Biological Sciences and Engineering

Indian Institute of Technology Palakkad&nbsp;(IIT Palakkad or IIT PKD) is a public autonomous&nbsp;engineering&nbsp;and&nbsp;research&nbsp;institute located in&nbsp;Palakkad,&nbsp;Kerala. It was&nbsp;one of the five new&nbsp;IITs&nbsp;proposed in the&nbsp;2014 Union budget of India. The campus was inaugurated on 3 August 2015. The institute has 94 faculty, 978 students, and 63 non-teaching staffs.

IT Palakkad currently offers four-year Bachelor of Technology (B.Tech) and two years MS programmes in 8 different engineering disciplines including&nbsp;Computer Science, Electrical, Mechanical, Civil among others.

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IIT Palakkad

A fraction of antibodies from healthy immune repertoires binds to heme and acquires the ability to recognize multiple antigens. The mechanism and functional consequences of heme-mediated antigen binding promiscuity (polyreactivity) are not understood. Here, we used SPE7, a mouse monoclonal IgE specific for dinitrophenyl that has been thoroughly characterized at the molecular level, as a model antibody to elucidate the mechanism and functional consequences of heme-mediated polyreactivity. We first demonstrate that exposure of SPE7 to heme results in a substantial increase in its antigen binding polyreactivity. Comparison of the binding kinetics and thermodynamics of interaction of native and heme-bound SPE7 indicates that the binding of heme to SPE7 confers binding affinities in the low nanomolar range toward several antigens but has no influence on the mechanism of recognition of dinitrophenyl. In vitro cellular assays further demonstrate that heme-bound SPE7 does not promote the degranulation of basophils in the presence of new target antigens, while degranulation is observed in the presence of dinitrophenyl. Molecular docking and fluorescence spectroscopy revealed binding of heme to the variable region of SPE7 at a distance from the conventional binding site for dinitrophenyl, explaining the extension of binding polyreactivity without abrogation of the interaction with its cognate antigen. In addition, our data suggest that heme, when bound to IgE, is solvent-exposed and may serve as an interfacial cofactor mediating binding to diverse proteins. This study contributes to the understanding of the mechanisms of heme-induced antibody polyreactivity. It also paves the way toward the delineation of the functional impact of polyreactivity and cross-reactivity of IgE. © 2015 American Chemical Society.

World University root node

Biochemistry

Mechanism and functional implications of the heme-induced binding promiscuity of IgE

Reports unraveling the beneficial effects of Viscum album (VA) preparations as complementary therapies for cancer have increasingly revealed the underlying molecular and cellular mechanisms, which encompass cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their propitious relevance to cancer therapy, VA preparations are also relevant for the treatment of several inflammatory pathologies. In view of the intricate association of inflammation and cancer and the fact that several anti-tumor phytotherapeutics exert potent anti-inflammatory effects, we believe that an anti-inflammatory effect is responsible for the therapeutic benefits of VA preparations. One of the underlying molecular mechanisms of this inflammatory response is the selective down-regulation of the cyclo-oxygenase (COX)-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2). This inhibitory action has been associated with reduced expression of COX-2, without modulating COX-1 expression. This mechanism is associated with VA-induced destabilization of COX-2 mRNA, thereby depleting the functional COX-2 mRNA available for protein synthesis and for subsequent induction of secretion of PGE2. Together, these results demonstrate a novel anti-inflammatory mechanism of action of VA preparation, wherein VAQUSpez an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2 and destabilization of COX-2 mRNA. © 2015 S. Karger AG, Basel.

Translational Research in Biomedicine

Dissecting the anti-inflammatory effects of viscum album: Inhibition of cytokine-induced expression of cyclo-oxygenase-2 and secretion of prostaglandin E2

Erratum: Mechanism and functional implications of the heme-induced binding promiscuity of IgE (Biochemitry (2015) 54:11 (2061-2072) DOI: 10.1021/bi501507m)

Basophils are the rare granulocytes and play an important role in the polarization of Th2 responses and protection against helminth parasites. In addition, basophils contribute to the pathogenesis of several diseases such as asthma, chronic allergy and lupus. Notably, Th17 cells are also implicated in the pathogenesis of these diseases suggesting that basophils support the activation and expansion of this subset of CD4+ T cells. Therefore, we explored whether basophils promote the expansion of human Th17 cells. We show that basophils lack the capacity to expand Th17 cells and to induce the secretion of Th17 cytokines either directly or indirectly via antigen presenting cells such as monocytes. As human basophils lack HLA-DR and co-stimulatory molecules, their inability to confer T cell receptor- and co-stimulatory molecule-mediated signals to CD4+ T cells might explain the lack of Th17 responses when memory CD4+ T cells were co-cultured with basophils. © 2014 American Society for Histocompatibility and Immunogenetics.

Fulltext

Human Immunology

Basophils are inept at promoting human Th17 responses

Trends in Pharmacological Sciences

Targeting CCR4 as an emerging strategy for cancer therapy and vaccines

A graphene-based electrochemical DNA sensor has been developed for the low-concentration detection of breast cancer-related BRCA1 gene. The DNA sensor used a "sandwich" detection strategy, in which capture probe (DNA-c) and reporter probe (DNA-r) DNAs hybridize to target probe DNA (DNA-t) in a sandwich arrangement on a graphene-modified glassy carbon electrode (GCE). The DNA-r was conjugated to gold nanoparticle and the oxidation of gold nanoparticle was used for the electrochemical detection of DNA-t. The sensor performance was monitored with cyclic voltammetry (CV) and chronoamperometry. The sensor was found to be stable, reproducible and sensitive and it could detect up to 1 femtomolar BRCA1 gene (5.896 femtogram/ml). {\textcopyright} 2014 Elsevier B.V.

Sensors and Actuators, B: Chemical

Graphene-DNA electrochemical sensor for the sensitive detection of BRCA1 gene

Dendritic cells (DCs) are professional antigen presenting cells that play a pivotal role in the initiation of immune responses. DCs ingest antigens and then present these antigens to T cells to initiate T cell activation and polarization. DCs receive signals both from environment and from endogenous molecules. DCs in the immune system constantly interact with immunoglobulins (or antibodies) and a substantial amount of these immunoglobulins are natural. We found that natural antibodies have a key role in regulating the DC functions and that CD40-reactive natural antibodies constitute one of the endogenous molecules that provide maturation-associated signals to DCs in physiology. In this chapter, we describe the isolation of anti-CD40 natural antibodies from pooled normal immunoglobulin preparations (intravenous immunoglobulin, IVIg) and their biological effects on human DC maturation and functions. © Springer Science+Business Media New York 2014.

Methods in Molecular Biology

Regulation of human dendritic cell functions by natural anti-CD40 antibodies

The presence of maternal antibodies is a major obstacle for eliciting protective immune responses to foot-and-mouth disease (FMD) vaccines in young, growing animals. In this report, we analyzed the ability of inactivated quadrivalent oil emulsified and aluminium hydroxide adjuvanted FMD vaccines to elicit neutralizing antibody responses in growing calves that had maternal antibodies. Our results demonstrate that oil emulsified vaccines but not aluminium hydroxide adjuvanted FMD vaccines could surmount maternal antibodies to elicit strong and significant levels of neutralizing antibody responses in growing claves. © 2014 Elsevier B.V.

Veterinary Microbiology

Neutralizing antibody responses to foot-and-mouth disease quadrivalent (type O, A, C and Asia 1) vaccines in growing calves with pre-existing maternal antibodies

The mechanisms underlying Japanese encephalitis virus (JEV) pathogenesis need to be thoroughly explored to delineate therapeutic approaches. It is believed that JEV manipulates the innate and adaptive compartments of the host's immune system to evade immune response and cross the blood-brain barrier. The present study was thus designed to investigate the functional modulation of DCs after exposure to JEV and to assess the consequences on CD4+ T-lymphocyte functions. Human monocyte-derived DCs were either infected with 1 MOI of live virus, UV-inactivated virus, or were mock-infected. Replication-competent JEV induced a significant increase in the expression of maturation markers 48 h postinfection, along with that of programmed cell death 1 ligand 1 (PD-L1; also called B7-H1 and CD274). JEV-infected DCs expanded the Treg cells in allogenic mixed lymphocyte reactions. The expansion of Treg cells by JEV-infected DCs was significantly reduced upon blocking PD-L1 using an antagonist. In addition, JEV-infected DCs significantly altered the proliferation and reduced the polarization of Th cells toward the Th1-cell phenotype. The results, for the first time, suggest that JEV evades the host's immune system by modulating the crosstalk between DCs and T lymphocytes via the PD-L1 axis. © 2014 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.

European Journal of Immunology

Japanese encephalitis virus expands regulatory T cells by increasing the expression of PD-L1 on dendritic cells

A considerable progress has been achieved in the comprehension of the cellular and molecular mechanisms that account for the therapeutic benefit of intravenous immunoglobulin (IVIg) in several autoimmune and inflammatory conditions. However, the precise mechanisms responsible for such a wide range of biological activities have not been proven unambiguously. A wide range of specificities have been identified within IVIg including idiotypes of immunoglobulins, Tcell receptor, HLA molecules, several cell surface molecules of immunological importance such as CD4, CD5, Fas, BAFF, cytokines and cytokine receptors, chemokine receptors, CD40 among others. Here we identify and characterize the natural autoantibodies of IgG isotype directed against the human Fc receptors. We show that the F(ab′)2 of IVIg recognize the FcγRIII (CD16) and FcγRII (CD32). Interestingly, the immunopurified anti-FcγIII and anti-FcγII antibodies isolated from IVIg bind soluble and membrane-bound FcR and inhibit rosette formation. Altogether, these results along with previous reports provide pointers on the existence of functionally relevant natural autoantibodies towards a wide range of self-motifs that may participate in regulation of the immune response. Their presence in the therapeutic immunoglobulin preparations may explain at least in part, the beneficial effect of IVIg in autoimmune diseases. © Springer Science+Business Media 2014.