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A potential role for vitamin D as a therapeutic immunomodulator in tuberculosis (TB) has been recognised for over 150 years, but has only recently returned to the centre of the research arena due to the increasing awareness of the global vitamin D deficiency epidemic. As early as birth a child is often deficient in vitamin D, which may not only affect their bone metabolism but also modulate their immune function, contributing to the increased susceptibility to many infections seen early in life. Recent studies have begun to explain the mechanisms by which vitamin D affects immunity. Antimicrobial peptides are induced in conjunction with stimulation of innate pattern recognition receptors enhancing immunity to particular infections. In contrast the role of vitamin D within the adaptive immune response appears to be more regulatory in function, perhaps as a mechanism to reduce unwanted inflammation. In this paper we focus on the effect of vitamin D on immunity to TB. Where much of the attention has been paid by past reviews to the role of vitamin D in adult TB patients, this paper, where possible, focuses on research in paediatric populations [ABSTRACT FROM AUTHOR]

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, andmodulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered. [ABSTRACT FROM AUTHOR]

Zoonoses include a broad range of diseases, that are becoming of great interest, due to the climate changing, that cause the adaptation of vectors to new niches and environments. Host immune responses play a crucial role in determining the outcome of infections, as documented by expansion of antigen-specific T cells during several zoonotic infections. Thus, understanding of the contribution of antigen-specific T-cell subsets in the host immune response is a powerful tool to evaluate the different immunological mechanisms involved in zoonotic infections and for the development of effective vaccines. In this paper we discuss the role of T cells in some eukaryotic and prokaryotic infectious models. [ABSTRACT FROM AUTHOR]

Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200-800 mg/day for 4 weeks. Blood samples were collected before and after treatment. Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group. Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editors discuss various reports within the issue on topics including HIV, highly active antiretroviral therapy (HAART) and immunity.

Candida albicans is an opportunistic fungal pathogen that normally exists as a harmless commensal in humans. In instances where host debilitation occurs, Candida can cause a range of clinical infections, and whilst these are primarily superficial, effecting mucosal membranes, systemic infections can develop in severely immunocompromised individuals. The mechanism of host immunity during commensal carriage of C. albicans has been intensively studied. In this paper, we present the most recent information concerning host recognition of C. albicans leading to cytokine production and the subsequent T-cell responses generated in response to C. albicans. Particular focus is given to the role of the IL-12 cytokine family including IL-12, IL-23, IL-27, and IL-35, in host immunity to Candida. CD4+ T-cells are considered crucial in the regulation of immunity and inflammation. In this regard, the role of Th1/2, helper cells, together with the recently identified Th17 and Treg cells in candidosis will be discussed. Understanding the detailed mechanisms that underlie host immunity to Candida not only will be of benefit in terms of the infections caused by this organism but could also be exploited in the development of therapeutic interventions for other diseases. [ABSTRACT FROM AUTHOR]

IL-12 is a cytokine with links to both innate and adaptive immunity systems. Inmice, its deletion leads to acute susceptibility to oral infection with the yeast Candida albicans, whereas such mice are resistant to systemic disease.However, it is an essential component of the adaptive response that leads to the generation of Th1-type cytokine responses and protection against disseminated disease. This paper presents an overview of the role of IL-12 in models of systemic and mucosal infection and the possible relationships between them. [ABSTRACT FROM AUTHOR]

B7-H3 is one of the most recently identified members of the B7/CD28 superfamily of costimulatory molecules serving as an accessory modulator of T-cell response. Recently, B7-H3 expression has been reported in several human cancers indicating an additional function of B7-H3 as a regulator of antitumor immunity. However, its precise physiologic role is still elusive, because both stimulatory and inhibitory capacities have been demonstrated. This paper summarizes the available data on B7-H3 in the regulation of T-cell response focusing on its potential role in antitumor immunity. [ABSTRACT FROM AUTHOR]

The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment. [ABSTRACT FROM AUTHOR]

Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In the majority of cases, herpes infections are clinically asymptomatic. However, in symptomatic individuals, the latent HSV can spontaneously and frequently reactivate, reinfecting the muco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed.

Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander) cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203). Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques. [ABSTRACT FROM AUTHOR]