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Cutaneous leishmaniasis (CL) is a major public health problem worldwide and spreads to human via the bite of sand flies during blood meal. Following its inoculation, the promastigotes are immediately taken up by phagocytic cells and these leishmania-infected host cells produce proinflammatory cytokines that activate other immune cells and these infected host cells produce more cytokines and reactive nitrogen and oxygen species for efficient control of leishmania infection. Many experimental studies showed that resistance to infection with leishmania paraites is associated with the production of proinflammatory cytokines and activation of CD4+ Th1 response. On the other hand, vulnerability to this parasitic infection is correlated to production of T helper 2 cytokines that facilitate persistence of parasites and disease progression. In addition, some studies have also indicated that CD8+ T cells play a vital role in immune defense through cytokine production and their cytotoxic activity and excessive production of proinflammatory mediators promote amplified recruitment of cells. This could be correlated with excessive inflammatory reaction and ultimately resulted in tissue destruction and development of immunopathogenesis. Thus, there are contradictions regarding the role of immune responses in protection and immunopathogenesis of CL disease. Therefore, the aim of this paper was to review the role of host immune response in protection and its contribution to disease severity for CL infection. In order to obtain more meaningful data regarding the nature of immune response to leishmania, further in-depth studies focused on immune modulation should be conducted to develop better therapeutic strategies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and CD4+ T cells formthe core immunopathogenic cascade leading to chronic inflammation. Traditionally, Th1 cells (interferon-γ-producing CD4+ T cells) driven by interleukin 12 (IL12) were considered to be the encephalitogenic T cells in MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Currently, Th17 cells (Il17-producing CD4+ T cells) are considered to play a fundamental role in the immunopathogenesis of EAE. This paper highlights the growing evidence that Th17 cells play the core role in the complex adaptive immunity of EAE/MS and discusses the roles of the associated immune cells and cytokines. These constitute the modern immunological basis for the development of novel clinical and preclinical immunomodulatory therapies for MS discussed in this paper. [ABSTRACT FROM AUTHOR]

In the last decades a new class of therapeutic drugs have been developed that block tumor angiogenesis. These antiangiogenic molecules, which target VEGF or VEGFR, PDGFR, and c-kit, can act not only on endothelial cells but also on immune cells. Some antiangiogenic molecules inhibit the development of immunosuppressive mechanisms developed by the tumors to escape the immune system (such as regulatory T cells, myeloid-derived suppressor cells, and immunosuppressive cytokines). These immunomodulatory effects must be characterized in detail to enable a better prescription of these treatments. In this paper we will focus on the impact of anti-angiogenic drugs on immunosuppression and their potential combination with immunotherapeutic strategies. Interestingly, immune parameters or their modulation during treatment could serve as potential biomarkers of response or resistance to anti-angiogenic therapies. [ABSTRACT FROM AUTHOR]

The existence of T-cell subsets naturally committed to perform immunoregulation has led to enthusiastic efforts to investigate their role in the immunopathogenesis of transplantation. Being able to modulate alloresponses, regulatory T cells could be used as an immunodiagnostic tool in clinical kidney transplantation. Thus, the measurement of Foxp3 transcripts, the presence of regulatory T cells in kidney biopsies, and the phenotypic characterisation of the T-cell infiltrate could aid in the diagnosis of rejection and the immune monitoring and prediction of outcomes in kidney transplantation. Interestingly, the adoptive transfer of regulatory T cells in animal models has been proven to downmodulate powerful alloresponses, igniting translational research on their potential use as an immunomodulatory therapy. For busy transplant clinicians, the vast amount of information in the literature on regulatory T cells can be overwhelming. This paper aims to highlight the most applicable research findings on the use of regulatory T cells in the immune diagnosis and potential immunomodulatory therapy of kidney transplant patients. However, can we yet rely on differential regulatory T-cell profiles for the identification of rejection or to tailor patient's immunosuppression? Are we ready to administer regulatory T cells as inductive or adjunctive therapy for kidney transplantation? [ABSTRACT FROM AUTHOR]

The study of immune regulation and tolerance has been traditionally associated with self/nonself-discrimination. However, the finding that dominant tolerance, a model that puts in evidence the active role of regulatory T cells, can develop to nonself-antigens suggests that the imposition of tolerance can be context dependent. This paper reviews the emerging field of acquired immune tolerance to non-self antigens, with an emphasis on the different subsets of induced regulatory T cells that appear to specialize in specific functional niches. Such regulatory mechanisms are important in preventing the onset of allergic diseases in healthy individuals. In addition, it may be possible to take advantage of these immune regulatory mechanisms for the induction of tolerance in cases where pathological immune responses are generated to allergens occurring in nature, but also to other immunogens such as biological drugs developed for medical therapies. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response.We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis. [ABSTRACT FROM AUTHOR]

With an incidence that is increasing at 2-5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despitemuch research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations. [ABSTRACT FROM AUTHOR]