Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune thrombocytopenic purpura (ITP) can be classified as primary (known also as idiopathic thrombocytopenic purpura) or as secondary to an underlying condition such as a malignant or nonmalignant disorder. Commonly occurring conditions associated with secondary ITP include lymphoproliferative disorders (chronic lymphocytic leukemia [CLL], Hodgkin's disease and non-Hodgkin's lymphomas), autoimmune collagen vascular diseases (systemic lupus erythematosus [SLE], thyroid disease, antiphospholipid syndrome [APS]), and chronic infections (human immunodeficiency virus [HIV], Helicobacter pylori, hepatitis C virus [HCV]). The mechanism of platelet destruction in thrombocytopenias associated with lymphoproliferative disorders and collagen vascular diseases is identical to the autoimmune mechanism seen in primary ITP. Drug-induced thrombocytopenias are uncommon and generally resolve quickly upon drug discontinuation, but are often attributed to other causes. Platelet destruction in infection-associated ITP occurs via various mechanisms including accelerated platelet clearance due to immune complex disease as seen in HIV infection or cross-reactivity of anti-platelet glycoprotein antibodies and viral antigens in HIV, HCV, and H pylori infections (antigenic mimicry). In patients with HCV-related cirrhotic liver disease, splenic sequestration secondary to portal hypertension and decreased production of thrombopoietin may further contribute to development of thrombocytopenia. The current treatment paradigm for secondary ITP varies according to the underlying condition. Standard treatments for primary ITP (corticosteroids, IVIG, anti-D, splenectomy) are often successful in secondary ITP. In cases of ITP with H pylori and HCV infection, treatment should focus on the underlying disorder.
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PMID:Other immune thrombocytopenias. 1809 69

A logical approach for prophylactic HIV-1 vaccine development begins by recognition that the regimen needs to contain viruses which are not cleared by primary host immune responses and develop persistent infection. Hence the required strategy is different from the one against self-remitting acute infections which aims at eliciting robust host immune responses in advance by infection mimicry. Host adaptive immune responses do play a central role in primary resolution from acute HIV-1 and simian immunodeficiency virus (SIV) infection, but as observed in the non-remitting disease course, their function is not fully exerted, leading to failure in viral containment. Either overcoming the limitations of antiviral immunity in natural infection or augmenting the effectors potentially capable of controlling virus replication would be essential for development of an effective HIV-1 vaccine. This approach is hand-in-hand with understanding of the reversibility of various steps leading to establishment of persistent HIV-1 infection. This article reviews the interplay between HIV-1/SIV and the infected host, mainly focusing on macaque models of SIV infection and characterization of the two major wings of adaptive immunity, cytotoxic T lymphocytes (CTLs) and neutralizing antibodies. Discussed in parallel are the up-to-date topics of HIV-1 vaccine development including our recent progress.
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PMID:[Virological and immunological bases for HIV-1 vaccine design]. 1835 51

Chemokines regulate leukocyte migration during physiological and pathological conditions. They exert their biological activity through interaction with 7-transmembrane spanning G protein-coupled receptors (GPCR) and are presented on glycosaminoglycans (GAG) linked to endothelial cell layers. Specific chemokines and chemokine receptors affect angiogenesis or are targets for viral mimicry, e.g. by human immunodeficiency virus (HIV). Several enzymes, in particular proteases, have been described to process chemokines at specific sites generating chemokine isoforms that were also identified from natural sources. For some chemokines, e.g. CXCL8 and CCL3L1, posttranslational modification results in enhanced biological activity. For CXCL7 and CCL14 truncation is even mandatory for receptor signaling and chemotactic properties. The activity of many other chemokines is down-regulated by processing and receptor antagonists are generated, e.g. for truncated CCL8 and CCL11. Moreover, some processed chemokines such as CCL5(3-68) show enhanced affinity for one receptor (CCR5) and reduced interaction with other receptors (CCR1 and CCR3) resulting in differential changes in leukocyte response. These posttranslational mechanisms, in addition to gene duplication, transcriptional and translational regulation of chemokine ligand and receptor expression, GAG binding properties, expression of "silent" receptors and synergistic interaction between chemokines, modulate chemokine activity in a complex manner. This report reviews current understanding on the regulation of the chemokine network through posttranslational modification and its consequences for leukocyte migration, angiogenesis and protection against viral infection.
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PMID:Regulation of chemokine activity by posttranslational modification. 1879 69

Reactive arthritis ReA is still an incompletely understood rheumatic disorder whose immunopathogeny involves several mechanisms. There is an association with Class-I histocompatibility antigens HLA-B27 and history of previous gastrointestinal or genitourinary infections. The molecular mimicry between bacterial and self antigens suggests the possibility of cross reactivity as a disease mechanism. The infection pandemics by the human immunodeficiency virus HIV changed the profile of the occurrence of a number of rheumatic diseases including ReA which appears to be more frequent more severe and refractory to the usual treatment for retrovirus-infected patients. The intensity of articular and extra-articular manifestations of ReA often makes the use of immunosuppressant drugs in these patients necessary. Due to the immunosuppression resulting from the retrovirosis itself the treatment becomes a dilemma for rheumatologists. HIV seems to play a role in the main ReA immunopathogenesis mechanisms either acting as direct arthritogenic agent or causing an immune dysfunction in the CD4 T lymphocytes T CD8 relationship leading to the deregulation in the production of cytokines or in advanced immunosuppression stages predisposing to infection by other arthritogenic pathogens. The use of highly active anti-retroviral therapy HAART has changed the profile of rheumatic events and the immunopathogeny of the HIV ReA association. The understanding of the basic ReA immunopathogenic mechanisms in HIV-infected patients is vital in the attempt of elucidating many still existing questions.
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PMID:[Reactive arthritis in HIV-infected patients: immunopathogenic aspects]. 1884 8

Infectious agents have been implicated in the etiopathogenesis of various vasculitides via numerous and overlapping mechanisms including direct microbial invasion of endothelial cells, immune complex mediated vessel wall damage and stimulation of autoreactive B and/or T cells through molecular mimicry and superantigens. While the causative role of hepatitis B virus in polyarteritis nodosa and hepatitis C virus in mixed cryoglobulinemia is clearly established, evidence for the association of other infectious agents with vasculitis, including human immunodeficiency virus, parvovirus B19, cytomegalovirus, varicella zoster virus, Staphylococcus aureus, rickettsiaceae, Treponema pallidum and Borrelia burgdorferi, among numerous others, is accumulating. The spectrum of association of infectious agents; bacteria, viruses and parasites, with systemic vasculitides, will be reviewed herewith.
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PMID:The infectious etiology of vasculitis. 1981 Dec 60

During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.
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PMID:Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. 2070 40

Computational grafting of functional motifs onto scaffold proteins is a promising way to engineer novel proteins with pre-specified functionalities. Typically, protein grafting involves the transplantation of protein side chains from a functional motif onto structurally homologous regions of scaffold proteins. Using this approach, we previously transplanted the human immunodeficiency virus 2F5 and 4E10 epitopes onto heterologous proteins to design novel "epitope-scaffold" antigens. However, side-chain grafting is limited by the availability of scaffolds with compatible backbone for a given epitope structure and offers no route to modify backbone structure to improve mimicry or binding affinity. To address this, we report here a new and more aggressive computational method-backbone grafting of linear motifs-that transplants the backbone and side chains of linear functional motifs onto scaffold proteins. To test this method, we first used side-chain grafting to design new 2F5 epitope scaffolds with improved biophysical characteristics. We then independently transplanted the 2F5 epitope onto three of the same parent scaffolds using the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone grafting designs showed close agreement with both the computational models and the desired epitope structure. In two cases, backbone grafting scaffolds bound antibody 2F5 with 30- and 9-fold higher affinity than corresponding side-chain grafting designs. These results demonstrate that flexible backbone methods for epitope grafting can significantly improve binding affinities over those achieved by fixed backbone methods alone. Backbone grafting of linear motifs is a general method to transplant functional motifs when backbone remodeling of the target scaffold is necessary.
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PMID:Computational design of high-affinity epitope scaffolds by backbone grafting of a linear epitope. 2206 Dec 65

Vitiligo and other autoimmune disorders are increasingly being reported in a background of immunosuppression. Viral-induced immune activation and molecular mimicry are the proposed mechanisms for the development of autoimmune diseases in individuals infected with human immunodeficiency virus (HIV). An association of vitiligo with Kaposi sarcoma (KS) rarely has been reported. The development of vitiligo preferentially around KS lesions in a patient with AIDS is unusual. We report a case of disseminated vitiligo that developed around KS nodules in a patient with AIDS.
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PMID:Disseminated vitiligo developing around Kaposi sarcoma nodules in an AIDS patient. 2227 87

The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.
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PMID:Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing. 2326 68

The kidneys are frequently targeted by pathogenic immune responses against renal autoantigens or by local manifestations of systemic autoimmunity. Recent studies in rodent models and humans have uncovered several underlying mechanisms that can be used to explain the previously enigmatic immunopathology of many kidney diseases. These mechanisms include kidney-specific damage-associated molecular patterns that cause sterile inflammation, the crosstalk between renal dendritic cells and T cells, the development of kidney-targeting autoantibodies and molecular mimicry with microbial pathogens. Conversely, kidney failure affects general immunity, causing intestinal barrier dysfunction, systemic inflammation and immunodeficiency that contribute to the morbidity and mortality of patients with kidney disease. In this Review, we summarize the recent findings regarding the interactions between the kidneys and the immune system.
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PMID:The immune system and kidney disease: basic concepts and clinical implications. 2403 18


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