Current Immunology Reviews (Discontinued) - Volume 12, Issue 1, 2016

Purpose: We aim to discuss the current status of knowledge on the role of recently identified cytokines in airway hyper responsiveness as well as the genetic predisposition conferred by their coding genes to asthma. Methods: We focused on three cytokines and their coding genes,IL-9, IL-17, and IL-22, and conducted a narrative review of all the relevant publications known to the authors. Results: A great body of evidence regarding the involvement of these three cytokines in asthma was discussed and interpreted. These range from studies on the murine models of asthma to clinical and human genetic approaches. Despite the large amounts of information existing on the genetics of IL-9 and IL-17, there is a lacking trend towards the IL-22 genetic studies in asthma. Conclusion: The emergence of new classes of T-helper effector cells and their cytokines has led to a change in our understanding of asthma pathogenesis. This has created both new opportunities and challenges for researchers involved in this field, and is likely to result in improvements and progress in identifying and developing novel therapeutic measures and innovative treatments for asthma.

Histamine, a prominent mediator of the symptoms and pathogenesis of allergic diseases, is produced not only by mast cells and basophils via the classical degranulation process but also by other immune cells including T cells via a neosynthesis process. Interestingly, T cells produce and are affected by histamine. Various T cell functions are also regulated by histamine via H1, H2, and H4 receptors. We recently demonstrated that T cells induce massive allergic inflammation without assistance from the immunoglobulin E (IgE)/mast cell-dependent pathway, and histamine may be involved in the development of allergic diseases via the functional modulation of and production by T cells. Based on these reports, we propose a new role of histamine and T cells in allergic diseases that differs from the established paradigm. Aside from our recent study showing the downregulation of regulatory T (Treg) cells by histamine via H1R and H4R in a murine allergic dermatitis model, the detailed roles of histamine and T cells in histamine production, expression of histamine receptors, and histamine-mediated activity for a series of T cell subsets remain to be elucidated.

Acute Lymphoblastic Leukemia (ALL) is a hematological malignancy and the most prevalent form of childhood leukemia. Development of ALL is related to the blockade of lymphocyte differentiation, which might affect B or T precursor cells, resulting in the accumulation of blasts in bone marrow. Moreover, immunopathogenesis of ALL involves T regulatory cells (Tregs), which have been investigated in leukemic patients, presenting more immunosuppressive ability than those from normal individuals. Tregs are critical for the maintenance of autoreactive cells, affecting both lineages CD4+ and CD8+, and immune vigilance. Evaluating the role of Tregs in ALL is possible by determining biomarkers related to these cells, such as FOXP3, CD25, CTLA-4 and other molecules that contribute to immunoregulation. In this context, leukemic cells produce ligands that recruit Tregs to the marrow microenvironment, suppressing the antitumor immune response and supporting cancer development. Overall, although Tregs are necessary to inhibit autoreactive T cells, the excessive stimulation of these cells leads to an immunosuppressive state. Immunosuppression in ALL may be partially attributed to the indirect effect of blast cells, which recruit and allow Treg cells to expand, as well as to increase immunosuppressive molecules secreted by both cells. The involvement of Tregs in the immunopathogenesis and their implications in ALL are under the scope of this review and may have important implications in the future.

The type of immune response a host can raise against an invading parasite may often be decisive between chronicity or clearance, and in the worst cases between host survival and death. Helper T cells are key to determining whether antibody-mediated, inflammatory or cytolytic responses will be predominant. Interleukin 10 (IL10) is widely recognized to be the most important cytokine for anti-inflammatory reactions and tends to be associated to chronicity in quite a few types of viral infections. On the other hand, it has also been associated to tissue preservation in chronic viral disease. This review summarizes the most recent data available in the literature on this pivotal cytokine during experimental viral infection and in the clinical setting.

The cells of the innate immune system continually undergo surveillance of the extracellular milieu to serve as the first line of defense against invading microbial pathogens. As a result, these innate immune cells have evolved receptors to sense microbial motifs and danger signals. The inflammasome is an important component of the innate immune system’s “arsenal” against invading microbes such as viruses and bacteria and acts as a homeostatic checkpoint to regulate inflammation. Inflammasomes are cytosolic multi-protein complexes that activate caspase 1 and 11, which result in the production of pro-inflammatory interleukin (IL)-1β and IL-18, and cell death. Several studies have uncovered the mechanisms of inflammasome activation in response to various stimuli ranging from environmental stimulants to microbial components. This mini-review summarizes the current developments and updates in the mechanism of action of inflammasomes.

Cardiovascular disease dependent on inflammatory accelerated atherosclerosis leads to increased mortality in rheumatoid arthritis (RA). In addition to traditional, Framingham risk factors, several immuno-inflammatory cells, mediators and molecules may link atherosclerosis to arthritis. Among immune cells, primarily TH1 cells, as well as endothelial cells play a crucial role in synovial and vascular inflammation. Various cell surface molecules, such as adhesion receptors, CD40-CD40 ligand or members of the RANK-RANK ligand-osteoprotegerin system, as well as soluble pro-inflammatory cytokines, chemokines, autoantibodies and proteases have been implicated in RA and vascular damage. The early assessment of atherosclerosis and early intervention would decrease cardiovascular risk in RA.

The bacterial surface is a complex combination of various immunogenic components of genus, species, and strain specificity. Polyclonal and monoclonal antibodies, used widely in the manufacture of diagnostic test systems, have traditionally served as biological components for the specific detection of bacterial cells. In molecular biology, bacterial cell detection is performed with the help of genetic engineering technologies for cloning recognizing fragments (hypervariable immunoglobulin domains (miniantibodies). These technologies are cheaper and can be competitive in selectivity with hybridoma technologies. At present, research is actively working to improve cell detection sensitivity with the use of electro-optical and electro-acoustical analysis, the main problem being to select antibodies with greater analytical sensitivity. This review highlights the use of specific antibodies and miniantibodies in electro-optical and electro-acoustical analysis for the detection of bacterial cells.

Developing an effective anti tuberculosis (TB) vaccine is a top priority for global control of TB. Since BCG has limited protection against Mycobacterium tuberculosis (MTB) infection, efforts are being made to improve its protective efficacy further. Prime-boost is a strategy whereby an individual is primed with BCG followed by boosting with a heterologous anti TB vaccine/antigen. In several instances, boosting involves up-modulation of CD4 Th1 mediated cellular immunity by stimulation with the corresponding antigen(s) as well as by down modulating the immunosuppressive regulatory T cells. In a recent trial with such a booster candidate vaccine (MVA85A) against TB, despite enhancing the IFN-γ+CD4+Th1 mediated immunity, no significant improvement in protective efficacy against TB was observed in the vaccinated group. A possible cause for under performance of this vaccine could be the lack of killing of MTB by invaded antigen presenting cells (APCs) such as macrophages and dendritic cells (either due to MTB itself or due to polymorphisms in interferon-γ receptors). Consequently, MTB would survive and multiply inside APCs and would lead to the development of TB reflecting the non-efficacy of the vaccine. In this communication, a concise description about the probable reasons for poor performance of MVA85A in providing protection against TB has been put forth.