Showing papers in "International Reviews of Immunology in 2019"

Immunoinformatics: In Silico Approaches and Computational Design of a Multi-epitope, Immunogenic Protein.

Abstract: Immunoinformatics is a new critical field with several tools and databases that conduct the eyesight of experimental selection and facilitate analysis of the great amount of immunologic data obtained from experimental researches and helps to design and introducing new hypothesis. Given these visages, immunoinformatics seems to be the way that develop and progress the immunological research. Bioinformatics methods and applications are successfully employed in vaccine informatics to assist different sites of the preclinical, clinical, and post-licensure vaccine enterprises. On the other hand, the progression of molecular biology and immunology caused epitope vaccines have become the focus of research on molecular vaccines. Moreover, reverse vaccinology could improve vaccine production and vaccination protocols by in silico prediction of protein-vaccine candidates from genome sequences. B- and T-cell immune epitopes could be predicted by immunoinformatics algorithms and computational methods to improve the vaccine design, protective immunity analysis, assessment of vaccine safety and efficacy, and immunization modeling. This review aims to discuss the power of computational approaches in vaccine design and their relevance to the development of effective vaccines. Furthermore, the various divisions of this field and available tools in each item are introduced and reviewed.

Chicken toll-like receptors and their significance in immune response and disease resistance

Abstract: Infectious diseases are a major challenge for the poultry industry that causes widespread production losses. Thus, management and control of poultry health and diseases are essential for the viability of the industry. Toll-like receptors are best characterized as membrane-bound receptors that perform a central role in immune homeostasis and disease resistance by recognition of pathogen-associated molecular patterns. In response to pathogen recognition, TLRs initiate both innate and adaptive immune responses which may help to develop immunomodulatory therapeutics for TLR associated diseases. Vaccination produces specific immunity in the animal's body towards pathogens. However, due to certain disadvantages of vaccines, (inactivation of attenuated pathogens into the virulent strains and weak immunogenicity of inactivated vaccines) there is a crucial need to develop the safe and effective therapeutic intervention. TLR ligands have been classified as a potential adjuvant against the infectious diseases in farm animals. TLR adjuvants induce both specific and nonspecific immune responses in chickens to combat several bacterial, viral and parasitic diseases. Therefore, the aim of this review was to explore the chicken TLR4 and their role in immune responses and disease resistance to develop disease resistance poultry breeds in future.

Synergy between Th1 and Th2 responses during Mycobacterium tuberculosis infection: A review of current understanding.

Abstract: Induction of Th1 (cell-mediated) immunity and associated production of IFN-γ by CD4+ T cells has been widely used as a marker of protective immunity against tuberculosis (TB). This is based on two assumptions. The first is the widely accepted view that Mycobacterium tuberculosis (Mtb), the causative agent of TB is an obligate intracellular pathogen, and the second is based on the Th1/Th2 paradigm, which posits that polarization of CD4+ T cells into type1 (cell-mediated) and type 2 (humoral) is central for proper induction of protective immunity against pathogens. However, almost all licensed vaccines currently in use are primarily anti-body based whether intracellular or extra-cellular. In addition, converging data from both animal models and humans indicate that the production of IFN-γ alone is not sufficient to confer protection against TB. In addition, a substantial body of the literature suggests that, in addition to Th1 cells, antibody classes and sub-classes are protective against TB. In a recent study, we have shown that there is a synergy between IFN-γ (cell-mediated) and IgA (humoral) in human population in an endemic setting. In this review, current data from both animal and human studies that support mixed Th1 and Th2 responses that are protective against Mtb and other pathogens are presented.

Inflammatory processes in obesity: focus on endothelial dysfunction and the role of adipokines as inflammatory mediators

Abstract: Obesity predisposes the affected individuals to several metabolic, inflammatory, cardiovascular and malignant pathologies and is a top risk factor for premature mortality. It is now well known that inflammation has a major causative role in obesity-associated disease development and that obesity favors the establishment of a pro-inflammatory milieu at the level of adipose microenvironment. These inflammatory signals result in a disruption of normal cellular-crosstalk between adipose and non-adipose components leading to an altered metabolic and immunological status and a dysfunctional phenotype. Abnormal secretion of adipokines - small adipose-derived signaling molecules - can further assist in the inflammatory processes to offset the adipose tissue towards a dysfunctional state. Although adipokines have been recognized as the link between obesity and pathogenesis, studies are needed to fully understand their mechanism of action and underscore their therapeutic value. Here, we have reviewed obesity-induced metabolic and immunological changes at the level of vasculature and emphasize on the importance of adipokines, particularly leptin, vaspin and visfatin, for their therapeutic relevance.

Psoriasis and cardiovascular disease: the elusive link

Abstract: Psoriasis, an autoimmune inflammatory disease, with its most common coexisting condition, psoriatic arthritis, seem to be more than just a local skin or joint disease, as evidence has accumulated over the years that it is associated with cardiovascular disease (CVD), which may confer an increased cardiovascular event and death rate. The data come mostly from observational studies and meta-analyses and indicate a potential pathogenetic link between these two systemic diseases, however definite proof of this detrimental relationship awaits further prospective studies. Newer anti-psoriatic biologic therapies seem to confer a cardiovascular benefit, but this needs future randomized controlled studies to confirm. All these intricate issues of a potential link between psoriasis and CVD are discussed and elaborated in this overview, in an attempt to shed further light on pivotal aspects of the association between psoriasis and CVD.

The complement system, toll-like receptors and inflammasomes in host defense: three musketeers' one target.

Abstract: The innate immune system-based recognition of the pathogens or their PAMPs initiates the pro-inflammatory immune response required for the maintenance of the homeostasis. The dysregulation of this innate immune response causes several diseases including sepsis, cancer and autoimmunity. However, pattern recognition receptors (PRRs) including toll-like receptors (TLRs), complement receptors (CRs) and NLRs of inflammasomes regulate both these processes of recognition of pathogens/PAMPs and their clearance. These three major components of the innate immune arm were studied independently/separately for a long time. Various studies have now shown that they work in close association and their crosstalk is required for the pathogen clearance via regulating the process of phagocytosis and mounting the controlled but potent immune response. The loss or inhibition of any of the three components affects the other in a positive/negative manner that can affect the immune process required for efficient host defense. The present review is designed to provide the current information on their evolution like the requirement of TLRs and inflammasomes for pathogen recognition even in the presence of complements system and their interaction during various immunological processes including phagocytosis, autophagy and inflammatory immune response.

The role of pro-inflammatory cytokines in lipid metabolism of metabolic diseases.

Abstract: Adipose tissue has been considered as a crucial source of certain pro-inflammatory cytokines; conversely, these pro-inflammatory cytokines are involved in regulating the proliferation and apoptosis of adipocytes, promoting lipolysis, inhibiting lipid synthesis and decreasing blood lipids, etc. In recent decades, extensive studies have indicated that pro-inflammatory cytokines play important roles in the development of lipid metabolism of metabolic diseases, including obesity, atherosclerosis, steatohepatitis and hyperlipoproteinemia. However, the involved pro-inflammatory cytokines types and the underlying mechanisms remain largely unknown. The "re-discovery" of cancer as a metabolic disorder largely occurred in the last five years. Although pro-inflammatory cytokines have been intensively investigated in cancer research, there are very few studies about the roles of pro-inflammatory cytokines in the lipid metabolism of cancer. In the current review, we provide an overview of the progress that has been made in the roles of different pro-inflammatory cytokines in lipid metabolism of metabolic diseases including cancer.

Blood coagulation: a powerful bactericidal mechanism of human innate immunity.

Abstract: Infection proliferates and disseminates rapidly and so innate immunity should react effectively and fast. Innate immunity mechanisms depend upon fluid dynamics and are different in compartments with slow (the tissues) and rapid (the bloodstream) liquid flow. In the tissues, coagulation initiated by clotting factors, platelets and erythrocytes, is prompt and effective mechanism of the first line of antibacterial defense. Resident macrophages, transmigrated neutrophils, monocytes, NETs and platelets are the second line of the defense. In the bloodstream the first line of innate immunity defense are erythrocytes that kill pathogens by oxygen, released from oxyhemoglobin (oxycytosis); the second line of the defense is coagulation that in case of overactivation may cause disseminated intravascular coagulation (DIC). Blood coagulation is the fastest mechanism of infection confinement and inactivation. It is the first and the last line of innate immunity defense and occurs both in the tissues and the bloodstream.

Rheumatoid arthritis: 'melting pot' of T helper subsets.

Abstract: Rheumatoid arthritis (RA) is an autoimmune disorder that affects joints associated with inflammation leading to poor quality of life. The phenotype of RA is distinct from osteoarthritis (OA), the degenerative joint disorder. The annual incidence of RA is approximately 4 in 10,000 individuals. Studies suggest dysregulated T cell activation in the initiation and progression of RA. Distinct RA-associated allelic variants encode molecules involved in T-cell activation pathways. Additionally, RA is also associated with aberrant regulation and function of T helper cells. The interplay of distinct T helper cell subsets adds complexity to the regulation of RA. In this review we have aimed to understand the currently known biology of different Th subsets in the context of an autoimmune disease like rheumatoid arthritis and find potential therapeutic approaches to tackle the disease through modulation of responsible T cells.

Many Ways-One Destination: Different Types of Neutrophils Death.

Abstract: Neutrophils constitute the most numerous populations of peripheral blood leukocytes, fulfilling the fundamental role in the development of the innate immune response. As the cells of the first line of defense, they guard the organism against the spread of pathogenic microorganisms. Neutrophils, similar to the other cells of the immune system, enter the path of death after fulfilling their biological function. Depending on the conditions that they are found in, they may undergo different types of cell death which requires the involvement of numerous signaling pathways. In this review article, we summarize the current state of knowledge regarding the different forms of neutrophil death, such as apoptosis, necrosis, necroptosis, autophagy, NETosis and pyroptosis.

ABO-Incompatible Liver Transplantation - A Review of the Historical Background and Results.

Abstract: ABO-incompatible liver transplantation (ABOi LT) using conventional immunosuppression has been considered a contraindication due to the high risk for antibody-mediated complications potentially resulting in graft loss. However, organ shortage has led to the development of anti-A/B antibody reducing immunosuppressive protocols which have made the outcome after living donor (LD) ABOi LT equivalent to that achieved with LD ABO-compatible (ABOc). The experience of deceased donor (DD) ABOi LT is however still limited. In this article, we discuss the historical background and the results after ABOi LT, in the setting of both LD and DD transplantation. We also discuss the remaining hurdles and future strategies in the breaching of the ABO barrier for LT.

Emerging roles of noncoding RNAs in T cell differentiation and functions in autoimmune diseases

Abstract: Noncoding RNA comprises of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that are abundantly present in mammalian transcriptome. These noncoding RNAs have been implicated in multiple biological processes through the regulation of gene expression. Each of these noncoding RNAs were found to have multiple genes targets. Emerging literature indicated the role of noncoding RNAs in shaping the immune responses which include immune cell development, helper T (Th) cell differentiation as well as maintenance of immune homeostasis by inducing the interplay between effector and regulatory T cells. Dysregulated expression and functions of noncoding RNAs in the immune system leads to aberrations in immune response that lead to the induction of tissue inflammation in autoimmune diseases. In this review, we summarize the current advances of post-transcriptional regulation, focusing on the functions of noncoding RNAs (miRNAs and lncRNAs) during differentiation of Th cells in tissue inflammation in autoimmune diseases.

Cancer Stem Cells Targeting; the Lessons from the Interaction of the Immune System, the Cancer Stem Cells and the Tumor Niche

Abstract: Failure of treatment strategies against cancers is a major issue engaging many scientists to investigate the possible resistance factors. Cancer stem cells (CSCs) subvert promising therapeutic methods by developing resistant cancers. These pluripotent cells are located in individual microenvironments called cancer niche. CSCs affect the immune cells and on the flip side, the immune cells in the cancer niche influence them. Thereby, the interaction between CSCs and immune cells in cancer niche needs to be clearly studied in order to develop novel efficient methods of immune-based cancer treatment. In this article, we review literature about the suggested methods of CSC escape from immune responses and the effect of cancer niche characteristics on the ability of CSCs to develop resistant strains of cancers. Moreover, we discuss immune-mediated tumor targeting methods and bring in trials focused on CSC targeted therapies. We aim to help physicians to reach a consensus about using CSC-targeted immunotherapy methods and emerge novel immunotherapy methods through disrupting the interaction between immune cells and CSCs in the tumor microenvironment.

Donor-specific antibodies following liver and intestinal transplantation: Clinical significance, pathogenesis and recommendations.

Abstract: A growing body of evidence shows that donor-specific antibodies (DSA) are associated with rejection and allograft failure following both liver and intestinal transplantation. However, data have clearly shown that not all DSA are injurious. The reasons for this remain unclear but appear to be multifactorial, impacted by clinical factors such as immunosuppression and infection as well as immunologic factors such as HLA expression and donor-specific antibodies affinity. Establishing a diagnosis of antibody-mediated rejection (AMR) remains clinically challenging, especially given that AMR can present as either acute or chronic graft dysfunction. These observations highlight the need for a better understanding of the immune mechanisms by which DSA and AMR contribute to rejection and allograft failure. This review focuses on current knowledge of DSA and AMR in liver and intestinal transplant recipients and specifically highlights the clinical impact, prevalence, and pathogenesis.

Asthma: An Undermined State of Immunodeficiency.

Abstract: Asthma is a heterogeneous chronic respiratory disease characterized by an increased burden of infections. Respiratory tract infections associated with an increased risk for asthma especially when occurring in the first months of life, also represent the most common cause of asthma exacerbations. The association between asthma and the increased frequency of infections and microbiota dysbiosis might be explained by a common mechanism, such as an underlying immune system defect. Apart from the well-established association between primary immunodeficiencies and asthma, several alterations in the immune response following infection have also been observed in asthmatic patients. An impairment in lung epithelial barrier integrity exists and is associated with both an increased susceptibility to infections and the development of asthma. Asthmatic patients are also found to have a deficient interferon (IFN) response upon infection. Additionally, defects in Toll-like receptor (TLR) signaling are observed in asthma and are correlated with both recurrent infections and asthma development. In this review, we summarize the common pathophysiological background of asthma and infections, highlighting the importance of an underlying immune system defect that predispose individuals to recurrent infections and asthma.

Emerging Roles of Th9 Cells as an Anti-tumor Helper T Cells.

Abstract: The newly discovered Th9 cells are the distinct subset of CD4+ T helper (Th) cells, which are involved in various pathophysiological conditions of an immune response. In addition to its role in allergic inflammation and elimination of extracellular pathogens, Th9 cells were found to play a key role in inducing anti-tumor immune response. Precisely, the anti-tumor functions of Th9 cells were found to be superior as compared to Th1 and other Th subsets. Th9 cells eliminate tumors via activating innate and adaptive immune cells, and in particular, generating a profound effector cytotoxic T lymphocyte (CTL) response against neo antigens. In addition, it was proposed that Th9 cells were found to induce effector functions of innate cells like dendritic cells, mast cells and NK cells, which further promote a robust anti-tumor immune response. In this review, we highlight the recent advances in differentiation and functions of Th9 cells in anti-tumor immunity.

Regulatory T cells as therapeutic targets and mediators

Abstract: With the advent of the concept of dominant tolerance and the subsequent discovery of CD4+ regulatory T cells expressing the transcription factor FOXP3 (Tregs), almost all productive as well as nonproductive immune responses can be compartmentalized to a binary of immune effector T cells and immune regulatory Treg populations. A beneficial immune response warrants the timely regulation by Tregs, whereas a nonproductive immune response indicates insufficient effector functions or an outright failure of tolerance. There are ample reports supporting role of Tregs in suppressing spontaneous auto-immune diseases as well as promoting immune evasion by cancers. To top up their importance, several non-immune functions like tissue homeostasis and regeneration are also being attributed to Tregs. Hence, after being in the center stage of basic and translational immunological research, Tregs are making the next jump towards clinical studies. Therefore, newer small molecules, biologics as well as adoptive cell therapy (ACT) approaches are being tested to augment or undermine Treg responses in the context of autoimmunity and cancer. In this brief review, we present the strategies to modulate Tregs towards a favorable clinical outcome.

Calcium Signaling Commands Phagosome Maturation Process.

Abstract: Phagosome-lysosome (P-L) fusion is one of the central immune-effector responses of host. It is known that phagosome maturation process is associated with numerous signaling cascades and among these, important role of calcium (Ca2+) signaling has been realized recently. Ca2+ plays key roles in actin rearrangement, activation of NADPH oxidase and protein kinase C (PKC). Involvement of Ca2+ in these cellular processes directs phagosomal maturation process. Some of the intracellular pathogens have acquired the strategies to modulate Ca2+ associated pathways to block P-L fusion process. In this review we have described the mechanism of Ca2+ signals that influence P-L fusion by controlling ROS, actin and PKC signaling cascades. We have also discussed the strategies implemented by the intracellular pathogens to manipulate Ca2+ signaling to consequently subvert P-L fusion. A detail study of factors associated in manipulating Ca2+ signaling may provide new insights for the development of therapeutic tools for more effective treatment options against infectious diseases.

How does blood coagulation/neutrophils shape innate immunity and uncontrolled inflammation to autoimmune disease?

Abstract: Continuous challenges of microbes, non-living entities or occasional trauma/injuries shape host defense systems at various hierarchical levels. The primary defense of the host is anatomical and biochemical barriers that continuously work to protect the host from common and pathogenic microbes. This specific defense barrier consists of various cell-types expressing molecular sensors that sense numerous pathogenspecific molecular signatures and activate complex signaling pathways for the synthesis of inflammatory cytokines and subsequently facilitate the elimination of invading microbes. Dysregulation of signaling pathways may lead to the heightened production of inflammatory cytokines that culminate to cause autoimmune diseases. This issue of International Reviews of Immunology focuses on innate immune defenses triggered through blood clotting and blood cells known as neutrophils. This issue also describes an autoimmune disease and its impact on various physiological systems such as connective tissue and blood vascular system (Figure 1). The wound or injury to the host not only causes pain and loss of blood, but it also opens the gates for microbes to establish themselves, colonize and cause disease. To overcome such multidimensional threats, the mammalian host evolved a unique, biochemically complex phenomenon known as blood clotting. Blood clotting is rapidly initiated through sequential activation of serine proteases at the wound site to convert fibrinogen (a soluble protein) to fibrin (insoluble network) and is further stablized by several other blood factors to stop blood loss and make a physical barrier against the invading microbes. The first review article in this issue by Minasyan et al. discusses the importance of blood clotting in innate immune defense, particularly how blood clots develop anti-bacterial responses by various mechanisms (Figure 1). The neutrophils are predominant cell-type in white blood cells and the first responders during infection, injuries or any homeostatic changes taking place within the host. Neutrophils are ephemeral and depend on physiological changes (due to infection, cancer or autoimmune diseases); the death signals to neutrophils are unique. The second review article in this issue, by Browska et al., focuses on different signaling events converging to the neutrophils for neutrophils death under various extrinsic and intrinsic stimuli. The authors also discuss the readout of these death pathways that may help in the development of diagnostics for different diseases. Additionally, manipulation of death signaling pathways may also be helpful in altering the disease condition. Since the field is in its infancy, the review article may be useful to basic and translational researchers working on interfaces of innate immunobiology and applying the knowledge to the development of innate immune parameter-based diagnostic or therapeutics (Figure 1). Psoriasis is primarily a skin autoimmune disease, and the severity of this disease is influenced by genetics and environment factors. This disease not only affects skin, but it also targets joints and the cardiovascular system, causing psoriatic arthritis and cardiovascular disease (CVD). The third review article in this issue by Manolis et al. discusses the beneficial effects of biomolecules used in therapy of psoriasis to psoriatic CVD. However, the authors suggest conducting large number patient-based studies before concluding its beneficial effects to CVD in psoriasis patients. This article is useful to broad readers working in clinics and conducting research in fundamental immunology, autoimmunity and associated fields (Figure 1).

Donor-specific anti-HLA antibodies by solid phase immunoassays: advantages and technical concerns.

Abstract: The detection of donor-specific antibodies (DSAs) is a cornerstone in the immunological risk assessment prior to organ transplantation. The detection methods have developed rapidly during the last decade, and the evidence for clinical interpretation of results obtained by solid phase immunoassays (SPI) is slowly accumulating. Nevertheless, technical limitations and theoretical concerns still mean that "expert opinions" govern clinical decision-making when results of bead-based arrays are applied in immunological risk assessment prior to transplantation. This article underlines the prognostic value of SPI in the immunized recipient of an organ transplant while cautioning uncritical clinical interpretation of mean fluorescence intensity (MFI) as a quantitative parameter in organ transplantation based on documented as well as theoretical shortcomings of the method. The role of SPI-based detection of anti-HLA antibodies in clinical transplantation diagnostics is summarized and put into perspective of the Sensitization in Transplantation: Assessment of Risk (STAR) working group report 2017.

Novel Methods to Improve the Efficiency of Radioimmunotherapy for Non-Hodgkin Lymphoma

Abstract: Radioimmunotherapy (RIT) is a novel strategy for treating non-Hodgkin lymphoma (NHL). Several studies have shown the promising results of using RIT in NHL, which have led to FDA approval for two RIT agents in treating low grade NHL. In spite of these favorable results in low-grade NHL, most of the aggressive or relapsed/refractory NHL subjects experience relapses following RIT. Although more aggressive treatments such as myeloablative doses of RIT followed by stem cell transplantation appear to be able to provide a longer survival for some patients these approaches are associated with significant treatment-related adverse events and challenging to deliver in most centers. Therefore, it seems reasonable to develop treatment approaches that enhance the efficiency of RIT, while reducing its toxicity. In this paper, novel methods that improve the efficiency of RIT and reduce its toxicity through various mechanisms are reviewed. Further clinical development of these methods could expand the NHL patient groups eligible for receiving RIT, and even extend the use of RIT to new indications and disease groups in future.

Immunity and its role in white plague and obesity.

Abstract: Multilayers of host immunity ensure quick, efficient and specific elimination of microbial pathogens without perturbing commensal microbes and host immune homeostasis. The elimination of microbes is accomplished by various cellular and biochemical processes. These processes result in the formation of pores in the microbial surface, phagocytosis, masking the pathogenic molecules by host defense molecules or initiation of programed cell death of infected host cells. The majority of microbes are cleared by one or several processes triggered through sensing and a complex cascade of signaling to develop relevant effector immune responses. This issue of International Reviews of Immunology focuses on key immunological processes of innate immunity that lead to inflammation, resulting in the elimination of microbial infection. Another article also discusses the correlation among obesity, inflammation, and obesity-associated metabolic diseases and interactions of specialized immune cells with Mycobacterium tuberculosis (Fig. 1). Natural immunity consists of various physical, biochemical, and cellular systems. These systems collectively inactivate or eliminate microbes, directly or indirectly through the recruitment of proteins known as complements on microbial surface, facilitating phagocytosis and/or inducing inflammation for the recruitment of professional immune cells at the site of infection. The first review article of this issue by Vijay Kumar discusses the complement system, Toll-like receptor family sensors, intracellular inflammasome pathway, and the crosstalk among them in terms of sensing and signaling. This article provides a deep insight into these phenomenon and

T cell subtypes and its therapeutic potential in autoimmune diseases and cancer.

Abstract: T cell subsets are the type of white blood cells tailoring specific immunity against different infections, the transformed cells, and perform an essential role in maintaining immune homeostasis. Ba...

Approaches for deciphering the molecular basis of disease and its translational benefits.

Abstract: A multidisciplinary approach among various disciplines of sciences is essential for gaining a deeper insight of host immunity. This approach also provides an opportunity to manipulate the defense s...

Donor-specific antibodies and organ transplantation: a dangerous mix.

Abstract: Scientific and technical advancements provided a deeper insight into the cellular and molecular processes of the host immunity and its clinical significance in various aspects of human health, incl...

Host defense: basic, disease and translational biology.

Abstract: To defend against microbial invasion, the mammalian host develops a precisely regulated and complex network of cells and molecules that are also capable of discriminating among self, nonself, or missing-self. This is host immune system. The immune system is comprised of two interlinked and dynamic systems known as the innate and adaptive immune systems, and these consist of various cell-types and effector molecules to eliminate diverse threats to the host. The fundamental understanding of cellular and molecular processes adopted by the host is essential for understanding the pathogenesis and development of therapeutic interventions of disease. This issue of International Reviews of Immunology discusses the signaling events that take place during phagocytosis, immune exacerbation leading to respiratory disease, and developments in immunotherapy for blood cancer. Phagocytosis, or “cellular eating,” is mediated by various phagocytic cells of the host and plays a crucial role in various immune and nonimmune processes to maintain physiological homeostasis. The nonimmune process is required for a cleaning of the host by removing dead, old, necrotic, or traumatized cells or cell debris, and also plays an important role in developmental processes of the host. On the other hand, immunological processes are mediated by specialized innate and adaptive phagocytic cells, such as neutrophils, dendritic cells, monocytes, tissue macrophages, and B cells. The key function of these phagocytic cells is eliminating microbial pathogens, inducing inflammation and processing and presentation of microbial antigens to the adaptive immune cells. Phagocytosis is a complex molecular process and the first review article of this issue by Pradhan et al. describes the molecular mechanism of one phagocytic event known as “phagosome maturation,” in terms of phagosome and lysosome fusion, the role of calcium ions to trigger the cascade of signaling, and how microbial pathogens subvert this signaling to establish an infection. The article also provides insight into manipulation of calcium ion signaling to combat various infectious disease (Figure 1). Asthma is an obstructive lung disease characterized by the thickening of airway walls and an overproduction of mucous leading to difficulty in breathing. The asthmatic condition could be triggered by environmental factors, microbial infection, or it is associated with the host genetics. Immunologically, it develops due to an excessive presence of eosinophils and a strong T helper type 2 response through the production of cytokines such as interleukin (IL)-4, IL-5, and IL-13. The second review article in this issue, by Evangelos et al., discusses the correlation between lung infection and asthma in the light of innate immune sensors, particularly toll-like receptors (Figure 1). Non-Hodgkin Lymphoma (NHL) is a malignant disease of lymphocytes originating from lymphatic tissue.