CXCL13 is a constitutively expressed chemokine that controls migration of immune cells to lymphoid follicles. Previously, we found CXCL13 mRNA levels increased in rhesus macaque spleen tissues during AIDS. This led us to examine the levels and locations of CXCL13 by detailed in situ methods in cynomolgus macaque lymphoid and intestinal tissues. Our results revealed that there were distinct localization patterns of CXCL13 mRNA compared to protein in germinal centers. These patterns shifted during the course of simian immunodeficiency virus (SIV) infection, with increased mRNA expression within and around follicles during AIDS compared to uninfected or acutely infected animals. Unexpectedly, CXCL13 expression was also found in abundance in Paneth cells in crypts throughout the small intestine. Therefore, we expanded our analyses to include chemokines and antimicrobial peptides (AMPs) not previously demonstrated to be expressed by Paneth cells in intestinal tissues. We examined the expression patterns of multiple chemokines, including CCL25, as well as α-defensin 6 (DEFA6), β-defensin 2 (BDEF2), rhesus θ-defensin 1 (RTD-1), and Reg3γ in situ in intestinal tissues. Of the 10 chemokines examined, CXCL13 was unique in its expression by Paneth cells. BDEF2...

The eye has been at the forefront of translational gene therapy largely owing to suitable disease targets, anatomic accessibility, and well-studied immunologic privilege. These advantages have fostered research culminating in several clinical trials and adeno-associated virus (AAV) has emerged as the vector of choice for many ocular therapies. Pre-clinical and clinical investigations have assessed the humoral and cellular immune responses to a variety of naturally occurring and engineered AAV serotypes as well as their delivered transgenes and these data have been correlated to potential clinical sequelae. Encouragingly, AAV appears safe and effective with clinical follow-up surpassing 5 years in some studies. As disease targets continue to expand for AAV in the eye, thorough and deliberate assessment of immunologic safety is critical. With careful study, the development of these technologies should concurrently inform the biology of the ocular immune response.

After a half-century of mouse-dominated research, human immunology is making a comeback. Informed by mouse studies and powered by new techniques, human immune research is both advancing disease treatment and providing new insights into basic biology.

The central nervous system (CNS) historically has been considered an immune-privileged organ, lacking a lymphatic system and shielded from the circulatory system by the blood-brain barrier. Microglia are an abundant portion of the CNS cell population, comprising 5% to 20% of the total glial cell population, and are as numerous as neurons. A crucial function of microglia is the ability to generate significant innate and adaptive immune responses. Microglia are involved in first line innate immunity of the CNS. Proper antigen presentation is critical in the generation of specific, durable responses by the adaptive immune system, and requires interaction between the T cell receptor and processed antigen peptide presented on major histocompatibility complex (MHC) molecules by the antigen presenting cells. Microglia also have a large regulatory role in CNS immunity. Histopathologic studies of glioma tissue have consistently shown high levels of infiltrating microglia. Microglia are also localized diffusely throughout the tumor, rather than to the areas of necrosis, and phagocytosis of glioma cells or debris by microglia is not observed. Recent evidence indicates that glioma-infiltrating microglia/macrophages might be promoting tumor growth by facilitating immunosuppression of the tumor microenvironment. When activated...

The mucosal immune system typically exists in a state of active tolerance to food antigens and commensal bacteria. Tolerance to food proteins is induced in part by dendritic cells residing in the intestinal mucosa and implemented by regulatory T cells. Food allergy occurs when immune tolerance is disrupted and a sensitizing immune response characterized by food-specific IgE production occurs instead. Experimental food allergy in mice requires use of adjuvant or exploitation of alternate routes of sensitization to induce allergic sensitization, and can aid in understanding the mechanisms of sensitization to food allergens and the pathophysiology of gastrointestinal manifestations of food allergy. Recent work in the understanding of mucosal immunology of tolerance and allergy in the gastrointestinal tract will be discussed.

Conventional vaccines have been extremely successful in preventing infections by pathogens expressing relatively conserved antigens through antibody‐mediated effector mechanisms. Thanks to vaccination some diseases have been eradicated and mortality due to infectious diseases has been significantly reduced. However, there are still many infections that are not preventable with vaccination, which represent a major cause of mortality worldwide. Some of these infections are caused by pathogens with a high degree of antigen variability that cannot be controlled only by antibodies, but require a mix of humoral and cellular immune responses. Novel technologies for antigen discovery, expression and formulation allow now for the development of vaccines that can better cope with pathogen diversity and trigger multifunctional immune responses. In addition, the application of new genomic assays and systems biology approaches in human immunology can help to better identify vaccine correlates of protection. The availability of novel vaccine technologies, together with the knowledge of the distinct human immune responses that are required to prevent different types of infection, should help to rationally design effective vaccines where conventional approaches have failed.

Iron status and immune response become impaired in situations that involve chronic inflammation, such as obesity or aging. Little is known, however, about the additional burden that obesity may place on the iron status and immune response in the elderly. This question is relevant given the rising numbers of elderly obese (BMI >30 kg/m2) individuals and the high prevalence of iron deficiency worldwide. Iron is necessary for proper function of both the innate and adaptive immune system. Hepcidin, a peptide hormone that regulates cellular iron export, is essential for the maintenance of iron homeostasis. Therefore, since immune cells require iron for proper function hepcidin may also play an important role in immune response. In this review, we summarize the evidence for hepcidin as a link between the fields of gerontology, obesity, iron biology, and immunology. We also identify several gaps in knowledge and unanswered questions pertaining to iron homeostasis and immunity in obese populations. Finally, we review studies that have shown the impact of weight loss, focusing on calorie restriction, iron homeostasis, and immunity. These studies are important both in elucidating mechanistic links between obesity and health impairments and identifying possible approaches to target immune impairment and iron deficiency as comorbidities of obesity.

On a population-based level, the incidence of reactive arthritis (ReA) is 0.6–27/100,000. The definition of ReA varies and its pathogenesis is not yet clear. Attempts in basic immunology to suggest hypotheses for proliferation of forbidden B cell clones, molecular mimicry, and involvement of cross-reactive antibodies are helpful but not sufficient. Importantly, for the clinical diagnosis of the preceding infection, serology is widely used. Unfortunately, the accuracy of associations between serologic findings and clinical conclusions is plagued by poor standardization of methods. So far, few attempts have been done to examine the pitfalls of different approaches. Here, we review several serologic techniques, their performance and limitations. We will focus on serology for Yersinia, Campylobacter, Salmonella, Shigella, and Chlamydia trachomatis because these bacteria have a longer history of being associated with ReA. We also address controversies regarding the role of serology for some other bacteria linked to autoimmune disorders.

Bioinformatics includes a suite of methods, which are cheap, approachable, and many of which are easily accessible without any sort of specialized bioinformatic training. Yet, despite this, bioinformatic tools are under-utilized by immunologists. Herein, we review a representative set of publicly available, easy-to-use bioinformatic tools using our own research on an under-annotated human gene, SCARA3, as an example. SCARA3 shares an evolutionary relationship with the class A scavenger receptors, but preliminary research showed that it was divergent enough that its function remained unclear. In our quest for more information about this gene – did it share gene sequence similarities to other scavenger receptors? Did it contain conserved protein domains? Where was it expressed in the human body? – we discovered the power and informative potential of publicly available bioinformatic tools designed for the novice in mind, which allowed us to hypothesize on the regulation, structure, and function of this protein. We argue that these tools are largely applicable to many facets of immunology research.

It is becoming increasingly clear that glycosylation plays important role in intercellular communication within the immune system. Glycosylation-dependent interactions are crucial for the innate and adaptive immune system and regulate immune cell trafficking, synapse formation, activation, and survival. These functions take place by the cis or trans interaction of lectins with glycans. Classical immunological and biochemical methods have been used for the study of lectin function; however, the investigation of their counterparts, glycans, requires very specialized methodologies that have been extensively developed in the past decade within the Glycobiology scientific community. This mini-review intends to summarize the available technology for the study of glycan biosynthesis, its regulation and characterization for their application to the study of glycans in immunology.

Viral immunology is a rapidly evolving field. Major strides have been made in our understanding of innate and adaptive immune responses to viruses, largely based on highly reductionistic animal infection models, but more recently in humans, with validation that fundamental immunological concepts do in fact translate into clinical science well. From these studies has emerged an appreciation of the enormous complexity of the immune response to viral infections as well as the diverse array of strategies developed by viruses to deal with immune detection. In this review, we highlight some of the major challenges we face in unraveling this complexity and summarize current efforts under way to improve the efficacy of viral vaccines.

No method has been reported to predict, even approximately, the impact of mild-to-moderate changes in several immunological parameters on resistance to infection. The ability to make such predictions would be useful in risk assessment. In addition, equations that predict host resistance on the basis of changes in components of a complex biological system (the immune system) would fulfill one of the major goals of systems biology. In this study, multiple machine learning classification methods were used to predict the effects of a series of drugs and chemicals on host resistance to Listeria monocytogenes in mice on the basis of changes in several holistic immunological parameters. A data set produced under the sponsorship of the National Toxicology Program (NTP) was used in this study. The NTP data set was found to have a high percentage of missing data and to be noisy (probably due to the intrinsically stochastic nature of immune responses). Data preprocessing steps were used to mitigate these problems. In evaluating the machine learning classifiers, we first randomly partitioned the NTP data set into 10 subsets. Each time, we used nine subsets of the data to train the machine learning classifiers, and the remaining single subset to predict outcomes with regard to host resistance. This process was repeated until all 10 combinations of the 9-1 split of the subsets have been tested. The best of the classifiers predicted host resistance outcome correctly for 94.7% of cases...

One of the hallmarks of the adaptive immune system is the specificity of B and T cell receptors. Thanks to somatic recombination, a large repertoire of receptors can be generated within an individual that guarantee the recognition of a vast number of antigens. Monoclonal antibodies have limited applicability, given the high degree of diversity among these receptors, in BCR and TCR monitoring. Furthermore, with regard to cancer, better characterization of complex genomes and the ability to monitor tumor-specific cryptic mutations or translocations are needed to develop better tailored therapies. Novel technologies, by enhancing the ability of BCR and TCR monitoring, can help in the search for minimal residual disease during hematological malignancy diagnosis and follow-up, and can aid in improving bone marrow transplantation techniques. Recently, a novel technology known as next generation sequencing has been developed; this allows the recognition of unique sequences and provides depth of coverage, heterogeneity, and accuracy of sequencing. This provides a powerful tool that, along with microarray analysis for gene expression, may become integral in resolving the remaining key problems in hematology. This review describes the state of the art of this novel technology...

Ubiquitination (Ubiquitylation) is a common protein modification that regulates a multitude of processes within the cell. This modification is typically accomplished through the covalent binding of ubiquitin to a lysine residue onto a target protein and is catalyzed by the presence of three enzymes: an activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin-protein ligase (E3). In recent years, ubiquitination has risen as a major signaling regulator of immunity and microbial pathogenesis in the mammalian system. Still, little is known about how ubiquitin relates specifically to vector immunology. Here, we provide a brief overview of ubiquitin biochemistry and describe how ubiquitination regulates immune responses in arthropods of medical relevance. We also discuss scientific gaps in the literature and suggest that, similar to mammals, ubiquitin is a major regulator of immunity in medically-important arthropods.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2011 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology: 1) immunology; 2) epigenetics; 3) comparative placentation; 4) trophoblast differentiation; 5) stem cells.

Various T cells and macrophages as well as cytokines are involved in the immunopathogenesis of tuberculosis (TB). A better understanding of immunology of TB can not only lead to the discovery of new immunodiagnostic tools, accelerate and facilitate the assessment of new therapeutic methods, but also find new treatment regimens. In this highlight topic we cover the latest developments in the role of T cells, macrophages, Natural killer (NK) cells, invariant NK T (iNKT) cells and γδ T cells with TB infection. Histologically, TB displays exudative inflammation, proliferative inflammation and productive inflammation depending on the time course. T cells first recognize antigen within the mycobacterially-infected lung, and then activate, differentiate, but the first T cell activation occurs in the draining lymph nodes of the lung. When protective T cells reach sufficient numbers, they can stop bacterial growth. Except for T cells, neutrophils also participate actively in defense against early-phase TB. NK cells are innate lymphocytes which are a first line of defense against mycobacterial infection. Human NK cells use the NKp46, NCRs and NKG2D receptors to lyse Mycobacterium TB-infected monocytes and alveolar macrophages. NK cells produce not only interferon-γ...

Recent advances that have been made in our understanding of cancer biology and immunology show that infiltrated immune cells and cytokines in the tumor microenvironment may play different functions that appear tightly related to clinical outcomes. Strategies aimed at interfering with the cross-talk between microenvironment tumor cells and their cellular partners have been considered for the development of new immunotherapies. These novel therapies target different cell components of the tumor microenvironment and importantly, they may be coupled and boosted with classical treatments, such as radiotherapy. In this work, we try to summarize recent data on the microenvironment impact of radiation therapy, from pre-clinical research to the clinic, while taking into account that this new knowledge will probably translate into indication and objective of radiation therapy changes in the next future.