Current Immunology Reviews (Discontinued) - Volume 12, Issue 2, 2016

Background: Despite the significant improvement of survival outcomes in childhood cancers over the last four decades, the decline of mortality has slowed down and the intensity of using chemotherapeutic combinations has reached maximum tolerable level. To further improve outcomes, there has been increasing focus on immunotherapy. Objective: We will review the various immunotherapeutic options for pediatric malignancies, with their current issues, and assess future directions for the field. Methods: Literature review of the field of immunology and immunotherapies for pediatric and adult cancers. Results: Monoclonal antibodies and chimeric antigen receptor (CAR) T cell therapies are demonstrating promising clinical activity but there are lags in development and clinical application of other specific immunotherapies for pediatric patients. Conclusion: The robust immunological responsiveness of pediatric patients constitutes a unique opportunity for maximum therapeutic impact but additional investigation needs to be directed toward further understanding the operational mechanisms of immune suppression in pediatric tumors and alternative approaches for antigenically bland tumors.

The NF-κB (nuclear factor κappa B) belongs to a family of transcription factors that regulate a number of key cellular pathways and control many physiological processes, including the immune and inflammatory responses. The beneficial effect of probiotics is presently recognized in both the intestinal and extra-intestinal development. The growing literature on the subject suggests an important role of specific probiotic strains, mixtures of strains, and secreted products, all of which have a role in either the preventive or therapeutic treatment of certain human disorders. During the last two decades, a number of studies have shown that probiotic strains and their extracellular products can join the immune system and activate receptors in different key pro-inflammatory pathways such as the NF-κB route, either by increasing or suppressing the signaling pathways. This brief review does not include an exhaustive bibliography of the subject, but focuses instead on an update to the latest research of the past three years on the role of the NF-κB signaling pathway in the anti-inflammatory effect of probiotics.

Chronic hepatitis C virus (HCV) infection is a major health problem worldwide, affecting approximately 3% of the human population. Although decades of research have amassed since the virus was characterized in 1989, there remains no prophylactic HCV vaccine approved for clinical use. The vast genetic variability of HCV, together with weak host immune responses following infection, and a paucity of suitable animal models for HCV vaccine research, have made HCV an elusive vaccine target. Despite the recent advances in medical treatment enjoyed by wealthy nations, there remains an unmet need for an affordable, effective, and accessible means to control HCV disease burden in areas of limited resources, where HCV is most problematic. To this end, several promising HCV vaccine candidates have been reported in recent preclinical and clinical trials. Here we review HCV virology and immunology relevant to rational design of a prophylactic HCV vaccine, and recent studies of preclinical and clinical HCV vaccine candidates.

A defective immunorregulation has been demonstrated at different levels in autoimmune disease and in multiple sclerosis (MS) in particular, which can be partly restored by therapies used for MS. This fact highlights the relevance of promoting specific tolerance for central nervous system antigens for the prevention of MS. In the present review, we summarize recent findings on the role of the diverse regulatory immune cell subsets to convey an integrated view of MS pathogenesis in the framework of the immune and psychoneuroendocrine metasystem. We also discuss the effects of MS therapies on these regulatory cells’ subsets, and their implications in the cellular therapy of the disease.

Psoriasis is a complex autoimmune inflammatory disease with a genetic basis. The increased expression of IL-17F gene and protein is observed in the lesional skins of psoriatic patients. We and other groups discovered human IL-17F gene that shows the highest homology with IL-17A. IL-17F induces various inflammatory molecules, such as IL-6 and IL-8. IL-17F is mainly derived from Th17, Tc17 and ILC3 cells, and induces CCL20 expression, resulting in the recruitment of additional IL-17F-producing cells to enhance skin inflammation via CCR6. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and several signaling pathways have been identified. Injection with IL-17F in mice revealed marked neutrophilia in dermis, and its infiltration was significantly inhibited by anti-IL-8 antibody. Sequence variants of the IL-17F gene are associated with response to treatments, and a variant (rs763780) of IL-17F encodes an antagonist for the wild-type IL-17F. Hence, IL-17F may play a pivotal role in the pathogenesis of psoriasis, and may provide a promising therapeutic target for development of novel strategies.

Antibody-dependent enhancement of infection is among the main challenges for HIV vaccines. Neutralization-enhancing RF antibodies (NeRFa) arising against immune complexes during secondary immune response not only enhance the action of neutralizing antibodies but also make infectionenhancing antibodies neutralizing in a sensitized virus. NeRFa represent the oldest type of immune response since it protects a fetus with unformed immune system from maternally acquired infections. Vaccination with HIV gp120 glycoprotein each 3 weeks may be a strategy to induce NeRFa both in prophylactic and therapeutic immunizations. Twenty-fold reduction in amount of protein for secondary immunization is important for an optimal induction of NeRFa. Auto-vaccination via transient immune suppression with dexamethasone might be a promising way to induce NeRFa in HIV-infected patients.

Objective: Several studies demonstrated some alterations in immune system of patients with β-thalassemia major. The aim of study was to investigate the function and number of lymphocyte subsets of patients with β-thalassemia major. Materials and Methods: Quantitative and qualitative assessment of cellular and humoral immune system and population of natural killer lymphocytes in patients with β-thalassemia major and similar age and sex matched healthy controls were done. Complete blood count and serum iron and ferritin levels were also measured. Data was analyzed by SPSS (V.16) software. Results: We did not find any alteration in number and function of B and T lymphocytes. However, natural killer cells level in thalassemia group was significantly lower than control group (6.54±2.87% vs. 9.13±4.01%; P=0.006). Number of T helper cells in thalassemia patients with spelenectomy was significantly lower than patients without splenectomy (31.8±6.55% vs. 40.3±9.2%; P=0.02). Conclusion: In our study the patients with β-thalassemia major had lower natural killer (NK) lymphocytes than healthy control.