Norwegian validation cohort (P = .0015; OR, 1.41; 95% CI, 1.14-1.75). Subgroup analysis showed that this association is present in subjects with both isolated AAD (OR, 1.53; 95% CI, 1.22-1.92) and autoimmune polyglandular syndrome type 2 (OR, 1.37; 95% CI, 1.12-1.69) in the UK cohort, and with autoimmune polyglandular syndrome type 2 in the Norwegian cohort (OR, 1.58; 95% CI, 1.22-2.06). We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a "universal" autoimmune susceptibility locus.

  19. Mucosal Immunology of HIV Infection

    OpenAIRE

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

    2013-01-01

    Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicti...

  20. Human T-Cell Lymphotropic Virus Type I (HTLV-1: implications for autoimmune diseases Vírus linfotrópico de células T humano tipo 1 (HTLV-1: implicações em doenças autoimunes

    Directory of Open Access Journals (Sweden)

    Dênis Augusto Santana Reis

    2012-06-01

    Full Text Available Autoimmunity is characterized by tissue destruction that implicates functional damages caused by self-reactive cells that escape self-tolerance mechanisms. Autoimmune diseases can be initiated by viral infections and the study of the association between these viruses and autoimmunity has advanced the understanding of the molecular mechanisms involved in autoimmune diseases. The Human T-Cell Lymphotropic Virus Type I (HTLV-1 is a deltavirus that infects preferentially lymphocytes. Retrovirus particles like has been identified in patients with autoimmune diseases. Therefore this review had by objective approach the main aspects involving HTLV-1 with systemic lupus erythematosus and rheumatoid arthritis. Studies show that retroviruses can integrate their genetic material in host DNA, changing the expression gene profile related with apoptosis and immunologic system molecules. It’s known that HTLV-1 can cause different clinical manifestations in their careers and the mechanisms that triggers the HTLV-1 associated autoimmune diseases are not well known. Besides the perpetuation and marked production of pro-inflammatory cytokines, studies have demonstrated that both Th17 cells and T regulatory cells (Tregs are involved in autoimmune diseases pathogenesis. Therefore the HTLV-1 viral particles recognized could be used as a risk marker in the development of autoimmune diseases.A autoimunidade é caracterizada pela destruição tecidual, que acarreta danos funcionais, causados por células autoreativas que escapam dos mecanismos de autotolerância. Doenças autoimunes podem ser iniciadas por infecções virais e o estudo da associação entre essas viroses e a autoimunidade tem possibilitado melhor conhecimento dos mecanismos moleculares envolvidos nas doenças autoimunes. O vírus linfotrópico de células T humano tipo 1 (HTLV-1 é um delta vírus que infecta preferencialmente linfócitos. Partículas semelhantes aos retrovírus foram identificadas em

  1. Hashimoto’s Thyroiditis and Autoimmune Gastritis

    Science.gov (United States)

    Cellini, Miriam; Santaguida, Maria Giulia; Virili, Camilla; Capriello, Silvia; Brusca, Nunzia; Gargano, Lucilla; Centanni, Marco

    2017-01-01

    The term “thyrogastric syndrome” defines the association between autoimmune thyroid disease and chronic autoimmune gastritis (CAG), and it was first described in the early 1960s. More recently, this association has been included in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis represents the pivotal disorder. Hashimoto’s thyroiditis (HT) is the most frequent autoimmune disease, and it has been reported to be associated with gastric disorders in 10–40% of patients while about 40% of patients with autoimmune gastritis also present HT. Some intriguing similarities have been described about the pathogenic mechanism of these two disorders, involving a complex interaction among genetic, embryological, immunologic, and environmental factors. CAG is characterized by a partial or total disappearance of parietal cells implying the impairment of both hydrochloric acid and intrinsic factor production. The clinical outcome of this gastric damage is the occurrence of a hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia concomitant with the progression to a severe gastric atrophy. Malabsorption of levothyroxine may occur as well. We have briefly summarized in this minireview the most recent achievements on this peculiar association of diseases that, in the last years, have been increasingly diagnosed. PMID:28491051

  2. Hashimoto’s Thyroiditis and Autoimmune Gastritis

    Directory of Open Access Journals (Sweden)

    Marco Centanni

    2017-04-01

    Full Text Available The term “thyrogastric syndrome” defines the association between autoimmune thyroid disease and chronic autoimmune gastritis (CAG, and it was first described in the early 1960s. More recently, this association has been included in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis represents the pivotal disorder. Hashimoto’s thyroiditis (HT is the most frequent autoimmune disease, and it has been reported to be associated with gastric disorders in 10–40% of patients while about 40% of patients with autoimmune gastritis also present HT. Some intriguing similarities have been described about the pathogenic mechanism of these two disorders, involving a complex interaction among genetic, embryological, immunologic, and environmental factors. CAG is characterized by a partial or total disappearance of parietal cells implying the impairment of both hydrochloric acid and intrinsic factor production. The clinical outcome of this gastric damage is the occurrence of a hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia concomitant with the progression to a severe gastric atrophy. Malabsorption of levothyroxine may occur as well. We have briefly summarized in this minireview the most recent achievements on this peculiar association of diseases that, in the last years, have been increasingly diagnosed.

  3. Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis.

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    Belén de la Hera

    Full Text Available BACKGROUND: Human endogenous retroviruses (HERVs are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS. The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility. METHODS: Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942, rheumatoid arthritis (n = 462 and ethnically matched controls (n = 601. Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls. RESULTS: Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI = 1.5 (1.04-2.17 and 154W/Stop: p = 0.001; OR (95% CI = 1.6 (1.19-2.16]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H = 0.0008; OR(M-H (95% CI = 1.22 (1.09-1.38]. CONCLUSION: Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

  4. Modulation of autoimmunity with artificial peptides

    Science.gov (United States)

    La Cava, Antonio

    2010-01-01

    The loss of immune tolerance to self antigens leads to the development of autoimmune responses. Since self antigens are often multiple and/or their sequences may not be known, one approach to restore immune tolerance uses synthetic artificial peptides that interfere or compete with self peptides in the networks of cellular interactions that drive the autoimmune process. This review describes the rationale behind the use of artificial peptides in autoimmunity and their mechanisms of action. Examples of use of artificial peptides in preclinical studies and in the management of human autoimmune diseases are provided. PMID:20807590

  5. Everything is autoimmune until proven otherwise.

    Science.gov (United States)

    Shoenfeld, Yehuda

    2013-10-01

    It is astounding to consider that virtually, every textbook of physiology in every medical school in the world does not include a chapter on immunology. On the other hand, virtually, in every textbook in internal medicine, immunology and immune response overlaps with every tissue and every organ. Indeed, historically, the concept of the immune response was recognized primarily in the setting of allergy and/or anaphylaxis. Indeed, the very concepts of infection, microbiology and host protection are relatively new sciences. In fact, it was little more than 100 years ago when washing hands became what is now coined "standard of care." How different it is in 2013, where one finds Handi Wipes for shoppers to use at grocery stores to protect themselves from the flora on shopping cart handles. Autoimmunity is even a newer concept without going into the well-known history of Paul Ehrlich and hemolytic anemias, the LE cell, and the beginning field of serology (and rheumatoid factor discovery). It is apparent that our understanding of autoimmunity has become linked hand-in-glove with new tools and investigational probes into serology and, more recently, the cellular immune response. With such discoveries, a number of key observations stand out. Firstly, there are a great deal more autoantibodies than there are autoimmune diseases. Second, there are a great deal more of autoimmune diseases than was believed in 1963 on the occasion of the publication of the first textbook of autoimmune diseases. Third, autoimmune diseases are, for the most part, orphan diseases, with many entities afflicting too few patients to excite the financial limb of pharmaceutical companies. In this special issue, we have grouped a number of papers, many of which were presented at the recent Congress of Autoimmunity that focus on issues that are not commonly discussed in autoimmunity. It reminds us that due to the ubiquitous nature of the innate and adaptive response, that there are a large number of

  6. Cancer immunotherapy and immunological memory.

    Science.gov (United States)

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

      Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

  7. Breaking Immunological Tolerance through OX40 (CD134

    Directory of Open Access Journals (Sweden)

    Pratima Bansal-Pakala

    2001-01-01

    Full Text Available Immunological tolerance represents a mechanism by which cells of the host remain protected from the immune system. Breaking of immunological tolerance can result in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis. The reasons for tolerance breaking down and autoimmune processes arising are largely unknown but of obvious interest for therapeutic intervention of these diseases. Although reversal of the tolerant state is generally unwanted, there are instances where this may be of benefit to the host. In particular, one way a cancerous cell escapes being targeted by the immune system is through tolerance mechanisms that in effect turn off the reactivity of T lymphocytes that can respond to tumor-associated peptides. Thus tolerance represents a major obstacle in developing effective immunotherapy against tumors. The molecules that are involved in regulating immunological tolerance are then of interest as they may be great targets for positively or negatively manipulating the tolerance process.

  8. Immunological markers of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Agnieszka Matuszewska

    2016-03-01

    Full Text Available Rheumatoid arthritis (RA is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement. In 2010 the American College of Rheumatology (ACR and The European League Against Rheumatism (EULAR established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF and anti-citrullinated protein antibodies (anti-CCP antibodies. RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%. New immunologic markers include anti-carbamylated protein antibodies (anti-CarP and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33. Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.

  9. [Immunological markers of rheumatoid arthritis].

    Science.gov (United States)

    Matuszewska, Agnieszka; Madej, Marta; Wiland, Piotr

    2016-03-25

    Rheumatoid arthritis (RA) is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement. In 2010 the American College of Rheumatology (ACR) and The European League Against Rheumatism (EULAR) established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF) and anti-citrullinated protein antibodies (anti-CCP antibodies). RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%. New immunologic markers include anti-carbamylated protein antibodies (anti-CarP) and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33). Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.

  10. Immunological markers of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Agnieszka Matuszewska

    2016-03-01

    Full Text Available Rheumatoid arthritis (RA is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement.In 2010 the American College of Rheumatology (ACR and The European League Against Rheumatism (EULAR established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF and anti-citrullinated protein antibodies (anti-CCP antibodies. RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%.New immunologic markers include anti-carbamylated protein antibodies (anti-CarP and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33. Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.

  11. Characterization of the in vitro expressed autoimmune rippling muscle disease immunogenic domain of human titin encoded by TTN exons 248-249

    Energy Technology Data Exchange (ETDEWEB)

    Zelinka, L. [Biomedical Sciences Program, Kent State University, Kent, OH (United States); McCann, S.; Budde, J.; Sethi, S.; Guidos, M.; Giles, R. [Center for Applied Chemical Biology, Department of Biological Sciences, Youngstown State University, One University Plaza, Youngstown, OH 44555 (United States); Walker, G.R., E-mail: grwalker@ysu.edu [Center for Applied Chemical Biology, Department of Biological Sciences, Youngstown State University, One University Plaza, Youngstown, OH 44555 (United States); Biomedical Sciences Program, Kent State University, Kent, OH (United States)

    2011-08-05

    Highlights: {yields} Affinity purification of the autoimmune rippling muscle disease immunogenic domain of titin. {yields} Partial sequence analysis confirms that the peptides is in the I band region of titin. {yields} This region of the human titin shows high degree of homology to mouse titin N2-A. -- Abstract: Autoimmune rippling muscle disease (ARMD) is an autoimmune neuromuscular disease associated with myasthenia gravis (MG). Past studies in our laboratory recognized a very high molecular weight skeletal muscle protein antigen identified by ARMD patient antisera as the titin isoform. These past studies used antisera from ARMD and MG patients as probes to screen a human skeletal muscle cDNA library and several pBluescript clones revealed supporting expression of immunoreactive peptides. This study characterizes the products of subcloning the titin immunoreactive domain into pGEX-3X and the subsequent fusion protein. Sequence analysis of the fusion gene indicates the cloned titin domain (GenBank ID: (EU428784)) is in frame and is derived from a sequence of N2-A spanning the exons 248-250 an area that encodes the fibronectin III domain. PCR and EcoR1 restriction mapping studies have demonstrated that the inserted cDNA is of a size that is predicted by bioinformatics analysis of the subclone. Expression of the fusion protein result in the isolation of a polypeptide of 52 kDa consistent with the predicted inferred amino acid sequence. Immunoblot experiments of the fusion protein, using rippling muscle/myasthenia gravis antisera, demonstrate that only the titin domain is immunoreactive.

  12. Guillain-Barré Syndrome Animal Model: The First Proof of Molecular Mimicry in Human Autoimmune Disorder

    OpenAIRE

    2010-01-01

    Molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases, and this hypothesis is proven in Guillain-Barré syndrome. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni enteritis. Gangliosides are predominantly cell-surface glycolipids highly expressed in nervous tissue, whilst lipo-oligosaccharides are major components of the Gram-negative bacterium C....

  13. Evidence from human and animal studies: Pathological roles of CD8+ T cells in autoimmune peripheral neuropathies

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    Mu eYang

    2015-10-01

    Full Text Available Autoimmune peripheral neuropathies such as Guillain Barre Syndrome (GBS and chronic inflammatory demyelinating polyneuropathy (CIDP affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN. As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicate that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathy. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice in which the T cell co-stimulator molecule B7.2 (CD86 is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies.

  14. Virtual Immunology: Software for Teaching Basic Immunology

    OpenAIRE

    Berçot', Filipe Faria; Fidalgo Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thaís; Alves,Luiz Anastacio

    2013-01-01

    The authors of this publication are on ResearchGate and have made the full-text available on their profiles. As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching–learning process in such areas has been improved with tools such as educational software. This article introduces “Virtual Immunology,” a software program available free of charge in Portuguese...

  15. Gene therapy of experimental autoimmune thyroiditis mice by in vivo administration of plasmid DNA coding for human interleukin-10

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhen-Lin; LINBo; YULu-Yang; SHENShui-Xian; ZHULi-Hua; WANGWui-Ping; GUOLi-He

    2003-01-01

    AIM: To investigate the effect of interleukin-10 (IL-10) gene on experimental autoimmune thyroiditis mice.METHODS: Mice were immunized to induce autoimmune thyroiditis with porcine thyroglobulin (pTg), and thyroids of mice were injected with IL-10 DNA. On d 28 after immunization with pTg, mRNA expression of IL-10 inthyroid glands was detected and thyroid specimens were histopathological studied. RESULTS: The mRNA expression of IL-10 was detected in thyroid glands on d 7 and 14 after injection of IL-10 plasmid DNA or on COS-7 cells48 h after IL-10 plasmid DNA transfection. In addition, hlL-10 levels in culture media significantly increased 48 hand 72 h after IL-10 plasmid DNA transfection. Infiltration index of lymphocytes (1.1±0.4) in thyroids ofIL-10-treated mice was significantly lower than that of pcDNA3-null-treated mice (2.2±0.5) (P<0.01). Comparedwith pcDNA3-null control mice, IL-10-treated mice had lower levels of serum IFN-γ(P<0.01). CONCLUSION:The direct injection of DNA expression vectors encoding IL-10 into thyroid significantly inhibited development oflymphocytic infiltration of thyroid of autoimmune th,yroiditis mice, and alleviated the progression of this disease.

  16. Hot topics in autoimmune diseases: perspectives from the 2013 Asian Congress of Autoimmunity.

    Science.gov (United States)

    Selmi, Carlo

    2014-08-01

    Our understanding of the pathogenic mechanisms and possible treatments of autoimmune diseases has significantly increased over the past decade. Nonetheless, numerous major issues remain open and such issues span from epidemiology to clinimetrics and from the role of infectious agents to the search for accurate biomarkers in paradigmatic conditions such as systemic lupus erythematosus, rheumatoid arthritis, and spondyloarthropathies. In the case of cardiovascular comorbidities of autoimmune diseases or, more generally, the pathogenesis of atherosclerosis, fascinating evidence points to a central role of autoimmunity and metabolic dysfunctions and a possible role of therapies targeting inflammation to ameliorate both conditions. Basic science and translational medicine contribute to identify common mechanisms that underlie different autoimmune diseases, as in the case of tumor necrosis factor alpha, and more recently vitamin D, autoantibodies, T and B regulatory cells, and microRNA. Finally, new therapies are expected to significantly change our approach to autoimmune diseases, as represented by the recent FDA approval of the first oral JAK inhibitor. The present article moves from the major topics that were discussed at the 2013 Asian Congress of Autoimmunity in Hong Kong to illustrate the most recent data from leading journals in autoimmunity and immunology.

  17. PI3K inhibitors as potential therapeutics for autoimmune disease.

    Science.gov (United States)

    Ball, Jennifer; Archer, Sophie; Ward, Stephen

    2014-08-01

    Aberrant overactivation of the immune system can give rise to chronic and persistent self-attack, culminating in autoimmune disease. This is currently managed therapeutically using potent immunosuppressive and anti-inflammatory drugs. Class I phosphoinositide 3-kinases (PI3Ks) have been identified as ideal therapeutic targets for autoimmune diseases given their wide-ranging roles in immunological processes. Recent studies into the function of selective PI3K inhibitors in vitro and in vivo have yielded encouraging results, allowing progression into the clinic. Here, we review their recent progress across a range of autoimmune diseases.

  18. Historical reflections on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Ian R Mackay

    2008-01-01

    Autoimmune hepatitis (AIH),initially known as chronic active or active chronic hepatitis (and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody (ANA),smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being (relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

  19. Palivizumab Exposure and the Risk of Autoimmune Disease

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Linder, Marie; Stokholm, Lonny Merete;

    2016-01-01

    children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS...... of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac...... disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80-2.95). CONCLUSION: The risk of autoimmune disease was not increased...

  20. Modelling Immunological Memory

    CERN Document Server

    Garret, Simon; Walker, Joanne; Wilson, William; Aickelin, Uwe

    2010-01-01

    Accurate immunological models offer the possibility of performing highthroughput experiments in silico that can predict, or at least suggest, in vivo phenomena. In this chapter, we compare various models of immunological memory. We first validate an experimental immunological simulator, developed by the authors, by simulating several theories of immunological memory with known results. We then use the same system to evaluate the predicted effects of a theory of immunological memory. The resulting model has not been explored before in artificial immune systems research, and we compare the simulated in silico output with in vivo measurements. Although the theory appears valid, we suggest that there are a common set of reasons why immunological memory models are a useful support tool; not conclusive in themselves.

  1. Immunologic, genetic and social human risk factors associated to histoplasmosis: studies in the State of Guerrero, Mexico.

    Science.gov (United States)

    Taylor, M L; Pérez-Mejía, A; Yamamoto-Furusho, J K; Granados, J

    1997-01-01

    Immunologic and occupational aspects of the susceptible population exposed to Histoplasma capsulatum, the causative agent of histoplasmosis were analyzed in the Mexican State of Guerrero. Three areas were studied, Juxtlahuaca, Olinala, and Coyuca; in the first two, their populations refer contact with bat guano and/or avian excreta, which contain nutrients for fungal growth, while the Coyuca population referred no contact with the above mentioned excreta. Previous infection with H. capsulatum was determined by histoplasmin-skin test, and the response was higher in men than in women (93.87, 85.71, and 6.6% for men, and 78.94, 66.6, and 0% for women) in Juxtlahuaca, Olinala, and Coyuca, respectively. Labor activities related to a persistent contact with the fungus were considered as an occupational risk factor, histoplasmin-skin test reached 88.57 and 36.36% of positive response in individuals with high and low risk activities. A high percentage of histoplasmin responses was observed in subjects with constant contact with H. capsulatum, such as, cave-tourist guides, peasants, and game-cock handlers, and generally they developed the largest diameter of skin reactions. Genetic risk factor was determined by studying the gene frequency of the Major Histocompatibility Complex antigens in a sample of individuals and their degree relatives in Juxtlahuaca, Olinala, and Coyuca. Significant differences were found for HLA-B22 and B17 antigens in Juxtlahuaca, and for HLA-B22 in Olinala, in comparison to the usual gene frequency observed in the normal Mexican population. HLA results were important, considering that HLA-B22 was previously found to be possibly related to pulmonary histoplasmosis in Guerrero.

  2. Epidemiology of tuberculosis immunology.

    Science.gov (United States)

    Fox, G J; Menzies, D

    2013-01-01

    Immunological impairment plays a major role in the epidemiology of TB. Globally, the most common causes of immunological impairment are malnutrition, diabetes, HIV/AIDS, aging, and smoking. With the notable exception of HIV, each factor leads to relatively mild immunological impairment in individuals. However, as these conditions affect a significant proportion of the population, they contribute substantially to the incidence of TB at a global scale. Understanding immunological impairment is central to understanding the global TB pandemic, and vital to the development of effective disease control strategies.

  3. The autoimmune tautology.

    Science.gov (United States)

    Anaya, Juan-Manuel

    2010-01-01

    Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates that the pathologic mechanisms may be similar among autoimmune diseases. Lastly, genetic evidence shows that autoimmune phenotypes might represent pleiotropic outcomes of the interaction of non-specific disease genes.

  4. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  5. Parasitic Helminths: New Weapons against Immunological Disorders

    Directory of Open Access Journals (Sweden)

    Yoshio Osada

    2010-01-01

    Full Text Available The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis. Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology.

  6. Electrosmog and autoimmune disease.

    Science.gov (United States)

    Marshall, Trevor G; Heil, Trudy J Rumann

    2016-07-13

    Studies in mice have shown that environmental electromagnetic waves tend to suppress the murine immune system with a potency similar to NSAIDs, yet the nature of any Electrosmog effects upon humans remains controversial. Previously, we reported how the human Vitamin-D receptor (VDR) and its ligand, 1,25-dihydroxyvitamin-D (1,25-D), are associated with many chronic inflammatory and autoimmune diseases. We have shown how olmesartan, a drug marketed for mild hypertension, acts as a high-affinity partial agonist for the VDR, and that it seems to reverse disease activity resulting from VDR dysfunction. We here report that structural instability of the activated VDR becomes apparent when observing hydrogen bond behavior with molecular dynamics, revealing that the VDR pathway exhibits a susceptibility to Electrosmog. Further, we note that characteristic modes of instability lie in the microwave frequency range, which is currently populated by cellphone and WiFi communication signals, and that the susceptibility is ligand dependent. A case series of 64 patient-reported outcomes subsequent to use of a silver-threaded cap designed to protect the brain and brain stem from microwave Electrosmog resulted in 90 % reporting "definite" or "strong" changes in their disease symptoms. This is much higher than the 3-5 % rate reported for electromagnetic hypersensitivity in a healthy population and suggests that effective control of environmental Electrosmog immunomodulation may soon become necessary for successful therapy of autoimmune disease.

  7. Allergy and Immunology

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009037 Passive transfer/of experimental autoimmune myasthenia gravis in rabbits with IgG of myasthenia gravis patients. LI Xiuhua(李秀华). et al. Neurol Dept, Tianjin Med Univ General Hosp, Tianjin 300052. Chin J Ment Nerv Dis 2009;35(1):7-10. Objective To create experimental autoimmune myasthenia gravis (EAMG) rabbits by passive transfer the IgG.

  8. 21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-macroglobulin immunological test system. 866.5620 Section 866.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5620 Alpha-2-macroglobulin immunological...

  9. 21 CFR 866.5420 - Alpha-1-glycoproteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-glycoproteins immunological test system. 866.5420 Section 866.5420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5420 Alpha-1-glycoproteins immunological...

  10. 21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. ...

  11. 21 CFR 866.5130 - Alpha-1-antitrypsin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antitrypsin immunological test system. 866.5130 Section 866.5130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5130 Alpha-1-antitrypsin immunological test...

  12. 21 CFR 866.5425 - Alpha-2-glycoproteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-glycoproteins immunological test system. 866.5425 Section 866.5425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5425 Alpha-2-glycoproteins immunological...

  13. Rare phenotypes in the understanding of autoimmunity.

    Science.gov (United States)

    Zeissig, Yvonne; Petersen, Britt-Sabina; Franke, Andre; Blumberg, Richard S; Zeissig, Sebastian

    2016-11-01

    The study of rare phenotypes has a long history in the description of autoimmune disorders. First Mendelian syndromes of idiopathic tissue destruction were defined more than 100 years ago and were later revealed to result from immune-mediated reactivity against self. In the past two decades, continuous advances in sequencing technology and particularly the advent of next-generation sequencing have allowed to define the genetic basis of an ever-growing number of Mendelian forms of autoimmunity. This has provided unique insight into the molecular pathways that govern immunological homeostasis and that are indispensable for the prevention of self-reactive immune-mediated tissue damage and 'horror autotoxicus'. Here we will discuss selected examples of past and recent investigations into rare phenotypes of autoimmunity that have delineated pathways critical for central and peripheral control of the adaptive immune system. We will outline the implications of these findings for rare and common forms of autoimmunity and will discuss the benefits and potential pitfalls of the integration of next-generation sequencing into algorithms for clinical diagnostics. Because of the concise nature of this review, we will focus on syndromes caused by defects in the control of adaptive immunity as innate immune-mediated autoinflammatory disorders have been covered in excellent recent reviews on Mendelian and polygenic forms of autoimmunity.

  14. Accumulation of VH Replacement Products in IgH Genes Derived from Autoimmune Diseases and Anti-Viral Responses in Human.

    Science.gov (United States)

    Lange, Miles D; Huang, Lin; Yu, Yangsheng; Li, Song; Liao, Hongyan; Zemlin, Michael; Su, Kaihong; Zhang, Zhixin

    2014-01-01

    VH replacement refers to RAG-mediated secondary recombination of the IgH genes, which renews almost the entire VH gene coding region but retains a short stretch of nucleotides as a VH replacement footprint at the newly generated VH-DH junction. To explore the biological significance of VH replacement to the antibody repertoire, we developed a Java-based VH replacement footprint analyzer program and analyzed the distribution of VH replacement products in 61,851 human IgH gene sequences downloaded from the NCBI database. The initial assignment of the VH, DH, and JH gene segments provided a comprehensive view of the human IgH repertoire. To our interest, the overall frequency of VH replacement products is 12.1%; the frequencies of VH replacement products in IgH genes using different VH germline genes vary significantly. Importantly, the frequencies of VH replacement products are significantly elevated in IgH genes derived from different autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and allergic rhinitis, and in IgH genes encoding various autoantibodies or anti-viral antibodies. The identified VH replacement footprints preferentially encoded charged amino acids to elongate IgH CDR3 regions, which may contribute to their autoreactivities or anti-viral functions. Analyses of the mutation status of the identified VH replacement products suggested that they had been actively involved in immune responses. These results provide a global view of the distribution of VH replacement products in human IgH genes, especially in IgH genes derived from autoimmune diseases and anti-viral immune responses.

  15. Autoimmune Inner Ear Disease

    Science.gov (United States)

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  16. Overview of models, methods, and reagents developed for translational autoimmunity research in the common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Jagessar, S Anwar; Vierboom, Michel; Blezer, Erwin L A; Bauer, Jan; Hart, Bert A 't; Kap, Yolanda S

    2013-01-01

    The common marmoset (Callithrix jacchus) is a small-bodied Neotropical primate and a useful preclinical animal model for translational research into autoimmune-mediated inflammatory diseases (AIMID), such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The animal model for MS established in marmosets has proven their value for exploratory research into (etio) pathogenic mechanisms and for the evaluation of new therapies that cannot be tested in lower species because of their specificity for humans. Effective usage of the marmoset in preclinical immunological research has been hampered by the limited availability of blood for immunological studies and of reagents for profiling of cellular and humoral immune reactions. In this paper, we give a concise overview of the procedures and reagents that were developed over the years in our laboratory in marmoset models of the above-mentioned diseases.

  17. The immunology of filariasis*

    OpenAIRE

    1981-01-01

    This report summarizes the available information on the immunology of filariasis, and discusses immunodiagnosis and the immunological factors influencing the host—parasite relationship in lymphatic filariasis and onchocerciasis. Several areas that require further research are identified, particularly concerning the development of new serological techniques, and the fractionation of specific antigens. The problems associated with vaccine development are considered and the importance of finding...

  18. Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Liebman, Howard A; Weitz, Ilene C

    2017-03-01

    Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

  19. The Use of Mesenchymal Stem Cells for the Treatment of Autoimmunity: From Animals Models to Human Disease.

    Science.gov (United States)

    Fierabracci, Alessandra; Del Fattore, Andrea; Muraca, Marta; Delfino, Domenico Vittorio; Muraca, Maurizio

    2016-01-01

    Mesenchymal stem cells are multipotent progenitors able to differentiate into osteoblasts, chondrocytes and adipocytes. These cells also exhibit remarkable immune regulatory properties, which stimulated both in vitro and in vivo experimental studies to unravel the underlying mechanisms as well as extensive clinical applications. Here, we describe the effects of MSCs on immune cells and their application in animal models as well as in clinical trials of autoimmune diseases. It should be pointed out that, while the number of clinical applications is increasing steadily, results should be interpreted with caution, in order to avoid rising false expectations. Major issues conditioning clinical application are the heterogeneity of MSCs and their unpredictable behavior following therapeutic administration. However, increasing knowledge on the interaction between exogenous cell and host tissue, as well as some encouraging clinical observations suggest that the therapeutic applications of MSCs will be further expanded on firmer grounds in the near future.

  20. Immunology of Gut Mucosal Vaccines

    Science.gov (United States)

    Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

    2011-01-01

    Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

  1. Exposure to negatively charged-particle dominant air-conditions on human lymphocytes in vitro activates immunological responses.

    Science.gov (United States)

    Nishimura, Yasumitsu; Takahashi, Kazuaki; Mase, Akinori; Kotani, Muneo; Ami, Kazuhisa; Maeda, Megumi; Shirahama, Takashi; Lee, Suni; Matsuzaki, Hidenori; Kumagai-Takei, Naoko; Yoshitome, Kei; Otsuki, Takemi

    2015-12-01

    Indoor air-conditions may play an important role in human health. Investigation of house conditions that promote health revealed that negatively charged-particle dominant indoor air-conditions (NAC) induced immune stimulation. NAC was established using fine charcoal powder on walls and ceilings and utilizing forced negatively charged particles (approximate diameter: 20 nm) dominant in indoor air-conditions created by applying an electric voltage (72 V) between the backside of the walls and the ground. We reported previously that these conditions induced a slight and significant increase of interleukin-2 during 2.5 h stay, and an increase of natural killer (NK) cell cytotoxicity, when examining human subjects after a two-week night stay under these conditions. In the present study, we investigated whether exposure to NAC in vitro affects immune conditions. Although the concentrations of particles were different, an incubator for cell culture with NAC was set and cellular compositions and functions of various freshly isolated human lymphocytes derived from healthy donors were assayed in the NAC incubator and compared with those of cultures in a standard (STD) incubator. Results showed that NAC cultivation caused an increase of CD25 and PD-1 expressing cells in the CD4 positive fraction, enhancement of NK cell cytotoxicity, production of interferon-y (IFNγ), and slight enhancement of regulatory T cell function. In addition, the formula designated as the "immune-index" clearly differed between STD and NAC culture conditions. Thus, NAC conditions may promote human health through slight activation of the immune system against cancer cells and virus infection as shown by this in vitro study and our previously reported human studies.

  2. Novel Immunotherapies for Autoimmune Hepatitis

    Science.gov (United States)

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

  3. Novel Immunotherapies for Autoimmune Hepatitis.

    Science.gov (United States)

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects.

  4. Selected Aspects in the Pathogenesis of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    György Nagy

    2015-01-01

    Full Text Available Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  5. Selected Aspects in the Pathogenesis of Autoimmune Diseases.

    Science.gov (United States)

    Nagy, György; Huszthy, Peter C; Fossum, Even; Konttinen, Yrjö; Nakken, Britt; Szodoray, Peter

    2015-01-01

    Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.

  6. Zebrafish to humans: evolution of the alpha3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome.

    Science.gov (United States)

    MacDonald, Brian A; Sund, Malin; Grant, Marianne A; Pfaff, Kathleen L; Holthaus, Kathryn; Zon, Leonard I; Kalluri, Raghu

    2006-03-01

    Goodpasture syndrome is an autoimmune vascular disease associated with kidney and lung failure, with pathogenic circulating autoantibodies targeted to a set of discontinuous epitope sequences within the noncollagenous domain-1 (NC1) of the alpha3 chain of type IV collagen (alpha3(IV)NC1), the Goodpasture autoantigen. We demonstrate that basement membrane extracted NC1 domain preparations from Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio do not bind Goodpasture autoantibodies, while Xenopus laevis, chicken, mouse and human alpha3(IV)NC1 domains bind autoantibodies. The alpha3(IV) chain is not present in C elegans and Drosophila melanogaster, but is first detected in the Danio rerio. Interestingly, native Danio rerio alpha3(IV)NC1 does not bind Goodpasture autoantibodies. Next, we cloned, sequenced, and generated recombinant Danio rerio alpha3(IV)NC1 domain. In contrast to recombinant human alpha3(IV)NC1 domain, there was complete absence of autoantibody binding to recombinant Danio rerio alpha3(IV)NC1. Three-dimensional molecular modeling from existing x-ray coordinates of human NC1 domain suggest that evolutionary alteration of electrostatic charge and polarity due to the emergence of critical serine, aspartic acid, and lysine residues, accompanied by the loss of asparagine and glutamine, contributes to the emergence of the 2 major Goodpasture epitopes on the human alpha3(IV)NC1 domain, as it evolved from the Danio rerio over 450 million years.

  7. Zebrafish to humans: evolution of the α3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome

    Science.gov (United States)

    MacDonald, Brian A.; Sund, Malin; Grant, Marianne A.; Pfaff, Kathleen L.; Holthaus, Kathryn; Zon, Leonard I.; Kalluri, Raghu

    2006-01-01

    Goodpasture syndrome is an autoimmune vascular disease associated with kidney and lung failure, with pathogenic circulating autoantibodies targeted to a set of discontinuous epitope sequences within the noncollagenous domain-1 (NC1) of the α3 chain of type IV collagen (α3(IV)NC1), the Goodpasture autoantigen. We demonstrate that basement membrane extracted NC1 domain preparations from Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio do not bind Goodpasture autoantibodies, while Xenopus laevis, chicken, mouse and human α3(IV)NC1 domains bind autoantibodies. The α3(IV) chain is not present in C elegans and Drosophila melanogaster, but is first detected in the Danio rerio. Interestingly, native Danio rerio α3(IV)NC1 does not bind Goodpasture autoantibodies. Next, we cloned, sequenced, and generated recombinant Danio rerio α3(IV)NC1 domain. In contrast to recombinant human α3(IV)NC1 domain, there was complete absence of autoantibody binding to recombinant Danio rerio α3(IV)NC1. Three-dimensional molecular modeling from existing x-ray coordinates of human NC1 domain suggest that evolutionary alteration of electrostatic charge and polarity due to the emergence of critical serine, aspartic acid, and lysine residues, accompanied by the loss of asparagine and glutamine, contributes to the emergence of the 2 major Goodpasture epitopes on the human α3(IV)NC1 domain, as it evolved from the Danio rerio over 450 million years. PMID:16254142

  8. Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

    Science.gov (United States)

    Nagy, K; Marschalkó, Márta; Kemény, B; Horváth, A

    2005-01-01

    The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

  9. Immunology of Psoriasis

    Science.gov (United States)

    Lowes, Michelle A.; Suárez-Fariñas, Mayte; Krueger, James G.

    2014-01-01

    The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases. PMID:24655295

  10. Coeliac disease: a unique model for investigating broken tolerance in autoimmunity.

    Science.gov (United States)

    Hardy, Melinda Y; Tye-Din, Jason A

    2016-11-01

    Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II association and the presence of pathogenic CD4(+) T cells and autoantibodies. CD8(+) intraepithelial lymphocytes specifically target and destroy intestinal epithelium in response to stress signals and not a specific antigen. A unique feature of coeliac disease is the ability to remove gluten to induce disease remission and reintroduce it to trigger a memory response. This provides an unparalleled opportunity to study disease-relevant CD4(+) T cells that have been expanded in vivo. As a result, the causative peptides have been characterised at a level unprecedented for any autoimmune disease. Despite the complexity of the gluten proteome, resistance to gastrointestinal proteolysis and susceptibility to post-translational modification by transglutaminase help shape a restricted repertoire of immunogenic gluten peptides that have high affinity for disease-associated HLA. The critical steps in coeliac disease pathogenesis have been broadly elucidated and provide the basis for experimental therapies in pre-clinical or clinical development. However, little is known about how and why tolerance to gluten sometimes breaks or fails to develop. Understanding the interactions between genes, the environment, gluten immunity and the microbiome may provide novel approaches for the prevention and treatment of disease.

  11. Pathophysiology and immunological profile of myasthenia gravis and its subgroups.

    Science.gov (United States)

    Romi, Fredrik; Hong, Yu; Gilhus, Nils Erik

    2017-08-03

    Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present. Copyright © 2017. Published by Elsevier Ltd.

  12. Multiple etiologies of equine recurrent uveitis--A natural model for human autoimmune uveitis: A brief review.

    Science.gov (United States)

    Witkowski, Lucjan; Cywinska, Anna; Paschalis-Trela, Katarzyna; Crisman, Mark; Kita, Jerzy

    2016-02-01

    Equine recurrent uveitis (ERU) has various etiologies, with Leptospira infection and genetic predisposition being the leading risk factors. Regardless of etiology, expression of ocular proteins associated with maintenance of the blood-ocular barrier is impaired in ERU. The recurring-remitting cycle of ERU repeatedly disrupts the blood-ocular barrier, allowing the previously immune-privileged ocular environment to become the site of a progressive local autoimmune pathology that ultimately results in tissue destruction and vision loss. The immune-mediated process involves humoral and cellular mechanisms. Intraocular antibodies either produced in the eye or that leak through the blood-ocular barrier, are often present at higher levels than in serum and react with antigens in ocular tissue of horses with ERU. Ocular infiltration of auto-aggressive lymphocytes occurs with each uveitis episode and is the most crucial contributor to inflammation and eye damage. Recurring uveitis episodes may be initiated when epitopes of an ocular antigen become visible to the immune system (intramolecular spreading) or another autoantigen (intermolecular spreading), resulting in a new inflammatory reaction.

  13. Cutting edge issues in autoimmune gastritis.

    Science.gov (United States)

    Toh, Ban-Hock; Chan, James; Kyaw, Tin; Alderuccio, Frank

    2012-06-01

    Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated autoimmune response directed against the gastric H/K-ATPase. Silent initially, the gastric lesion becomes manifest in humans by the development of megaloblastic pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in this disease relate to its epidemiology, immunogenetics, a role for Helicobacter pylori as an infective trigger through molecular mimicry, its immunopathogenesis, associated organ-specific autoimmune diseases, laboratory diagnosis, and approaches to curative therapy.

  14. One-health approach as counter-measure against "autoimmune" responses in biosecurity.

    Science.gov (United States)

    Mutsaers, Inge

    2015-03-01

    This Swine flu pandemic of 2009 and the potential Avian flu threat of 2011-2012 have revived a most challenging debate on protection against infectious diseases. The response to the Swine flu pandemic has been ambivalent, both on the societal (political) and the scientific level. While some scientists warned against potential massive loss of human lives and urged for immediate and large-scale vaccination, others accused them of unnecessary scaremongering, arguing that the pandemic would not be that severe. The lab-created virulent Avian flu virus - which has been created in order to 'fight' a potential Avian flu pandemic - sparked a fierce debate on the dual-use risks of such a pre-emptive strategy. This article involves an analysis of the medical-political response to these recent viral threats using Peter Sloterdijk's immunological framework as diagnostic tool. In his trilogy Spheres Sloterdijk uses immunological concepts to analyse and assess the contemporary biopolitical situation. It shows how drawing a parallel between the functioning of the biological immune system and "immune responses" on socio-political level enables to assess and reconceptualise biosecurity. It demonstrates that ideas such as "nature is the biggest terrorist" - as advanced by many virologists - sometimes result in exaggerated "immunisation responses". This strong defensive attitude sometimes brings about collateral damage. In other words, fierce biosecurity measures sometimes risk developing into "autoimmune" responses that actually destruct the body politic they are meant to protect. By drawing on recent insights in the functioning of the biological immune system it is shown how a One-Health approach that incorporates a broader and nuanced "immunological" repertoire could act as counter-measure against "autoimmune" responses in biosecurity.

  15. Alterations in immune function with biologic therapies for autoimmune disease.

    Science.gov (United States)

    Her, Minyoung; Kavanaugh, Arthur

    2016-01-01

    Autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and others, are characterized by dysregulation of various aspects of normal immunity and inflammation. Biologic agents targeting key components of the dysregulated immune response have dramatically improved patient outcomes and transformed treatment paradigms for a number of systemic inflammatory autoimmune diseases. Despite their excellent efficacy, because they do affect normal immune responsiveness, biologic agents can potentially be associated with a variety of adverse effects. Important potential adverse effects related to the use of biologic agents include immunosuppression, which might result in outcomes such as infection, and autoimmunity, that could result in paradoxical inflammation or even autoimmune disease. In this article the current clinical evidence and immunologic mechanisms of the adverse effects related to biologic agents are discussed.

  16. Autoimmune regulator and self-tolerance - molecular and clinical aspects.

    Science.gov (United States)

    Abramson, Jakub; Husebye, Eystein S

    2016-05-01

    The establishment of central tolerance in the thymus is critical for avoiding deleterious autoimmune diseases. Autoimmune regulator (AIRE), the causative gene in autoimmune polyendocrine syndrome type-1 (APS-1), is crucial for the establishment of self-tolerance in the thymus by promoting promiscuous expression of a wide array of tissue-restricted self-antigens. This step is critical for elimination of high-affinity self-reactive T cells from the immunological repertoire, and for the induction of a specific subset of Foxp3(+) T-regulatory (Treg ) cells. In this review, we discuss the most recent advances in our understanding of how AIRE operates on molecular and cellular levels, as well as of how its loss of function results in breakdown of self-tolerance mechanisms characterized by a broad and heterogeneous repertoire of autoimmune phenotypes.

  17. Sirolimus for Autoimmune Disease of Blood Cells

    Science.gov (United States)

    2017-03-16

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  18. Galectin-3 in autoimmunity and autoimmune diseases.

    Science.gov (United States)

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2015-08-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases.

  19. THE CONSEQUENCES OF APOPTOSIS IN AUTOIMMUNITY

    Science.gov (United States)

    Lleo, Ana; Selmi, Carlo; Invernizzi, Pietro; Podda, Mauro; Gershwin, M. Eric

    2008-01-01

    The clearance of apoptotic cells is a highly regulated mechanism, normally associated with anti-inflammatory response. During early stages of apoptosis the cell is promptly recognized and engulfed by professional phagocytes or tissue cells to avoid the outflow of intracellular content and limit the immunological reaction against released antigens. However, increasing evidences suggest that impairment in the uptake of apoptotic cell debris is linked to the development of autoimmunity. In fact, autoantigens have been demonstrated to be content within apoptotic bodies and apoptotic cells seems to be critical in the presentation of antigens, activation of innate immunity and regulation of macrophage cytokine secretion. We herein review the known mechanisms for regulating the uptake of the products of apoptosis in the development of autoimmunity. PMID:18513925

  20. Serological Diagnosis of Autoimmune Blistering Diseases

    Directory of Open Access Journals (Sweden)

    Birgül Özkesici

    2016-03-01

    Full Text Available Autoimmune blistering diseases are a rare diseases, characterized by development of autoantibodies against the structural proteins of the epidermis or dermoepidermal junction, and blisters and erosions on skin and/or mucous membranes clinically. Clinical features are important guiding findings for suspicious of this group of diseases. The diagnosis is achieved by the evaluation together of clinical features, histological and immunological findings. The gold standard in the diagnosis of this group diseases are demonstration of tissue bound and/or circulating autoantibodies. Methods for this purpose are; direct and indirect immunofluorescence, Enzyme Linked Immunosorbent Assay (ELISA, immunoprecipitation and immunoblotting. The aim of this paper is to review serological diagnostic methods in the diagnosis of autoimmune bullous diseases and to present developments in recent years.

  1. Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

    Science.gov (United States)

    Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona

    2015-03-01

    Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

  2. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.

    Science.gov (United States)

    Oftedal, Bergithe E; Hellesen, Alexander; Erichsen, Martina M; Bratland, Eirik; Vardi, Ayelet; Perheentupa, Jaakko; Kemp, E Helen; Fiskerstrand, Torunn; Viken, Marte K; Weetman, Anthony P; Fleishman, Sarel J; Banka, Siddharth; Newman, William G; Sewell, W A C; Sozaeva, Leila S; Zayats, Tetyana; Haugarvoll, Kristoffer; Orlova, Elizaveta M; Haavik, Jan; Johansson, Stefan; Knappskog, Per M; Løvås, Kristian; Wolff, Anette S B; Abramson, Jakub; Husebye, Eystein S

    2015-06-16

    The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1. These missense PHD1 mutations suppressed gene expression driven by wild-type AIRE in a dominant-negative manner, unlike CARD or truncated AIRE mutants that lacked such dominant capacity. Exome array analysis revealed that the PHD1 dominant mutants were found with relatively high frequency (>0.0008) in mixed populations. Our results provide insight into the molecular action of AIRE and demonstrate that disease-causing mutations in the AIRE locus are more common than previously appreciated and cause more variable autoimmune phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. New mechanism revealed for regulation of autoimmunity

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ A healthy human body is equipped with a powerful immune system for resisting the attack of invading microorganisms. Unfortunately, the system sometimes goes awry and attacks the body itself.Autoimmunity is the failure of an organism to recognize its own constituent parts as"self," resulting in an immune response against its own cells and tissues. A disorder that results from such an aberrant immune response is termed an autoimmune disease.

  4. Aspects of the role of mineral oil as immunological adjuvants in rheumatoid arthritis

    OpenAIRE

    Sverdrup, Berit

    2007-01-01

    Environmental factors are likely contributing factors in the development of Rheumatoid Arthritis (RA), an autoimmune disease, for which etiologic factors are still poorly known. Mineral oils are efficient adjuvants which increase immunological responses and are used in animal immunization and for induction of different experimental autoimmune diseases including arthritis. The relationship between environmental exposure to mineral oil and the risk of developing RA is the ...

  5. Long term immunologic consequences of experimental stroke and mucosal tolerance

    Directory of Open Access Journals (Sweden)

    Gee J Michael

    2009-10-01

    Full Text Available Abstract Background An inflammatory insult following middle cerebral artery occlusion (MCAO is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP. Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional outcome early after stroke. In this study, we sought to determine the long term immunologic consequences of experimental stroke and induction of mucosal tolerance. Methods Male Lewis rats were tolerized to MBP or ovalbumin (OVA by intranasal administration prior to MCAO and administration of lipopolysaccharide (LPS. Neurological outcome was assessed at set points after MCAO and animals sacrificed at 3 months; the immune response to MBP in brain and spleen was determined using ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by immunocytochemistry. Results Animals that developed a pro-inflammatory (TH1 response to MBP experienced worse outcome, while those that developed a regulatory response (TREG experienced better outcome. A TREG response in spleen was also associated with decreased inflammation and an increase in the number of FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO was associated with a tendency to develop a TH1 response to MBP by 3 months after MCAO. Conclusion These data show that induction of immunological tolerance to MBP is associated with improved outcome after stroke. This study, however, raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.

  6. Autoimmune pancreatitis: A review

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  7. Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM(2.5) organic extract from Puerto Rico.

    Science.gov (United States)

    Fuentes-Mattei, Enrique; Rivera, Evasomary; Gioda, Adriana; Sanchez-Rivera, Diana; Roman-Velazquez, Felix R; Jimenez-Velez, Braulio D

    2010-03-15

    Fine particulate air pollutants, mainly their organic fraction, have been demonstrated to be associated with cardiovascular and respiratory health problems. Puerto Rico has been reported to have the highest prevalence of pulmonary diseases (e.g., asthma) in the United States. The aim of this study was to assess, for the first time, the immunological response of human bronchial epithelial cells (BEAS-2B) to organic extracts isolated from airborne particulate matter (PM(2.5)) in Puerto Rico. Organic extracts from PM(2.5) collected throughout an 8-month period (2000-2001) were pooled (composite) in order to perform chemical analysis and biological activity testing. BEAS-2B cells were exposed to PM(2.5) organic extract to assess cytotoxicity, levels of cytokines and relative gene expression of MHC-II, hPXR and CYP3A5. Our findings show that organic PM(2.5) consist of toxic as well as bioactive components that can regulate the secretion of cytokines in BEAS-2B, which could modulate inflammatory response in the lung. Trace element analyses confirmed the presence of metals in organic extracts highlighting the relative high abundance of Cu and Zn in polar organic extracts. Polar organic extracts exhibited dose-dependant toxicity and were found to significantly induce the release of interleukin 6 (IL-6), IL-1beta and IL-7 while significantly inhibiting the secretion of IL-8, G-CSF and MCP-1. Moreover, MHC-II transcriptional activity was up-regulated after 24 h of exposure, whereas PXR and CYP3A5 were down-regulated. This research provides a new insight into the effects of PM(2.5) organic fractions on specific effectors and their possible role in the development of respiratory inflammatory diseases in Puerto Rico.

  8. CCL8 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of CCL8.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...... suitable biological samples. The methods of the present invention are useful in therapeutic and diagnostic protocols for human, livestock and veterinary and wild life applications, thus the invention further relates to a method for diagnosing an infection in a mammal....

  9. An immunological insight into premature ovarian failure (POF).

    Science.gov (United States)

    Dragojević-Dikić, Svetlana; Marisavljević, Dragomir; Mitrović, Ana; Dikić, Srdjan; Jovanović, Tomislav; Janković-Raznatović, Svetlana

    2010-09-01

    Premature ovarian failure (POF), a serious life-changing condition that affects young women, remains an enigma and the researchers' challenge. The term POF generally describes a syndrome of gonadal failure before the age of 40, characterized by amenorrhea, sex steroid deficiency and elevated levels of gonadotropins. Infertility and psychological stress are common consequences of this entity the prevalence of which is 0.9-3%. The known cause of this condition includes: genetic aberrations, autoimmune ovarian damage, iatrogenic and environmental factors, although in majority of cases the underlying cause is not identified. For many women in whom the cause of ovarian failure is unknown, autoimmunity may be the pathogenic mechanism. There is currently evidence that some cases of POF are due to faulty recognition of self in the ovary by the immune system, possibly provoked by genetic or environmental factors initiating such immune response. Numerous evidence, including association with multiple autoimmune endocrine disorders, clinical reversibility, transitory estrogen deficiency, histological and immunological features and the demonstration of circulating ovarian antibodies in serum samples from women with POF, have suggested its immunological origin. We discuss the possible role of such an autoimmune process as a cause or consequence of POF including treatment strategies in POF patients.

  10. Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

    Science.gov (United States)

    Aira, Lazaro E.; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A.; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima

    2016-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:26466969

  11. Immunological evaluation of rheumatoid arthritis patients treated with itolizumab.

    Science.gov (United States)

    Aira, Lazaro E; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima

    2016-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.

  12. The role of cytokines in immunological tolerance: potential for therapy.

    Science.gov (United States)

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  13. Rituximab-based immunosuppression for autoimmune haemolytic anaemia in infants.

    Science.gov (United States)

    Svahn, Johanna; Fioredda, Francesca; Calvillo, Michaela; Molinari, Angelo C; Micalizzi, Concetta; Banov, Laura; Schmidt, Madalina; Caprino, Daniela; Marinelli, Doretta; Gallisai, Domenico; Dufour, Carlo

    2009-04-01

    We report a case series of four infants with severe autoimmune haemolytic anaemia (AIHA) who responded to treatment with rituximab and cyclosporine after having failed first line therapy with high-dose steroid (prednisolone 4-8 mg/kg/d). Rituximab was started at 11-90 d from onset due to continued haemolysis; three infants also received cyclosporine A. Three of four infants reached complete response, defined as normal haemoglobin, reticulocytes and negative indices of haemolysis, at 7-21 months from diagnosis. In long-term follow-up two infants remained disease-free with normal immunology, one had undefined immunodeficiency and one had autoimmune lymphoproliferative syndrome.

  14. [Autoimmune diseases in type 1A diabetes mellitus].

    Science.gov (United States)

    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario Antonio

    2015-08-01

    Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

  15. Age impact on autoimmune thyroid disease in females

    Science.gov (United States)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  16. Immigrants in immunology: the benefits of lax borders.

    Science.gov (United States)

    Stagaman, Keaton; Martinez, Emily S; Guillemin, Karen

    2015-05-01

    The field of immunology has a long history of illuminating fundamental biological processes of critical importance to human health. From an outsider's perspective, the questions are profoundly philosophical and the experimental approaches are elegantly precise. Yet immunology can also appear impenetrable. Here we recount the experience of two graduate students from the fields of ecology and computer science, who have immigrated into immunological terrain attracted by systems-level questions. We argue that such migrations enrich the field of immunology, and that cultural and institutional changes are needed to promote more interdisciplinary explorations.

  17. Immunological memory is associative

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.J.; Forrest, S. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Computer Science; Perelson, A.S. [Los Alamos National Lab., NM (United States)

    1996-12-31

    The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.

  18. Evolution of Immunological Thinking

    Directory of Open Access Journals (Sweden)

    Alaín Alonso Remedios

    2016-04-01

    Full Text Available At present, the mechanisms involved in the "decision" of the immune system to promote an essentially effector response or a tolerant response are not fully known. Throughout history, immunological thinking has changed as the available technologies have led to a better understanding of the immune system. For these reasons, the present literature review was conducted to summarize the changes in immunological thinking regarding the fundamental problem of immunology. The concept of horror autotoxicus proposed by Erlich and the meaning of the clonal selection theory for understanding central tolerance were discussed. The two-signal model, Jerne’s contributions and his immune network theory were also addressed. Finally, the danger model and the theory of dominant tolerance were analyzed. The contributions of each theory to understanding how the immune system works were included.

  19. Immunology of methanogenic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Macario, A.J.L.; Macario, E.C. de (New York State Dept. of Health, Albany, NY (United States). Wadsworth Center for Labs. and Research School of Public Health, Albany, NY (United States))

    1993-01-01

    The purpose of this brief review is to highlight some findings using immunologic methods and antibody probes developed for analysis of methanogens directly in samples from bioreactors, avoiding culture isolation. A considerable diversity of methanogens was revealed by antigenic fingerprinting in bioreactors, larger than previously suspected. It was also found that the number and immunologic characteristics of the methanogenic subpopulations form a pattern distinctive of bioreactor type, feedstocks and operating conditions. This pattern changed in response to perturbations and to temperature shifts. Time course quantitative measurements of methanogenic subpopulations demonstrated that these subpopulations undergo sequential changes during bioreactor operation. Parallel microbiologic, physiologic, and chemical determinations demonstrated the reliability of the immunologic methods and their potential for bioreactor monitoring and for manipulating microprobes (e.g. to exclude a strain from a bioreactor). (author)

  20. Investigation of epididymal immunology

    Institute of Scientific and Technical Information of China (English)

    CHANG Zong-Liang

    2005-01-01

    Immunology is the study of the structure and function of the immune system. The immune system consists of an earlier-stage innate immunity and a later-stage adaptive immunity. The task of the immune system is to efficiently respond to non-self antigens and the invasion of pathogens, thereby protecting the host's homeostasis. This review article discusses the structure and function of the epididymis, including the composition of the epithelial cells of the epididymis and their relationship to the immune system, through the assessment of alterations in the immune cells of the epididymis. The review also shows the anti-inflammatory properties of rat epididymal defensin and the description of the blood-epididymis barrier, immune barrier, epididymitis and pathological mechanisms of infertility in males. Taken together, we see that the epididymis possesses a close link with immunology. Finally, this review discusses the future of studies involving epididymal immunology.

  1. Systems Theory in Immunology

    CERN Document Server

    Doria, Gino; Koch, Giorgio; Strom, Roberto

    1979-01-01

    This volume collects the contributions presented at the "Working Conference on System Theory in Immunology", held in Rome, May 1978. The aim of the Conference was to bring together immunologists on one side and experts in system theory and applied mathematics on the other, in order to identify problems of common interest and to establish a network of joint effort toward their solution. The methodologies of system theory for processing experimental data and for describing dynamical phenomena could indeed contribute significantly to the under­ standing of basic immunological facts. Conversely, the complexity of experimental results and of interpretative models should stimulate mathematicians to formulate new problems and to design appropriate procedures of analysis. The multitude of scientific publications in theoretical biology, appeared in recent years, confirms this trend and calls for extensive interaction between mat- matics and immunology. The material of this volume is divided into five sections, along ...

  2. Studies on the release of leukotrienes and histamine by human lung parenchymal and bronchial fragments upon immunologic and nonimmunologic stimulation. Effects of nordihydroguaiaretic acid, aspirin, and sodium cromoglycate

    Science.gov (United States)

    1985-01-01

    Fragments of human lung parenchyma or bronchi were studied by high performance liquid chromatography, gas chromatography-mass spectrometry, and bioassay for the biosynthesis of 5-lipoxygenase metabolites of arachidonic acid, and by radioenzymatic assay for the release of histamine, upon immunologic and nonimmunologic stimulation. Human lung parenchyma were passively sensitized with serum from timothy- positive allergic patients (radioallergosorbent test, 30-40%) and challenged with 0.5 microgram/ml of timothy allergen. Analysis of the incubation media showed the presence of LTB4, LTC4, LTD4, LTE4, and histamine. Maximum release of LTB4 and LTD4 was observed after 15 min of challenge (92.8 +/- 21, and 67.8 +/- 14 pmol/g tissue wet weight, respectively; mean +/- SEM) whereas maximum release of LTC4 was observed after 5 min of challenge (25 +/- 7.1 pmol). In parallel to leukotriene formation, histamine was released rapidly and reached a maximum after approximately 15 min of challenge (2.85 +/- 0.76 nmol/g tissue). When fragments of human lung parenchyma were stimulated with ionophore A23187 (4 microM), we observed a profile of leukotriene and histamine release similar to that seen in response to the allergen. Ionophore A23187 stimulated the release of two- to fivefold greater amounts of leukotrienes and histamine than did the allergen. Release of LTC4 and histamine was maximal after 5 min of stimulation (83 +/- 22.2 and 5.2 +/- 0.95 nmol/g tissue, respectively), whereas LTB4 and LTD4 release reached a maximum after 15 min (438 +/- 66.6 and 205 +/- 68 nmol/g tissue, respectively). In addition, human lung parenchyma metabolized LTB4 into omega-OH-LTB4 and omega-COOH-LTB4. This tissue also released 5-hydroxy-eicosatetraenoic acid (5-Hete), 12-Hete, and 15- Hete. Fragments of human lung bronchi also released a similar profile of leukotrienes (except LTC4) and histamine when challenged with the allergen or ionophore A23187. Maximum release of LTB4 and LTD4 by allergen or

  3. [Syndrome overlap: autoimmune hepatitis and autoimmune cholangitis].

    Science.gov (United States)

    Guerra Montero, Luis; Ortega Alvarez, Félix; Marquez Teves, Maguin; Asato Higa, Carmen; Sumire Umeres, Julia

    2016-01-01

    Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune cholangitis are chronic autoimmune liver disease, usually present separate, the cases where characteristics of two of the above is observed liver disease is commonly referred to as Overlap Syndromes (OS). Although there is no consensus on specific criteria for the diagnosis of OS identification of this association is important for initiating appropriate treatment and prevent its progression to cirrhosis or at least the complications of cirrhosis and death. We report the case of awoman aged 22 cirrhotic which debuted are edematous ascites, severe asthenia and jaundice compliant diagnostics SS criteria and initially present any response to treatment with ursodeoxycholic acid and oral corticosteroids, but ultimately finished performing a transplant orthotopic liver.

  4. THE AUTOIMMUNE ECOLOGY.

    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya

    2016-04-01

    Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  5. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...

  6. The Autoimmune Ecology.

    Science.gov (United States)

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  7. Immunologic lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Harman, E.M.

    1985-07-01

    The term immunologic lung disease comprises a broad spectrum of disease. The authors have covered a few entities in which recent studies have been particularly helpful in elucidating pathophysiology though not in uncovering the inciting cause. Common to all of these entities is the problem of finding appropriate methods of defining disease activity and response to treatment. As exemplified by the improved outlook for Goodpasture's syndrome with elucidation of its underlying immunopathology, it is likely that better understanding of the immunologic basis of sarcoid and interstitial disease may be helpful in planning more effective treatment strategies. 44 references.

  8. Identification and characterization of a new multigene family in the human MHC: A candidate autoimmune disease susceptibility element (3.8-1)

    Energy Technology Data Exchange (ETDEWEB)

    Harris, J.M.; Venditti, C.P.; Chorney, M.J. [Pennsylvania State Univ. College of Medicine, Hershey, PA (United States)

    1994-09-01

    An association between idiopathic hemochromatosis (HFE) and the HLA-A3 locus has been previously well-established. In an attempt to identify potential HFE candidate genes, a genomic DNA fragment distal to the HLA-A9 breakpoint was used to screen a B cell cDNA library; a member (3.8-1) of a new multigene family, composed of five distinct genomic cross-reactive fragments, was identified. Clone 3.8-1 represents the 3{prime} end of 9.6 kb transcript which is expressed in multiple tissues including the spleen, thymus, lung and kidney. Sequencing and genome database analysis indicate that 3.8-1 is unique, with no homology to any known entries. The genomic residence of 3-8.1, defined by polymorphism analysis and physical mapping using YAC clones, appears to be absent from the genomes of higher primates, although four other cross-reactivities are maintained. The absence of this gene as well as other probes which map in the TNF to HLA-B interval, suggest that this portion of the human HMC, located between the Class I and Class III regions, arose in humans as the result of a post-speciation insertional event. The large size of the 3.8-1 gene and the possible categorization of 3.8-1 as a human-specific gene are significant given the genetic data that place an autoimmune susceptibility element for IDDM and myasthenia gravis in the precise region where this gene resides. In an attempt to isolate the 5{prime} end of this large transcript, we have constructed a cosmid contig which encompasses the genomic locus of this gene and are progressively isolating coding sequences by exon trapping.

  9. The size of the thymus: an important immunological diagnostic tool?

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth

    2003-01-01

    of the thymus relevant to its function and could measurement of the thymus be a useful immunological diagnostic tool in the investigation of thymic function in humans with a depressed immune system? Conclusion: Studies using the size of the thymus as an immunological diagnostic tool should be encouraged....

  10. 21 CFR 866.5180 - Fecal calprotectin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fecal calprotectin immunological test system. 866....5180 Fecal calprotectin immunological test system. (a) Identification. A fecal calprotectin... measure, by immunochemical techniques, fecal calprotectin in human stool specimens. The device is...

  11. Ameliorative effects of human adipose tissue-derived mesenchymal stem cells on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats

    Institute of Scientific and Technical Information of China (English)

    Myung-Soon Ko; Hyeong-geun Park; Young-Min Yun; Jeong Chan Ra; Taekyun Shin; Kyoung-Kap Lee

    2011-01-01

    Mesenchymal stem cells have been previously shown to exert an immunomodulatory function. The present study sought to investigate the effects of multipotential human adipose tissue-derived mesenchymal stem cells (hAdMSCs) on disease progression and cytokine expression in Lewis rats with experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein. The duration of EAE paralysis in the group treated on day 7 postimmunization with 5 × 106 hAdMSCs was significantly reduced compared with the vehicle-treated controls and the 1 × 106 hAdMSC- treated group. The duration of EAE paralysis in the groups treated with 5 × 106 hAdMSCs on both day 1 and day 7 postimmunization was significantly reduced compared with the vehicle-treated controls and the groups treated with 5 × 106 hAdMSCs on both day 7 and day 10 postimmunization. The mRNA expression of interleukin-10 and indoleamine 2, 3-dioxygenase was significantly decreased in the hAdMSC-treated group compared with the vehicle-treated group. These findings suggest that the ameliorative effects of hAdMSCs on EAE symptoms operate in a dose- and time-dependent manner and can be mediated in part by the ample production of anti-inflammatory cytokines.

  12. Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody).

    Science.gov (United States)

    Karlsson, C; Hansson, L; Celsing, F; Lundin, J

    2007-03-01

    Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions. All 5 patients responded with a >or=2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.

  13. Rational design and synthesis of altered peptide ligands based on human myelin oligodendrocyte glycoprotein 35-55 epitope: inhibition of chronic experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Tselios, Theodore; Aggelidakis, Mihalis; Tapeinou, Anthi; Tseveleki, Vivian; Kanistras, Ioannis; Gatos, Dimitrios; Matsoukas, John

    2014-11-04

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35-55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR) contact residues of the human MOG35-55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35-55 peptide at the time of immunization.

  14. Rational Design and Synthesis of Altered Peptide Ligands based on Human Myelin Oligodendrocyte Glycoprotein 35–55 Epitope: Inhibition of Chronic Experimental Autoimmune Encephalomyelitis in Mice

    Directory of Open Access Journals (Sweden)

    Theodore Tselios

    2014-11-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS. Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35–55 epitope of myelin oligodendrocyte glycoprotein (MOG, plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR contact residues of the human MOG35–55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35–55 peptide at the time of immunization.

  15. Genomics and proteomics: Applications in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang Hueber

    2009-08-01

    Full Text Available Wolfgang Hueber1,2,3, William H Robinson1,21VA Palo Alto Health Care System, Palo Alto, CA, USA; 2Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA; 3Novartis Institutes of Biomedical Research, Novartis, Basle, SwitzerlandAbstract: Tremendous progress has been made over the past decade in the development and refinement of genomic and proteomic technologies for the identification of novel drug targets and molecular signatures associated with clinically important disease states, disease subsets, or differential responses to therapies. The rapid progress in high-throughput technologies has been preceded and paralleled by the elucidation of cytokine networks, followed by the stepwise clinical development of pathway-specific biological therapies that revolutionized the treatment of autoimmune diseases. Together, these advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of autoimmune disease. The ever-increasing numbers of novel, innovative therapies will need to be harnessed wisely to achieve optimal long-term outcomes in as many patients as possible while complying with the demands of health authorities and health care providers for evidence-based, economically sound prescription of these expensive drugs. Genomic and proteomic profiling of patients with autoimmune diseases holds great promise in two major clinical areas: (1 rapid identification of new targets for the development of innovative therapies and (2 identification of patients who will experience optimal benefit and minimal risk from a specific (targeted therapy. In this review, we attempt to capture important recent developments in the application of genomic and proteomic technologies to translational research by discussing informative examples covering a diversity of autoimmune diseases.Keywords: proteomics, genomics, autoimmune diseases, antigen microarrays, 2-Dih, rheumatoid arthritis

  16. ALLERGY AND IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    4.1 Autoimmune disease2003169 Investigation of signaling pathway by LFA-1 costimulation in PBMC of active lupus nephritis.WANG Jianqin(王俭勤),et al.Dept Nephrol, 1st Affili Hosp, Sun Yat-sen Univ, Guangzhou 510080. Chin J

  17. ALLERGY AND IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    3.1 Autoimmune disease2003266 Using GST-tag to capture protein interaction of an interferon-inducible systemic lupus associated gene, IFIT1. YE Shuang(叶霜), et al. Dept Rheumatol, Renji Hosp, Clin Center Rheum Dis, Shanghai 2nd Med

  18. ALLERGY AND IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    4.1 Autoimmune disease2004321 Predictors at the nadir of severity in patients with Guillain-Barre syndrome. PENG Mao( 彭茂),et al. Dept Neurol, Xuanwu Hosp,Capit Univ Med Sci,Beijing 100053. Chin J Neurol 2004;37(2): 154 - 157.

  19. Helminth Immunomodulation in Autoimmune Disease.

    Science.gov (United States)

    Smallwood, Taylor B; Giacomin, Paul R; Loukas, Alex; Mulvenna, Jason P; Clark, Richard J; Miles, John J

    2017-01-01

    Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating "talents" of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.

  20. Travels and travails of autoimmunity: a historical journey from discovery to rediscovery.

    Science.gov (United States)

    Mackay, Ian R

    2010-03-01

    Consideration on autoimmunity began, as did immunology itself, around year 1900, first with Ehrlich's doctrine of 'horror autotoxicus', then interpreted as 'autoimmunity cannot happen'. Yet by 1904 the antibody nature of the autohemolysin responsible for cold hemoglobinuria was described, and soon confirmed, but without generating any durable concept on autoimmunization as a cause of disease. Reasons included Ehrlich's doctrine, the particular directions that immunology was to take after the initial advances, and a greater preoccupation with bodily responses to extrinsic rather than autologous substances. So, during 1915-1945, autoimmunity underwent a long eclipse despite, during this time, some potentially telling studies relating to brain, kidney and other diseases. The 'awakening' dates from 1945 when a general theoretical concept did appear feasible. Knowledge accrued from applications of several research undertakings mostly for purposes quite unrelated to the proof of autoimmunization: the use of adjuvants; the Coombes anti-globulin reaction; the Waaler-Rose rheumatoid factor; Hargraves' LE cell; the Witebsky-Rose experimental induction of thyroiditis with autologous thyroid gland, and others. By the early 1960s resistance to the idea of autoimmunization had weakened, perhaps hastened by a monograph on autoimmune disease published in 1963, and surely by the consensus reached at a large international conference published as proceedings in 1965. This present conspectus arbitrarily concludes at year 1965, recognizing that the history of autoimmunity even now is far from over.

  1. Immunological Treatments for Autism.

    Science.gov (United States)

    Gupta, Sudhir

    2000-01-01

    This article discusses research findings that indicate immunological abnormalities in children with autism, including the dysregulation of the immune system, and concludes that there are sufficient data to suggest a role of the immune system in the pathogenesis of autism. Various biological therapies are analyzed, including intravenous…

  2. Oral Microbiology and Immunology

    DEFF Research Database (Denmark)

    Dahlén, Gunnar; Fiehn, Nils-Erik; Olsen, Ingar

    , dental assistants and trainees may find it a useful source of reference. The contents are based on general microbiology and immunology. Oral microbiology is given particular attention, with examples relevant to oral infectious diseases. Each chapter opens with a relatively short pre-reading section...

  3. Cancer Immunology and Immunotherapy.

    Science.gov (United States)

    Sukari, Ammar; Nagasaka, Misako; Al-Hadidi, Ameer; Lum, Lawrence G

    2016-11-01

    Hanahan and Weinberg described six distinct biological properties of cancer cells that enable tumor growth and metastasis. These properties were referred to as the traditional hallmarks of cancer. Recent discoveries further elucidated hallmarks including evasion of immune destruction by tumor cells that disrupt anticancer response pathways. This review discusses cancer immunology and new treatment strategies aimed at restoration of antitumor immune responses.

  4. Immunology's theories of cognition.

    Science.gov (United States)

    Tauber, Alfred I

    2013-01-01

    Contemporary immunology has established its fundamental theory as a biological expression of personal identity, wherein the "immune self" is defended by the immune system. Protection of this agent putatively requires a cognitive capacity by which the self and the foreign are perceived and thereby discriminated; from such information, discernment of the environment is achieved and activation of pathways leading to an immune response may be initiated. This so-called cognitive paradigm embeds such functions as "perception," "recognition," "learning," and "memory" to characterize immune processes, but the conceptual character of such functions has meanings that vary with the particular theory adopted. When different formulations of cognition are considered, immunology's conceptual infrastructure shifts: Extensions of conventional psychological understanding of representational cognition based on a subject-object dichotomy support notions of immune agency; alternatively, formulations of perception that dispense with representations and attendant notions of agency reconfigure the predicate epistemology dominating current immune theory. Reviewing immunological literature of the past five decades, these two understandings of perception--representational and non-representational (considered here from ecological, enactivist, and autopoietic perspectives)--offer competing views of immune cognitive functions. These, in turn, provide competing philosophical understandings of immunology's conceptual foundations, which reflect parallel controversies dominating current debates in philosophy of mind and attendant discussions about personal identity.

  5. The immunologic revolution: photoimmunology.

    Science.gov (United States)

    Ullrich, Stephen E; Byrne, Scott N

    2012-03-01

    UV radiation targets the skin and is a primary cause of skin cancer (both melanoma and nonmelanoma skin cancer). Exposure to UV radiation also suppresses the immune response, and UV-induced immune suppression is a major risk factor for skin cancer induction. The efforts of dermatologists and cancer biologists to understand how UV radiation exposure suppresses the immune response and contributes to skin cancer induction led to the development of the subdiscipline we call photoimmunology. Advances in photoimmunology have generally paralleled advances in immunology. However, there are a number of examples in which investigations into the mechanisms underlying UV-induced immune suppression reshaped our understanding of basic immunological concepts. Unconventional immune regulatory roles for Langerhans cells, mast cells, and natural killer T (NKT) cells, as well as the immune-suppressive function of lipid mediators of inflammation and alarmins, are just some examples of how advances in immunodermatology have altered our understanding of basic immunology. In this anniversary issue celebrating 75 years of cutaneous science, we provide examples of how concepts that grew out of efforts by immunologists and dermatologists to understand immune regulation by UV radiation affected immunology in general.

  6. Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis

    OpenAIRE

    Brij Sharma; Sujeet Raina; Rajesh Sharma

    2014-01-01

    Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis.

  7. Expression of innate immunity genes and damage of primary human pancreatic islets by epidemic strains of Echovirus: implication for post-virus islet autoimmunity.

    Directory of Open Access Journals (Sweden)

    Luis Sarmiento

    Full Text Available Three large-scale Echovirus (E epidemics (E4,E16,E30, each differently associated to the acute development of diabetes related autoantibodies, have been documented in Cuba. The prevalence of islet cell autoantibodies was moderate during the E4 epidemic but high in the E16 and E30 epidemic. The aim of this study was to evaluate the effect of epidemic strains of echovirus on beta-cell lysis, beta-cell function and innate immunity gene expression in primary human pancreatic islets. Human islets from non-diabetic donors (n = 7 were infected with the virus strains E4, E16 and E30, all isolated from patients with aseptic meningitis who seroconverted to islet cell antibody positivity. Viral replication, degree of cytolysis, insulin release in response to high glucose as well as mRNA expression of innate immunity genes (IFN-b, RANTES, RIG-I, MDA5, TLR3 and OAS were measured. The strains of E16 and E30 did replicate well in all islets examined, resulting in marked cytotoxic effects. E4 did not cause any effects on cell lysis, however it was able to replicate in 2 out of 7 islet donors. Beta-cell function was hampered in all infected islets (P<0.05; however the effect of E16 and E30 on insulin secretion appeared to be higher than the strain of E4. TLR3 and IFN-beta mRNA expression increased significantly following infection with E16 and E30 (P<0.033 and P<0.039 respectively. In contrast, the expression of none of the innate immunity genes studied was altered in E4-infected islets. These findings suggest that the extent of the epidemic-associated islet autoimmunity may depend on the ability of the viral strains to damage islet cells and induce pro-inflammatory innate immune responses within the infected islets.

  8. Immunological parameters in girls with Turner syndrome

    Science.gov (United States)

    Stenberg, Annika E; Sylvén, Lisskulla; Magnusson, Carl GM; Hultcrantz, Malou

    2004-01-01

    Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X), thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder). Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls. PMID:15563731

  9. Immunological parameters in girls with Turner syndrome

    Directory of Open Access Journals (Sweden)

    Magnusson Carl GM

    2004-11-01

    Full Text Available Abstract Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X, thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder. Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls.

  10. Immunological HCV-Associated Thrombocytopenia: Short Review

    Directory of Open Access Journals (Sweden)

    Dimitrios Dimitroulis

    2012-01-01

    Full Text Available Infection with Hepatitis C virus (HCV is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature.

  11. Immunometabolism and autoimmunity.

    Science.gov (United States)

    Freitag, Jenny; Berod, Luciana; Kamradt, Thomas; Sparwasser, Tim

    2016-11-01

    A continuous increase in the prevalence of autoimmune diseases is to be expected in the aging societies worldwide. Autoimmune disorders not only cause severe disability and chronic pain, but also lead to considerable socio-economic costs. Given that the current treatment options are not curative, have substantial side effects and a high percentage of non-responders, innovative options to the existing therapeutic armament against autoimmune diseases are urgently required. Accumulating evidence suggests that changes in the metabolism of immune cells are associated with, and contribute to the pathogenesis of autoimmunity. Additionally, some autoimmune diseases share alterations in metabolic pathways, key metabolites or metabolic byproducts such as reactive oxygen species. Other examples for metabolic changes in autoimmune settings include modifications in amino acid and cholesterol levels or glucose catabolism. Thus, the emerging field of immunometabolism may hold the potential to discover new therapeutic targets. Here, we discuss recent findings describing metabolic changes in autoimmune arthritis, multiple sclerosis as well as type 1 diabetes, focusing on pathophysiological aspects.

  12. Molecular imaging applications for immunology.

    Science.gov (United States)

    Hildebrandt, Isabel Junie; Gambhir, Sanjiv Sam

    2004-05-01

    The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.

  13. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturb...

  14. AAV-mediated pancreatic overexpression of Igf1 counteracts progression to autoimmune diabetes in mice.

    Science.gov (United States)

    Mallol, Cristina; Casana, Estefania; Jimenez, Veronica; Casellas, Alba; Haurigot, Virginia; Jambrina, Claudia; Sacristan, Victor; Morró, Meritxell; Agudo, Judith; Vilà, Laia; Bosch, Fatima

    2017-07-01

    Type 1 diabetes is characterized by autoimmune destruction of β-cells leading to severe insulin deficiency. Although many improvements have been made in recent years, exogenous insulin therapy is still imperfect; new therapeutic approaches, focusing on preserving/expanding β-cell mass and/or blocking the autoimmune process that destroys islets, should be developed. The main objective of this work was to test in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, the effects of local expression of Insulin-like growth factor 1 (IGF1), a potent mitogenic and pro-survival factor for β-cells with immunomodulatory properties. Transgenic NOD mice overexpressing IGF1 specifically in β-cells (NOD-IGF1) were generated and phenotyped. In addition, miRT-containing, IGF1-encoding adeno-associated viruses (AAV) of serotype 8 (AAV8-IGF1-dmiRT) were produced and administered to 4- or 11-week-old non-transgenic NOD females through intraductal delivery. Several histological, immunological, and metabolic parameters were measured to monitor disease over a period of 28-30 weeks. In transgenic mice, local IGF1 expression led to long-term suppression of diabetes onset and robust protection of β-cell mass from the autoimmune insult. AAV-mediated pancreatic-specific overexpression of IGF1 in adult animals also dramatically reduced diabetes incidence, both when vectors were delivered before pathology onset or once insulitis was established. Transgenic NOD-IGF1 and AAV8-IGF1-dmiRT-treated NOD animals had much less islet infiltration than controls, preserved β-cell mass, and normal insulinemia. Transgenic and AAV-treated islets showed less expression of antigen-presenting molecules, inflammatory cytokines, and chemokines important for tissue-specific homing of effector T cells, suggesting IGF1 modulated islet autoimmunity in NOD mice. Local expression of Igf1 by AAV-mediated gene transfer counteracts progression to diabetes in NOD mice. This study suggests a

  15. Immunological aspects of human papiloma virus (HPV infection Aspectos imunológicos da infecção pelo vírus do papiloma humano (HPV

    Directory of Open Access Journals (Sweden)

    Maria Angelica Ehara Watanabe

    2012-06-01

    Full Text Available The human papilloma virus (HPV-human papilloma virus can infect up to 80% of people, especially sexually active. The risk of infection and symptoms are different between the sexes. It is known that there are over 150 serotypes and these are grouped by their tropism. Although most infections follow a benign course, the persistent infection with certain serotypes may lead to the development of cancer. The serotypes 16 and 18 are involved in a severe form of injury, resulting in cancer, particularly cervical cancer. Serotypes 6 and 11 are described as causes of anogenital warts. The virus, approximately 8.000 bp, it installs itself in the cell and through the expression of oncoproteins E6 and E7 leading to inhibition of proteins such as p53 and pRB, important in apoptosis and cell cycle arrest. Current vaccines generate immunity against serotypes 6, 11, 16 and 18. The vaccine can be tetravalent (four serotypes 6, 11, 16 and 18 or bivalent (16, 18. Both have cross-protection against infection by serotypes not included in the vaccines, but have no therapeutic character. This study was proposed to review progress on the HPV infection, the immunological aspects and prophylactic vaccines available.O vírus do papiloma humano (HPV-human papiloma virus pode infectar até 80% das pessoas, principalmente as sexualmente ativas. O risco e a sintomatologia da infecção são distintos entre os gêneros. Sabe-se que existem mais de 150 sorotipos e estes são agrupados por seu tropismo. Embora a maioria das infecções siga um curso benigno, a infecção persistente por certos sorotipos pode levar ao desenvolvimento de câncer. Os sorotipos 16 e 18 estão envolvidos com uma forma grave de lesão, acarretando câncer, principalmente do colo do útero. Os sorotipos 6 e 11 são descritos como causadores de verrugas anogenitais. O vírus, de aproximadamente 8.000 pb, se instala na célula e por meio da expressão das oncoproteínas E6 e E7, levando à inibição de

  16. Autoimmunity in visual loss.

    Science.gov (United States)

    Petzold, Axel; Wong, Sui; Plant, Gordon T

    2016-01-01

    There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies - to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein - have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular

  17. [Non-autoimmune thyroiditis].

    Science.gov (United States)

    Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

    2014-01-01

    The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

  18. Autoimmunity in Immunodeficiency

    Science.gov (United States)

    Todoric, Krista; Koontz, Jessica B.; Mattox, Daniel; Tarrant, Teresa K.

    2013-01-01

    Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. PMID:23591608

  19. Leptin and autoimmune disease.

    Science.gov (United States)

    Fujita, Yoshimasa

    2017-01-01

      Leptin is secreted from adipocytes and acts mainly on the hypothalamus causing weight loss due to suppression of appetite and increased energy expenditure. On the other hand, the leptin receptor is also expressed in hematopoietic cells and its action on the immune system has become known, and the significance of leptin in autoimmune diseases has gradually become clear. It has been shown that leptin acts as an exacerbating factor in many autoimmune diseases and it is suggested that inhibition of leptin signal may be a novel therapeutic method for autoimmune diseases. In this article, we will outline the significance of leptin in the immune system based on the current reports.

  20. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  1. Autoimmune-mediated peripheral neuropathies and autoimmune pain.

    Science.gov (United States)

    Klein, Christopher J

    2016-01-01

    Peripheral neuropathies have diverse acquired and inherited causes. The autoimmune neuropathies represent an important category where treatment is often available. There are overlapping signs and symptoms between autoimmune neuropathies and other forms. Making a diagnosis can be challenging and first assisted by electrophysiologic and sometimes pathologic sampling, with autoimmune biomarkers providing increased assistance. Here we provide a review of the autoimmune and inflammatory neuropathies, their available biomarkers, and approaches to treatment. Also discussed is new evidence to support a mechanism of autoimmune pain.

  2. Autoimmune diseases and HIV infection

    Science.gov (United States)

    Virot, Emilie; Duclos, Antoine; Adelaide, Leopold; Miailhes, Patrick; Hot, Arnaud; Ferry, Tristan; Seve, Pascal

    2017-01-01

    Abstract To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients. All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included. Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain–Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves’ disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm3 in 63% of patients, between 200 and 350/mm3 in 19% and less than 200/mm3 in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance. ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated. PMID:28121924

  3. CLINICAL, NEUROPHYSIOLOGICAL AND IMMUNOLOGICAL STUDIES OF CANCER PATIENTS WITH LESIONS OF THE PERIPHERAL NERVES

    Directory of Open Access Journals (Sweden)

    Ye. S. Korolyova

    2013-01-01

    Full Text Available Clinical electrophysiological and immunological studies of 88 cancer patients showed that in breast cancer and small lung cancer takes place symmetric, distal, sensory-motor, axonal-demyelinating polyneuropathy. Autoimmune nature of the disease confirmed onconeural antigens detected in the serum of more than half of the study participants. 

  4. Clinical genetics in 2014: New monogenic diseases span the immunological disease continuum.

    Science.gov (United States)

    Savic, Sinisa; McDermott, Michael F

    2015-02-01

    Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described for the first time in 2014. As well as providing insights into the molecular basis of several rare immunological disorders, the discoveries have implications for their diagnosis and treatment.

  5. 21 CFR 866.5820 - Systemic lupus erythema-tosus immunological test system.

    Science.gov (United States)

    2010-04-01

    ... diagnosis of SLE (a multisystem autoimmune disease in which tissues are attacked by the person's own... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Systemic lupus erythema-tosus immunological test system. 866.5820 Section 866.5820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH...

  6. 21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... autoimmune connective tissue diseases (diseases resulting from antibodies produced against the body's own... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antismooth muscle antibody immunological test system. 866.5120 Section 866.5120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH...

  7. 21 CFR 866.5320 - Properdin factor B immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... autoimmune disease, systemic lupus erythematosus), as well as several skin diseases, e.g., dermititis... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Properdin factor B immuno-logical test system. 866.5320 Section 866.5320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  8. Immunoregulatory T cells, LFA-3 and HLA-DR in autoimmune thyroid diseases

    Directory of Open Access Journals (Sweden)

    Aml Mohamed Nada

    2014-01-01

    Full Text Available Several reports have claimed a role for T regulatory cells (Tregs in the pathogenesis of various autoimmune diseases, including autoimmune thyroid diseases (AITD. Naturally occurring CD4+ regulatory T cells, the majority of which express CD25, are engaged in dominant control of self-reactive T cells, contributing to the maintenance of immunologic self-tolerance. Their depletion or functional alteration leads to the development of autoimmune diseases. CD8+ Tcells are also claimed to have a suppressive effect on autoimmune diseases. Lymphocyte function antigen-3 and human leucocyte antigen (HLA-DR are involved in antigen presentation, initiation, and maintenance of autoimmune processes. Aim: The aim of the present study was to examine the changes in the expression of T-cell activation markers, namely CD4+ CD25+ and CD8+ in patients with AITD, namely Graves′ disease and Hashimoto′s thyroiditis as well as colloid nodular goitre. HLA-DR, LFA-3, and peripheral total lymphocytic count are also measured. Materials and Methods: We compared the expression of CD4, CD25, and CD8 surface markers in peripheral blood lymphocyte in Graves′ disease and Hashimoto′s thyroiditis as autoimmune thyroid diseases, as well as colloid goitre in comparison with healthy controls. Also, LFA-3 and HLA-DR were measured in the same groups using three-color flow cytometry. Total lymphocytic count in peripheral blood, thyroid function tests, antithyroid antibodies were also included in the laboratory investigations. The total number of participants was 65. All were recruited from endocrine clinics in a tertiary care hospital in the southern region of Saudi Arabia. All participants underwent history taking, clinical examination, laboratory workup, and radiological investigations. Neck ultrasound, technecium pertechnetateψψ thyroid uptake, and fine-needle aspiration and cytology (FNAC of the thyroid were done when indicated. The study was approved by the Hospital

  9. Human Tregs Made Antigen Specific by Gene Modification: The Power to Treat Autoimmunity and Antidrug Antibodies with Precision

    Directory of Open Access Journals (Sweden)

    Patrick R. Adair

    2017-09-01

    Full Text Available Human regulatory CD4+ T cells (Tregs are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII. Seminal clinical trials have used polyclonal Tregs, but the frequency of antigen-specific Tregs among polyclonal populations is low, and polyclonal Tregs may risk non-specific immunosuppression. Antigen-specific Treg therapy, which uses genetically modified Tregs expressing receptors specific for target antigens, greatly mitigates this risk. Building on the principles of T-cell receptor cloning, chimeric antigen receptors (CARs, and a novel CAR derivative, called B-cell antibody receptors, our lab has developed different types of antigen-specific Tregs. This review discusses the current research and optimization of gene-modified antigen-specific human Tregs in our lab in several disease models. The preparations and considerations for clinical use of such Tregs also are discussed.

  10. Candidate SNP markers of gender-biased autoimmune complications of monogenic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters

    Directory of Open Access Journals (Sweden)

    Mikhail P. Ponomarenko

    2016-04-01

    Full Text Available Some variations of human genome (for example, single nucleotide polymorphisms [SNPs] are markers of hereditary diseases and drug responses. Analysis of them can help to improve treatment. Computer-based analysis of millions of SNPs in the 1000 Genomes project makes a search for SNP markers more targeted. Here we combined two computer-based approaches: DNA sequence analysis and keyword search in databases. In the binding sites for TATA-binding protein (TBP in human gene promoters, we found candidate SNP markers of gender-biased autoimmune diseases, including rs1143627 (cachexia in rheumatoid arthritis [double prevalence among women]; rs11557611 (demyelinating diseases [thrice more prevalent among young white women than among nonwhite individuals]; rs17231520 and rs569033466 (both: atherosclerosis comorbid with related diseases [double prevalence among women]; rs563763767 (Hughes syndrome-related thrombosis [lethal during pregnancy]; rs2814778 (autoimmune diseases [excluding multiple sclerosis and rheumatoid arthritis] underlying hypergammaglobulinemia in women; rs72661131 and rs562962093 (both: preterm delivery in pregnant diabetic women; and rs35518301, rs34166473, rs34500389, rs33981098, rs33980857, rs397509430, rs34598529, rs33931746, rs281864525, and rs63750953 (all: autoimmune diseases underlying hypergammaglobulinemia in women. Validation of these predicted candidate SNP markers using the clinical standards may advance personalized medicine.

  11. 21 CFR 866.6030 - AFP-L3% immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AFP-L3% immunological test system. 866.6030... Systems § 866.6030 AFP-L3% immunological test system. (a) Identification. An AFP-L3% immunological test... measure, by immunochemical techniques, AFP and AFP-L3 subfraction in human serum. The device is...

  12. 21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antichymotrypsin immunological test system. 866.5080 Section 866.5080 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5080 Alpha-1-antichymotrypsin...

  13. 21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inter-alpha trypsin inhibitor immunological test system. 866.5890 Section 866.5890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5890 Inter-alpha trypsin inhibitor...

  14. Autoimmunity and inflammation in status epilepticus: from concepts to therapies.

    Science.gov (United States)

    Holzer, Franz Josef; Seeck, Margitta; Korff, Christian M

    2014-10-01

    The understanding of immunological mechanisms underlying some forms of epilepsy and encephalitis has rapidly increased for the last 10 years leading to the concept of status epilepticus of autoimmune origin. Actual treatment recommendations regarding autoimmune status epilepticus are based on retrospective case studies, pathophysiological considerations and experts' opinion. In addition, there are no clear indicators to predict outcome. In situations where autoimmune mechanisms are suspected in patients with status epilepticus, there is evidence that earlier treatment is related to better outcome. Increased awareness is mandatory to decrease the number of patients with major neurological problems or fatal outcome, which is overall about 50%. We here summarize findings of all pediatric and adult patients reported to date, and review the current state of knowledge in the field of immune therapeutic approaches of status epilepticus.

  15. Immunological aspects on IDDM in children.

    Science.gov (United States)

    Ludvigsson, J

    1989-01-01

    Diabetes mellitus in childhood is connected to several immunological phenomena which per se do not prove that immunological mechanisms do cause the beta cell destruction, as such mechanisms could be just secondary. However, there is now evidence which strongly supports the autoimmune hypothesis, like the beta-cell destruction in the transplant given from a healthy twin to the diabetic monozygotic co-twin, the effect in newly-diagnosed diabetes of immunosuppression, the passive transfer in experimental animals of an immune process creating diabetes etc. Several facts such as presence of activated T-cells in the insulitis indicate that the cell-mediated immunity is important, while it is still debatable whether humoral factors, and if so which, alone could be responsible for the beta cell destruction. Recently interleukins and other lymphokines have shown to be of great interest as well as the release of free radicals. This knowledge opens new views on the possibility to put an end to or even prevent the beta cell destruction. Rough immunosuppression with cytostatics or cyclosporin has such severe side-effects that such therapy is contra-indicated at least in children. Until more specific therapies are discovered e.g. vaccination with lymphoblasts or blocking the autoantigens with monoclonal antibodies, supportive measures to protect the beta cells may be one practical way.

  16. Lithium associated autoimmune thyroiditis.

    OpenAIRE

    Shimizu, M; Hirokawa, M.; T. Manabe; Shimozuma, K; Sonoo, H; Harada, T.

    1997-01-01

    A case of autoimmune thyroiditis after long term treatment with lithium is described in a 29 year old Japanese woman with manic depression. Positive serum antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic chronic thyroiditis, as well as the clinical history of long term lithium treatment were suggestive of lithium associated autoimmune thyroiditis. Microscopically, there was a mild degree of interstitial fibrosis and a moderate degree of lymphocytic infiltration...

  17. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková

    2017-04-01

    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  18. The epigenetics of autoimmunity

    Science.gov (United States)

    Meda, Francesca; Folci, Marco; Baccarelli, Andrea; Selmi, Carlo

    2011-01-01

    The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases. In recent years, several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, in some cases based on mechanistical observations. We herein discuss what we currently know and what we expect will come in the next future. Ultimately, epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases. PMID:21278766

  19. Immunology and Epidemiology

    CERN Document Server

    Hraba, Tomáš

    1986-01-01

    In February 1985 a small international meeting of scientists took place at the recreation resort of the Polish Academy of Sci­ ences in Mogilany, near Cracow, Poland. The initiative for holding the workshop came from a working meeting on mathematical immunology and related topics at the International Institute for Applied Sys­ tems Analysis in Laxenburg, Austria, in November 1983. In addition to representatives of IIASA, delegates of the IIASA National Member Organizations (NMO) of Czechoslovakia, Italy, and the soviet Union took part in that working meeting. The participants came to the conclusion that IIASA could play an important role in facilitating the development of research in this field. The first step that they recommended to I IASA was to organize a workshop on mathematical immunology. The purpose of the workshop was to review the progress that has been made in applying mathematics to problems in immunology and to explore ways in which further progress might be achieved, especially by more efficie...

  20. The Immunology Database and Analysis Portal (ImmPort)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The ImmPort system serves as a long-term, sustainable archive of immunology research data generated by investigators mainly funded through the NIAID/DAIT. The core...

  1. Equine recurrent uveitis: Human and equine perspectives.

    Science.gov (United States)

    Malalana, Fernando; Stylianides, Amira; McGowan, Catherine

    2015-10-01

    Equine recurrent uveitis (ERU) is a spontaneous disease characterised by repeated episodes of intraocular inflammation. The epidemiology of ERU has not been fully elucidated, but the condition appears to be much more common in horses than is recurrent uveitis in humans, especially in certain breeds and geographical regions. Both humans and horses show a similarly altered immune response and a marked autoimmune response as the primary disease pathophysiology. However, an inciting cause is not always clear. Potential inciting factors in horses include microbial agents such as Leptospira spp. Microbial factors and genetic predisposition to the disease may provide clues as to why the horse appears so susceptible to this disease. The aim of this review is to discuss the immunology and genetics of ERU, compare the disease in horses with autoimmune anterior uveitis in humans, and discuss potential reasons for the increased prevalence in the horse.

  2. Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab.

    Science.gov (United States)

    Hernández, Patricia; Moreno, Ernesto; Aira, Lazaro E; Rodríguez, Pedro C

    2016-01-01

    The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively established. It is probable that this molecule plays a dual role as a modulator of intracellular signaling. Itolizumab is a humanized monoclonal antibody specific for human CD6, developed at the Center of Molecular Immunology in Havana, Cuba. Its parent murine antibody, the IOR-T1 mAb, had been obtained in the 80's at the Institute of Oncology and Radiology, also in Havana. This article provides an overview of the clinical data obtained in Cuban patients with autoimmune diseases who have been treated with IOR-T1 mAb or itolizumab. Furthermore, we discuss the possible mechanism of action of itolizumab basing the analysis on recent site mutagenesis and structural data, which, contrary to previous interpretations, points to a steric blocking of the CD6-CD166 interaction in the cellular context. Overall, the conducted clinical studies have demonstrated that itolizumab has favorable clinical effects and a safety profile when used as monotherapy in patients with rheumatoid arthritis and psoriasis. So far, in vitro and in vivo evidences indicate that itolizumab has immunomodulatory and anti-inflammatory effects. Hence, itolizumab represents a new therapeutic option for autoimmune diseases such as rheumatoid arthritis and psoriasis.

  3. Myeloid glycosylation defects lead to a spontaneous common variable immunodeficiency-like condition with associated hemolytic anemia and antilymphocyte autoimmunity.

    Science.gov (United States)

    Ryan, Sean O; Abbott, Derek W; Cobb, Brian A

    2014-06-15

    Common variable immunodeficiency (CVID), the most frequent symptomatic primary immune deficiency in humans, is a heterogeneous group of immunologic disorders estimated to affect 1:10,000-1:50,000. Although a clear disease etiology remains elusive, a common characteristic of CVID is deficient IgG Ab production in response to infection or vaccination. Patients often also exhibit autoimmune cytopenias with symptoms of abnormal T cell function, including reductions in naive T cells, which correlate with clinical severity. In this study, we discovered that targeted alterations in the glycome of the myeloid lineage lead to spontaneous immunodeficiency characteristic of both humoral and T cell dysfunction regularly found in human CVID. Mice carrying a myeloid-specific knockout of the Mgat2 gene encoding UDP-GlcNAc:α-6-d-mannoside β-1,2-N-acetylglucosaminyltransferase II enzyme exhibit deficiencies in IgG responses to both protein and polysaccharide conjugate vaccines. Interestingly, the immunodeficiency is associated with decreased T cell activity because of a persistent autoimmune-mediated depletion of naive T cells, which is induced by changes in erythrocyte surface glycosylation. The N-glycosylation dependent autoepitopes that emerge on erythrocytes lead to autoimmune hemolytic anemia, and the causative auto-IgM cross-reacts with naive T cells despite the lack of glycan change on T cells. These findings demonstrate that alterations in erythrocyte glycosylation trigger the development of autoantibodies directed at both erythrocytes and naive T cells, revealing a possible mechanistic link between the induction of autoimmune hemolytic anemia, the reduction in naive T cells, and poor Ab responses to vaccine in severe CVID patients.

  4. Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

    Directory of Open Access Journals (Sweden)

    Donald R. Staines

    2006-01-01

    Full Text Available Disorders such as chronic fatigue syndrome (CFS and gulf war syndrome (GWS are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN in the context of molecular mimicry, inappropriate immunological memory and autoimmunity.

  5. CLINICAL SIGNIFICANCE OF IMMUNE IMBALANCE AND AUTOIMMUNITY IN NERVOUS SYSTEM DISORDERS (NSDs

    Directory of Open Access Journals (Sweden)

    Vijendra K. SINGH

    2015-11-01

    Full Text Available In recent years, the role of immune imbalance and autoimmunity has been experimentally demonstrated in nervous system disorders (NSDs that include Alzheimer’s disease, autism, obsessive-compulsive disorder (OCD, tics and Tourette’s syndrome, schizophrenia, and some other NSDs. And yet, these NSDs are never counted as autoimmune diseases. Deriving from the rapidly expanding knowledge of neuro-immunology and auto-immune diseases, for example multiple scle-rosis (MS, the author of this mini-review strongly recommends that these NSDs should be included while tallying the number of autoimmune diseases. This effort will help create an updated global database of all autoimmune diseases as well as it should help treat millions of patients who are suffering from debilitating NSDs for which there is no known cure or treatment currently.

  6. Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis.

    Directory of Open Access Journals (Sweden)

    Anna Beltrame

    2017-06-01

    Full Text Available Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting.A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA dipstick test, ELISA, Western blot, immune-chromatographic test (ICT. Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard: ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively, with a high NPV (98%. CCA showed the highest specificity (93%, but low sensitivity (48%. The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests and Latent Class Analysis (LCA. The latter two models demonstrated excellent agreement (Cohen's kappa: 0.92 for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96% and NPV (97%, moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively. ELISA resulted the most specific immunological test (over 99%. The ICT appears to be a suitable screening test, even when used alone.The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.

  7. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases.

    Science.gov (United States)

    Orbach, Hedi; Zandman-Goddard, Gisele; Amital, Howard; Barak, Vivian; Szekanecz, Zoltan; Szucs, Gabriella; Danko, Katalin; Nagy, Endre; Csepany, Tunde; Carvalho, Jozelio F; Doria, Andrea; Shoenfeld, Yehuda

    2007-08-01

    The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.

  8. ALLERGY AND IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    4.1 Autoimmune Disease2007019 The clinical significance of epitopes of SmB and SmD in systemic lupus erythemotosus. XUE Jing(薛静), et al. Dept Rheumotol, 2nd Affili Hosp, Sch Med, Zhejiang Univ, Hangzhou 310008. Chin J Lab Med 2006;29(11):996-1000. Objective To assess the presence of autoantibodies directed against the epitopes of Stub and SmD in systemic lupus erythemotosus (SLE) as well as other different connective tissue diseases (CTDs) and analyze their clinical significance .

  9. Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the immunologic facet of oncolytic therapy

    Directory of Open Access Journals (Sweden)

    Liu Hui

    2009-07-01

    Full Text Available Abstract Background GLV-1h68 is an attenuated recombinant vaccinia virus (VACV that selectively colonizes established human xenografts inducing their complete regression. Results Here, we explored xenograft/VACV/host interactions in vivo adopting organism-specific expression arrays and tumor cell/VACV in vitro comparing VACV replication patterns. There were no clear-cut differences in vitro among responding and non-responding tumors, however, tumor rejection was associated in vivo with activation of interferon-stimulated genes (ISGs and innate immune host's effector functions (IEFs correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR. Conclusion This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance.

  10. Autoimmune gastritis: Pathologist's viewpoint.

    Science.gov (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

    2015-11-14

    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

  11. Vaccines and autoimmunity.

    Science.gov (United States)

    Agmon-Levin, Nancy; Paz, Ziv; Israeli, Eitan; Shoenfeld, Yehuda

    2009-11-01

    Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

  12. Autoimmunity and Asbestos Exposure

    Directory of Open Access Journals (Sweden)

    Jean C. Pfau

    2014-01-01

    Full Text Available Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA, a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a a lack of statistical power due to relatively small or diffuse exposure cohorts, (b exposure misclassification, (c latency of clinical disease, (d mild or subclinical entities that remain undetected or masked by other pathologies, or (e effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

  13. Pregnancy with autoimmune hepatitis

    Science.gov (United States)

    Braga, António Costa; Vasconcelos, Carlos; Braga, Jorge

    2016-01-01

    Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectation in patients with autoimmune hepatitis. Tight monitoring and control of asymptomatic and unpredictable exacerbations, which are unrelated to the severity of the underlying disease, are essential to the prognosis of the current pregnancy. PMID:27458515

  14. Autoimmune movement disorders.

    Science.gov (United States)

    Mckeon, Andrew; Vincent, Angela

    2016-01-01

    Autoimmune movement disorders encapsulate a large and diverse group of neurologic disorders occurring either in isolation or accompanying more diffuse autoimmune encephalitic illnesses. The full range of movement phenomena has been described and, as they often occur in adults, many of the presentations can mimic neurodegenerative disorders, such as Huntington disease. Disorders may be ataxic, hypokinetic (parkinsonism), or hyperkinetic (myoclonus, chorea, tics, and other dyskinetic disorders). The autoantibody targets are diverse and include neuronal surface proteins such as leucine-rich, glioma-inactivated 1 (LGI1) and glycine receptors, as well as antibodies (such as intracellular antigens) that are markers of a central nervous system process mediated by CD8+ cytotoxic T cells. However, there are two conditions, stiff-person syndrome (also known as stiff-man syndrome) and progressive encephalomyelitis with rigidity and myoclonus (PERM), that are always autoimmune movement disorders. In some instances (such as Purkinje cell cytoplasmic antibody-1 (PCA-1) autoimmunity), antibodies detected in serum and cerebrospinal fluid can be indicative of a paraneoplastic cause, and may direct the cancer search. In other instances (such as 65kDa isoform of glutamic acid decarboxylase (GAD65) autoimmunity), a paraneoplastic cause is very unlikely, and early treatment with immunotherapy may promote improvement or recovery. Here we describe the different types of movement disorder and the clinical features and antibodies associated with them, and discuss treatment.

  15. Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype

    NARCIS (Netherlands)

    Hubert, Francois-Xavier; Kinkel, Sarah A.; Crewther, Pauline E.; Cannon, Ping Z. F.; Webster, Kylie E.; Link, Maire; Uibo, Raivo; O'Bryan, Moira K.; Meager, Anthony; Forehan, Simon P.; Smyth, Gordon K.; Mittaz, Laureane; Antonarakis, Stylianos E.; Peterson, Paert; Heath, William R.; Scott, Hamish S.

    2009-01-01

    Autoimmune regulator (AIRE) is an important transcription regulator that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags in the thymus. Although several mouse models of Aire deficiency have been described, none has analyzed the phenotype induced

  16. Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype

    NARCIS (Netherlands)

    Hubert, Francois-Xavier; Kinkel, Sarah A.; Crewther, Pauline E.; Cannon, Ping Z. F.; Webster, Kylie E.; Link, Maire; Uibo, Raivo; O'Bryan, Moira K.; Meager, Anthony; Forehan, Simon P.; Smyth, Gordon K.; Mittaz, Laureane; Antonarakis, Stylianos E.; Peterson, Paert; Heath, William R.; Scott, Hamish S.

    2009-01-01

    Autoimmune regulator (AIRE) is an important transcription regulator that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags in the thymus. Although several mouse models of Aire deficiency have been described, none has analyzed the phenotype induced

  17. The immunological synapse

    DEFF Research Database (Denmark)

    Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten

    2003-01-01

    . A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...... IS formation, appearance, and cessation. In addition, proposed functions of the IS are discussed. The process of IS formation occurs in a sequential manner, initially causing a remarkable large-scale redistribution of a number of integral membrane and cytosolic proteins. At the T cell/APC interface...

  18. Immunology in Africa.

    Science.gov (United States)

    Cose, Stephen; Bagaya, Bernard; Nerima, Barbara; Joloba, Moses; Kambugu, Andrew; Tweyongyere, Robert; Dunne, David W; Mbidde, Edward; Kaleebu, Pontiano; Elliott, Alison M

    2015-12-01

    Africa is a continent with a large burden of both infectious and non-communicable diseases. If we are to move forward as a continent, we need to equip our growing cadre of exceptional young scientists with the skills needed to tackle the diseases endemic to this continent. For this, immunology is among the key disciplines. Africans should be empowered to study and understand the diseases that affect them, and to perform their cutting-edge research in their country of origin. This requires a multifaceted approach, with buy-in from funders, overseas partners and perhaps, most important of all, African governments themselves.

  19. Mathematics in modern immunology.

    Science.gov (United States)

    Castro, Mario; Lythe, Grant; Molina-París, Carmen; Ribeiro, Ruy M

    2016-04-01

    Mathematical and statistical methods enable multidisciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. We collect a representative sample of studies in T-cell biology that illustrate the benefits of modelling-experimental collaborations and that have proven valuable or even groundbreaking. We conclude that it is possible to find excellent examples of synergy between mathematical modelling and experiment in immunology, which have brought significant insight that would not be available without these collaborations, but that much remains to be discovered.

  20. Lupus and autoimmune shock: Use of intravenous gammaglobulin. Case report and proposal for a new designation

    Directory of Open Access Journals (Sweden)

    Hernández Bautista Victor Manuel

    2014-07-01

    Full Text Available Shock is a state of hypotension and hypoperfusion which in turn leads to cellular dysfunction, neuroendocrine responses, inflam- matory mediator release, and alterations of the microcirculation. There are various ways of classifying tissue perfusion failure. A simple method is dividing them into a distributive category, such as septic or anaphylactic shock, and a non-distributive category such as hypovolemic shock. There is extensive knowledge on septic shock; the interaction between bacteria and the antigen presenting cell receptor (TRL-2, TRL-4 releases a proinflammatory cytokine storm, favoring the production of nitric oxide, thus perpetuating the hypotensive state. The imbalance between proinflammatory and anti-inflammatory cytokines creates an immunologic dysfunction, which favors the systemic inflammatory response syndrome and unleashes a shock state, a situation named immunologic disso- nance by Dr. Roger Bone in 1996. From our perspective, this term explains the alterations presented in one particular case, where the cornerstone is the dysfunction of the patient’s immune system and its culmination in a distributive form of shock, which from our hypotheti- cal perspective is of autoimmune origin. We consider autoimmunity to be the platform leading to the state of immunologic dissonance responsible for autoimmune shock, which we believe merits a non-traditional approach. For this reason in a case in which we suspect shock based on autoimmunity, intravenous gammaglobulin was used in conjunction with a bolus of methylprednisolone in an attempt to counteract the immunologic dissonance; satisfactory results were obtained.

  1. Maturation, reactivity and therapy induced changes of memory T-cells in rheumatic autoimmune diseases

    NARCIS (Netherlands)

    Fritsch, R.D.E.

    2014-01-01

    This thesis covers different aspects of CD4+T-cells (maturational pathway, auto-reactive potential and differential reaction to glucocorticoid-therapy) in two auto-immune diseases: systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA). Immunological memory is important for an adequate res

  2. Maturation, reactivity and therapy induced changes of memory T-cells in rheumatic autoimmune diseases

    NARCIS (Netherlands)

    Fritsch, R.D.E.

    2014-01-01

    This thesis covers different aspects of CD4+T-cells (maturational pathway, auto-reactive potential and differential reaction to glucocorticoid-therapy) in two auto-immune diseases: systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA). Immunological memory is important for an adequate

  3. Autoimmunity : Break-through in the diagnosis and treatment of immune-mediated inflammatory diseases

    NARCIS (Netherlands)

    Kroese, Frans G. M.; Baeten, Dominique; Huizinga, Tom W. J.

    2014-01-01

    The study of fundamental mechanisms of autoimmunity has been instrumental to clinical progress in the diagnosis and treatment of a range of immune-mediated inflammatory disorders. Dutch immunology has made major contributions to these developments, ranging from fundamental studies on immune cells, a

  4. Kinetics Modeling of Cancer Immunology.

    Science.gov (United States)

    1986-05-09

    CANCER IMMUNOLOGY -1 DTICS ELECTED SEP 9 8 UNITED STATES NAVAL ACADEMY ANNAPOLIS, MARYLAND V ,1986 %,e docment ha le approved for public A." I and sale...1986 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED KINETICS MODELING OF CANCER IMMUNOLOGY Final: 1985/1986 6. PERFORMING ORG. REPORT...137 (1986) "Kinetics Modeling of Cancer Immunology " A Trident Scholar Project Report by Midn I/C Scott Helmers, Class of 1986 United States Naval

  5. Acquired immunologic tolerance in chimeras and histocompatibility factors in cattle and their relationship to those in humans. Final report. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Stone, W.H.

    1976-03-01

    During the course of this project we have studied 35 pairs of chimeric cattle twins. It is now clear that fractionated doses of whole-body /sup 60/Co irradiation can cause marked shifts in the proportions of the two erythrocyte populations that make up the chimeric mixture. However, it has not been possible to eliminate one of the two cell types and thus abrogate the acquired immunologic tolerance. The results of our extensive skin-grafting experiments are remarkable because they show that a chimeric twin may mount a sufficient immune response to reject its cotwin's skin while remaining completely tolerant to erythropoietic elements of its cotwin. In conjunction with these studies, we have acquired sufficient data to define a major histocompatibility locus in cattle using alloimmune anti-lymphocyte typing sera as well as the mixed lymphocyte culture technic. This project has also yielded a considerable number of new immunogenetic parameters for cattle, monkeys and birds. Such parameters are useful for basic and applied studies in immunology.

  6. Antibodies as predictors of complex autoimmune diseases.

    Science.gov (United States)

    Vojdani, A

    2008-01-01

    Emerging evidence has suggested environmental factors such as infections and xenobiotics and some dietary proteins and peptides in the pathogenesis of many autoimmune diseases. Considering the fact that autoantibodies can often be detected prior to the onset of a disease, in this study an enzyme immunoassay was used for measurement of antibodies against different highly purified antigens or synthetic peptides originating not only from human tissue, but also from cross-reactive epitopes of infectious agents, dietary proteins and xenobiotics. The measurement of antibodies against a panel of antigens allows for identification of patterns or antibody signatures, rather than just one or two markers of autoimmunity, thus establishing the premise for increased sensitivity and specificity of prediction, as well as positive predictive values. This panel of different autoantibodies was applied to 420 patients with different autoimmune diseases, including pernicious anemia, celiac disease, thyroiditis, lupus, rheumatoid arthritis, osteoarthritis, Addison's disease, type 1 diabetes, cardiovascular disease and autoimmunity, which are presented in this article. In all cases, the levels of these antibodies were significantly elevated in patients versus controls. Antibody patterns related to neuroautoimmune disorders, cancer, and patients with somatic hypermutation will be shown in a subsequent article. We believe that this novel 96 antigen-specific autoantibody or predictive antibody screen should be studied for its incorporation into routine medical examinations. Clinicians should be aware that the detection of antibodies should not automatically mean that a patient will definitely become ill, but would rather give a percentage of risk for autoimmune disease over subsequent months or years.

  7. Microvesicles in Autoimmune Diseases.

    Science.gov (United States)

    Liu, M-L; Williams, K J; Werth, V P

    During apoptosis or activation, cells can release a subcellular structure, called a membrane microvesicle (also known as microparticle) into the extracellular environment. Microvesicles bud-off as a portion of cell membrane with its associated proteins and lipids surrounding a cytosolic core that contains intracellular proteins, lipids, and nucleic acids (DNA, RNA, siRNA, microRNA, lncRNA). Biologically active molecules on the microvesicle surface and encapsulated within can act on recipient cells as a novel mode of intercellular communication. Apoptosis has long been known to be involved in the development of diseases of autoimmunity. Abnormally persistent microvesicles, particularly apoptotic microvesicles, can accelerate autoimmune responses locally in specific organs and tissues as well as systemically. In this review, we focus on studies implicating microvesicles in the pathogenesis of autoimmune diseases and their complications. © 2016 Elsevier Inc. All rights reserved.

  8. Headache in autoimmune diseases.

    Science.gov (United States)

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

    Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics.

  9. Broadening the translational immunology landscape.

    Science.gov (United States)

    Peakman, M

    2012-12-01

    It is just over 5 years since Clinical and Experimental Immunology came under the direction of a new team of Editors and made a concerted effort to refresh its approach to promoting clinical and applied immunology through its pages. There were two major objectives: to foster papers in a field which, at the time, we loosely termed 'translational immunology'; and to create a forum for the presentation and discussion of immunology that is relevant to clinicians operating in this space. So, how are we doing with these endeavours? This brief paper aims to summarize some of the key learning points and successes and highlight areas in which translational gaps remain.

  10. Coeliac disease and autoimmune disease-genetic overlap and screening.

    Science.gov (United States)

    Lundin, Knut E A; Wijmenga, Cisca

    2015-09-01

    Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

  11. B cells as therapeutic targets in autoimmune neurological disorders.

    Science.gov (United States)

    Dalakas, Marinos C

    2008-10-01

    B cells have a fundamental role in the pathogenesis of various autoimmune neurological disorders, not only as precursors of antibody-producing cells, but also as important regulators of the T-cell activation process through their participation in antigen presentation, cytokine production, and formation of ectopic germinal centers in the intermeningeal spaces. Two B-cell trophic factors-BAFF (B-cell-activating factor) and APRIL (a proliferation-inducing ligand)-and their receptors are strongly upregulated in many immunological disorders of the CNS and PNS, and these molecules contribute to clonal expansion of B cells in situ. The availability of monoclonal antibodies or fusion proteins against B-cell surface molecules and trophic factors provides a rational approach to the treatment of autoimmune neurological diseases. This article reviews the role of B cells in autoimmune neurological disorders and summarizes the experience to date with rituximab, a B-cell-depleting monoclonal antibody against CD20, for the treatment of relapsing-remitting multiple sclerosis, autoimmune neuropathies, neuromyelitis optica, paraneoplastic neurological disorders, myasthenia gravis, and inflammatory myopathies. It is expected that ongoing controlled trials will establish the efficacy and long-term safety profile of anti-B-cell agents in several autoimmune neurological disorders, as well as exploring the possibility of a safe and synergistic effect with other immunosuppressants or immunomodulators.

  12. Future perspective for diagnosis in autoimmune diseases

    OpenAIRE

    Luis E. C. Andrade

    2009-01-01

    Human beings have taken successive approaches for the understanding and management of diseases. Initially brewed in supernatural concepts and mystical procedures, a vigorous scientific approach has emerged on the grounds of fundamental disciplines such as anatomy, microbiology, biochemistry, physiology, immunology, pathology, and pharmacology. The resulting integrated knowledge contributed to the current classification of diseases and the way Medicine is carried out today. Despite considerabl...

  13. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    Science.gov (United States)

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Common mechanisms of autoimmune diseases (the autoimmune tautology).

    Science.gov (United States)

    Anaya, Juan-Manuel

    2012-09-01

    The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed.

  15. Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Johanna Prinz

    Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS.Twenty-two female C57BL/6 (B6 mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE and six months after onset of EAE (long-term EAE. The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT of the spinal cord.B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse

  16. Epigenomics of autoimmune diseases.

    Science.gov (United States)

    Gupta, Bhawna; Hawkins, R David

    2015-03-01

    Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

  17. Immunological memory within the innate immune system

    OpenAIRE

    Sun, J. C.; Ugolini, S.; Vivier, E

    2014-01-01

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which hav...

  18. [Autoimmune hemolytic anemia in children].

    Science.gov (United States)

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options.

  19. Helminth Immunomodulation in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    John J. Miles

    2017-04-01

    Full Text Available Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating “talents” of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases.

  20. 人心肌C蛋白诱导建立实验性自身免疫性心肌炎模型%Establishment of human cardiac C protein induced experimental autoimmune myocarditis model in rat

    Institute of Scientific and Technical Information of China (English)

    韩丽娜; 李铁岭; 丁国雷; 刘健伟; 丁宇; 张亚晶

    2012-01-01

    Objective To construct the recombinant plasmid of human cardiac C protein (CCP) peptide with immunogenicity and to express,purificate and renature fusion protein.The fusion protein was injected to Lewis rats to establish experimental autoimmune myocarditis ( EAM ) model.Methods Total RNA was extracted from human heart and used as the template for reverse transcriptase-directed cDNA synthesis.The cDNA was then amplified by polymerase chain reaction (PCR) using oligonucleotide primers specific for CCP peptide with immunogenicity.Subsequently,the purified CCP peptide gene was cloned into PEASY-T1 vector and the ligated product was identified by PCR and DNA sequence analysis.Then the CCP target gene of positive clone was inserted into the pQE30,a prokaryotic expression vector,and the inserting plasmid was transformed into Escherichia coli. host M15.The positive clone extracted from the bacterium liquid was sieved by insertional inactivation sieve method and identified by PCR of bacterium liquid,CCP immunological peptide was purified and renatured in semipermeable membrane. EAM model in Lewis rats was induced by injection of mixture of 100 μg CCP fusion protein immunological peptide and 2.5 g/L completed Freund adjuvant from two double foot pad and subsequent abdominal injection of 0.5 μg pertussis toxin.Two,four,six,and eight weeks after immunization,hemodynamic evaluation was made and hearts underwent histological examination.Results The DNA sequence analysis for cloning vector extraction revealed that the CCP target gene was cloned into pQE30 exactly.The DNA of 1000 bp length was obtained by PCR examination of bacterium liquid with transformation of express recombinants which were consistent with the expected size.Purified fusion protein in vertical slab gel clcctrophoresis showed 35 000 as expected.The recombinant CCP fusion protein existed in inclusion bodies of E.coli and amounted to 80% - 90% of the total protein. Hemodynamic and histological evaluations

  1. Parkinson's disease: Autoimmunity and neuroinflammation.

    Science.gov (United States)

    De Virgilio, Armando; Greco, Antonio; Fabbrini, Giovanni; Inghilleri, Maurizio; Rizzo, Maria Ida; Gallo, Andrea; Conte, Michela; Rosato, Chiara; Ciniglio Appiani, Mario; de Vincentiis, Marco

    2016-10-01

    Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and

  2. Immunological effects of vasectomy.

    Science.gov (United States)

    Sotolongo, J R

    1982-06-01

    It is only recently that the adverse effects of vasectomy have become the subject of numerous scientific and at times speculative articles in medical and in lay periodicals. In this review of the literature on the immunological effects of vasectomy, attention is directed to the following: immunological response; cellular immunity; effects on testes and epididymis, and systemic effects of sperm autoantibodies. In 1970, 50% of vasectomized men were found to have circulating spermatozoal antibodies. A more recent survey provides confirmation for this finding and presents an incidence of only 2% of agglutinating antibodies and 0% of immobilizing antibodies in a fertile control population. Some recent and convincing studies have shown sperm agglutinating and immobilizing antibodies to remain either at the same titer level or actually to increase 5-12 years postoperatively. Titers range from 2 to 2048 among different patients. The highest incidence of titers is 1 year after vasectomy, but titers can be found as early as 6 months or as late as 20 years postoperatively. The wide range in titers can be explained in terms of technical problems in immune assays, since only immunoglobulins and not those antibodies part of immune complex systems can be measured. Since sperm antigens are in abundant supply in vasectomized men because of the continuous resorption of spermatozoa after vasectomy, possibly undetectable antibody titers actually reflect high levels of antisperm antibodies circulating in the form of immune complexes. Also it may be possible that the variety in measured titers of autoantibodies, as well as the nonuniversal (70%) antibody response in a vasectomized population, is a variable dependent on genetic content and, therefore, an individual characteristic. The fact that hormonal reponse takes place rather readily after vasectomy makes at least some degree of cellular response a necessary occurrence. Studies by Alexander and Anderson, which show delayed

  3. Autoimmune muscular pathologies.

    Science.gov (United States)

    Dalakas, M C

    2005-05-01

    The T cell-mediated mechanism responsible for Polymyositis and inclusion Body Myositis and the complement-mediated microangiopathy associated with Dermatomyositis are reviewed. The management of autoimmune myopathies with the presently available immunotherapeutic agents as well as new therapies and ongoing trials are discussed.

  4. Autoimmune pancreatitis and cholangitis

    Institute of Scientific and Technical Information of China (English)

    Niraj; Jani; James; Buxbaum

    2015-01-01

    Autoimmune pancreatitis(AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4(Ig G4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreaticmanifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG 4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG 4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

  5. Ideernes epidemiologi og kulturens immunologi

    DEFF Research Database (Denmark)

    Sørensen, Jesper

    2007-01-01

    , suggested by Sperber, is extended by an ‘immunology of cultural systems’. In addition to the selective forces described by Sperber and Boyer, the immunological approach argues that the relative success of new representations is largely dependent on how well they fit already existing cultural models...

  6. Fundamentals of vaccine immunology

    Directory of Open Access Journals (Sweden)

    Angela S Clem

    2011-01-01

    Full Text Available From a literature review of the current literature, this article provides an introduction to vaccine immunology including a primer on the components of the immune system, passive vs. active immunization, the mechanism(s by which immunizations stimulate(s immunity, and the types of vaccines available. Both the innate and adaptive immune subsystems are necessary to provide an effective immune response to an immunization. Further, effective immunizations must induce long-term stimulation of both the humoral and cell-mediated arms of the adaptive system by the production of effector cells and memory cells. At least seven different types of vaccines are currently in use or in development that produce this effective immunity and have contributed greatly to the prevention of infectious disease around the world.

  7. Immunological Detection of Arbutin

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The relative molecular mass of Arbutin is small.Both fluorolabeling and radiolabeling may affect its properties and functions.Therefore, the immunoassay of Arbutin was studied.Arbutin was coupled to bovine serum albumin to get the Arbutin-BSA conjugate with high molar ratio of Arbutin to BSA.Two rabbits were injected with the conjugate to develop the anti-Arbutin serum.Ammonium sulfate precipitation and affinity chromatography were used to purify the antibody.Double agar diffusion test and enzyme-linked immunosorbent assay (ELISA) were adopted to identify the antibody titer.The results demonstrated that the purity and activity of the antibody are high.The method proposed is satisfactory for the immunological detection of Arbutin.

  8. Do we need autoimmune disease units in hospitals?

    Science.gov (United States)

    Vasconcelos, Carlos

    2009-09-01

    Autoimmune diseases are increasing worldwide, and associated morbidity, mortality, and health care costs are high. Biological therapies, however, have brought physicians an extraordinary opportunity to change natural disease history, although these therapies can also have high associated iatrogenic costs. These factors point to the necessity of having physicians that are dedicated to autoimmunology. The question regarding the creation of a new specialty, the autoimmunologist, should be addressed after an inquiry into the current practice in this field of medicine. This includes many classical specialties, such as internal medicine, rheumatology, and neurology, as well as clinical immunology. In clinical immunology, not counting the specialists in allergology and clinical immunology that mainly work only with allergies, heterogeneity is high in clinical practice, as the European Union of Medical Specialists documented some years ago. I am, at least for now, in favor of the creation of a transversal competency to which the different physicians working in the area could apply to in order to standardize the clinical practice in autoimmunology. It will be necessary to define a core curriculum, and in the end we shall have classical specialists and clinical immunologists with or without the competency of autoimmunology. Of utmost importance is that this new field of medicine should not be translated, as in the past happened with other areas, by walls between medical specialties. Instead it should help standardize and harmonize clinical practice. The time for autoimmunology is now, and, indeed, hospitals must have autoimmune disease units.

  9. Nonsegmental Vitiligo and Autoimmune Mechanism

    Directory of Open Access Journals (Sweden)

    Naoki Oiso

    2011-01-01

    Full Text Available Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo.

  10. Cytokines in autoimmunity: role in induction, regulation, and treatment.

    Science.gov (United States)

    Moudgil, Kamal D; Choubey, Divaker

    2011-10-01

    Cytokines play a pivotal role in the pathogenesis of autoimmune diseases. The precise triggers for the breakdown of self-tolerance and the subsequent events leading to the induction of pathogenic autoimmune responses remain to be defined for most of the naturally occurring autoimmune diseases. Studies conducted in experimental models of human autoimmune diseases and observations in patients have revealed a general scheme in which proinflammatory cytokines contribute to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate the regression of inflammation and recovery from acute phase of the disease. This idea is embodied in the T helper (Th) 1/Th2 paradigm, which over the past two decades has had a major influence on our thinking about the role of cytokines in autoimmunity. Interestingly, over the past decade, the interleukin (IL)-17/IL-23 axis has rapidly emerged as the new paradigm that has compelled us to critically re-examine the cytokine-driven immune events in the pathogenesis and treatment of autoimmunity. In this 2-volume special issue of the journal, leading experts have presented their research findings and viewpoints on the role of cytokines in the context of specific autoimmune diseases.

  11. Autoimmune diseases in the TH17 era

    Directory of Open Access Journals (Sweden)

    D. Mesquita Jr.

    2009-06-01

    Full Text Available A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases.

  12. Glutathione: a key player in autoimmunity.

    Science.gov (United States)

    Perricone, Carlo; De Carolis, Caterina; Perricone, Roberto

    2009-07-01

    Increasing attention in the physiopathology of inflammatory/immunomediated diseases has been focused on the role of reactive oxygen species (ROS), oxygen-based molecules possessing high chemical reactivity and produced by activated neutrophils during the inflammatory response. During chronic inflammation, when sustained production of ROS occurs, antioxidant defences can weaken, resulting in a situation termed oxidative stress. Moreover, antioxidant defence systems have been demonstrated to be constitutively lacking in patients affected with chronic degenerative diseases, especially inflammatory/immunomediated. Glutathione, a tripeptide, is the principal component of the antioxidant defence system in the living cells. Glutathione has been demonstrated to have diverse effects on the immune system, either stimulating or inhibiting the immunological response in order to control inflammation. The study of interactions between glutathione and the immune system has attracted many investigators. Altered glutathione concentrations may play an important role in many autoimmune pathological conditions prevalently elicited, detrimed and maintained by inflammatory/immune response mediated by oxidative stress reactions. The role of glutathione in autoimmunity will be reviewed herein.

  13. IL-35 and Autoimmunity: a Comprehensive Perspective.

    Science.gov (United States)

    Choi, Jinjung; Leung, Patrick S C; Bowlus, Christopher; Gershwin, M Eric

    2015-12-01

    Interleukin 35 (IL-35) is the most recently identified member of the IL-12 family of cytokines and offers the potential to be a target for new therapies for autoimmune, inflammatory, and infectious diseases. Similar to other members of the IL-12 family including IL-12, IL-23, and IL-27, IL-35 is composed of a heterodimer of α and β chains, which in the case of IL-35 are the p35 and Epstein-Barr virus-induced gene 3 (EBI3) proteins. However, unlike its proinflammatory relatives, IL-35 has immunosuppressive effects that are mediated through regulatory T and B cells. Although there are limited data available regarding the role of IL-35 in human autoimmunity, several murine models of autoimmunity suggest that IL-35 may have potent effects in regulating immunoreactivity via IL-10-dependent mechanisms. We suggest that similar effects are operational in human disease and IL-35-directed therapies hold significant promise. In particular, we emphasize that IL-35 has immunosuppressive ability that are mediated via regulatory T and B cells that are IL-10 dependent. Further, although deletion of IL-35 does not result in spontaneous breach of tolerance, recombinant IL-35 can improve autoimmune responses in several experimental models.

  14. Interaction of pregnancy and autoimmune rheumatic disease.

    Science.gov (United States)

    Østensen, Monika; Villiger, Peter M; Förger, Frauke

    2012-05-01

    During pregnancy, the fetus represents a natural allograft that is not normally rejected. While the maternal immune system retains the ability to respond to foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from immunologic attacks by the mother. The profound immunologic adaptations during and after pregnancy do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease. The review will discuss the mechanisms of increased susceptibility of rheumatoid arthritis (RA) in the first year post partum with a specific emphasis on the role of fetal cells or antigens persisting in the maternal circulation (so called microchimerism). Furthermore, the different influences of pregnancy on established rheumatic diseases will be highlighted. A marked beneficial effect of pregnancy is observed on RA whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no particular effect or an aggravation of symptoms during pregnancy. Differences emerging in regard to modulation of disease symptoms during pregnancy seem related to response to hormones, the type of cytokine profile and immune response prevailing as well as further downstream interactions of molecular pathways that are important in disease pathogenesis.

  15. Neuropsychiatric autoimmune encephalitis without VGKC-complex, NMDAR, and GAD autoantibodies: case report and literature review.

    Science.gov (United States)

    Najjar, Souhel; Pearlman, Daniel; Devinsky, Orrin; Najjar, Amanda; Nadkarni, Siddhartha; Butler, Tracy; Zagzag, David

    2013-03-01

    We report a patient with a seronegative autoimmune panencephalitis, adding a subtype to the emerging spectrum of seronegative autoimmune encephalitis, and we review the sparse literature on isolated psychiatric presentations of autoimmune encephalitis. (A PubMed search for "seronegative autoimmune encephalitis," "nonvasculitic autoimmune inflammatory meningoencephalitis," and related terms revealed VGKC)-complex, N-methyl-D-aspartate receptor (NMDAR), and glutamic acid decarboxylase (GAD) autoantibodies. We excluded genetic, metabolic, paraneoplastic, degenerative, and infectious etiologies. The patient's symptoms remitted fully with immune therapy, but recurred in association with widespread bihemispheric brain lesions. Brain biopsy revealed mild nonvasculitic inflammation and prominent vascular hyalinization. Immune therapy with plasma exchanges cleared the MRI abnormalities but, 10 years after onset, the patient still suffers neuropsychiatric sequelae. We conclude that autoimmune panencephalitis seronegative for VGKC-complex, NMDAR, and GAD autoantibodies is a subtype of autoimmune encephalitis that can present with pure neuropsychiatric features and a normal brain MRI. Immunologic mechanisms may account for psychiatric symptoms in a subset of patients now diagnosed with classical psychotic disorders. Delay in starting immune therapy can lead to permanent neuropsychiatric sequelae. We propose a standardized classification system for the autoimmune encephalitides, integrating earlier pathology-oriented terms with more recently defined serologic and clinical phenotypes.

  16. [Polyglandular autoimmune syndromes : An overview].

    Science.gov (United States)

    Komminoth, P

    2016-05-01

    Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.

  17. Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases.

    Science.gov (United States)

    Segni, Maria; Borrelli, Osvaldo; Pucarelli, Ida; Delle Fave, Gianfranco; Pasquino, Anna Maria; Annibale, Bruno

    2004-10-01

    Juvenile patients affected with autoimmune thyroid disorders showed a 14-21% prevalence of parietal cell antibodies (PCA) reacting against the H+/K+-ATPase of the gastric parietal cells. PCA are the principal immunological markers of atrophic body gastritis (ABG).ABG is characterized by loss of oxyntic glands, achlorhydria, and hypergastrinemia. The aim of this study was to determine whether PCA positivity could be associated with biochemical and histological manifestations of gastric autoimmunity in juvenile patients with autoimmune thyroid disease (AITD). We studied 129 children (96 females and 33 males) with chronic lymphocytic thyroiditis (n = 115) or Graves' disease (n = 14). Mean age at diagnosis of AITD was 9.7 +/- 3.3 yr, and mean age at sampling was 12.3 +/- 3.7 yr. We determined PCA and Helicobacter pylori antibodies, gastrin, and pepsinogen I plasma levels. Gastroscopy with multiple biopsies was carried out in a subgroup of patients with PCA positivity. We found that 30% of children had detectable PCA. Hypergastrinemia was found in 45% of the PCA-positive children (range, 40-675 pg/ml) vs. 12% of PCA-negative children (range, 35-65 pg/ml; P < 0.001). Eighteen patients with PCA positivity underwent gastroscopy; eight of these children had normogastrinemia, which showed no signs of ABG, and 10 children had hypergastrinemia, of whom five had mild to severe ABG. Our study shows that autoimmune gastritis is an early event in juvenile AITD with detectable PCA. Gastrin plasma level is a reliable marker of gastric atrophy.

  18. Findings of interest from immunology and psychoneuroimmunology.

    Science.gov (United States)

    Alford, Les

    2007-05-01

    The biopsychosocial paradigm is now the main model when dealing with most human health disorders. One of the strengths of this model is that it encourages broader thinking when assessing and managing patients. It also encourages broader reading into areas not traditionally associated with manual therapy. Immunology and neuroscience are amongst the fastest growing medical sciences. These fields come together in the relatively new area of psychoneuroimmunolgy. This article examines some findings from these fields that are not widely discussed in the physical therapy professions. These findings are of relevance to many of the disciplines within the physical therapies. It is the authors aim to stimulate further interest in the relevant, yet often under explored areas of immunology and psychoneuroimmunology.

  19. History and milestones of mouse models of autoimmune diseases.

    Science.gov (United States)

    Yu, Xinhua; Huang, Qiaoniang; Petersen, Frank

    2015-01-01

    Autoimmune diseases are a group of disorders mediated by self-reactive T cells and/or autoantibodies. Mice, as the most widely used animal for modeling autoimmune disorders, have been extensively used in the investigation of disease pathogenesis as well as in the search for novel therapeutics. Since the first mouse model of multiple sclerosis was established more than 60 years ago, hundreds of mouse models have been established for tens of autoimmune diseases. These mouse models can be divided into three categories based on the approaches used for disease induction. The first one represents the induced models in which autoimmunity is initiated in mice by immunization, adoptive transfer or environmental factors. The second group is formed by the spontaneous models where mice develop autoimmune disorders without further induction. The third group refers to the humanized models in which mice bearing humanized cells, tissues, or genes, develop autoimmune diseases either spontaneously or by induction. This article reviews the history and highlights the milestones of the mouse models of autoimmune diseases.

  20. Noncoding RNAs in Cancer Immunology.

    Science.gov (United States)

    Li, Qian; Liu, Qiang

    2016-01-01

    Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity.

  1. Sarcoidosis and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Piera Fazzi

    2017-08-01

    Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.

  2. Update on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Peter R Galle; Stephan Kanzler

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

  3. Inheritance of autoimmune neuroinflammation

    OpenAIRE

    Stridh, Pernilla

    2010-01-01

    Multiple sclerosis (MS) is a chronic neuro-inflammatory disease with anticipated complex etiology. Susceptibility to MS is conferred by numerous genes, with very low odds ratios that explain minute fractions of disease. This indicates that unknown factors are responsible for the remaining genetic contribution, termed the missing heritability . Due to the similarities to MS pathogenesis, we studied myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune ...

  4. IMMUNOLOGICAL STUDY OF SPONGIFORM ENCEPHALOPATHIES

    Directory of Open Access Journals (Sweden)

    J. Meenupriya

    2013-04-01

    Full Text Available Spongiform encephalopathies, categorized as a subclass of neuro-degenerative diseases and commonly known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. Prion diseases are common among cannibalistic communities; further research has revealed that the infected or malformed prion protein (named PrPsc spreads its virulence to the normal, healthy prion protein (named PrPc when people consume infected tissues. Knowing that a small interaction between normal and infected prion protein creates virulence, this relationship can be studied as a simple antigen-antibody interaction to understand the series of events that transform a normal prion protein into a virulent misfolded protein. Thoroughly modeled and validated structures of both PrPsc and PrPc can be effectively used to map the epitopes and thereby screen the antigen-antibody interaction using docking studies for a particular organism of concern. This simple immunological approach is used to understand the vital interaction between the normal and malformed proteins that is involved in the disease-spreading mechanism. Clarification of this mechanism could be used in various immune- and bioinformatics algorithms to map the interaction epitopes, furthering an understanding of these pathologies.

  5. The immunological barriers to xenotransplantation.

    Science.gov (United States)

    Vadori, M; Cozzi, E

    2015-10-01

    The availability of cells, tissues and organs from a non-human species such as the pig could, at least in theory, meet the demand of organs necessary for clinical transplantation. At this stage, the important goal of getting over the first year of survival has been reported for both cellular and solid organ xenotransplantation in relevant preclinical primate models. In addition, xenotransplantation is already in the clinic as shown by the broad use of animal-derived medical devices, such as bioprosthetic heart valves and biological materials used for surgical tissue repair. At this stage, however, prior to starting a wide-scale clinical application of xenotransplantation of viable cells and organs, the important obstacle represented by the humoral immune response will need to be overcome. Likewise, the barriers posed by the activation of the innate immune system and coagulative pathway will have to be controlled. As far as xenogeneic nonviable xenografts, increasing evidence suggests that considerable immune reactions, mediated by both innate and adaptive immunity, take place and influence the long-term outcome of xenogeneic materials in patients, possibly precluding the use of bioprosthetic heart valves in young individuals. In this context, the present article provides an overview of current knowledge on the immune processes following xenotransplantation and on the possible therapeutic interventions to overcome the immunological drawbacks involved in xenotransplantation.

  6. Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein.

    OpenAIRE

    Elias, D; Reshef, T; Birk, O S; van der Zee, R; Walker, M D; Cohen, I R

    1991-01-01

    Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-producing beta cells resident in the pancreatic islets. We recently discovered that the pathogenesis of diabetes in NOD strain mice was associated with T-cell reactivity to an antigen cross-reactive with a mycobacterial 65-kDa heat shock protein. To identify peptide epitopes critical to the insulin-dependent diabetes mellitus of NOD mice, we studied the specificities of helper T-cell clones capable of causi...

  7. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk

    2012-01-01

    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  8. Complement in autoimmune diseases.

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    Vignesh, Pandiarajan; Rawat, Amit; Sharma, Madhubala; Singh, Surjit

    2017-02-01

    The complement system is an ancient and evolutionary conserved element of the innate immune mechanism. It comprises of more than 20 serum proteins most of which are synthesized in the liver. These proteins are synthesized as inactive precursor proteins which are activated by appropriate stimuli. The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to exponential generation of final effectors. Three major pathways of complement pathways have been described, namely the classical, alternative and lectin pathways which are activated by different stimuli. However, all the 3 pathways converge on Complement C3. Cleavage of C3 and C5 successively leads to the production of the membrane attack complex which is final common effector. Excessive and uncontrolled activation of the complement has been implicated in the host of autoimmune diseases. But the complement has also been bemusedly described as the proverbial "double edged sword". On one hand, complement is the final effector of tissue injury in autoimmune diseases and on the other, deficiencies of some components of the complement can result in autoimmune diseases. Currently available tools such as enzyme based immunoassays for functional assessment of complement pathways, flow cytometry, next generation sequencing and proteomics-based approaches provide an exciting opportunity to study this ancient yet mysterious element of innate immunity.

  9. Etiopathogenesis of Insulin Autoimmunity

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    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  10. Autoimmune Progesterone Anaphylaxis

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    Mohammad Hassan Bemanian

    2007-06-01

    Full Text Available Progesterone induced dermatitis is a rare disorder. It typically occurs in females due to anautoimmune phenomenon to endogenous progesterone production, but can also be caused byexogenous intake of a synthetic progestin. Here in, we present a case of autoimmune progesterone anaphylaxis (AIPA observed in an adolescent female.The patient is an 18-year-old Caucasian female with no significant past medical history and noprior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions with dyspnea, cough and respiratory distress. She noted that her symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cml of progesterone was performed. The patient developed a 15mm wheal after 15 minutes, confirming the diagnosis of AIPA.The patient was started on a continuous regimen of an oral conjugated estrogen (0.625mg. The skin eruptions and respiratory symptoms have not returned since the initiation of this therapy.Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions.Women with the disorder commonly present with dermatologic lesions in the luteal phase of themenstrual cycle, if there are any other organ involvement in addition to skin (e.g. lung, GI thereaction should be called as autoimmune progesterone anaphylaxis. Diagnosis of AIPA is confirmed by performing a skin allergen test using progesterone.

  11. LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity.

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    Proekt, Irina; Miller, Corey N; Jeanne, Marion; Fasano, Kayla J; Moon, James J; Lowell, Clifford A; Gould, Douglas B; Anderson, Mark S; DeFranco, Anthony L

    2016-10-03

    Studies of the genetic factors associated with human autoimmune disease suggest a multigenic origin of susceptibility; however, how these factors interact and through which tolerance pathways they operate generally remain to be defined. One key checkpoint occurs through the activity of the autoimmune regulator AIRE, which promotes central T cell tolerance. Recent reports have described a variety of dominant-negative AIRE mutations that likely contribute to human autoimmunity to a greater extent than previously thought. In families with these mutations, the penetrance of autoimmunity is incomplete, suggesting that other checkpoints play a role in preventing autoimmunity. Here, we tested whether a defect in LYN, an inhibitory protein tyrosine kinase that is implicated in systemic autoimmunity, could combine with an Aire mutation to provoke organ-specific autoimmunity. Indeed, mice with a dominant-negative allele of Aire and deficiency in LYN spontaneously developed organ-specific autoimmunity in the eye. We further determined that a small pool of retinal protein-specific T cells escaped thymic deletion as a result of the hypomorphic Aire function and that these cells also escaped peripheral tolerance in the presence of LYN-deficient dendritic cells, leading to highly destructive autoimmune attack. These findings demonstrate how 2 distinct tolerance pathways can synergize to unleash autoimmunity and have implications for the genetic susceptibility of autoimmune disease.

  12. Saving Death: Apoptosis for Intervention in Transplantation and Autoimmunity

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    Alice Li

    2006-01-01

    Full Text Available Long considered immunologically “bland,” apoptotic cells are now recognized as important modulators of immune responses. The role of apoptosis in immunological homeostasis has been inferred from several findings, for example, induction of tolerance after injection of apoptotic cells and the capacity of APCs like macrophages and DCs to induce and maintain tolerance after phagocytosis of dead cells. Processing of apoptotic cells by DCs is of particular interest, because DCs are the only known APCs capable of activating naïve T lymphocytes to become effector or regulatory cells. In that regard, recent evidence suggests that phagocytosis of apoptotic cells by DCs can induce Tregs, a finding that has significant implications for the treatment of a variety of immune-mediated inflammatory disorders. Here, we review the relationship between apoptotic cells, DCs, and Tregs, and its impact on prevention of transplant rejection and treatment of autoimmune diseases.

  13. Immunological characteristics of mesenchymal stem cells

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    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  14. Sercarzian immunology--In memoriam. Eli E. Sercarz, 1934-2009.

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    Maverakis, Emanual

    2012-01-01

    During his long career as a principal investigator and educator, Eli Sercarz trained over 100 scientists. He is best known for developing hen egg white lysozyme (HEL) as a model antigen for immunologic studies. Working in his model system Eli furthered our understanding of antigen processing and immunologic tolerance. His work established important concepts of how the immune system recognizes antigenic determinants processed from whole protein antigens; specifically he developed the concepts of immunodominance and crypticity. Later in his career he focused more on autoimmunity using a variety of established animal models to develop theories on how T cells can circumvent tolerance induction and how an autoreactive immune response can evolve over time. His theory of "determinant spreading" is one of the cornerstones of our modern understanding of autoimmunity. This review covers Eli's entire scientific career outlining his many seminal discoveries.

  15. From Immunologically Archaic to Neoteric Glycovaccines

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    Marco Cavallari

    2017-01-01

    Full Text Available Polysaccharides (PS are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection.

  16. [Systemic autoimmune rheumatic diseases in 2013: problems of laboratory diagnosis].

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    Nasonov, E L; Aleksandrova, E N; Novikov, A A

    2014-01-01

    Progress in the laboratory diagnosis of systemic autoimmune rheumatic diseases (SRAD) is caused by the ever increasing clinical introduction of new highly productive methods for immune analysis using computer-aided systems and multiplex proteomic technologies. The urgent problem in the laboratory diagnosis of SRAD is the standardization of current methods for the detection of autoantibodies (autoAb), including the preparation of international reference materials for the calibration and external quality assessment of immunological assay. New autoAb technologies have a higher analytical validity than the previously used classical techniques immunodiffusion, agglutination, and immunofluorescence; however, their diagnostic sensitivity and specificity for SRAD have been poorly studied. Particular emphasis is laid on the standardization of the methods for examining antinuclear antibodies (ANAb), the major serologic marker of SRAD. According to the EULAR/ACR guidelines, indirect immunofluorescence reaction (IIFR) using human HEp-2 cells as substrate is the gold standard and a primary screening ANAb method. New methods for solid-phase analysis (enzyme immunoassay, multiplex test systems, etc.) cannot substitute the primary screening of ANAb using IIFR-HEp-2 as they identify antibodies to the limited number of antigens, increasing the number of false- negative results. The computer-aided systems for interpreting cell fluorescence tests contribute to the standardization and enhancement of the efficiency of detection of ANAb and other autoAb by IIFR. The use of complex diagnostic indices based on the multiparametric analysis of laboratory biomarkers in the serum makes it possible to most fully and objectively assess complex molecular mechanisms for the pathogenesis of SRAD, thus radically improving the early diagnosis, the estimation of the activity and severity of disease, the prediction of the outcomes of a pathological process and the response to treatment.

  17. Medullary Thymic Epithelial Cells and Central Tolerance in Autoimmune Hepatitis Development: Novel Perspective from a New Mouse Model

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    Konstantina Alexandropoulos

    2015-01-01

    Full Text Available Autoimmune hepatitis (AIH is an immune-mediated disorder that affects the liver parenchyma. Diagnosis usually occurs at the later stages of the disease, complicating efforts towards understanding the causes of disease development. While animal models are useful for studying the etiology of autoimmune disorders, most of the existing animal models of AIH do not recapitulate the chronic course of the human condition. In addition, approaches to mimic AIH-associated liver inflammation have instead led to liver tolerance, consistent with the high tolerogenic capacity of the liver. Recently, we described a new mouse model that exhibited spontaneous and chronic liver inflammation that recapitulated the known histopathological and immunological parameters of AIH. The approach involved liver-extrinsic genetic engineering that interfered with the induction of T-cell tolerance in the thymus, the very process thought to inhibit AIH induction by liver-specific expression of exogenous antigens. The mutation led to depletion of specialized thymic epithelial cells that present self-antigens and eliminate autoreactive T-cells before they exit the thymus. Based on our findings, which are summarized below, we believe that this mouse model represents a relevant experimental tool towards elucidating the cellular and molecular aspects of AIH development and developing novel therapeutic strategies for treating this disease.

  18. Autologous haemopoietic stem cell transplantation for autoimmune diseases.

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    Zeher, Margit; Papp, Gabor; Szodoray, Peter

    2011-09-01

    Autoimmune diseases are signified by complex errors of immune-regulation, and the development of autoreactive T and B cells targeting self-antigens, which eventually can lead to permanent organ damage. Despite novel therapeutic protocols, the disease course is chronic, debilitating and in some instances the outcome is lethal. Previously, stem cell transplantation has been reported to be beneficial in autoimmune animal models, as well as in autoimmune diseases related to hematological abnormalities, which opened potential new avenues in the treatment of human autoimmune diseases. In this review, the authors describe the compound cellular regulatory effects of autologous hemopoietic stem cell transplantation (ASCT) and also clinical observations, related to the therapy in a variety of organ-specific and systemic autoimmune diseases. ASCT has a broad effect on the re-populated immune system, complex regulatory potentials and long term beneficial effect via down-regulating immune-reactivity, yet its widespread use in autoimmune diseases is limited, mostly due to the serious side-effects of the conditioning treatments. However, in certain autoimmune diseases with severe debilitating, or even life-threatening course, including systemic lupus erythematosus, systemic sclerosis or multiple sclerosis, ASCT can be a reasonable choice when conventional therapy has failed.

  19. The Potential Roles of Bisphenol A (BPA Pathogenesis in Autoimmunity

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    Datis Kharrazian

    2014-01-01

    Full Text Available Bisphenol A (BPA is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA’s impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity.

  20. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...