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

Recent reports demonstrate that basophils act as antigen presenting cells to drive Th2 and IgE responses against protease and protein allergens and helminth parasites. Through MHC class II-dependent cognate interactions with CD4+ T cells in the context of co-stimulatory molecules, and through secretion of IL-4, IL-13 and thymic stromal lymphopoietin, basophils drive antigen-specific Th2 responses. These results have uncovered previously unknown functions of basophils, and should aid in designing novel therapeutic strategies for asthma and allergic conditions. © 2009 Elsevier Ltd. All rights reserved.

World University root node

Trends in Immunology

Basophils as antigen presenting cells

Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, infects one-third of the world's population. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). DCs are sentinels of the immune system and are important for eliciting both primary and secondary immune responses to pathogens. In this context, to understand the molecular pathogenesis of tuberculosis and host response to mycobacteria and to conceive prospective vaccine candidates, it is important to understand how cell wall Ags of M. tuberculosis and, in particular, the proline-glutamic acid-polymorphic guanine-cytosine-rich sequence (PE-PGRS) family of proteins modulate DC maturation and function. In this study, we demonstrate that two cell wall-associated/secretory PE-PGRS proteins, PE-PGRS 17 (Rv0978c) and PE-PGRS 11 (Rv0754), recognize TLR2, induce maturation and activation of human DCs, and enhance the ability of DCs to stimulate CD4+ T cells. We further found that PE-PGRS protein-mediated activation of DCs involves participation of ERK1/2, p38 MAPK, and NF-κB signaling pathways. Priming of human DCs with IFN-γ further augmented PE-PGRS 17 or PE-PGRS 11 Ag-induced DC maturation and secretion of key proinflammatory cytokines. Our results suggest that by activating DCs, PE-PGRS proteins, important mycobacterial cell wall Ags, could potentially contribute in the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis. Copyright ©2010 by The American Association of Immunologists, Inc. All rights reserved.

Journal of Immunology

PE-PGRS antigens of mycobacterium tuberculosis induce maturation and activation of human dendritic cells

Kawasaki disease (KD) is an acute febrile childhood vasculitis, associated with the development of coronary artery abnormalities in 25-30% of untreated patients. The aetiopathogenesis is not well known but it is accepted that an undefined infectious trigger in genetically predisposed individuals results in the disease. KD is characterized by an endothelial cell injury, which could be due to abnormal cytokine production and to generation of cytotoxic antibodies against the endothelial cells. Intravenous immunoglobulin IVIG is an effective treatment in preventing the occurrence of coronary artery abnormalities in KD. Several mechanisms may explain the anti-inflammatory effects of IVIG in this disease. They include modification of the cytokine balance, and alteration on both the differentiation and the function of monocytes/macrophages, neutrophils and lymphocytes. © 2009 Elsevier B.V. All rights reserved.

Autoimmunity Reviews

Kawasaki disease: Aetiopathogenesis and therapeutic utility of intravenous immunoglobulin

An altered immune homeostasis as a result of deficiency or defective function of CD4+CD25+FoxP3+ regulatory T cells (Tregs) is common in several autoimmune diseases. Hence, therapeutic strategies to render Tregs functionally competent are being investigated. Intravenous immunoglobulin (IVIG) is being increasingly used for the treatment of a wide range of autoimmune and inflammatory diseases. Recent studies have demonstrated that IVIG induces the expansion of Tregs and enhances their suppressive functions. These effects of IVIG on Tregs correlate with the beneficial effects of IVIG in patients with autoimmune diseases. Thus, modulation of Tregs by IVIG represents a novel mode of action that explains the therapeutic effects of IVIG in T cell-mediated autoimmune diseases. However, the molecular mechanisms involved in IVIG-mediated modulation of Tregs are unclear and need further investigation. © Springer Science+Business Media, LLC 2010.

Journal of Clinical Immunology

Immunomodulation by intravenous immunoglobulin: Role of regulatory T cells

Mycobacterium tuberculosis, an etiological agent of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Pathogenic mycobacteria survive in the host by subverting host innate immunity. Dendritic cells (DCs) are professional antigen-presenting cells that are vital for eliciting immune responses to infectious agents, including pathogenic mycobacteria. DCs orchestrate distinct Th responses based on the signals they receive. In this perspective, deciphering the interactions of the proline-glutamic acid/proline-proline-glutamic acid (PE/PPE) family of proteins of M. tuberculosis with DCs assumes significant pathophysiological attributes. In this study, we demonstrate that Rv1917c (PPE34), a representative member of the proline-proline-glutamic-major polymorphic tandem repeat family, interacts with TLR2 and triggers functional maturation of human DCs. Signaling perturbations implicated a critical role for integrated cross-talk among PI3K-MAPK and NF-κB signaling cascades in Rv1917c-induced maturation of DCs. However, this maturation of DCs was associated with a secretion of high amounts of anti-inflammatory cytokine IL-10, whereas Th1-polarizing cytokine IL-12 was not induced. Consistent with these results, Rv1917c-matured DCs favored secretion of IL-4, IL-5, and IL-10 from CD4+ T cells and contributed to Th2-skewed cytokine balance ex vivo in healthy individuals and in patients with pulmonary tuberculosis. Interestingly, the Rv1917c-skewed Th2 immune response involved induced expression of cyclooxygenase-2 (COX-2) in DCs. Taken together, these results indicate that Rv1917c facilitates a shift in the ensuing immunity toward the Th2 phenotype and could aid in immune evasion by mycobacteria. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Fulltext

Journal of Biological Chemistry

Src homology 3-interacting domain of Rv1917c of Mycobacterium tuberculosis induces selective maturation of human dendritic cells by regulating PI3K-MAPK-NF-κB signaling and drives Th2 immune responses

Nature

Erratum: Surface hydrophobin prevents immune recognition of airborne fungal spores (Nature (2009) 460 (1117-1121))

Intravenous immunoglobulin (IVIg) is increasingly being used in the treatment of a wide range of autoimmune and systemic inflammatory diseases involving distinct pathogenesis. However, the mechanism by which IVIg exerts its sustained therapeutic effects in these diverse diseases has remained enigmatic. Recent findings from experimental and clinical research have, however, provided new insights into the mechanisms of action of IVIg. IVIg targets various cellular (such as dendritic cells, macrophages, monocytes, B and T cells) and soluble compartments (cytokines, complements, autoantibodies and autoantigens) of the immune system that are involved in the pathogenesis of autoimmune diseases. Thus, the mechanisms of actions of IVIg are mutually non-exclusive and work in synergy to contribute to its therapeutic effects. © 2009 Elsevier Ltd. All rights reserved.

Drug Discovery Today: Therapeutic Strategies

Intravenous polyclonal immunoglobulin in autoimmune diseases: clinical indications and mechanisms of action

Background: Alloimmune responses to intravenously administered protein therapeutics are the most common cause of failure of replacement therapy in patients with defective levels of endogenous proteins. Such a situation is encountered in some patients with hemophilia A, who develop inhibitory anti-factor (F)VIII alloantibodies after administration of FVIII to treat hemorrhages. Objectives: The nature of the secondary lymphoid organs involved in the initiation of immune responses to human therapeutic has not been studied. We therefore investigated this in the case of FVIII, a self-derived exogenous protein therapeutic. Methods: The distribution of intravenously administered FVIII was followed after FVIII-deficient mice were injected with radiolabeled FVIII and using immunohistochemistry. The role of the spleen and antigen-presenting cells (APC) in the onset of the anti-FVIII immune response was analyzed upon splenectomy or treatment of the mice with APC-depleting compounds. Results: FVIII preferentially accumulated in the spleen at the level of metallophilic macrophages in the marginal zone (MZ). Surgical removal of the spleen or selective in vivo depletion of macrophages and CD11c-positive CD8α-negative dendritic cells resulted in a drastic reduction in anti-FVIII immune responses. Conclusions: Using FVIII-deficient mice as a model for patients with hemophilia A, and human pro-coagulant FVIII as a model for immunogenic self-derived protein therapeutics, our results highlight the importance of the spleen and MZ APCs in the initiation of immune responses to protein therapeutics. Identification of the receptors implicated in retention of protein therapeutics in the MZ may pave the way towards novel strategies aimed at reducing their immunogenicity. © 2009 International Society on Thrombosis and Haemostasis.

Journal of Thrombosis and Haemostasis

Splenic marginal zone antigen-presenting cells are critical for the primary allo-immune response to therapeutic factor VIII in hemophilia A

Anti-factor VIII (FVIII) inhibitory IgG may arise as alloantibodies to therapeutic FVIII in patients with congenital hemophilia A, or as autoantibodies to endogenous FVIII in individuals with acquired hemophilia. We have described FVIII-hydrolyzing IgG both in hemophilia A patients with anti-FVIII IgG and in acquired hemophilia patients. Here, we compared the properties of proteolytic auto- and allo-antibodies. Rates of FVIII hydrolysis differed significantly between the two groups of antibodies. Proline-phenylalanine-arginine-methylcoumarinamide was a surrogate substrate for FVIII-hydrolyzing autoantibodies. Our data suggest that populations of proteolytic anti-FVIII IgG in acquired hemophilia patients are different from that of inhibitor-positive hemophilia A patients. © 2009 Federation of European Biochemical Societies.