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

World University root node

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Proceedings of the National Academy of Sciences of the United States of America

DC-SIGN and α2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells

Vaccine

Thermostable foot-and-mouth disease virus as a vaccine candidate for endemic countries: A perspective

Despite being used for more than 80 years, the mechanisms of induction of immune responses by aluminum adjuvants, generically referred to as 'alum', remain largely unknown. However, substantial amounts of recently gathered data demonstrate that aluminum salts induce an innate immune reaction at the site of vaccination. Thus, aluminum salts activate dendritic cells, monocytes and macrophages with enhanced expression of adhesion molecules CD54 and CD58 and co-stimulatory molecules CD40 and CD86, which are crucial in T cell activation; induce chemokines CCL2, CCL3, CCL4 and CXCL8, which mediate recruitment of inflammatory cells at the site of vaccination; and stimulate cytokines crucial in the innate immune response. Aluminum adjuvants activate the nucleotide-binding domain and leucine-rich-repeat-containing gene family pyrin-domain-containing 3 (known as NLRP3 or NALP3) inflammasome to activate caspase-1 and to induce proinflammatory cytokines interleukin (IL)-1β and IL-18 by innate cells. Aluminum adjuvants activate NLRP3 by multiple mechanisms such as by causing damage and rupture of the phagolysosomes, generating reactive oxygen species, inducing K+ efflux and via release from injured tissues of molecules that constitute danger-associated molecular patterns (DAMPs) such as uric acid and ATP. These novel cellular and molecular mechanisms of aluminum salts are likely to influence how we design effective and safe adjuvants in the future. © 2009 Elsevier Ltd. All rights reserved.

Trends in Pharmacological Sciences

Novel cellular and molecular mechanisms of induction of immune responses by aluminum adjuvants

Background: Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. Methodology: Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4+ Tregs. Significance: Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice. © 2009 Davies et al.

PLoS ONE

Toward the Discovery of Vaccine Adjuvants: Coupling In Silico Screening and In Vitro Analysis of Antagonist Binding to Human and Mouse CCR4 Receptors

All B cell targeting therapeutic approaches used at present are unspecific and there is an urgent need for agents that silence selectively pathological autoreactive B lymphocytes only. We hypothesized that this aim could be achieved by chimeric antibodies that cross-link B cell immunoglobulin receptors with inhibitory receptors on the surface of the same targeted disease-associated cell. A hybrid molecule was constructed by coupling copies of the DNA-mimicking DWEYSVWLSN peptide and of the CD22-binding STN epitope with a free terminal sialic acid to a mouse monoclonal IgG antibody backbone. The DNA mimotope peptide binds to the immunoglobulin B cell receptor of pathological DNA-specific B cells of lupus mice, the STN epitope - to CD22 and the IgG by its Fc fragment - to FcγIIb on the surface of the same cell. Mass-spectra analysis showed that 4 STN epitopes plus 5 DNA mimotope peptides were coupled to a single light immunoglobulin chain and 4 STN - and 2 DNA mimotopes - to a heavy chain. Both FcγIIb and CD22 receptors on spleen cells from lupus MRL/lpr mice were phosphorylated after exposure to the chimeric antibody, indicating the involvement of both inhibitory pathways. The constructed chimera suppressed specifically in vitro as well as in vivo anti-DNA IgM and IgG antibody production and delayed the development of glomerulonephritis in the lupus-prone animals. The use of chimeric antibodies targeting two independent inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of pathological autoreactive B cells in autoimmune diseases. © 2009 Elsevier Ltd. All rights reserved.

Molecular Immunology

Simultaneous engagement of FcγIIb and CD22 inhibitory receptors silences targeted B cells and suppresses autoimmune disease activity

Journal of Infectious Diseases

B lymphocytes from patients with tuberculosis exhibit hampered antigen-specific responses with concomitant overexpression of Interleukin-8

The clinical use of intravenous immunoglobulin (IVIg) based on its immunomodulatory and anti-inflammatory potential remains an ongoing challenge. Fcγ receptor-mediated effects of IVIg, although well elucidated in certain pathologies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophylactic infusion of IVIg prevents the development of experimental autoimmune encephalomyelitis (EAE), an accepted animal model for multiple sclerosis (MS). The protection was associated with peripheral increase in CD4+CD25+Foxp3+ regulatory T cell (Treg) numbers and function. The protection was Treg-mediated because IVIg failed to protect against EAE in mice that were depleted of the Treg population. Rather than inducing de novo generation from conventional T cells, IVIg had a direct effect on proliferation of natural Treg. In conclusion, our results highlight a novel mechanism of action of IVIg and provide a rationale to test the use of IVIg as an immunomodulatory tool to enhance Treg in early onset MS and other autoimmune and inflammatory conditions. © 2008 by The American Society of Hematology.

Blood

Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: A critical factor in controlling experimental autoimmune encephalomyelitis

Nature Clinical Practice Neurology

Erratum: Shortage of human intravenous immunoglobulin - Reasons and possible solutions (Nature Clinical Practice Neurology (2007) vol. 3 (120-121) 10.1038/ncpneuro0429)

A post-translationally modified portion of IgG seems to be the critical agent that mediates the antiinflammatory effect of this molecule. Copyright © 2008 Massachusetts Medical Society. All rights reserved.

New England Journal of Medicine

The antiinflammatory IgG

Intravenous immunoglobulin (IVIg) is therapeutically used in a variety of immune-mediated diseases. The beneficial effects of IVIg in auto-antibody-mediated diseases can be explained by neutralization, accelerated clearance and prevention of Fcγ-receptor binding of auto-antibodies. However, the means by which IVIg exerts therapeutic effects in disorders mediated by cellular immunity have remained enigmatic. Clinical improvements, followed by IVIg treatment, often extend beyond the half-life of infused IgG, thereby indicating that IVIg modifies the cellular immune compartment for a prolonged period. Here, we discuss recent advances in the understanding of different, mutually non-exclusive mechanisms of action of IVIg on cells of the innate and adaptive immune system. These mechanisms might explain the beneficial effects of IVIg in certain autoimmune and inflammatory diseases. © 2008 Elsevier Ltd. All rights reserved.