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Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections, PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis, and treatment of the different PADs. [ABSTRACT FROM AUTHOR]

Recombinant Mycobacterium bovis BCG vaccines (rBCG) were first developed in the 1990s as a means of expressing antigens from multiple pathogens. This review examines the key structural factors of recombinant M. bovis that influence the expression of the heterologous antigens and the generation of genetic and functional stability in rBCG, which are crucial for inducing strong and lasting immune responses. The fundamental aim of this paper is to provide an overview of factors that affect the expression of recombinant proteins in BCG and the generation of the immune response against the target antigens, including mycobacterial promoters, location of foreign antigens, and stability of the vectors. The reporter systems that have been employed for evaluation of these molecular features in BCG are also reviewed here. [ABSTRACT FROM AUTHOR]

No consensus has been reached on how to determine if an immune response has been detected based on raw data from an ELISPOT assay. The goal of this paper is to enable investigators to understand and readily implement currently available methods for response determination. We describe empirical and statistical approaches, identifying the strengths and limitations of each approach to allow readers to rationally select and apply a scientifically sound method appropriate to their specific laboratory setting. Five representative approaches were applied to data sets from the CIMT Immunoguiding Program and the response detection and false positive rates were compared. Simulation studies were also performed to compare empirical and statistical approaches. Based on these, we recommend the use of a non-parametric statistical test. Further, we recommend that six medium control wells or four wells each for both medium control and experimental conditions be performed to increase the sensitivity in detecting a response, that replicates with large variation in spot counts be filtered out, and that positive responses arising from experimental spot counts below the estimated limit of detection be interpreted with caution. Moreover, a web-based user interface was developed to allow easy access to the recommended statistical methods. This interface allows the user to upload data from an ELISPOT assay and obtain an output file of the binary responses. [ABSTRACT FROM AUTHOR]

The currently accepted paradigm for the primary T cell response is that effector T cells commit to autonomous developmental programs. This concept is based on several experiments that have demonstrated that the dynamics of a T cell response is largely determined shortly after antigen exposure and that T cell dynamics do not depend on the level and duration of antigen stimulation. Another experimental study has also shown that T cell responses are robust to variations in antigen-specific precursor frequency. Various mathematical models have corroborated the first result that programmed T cell responses are insensitive to the level of antigen stimulation. However, this paper proposes that programmed responses do not entirely explain the robustness of T cell dynamics to variations in precursor frequency. This work studies the hypothesis that the dynamics of a T cell response may also be governed by a feedback loop involving adaptive regulatory cells rather than by intrinsic developmental programs. We formulate two mathematical models based on T cell developmental programs. In one model, effector cells undergo a fixed number of divisions before dying. In the second model, effector cells live for a fixed time during which they may divide. The study of these models suggests that developmental programs are not sufficiently robust as they produce an immune response that directly scales with precursor frequencies. Consequently, we derive a third model based on the principle that adaptive regulatory T cells develop in the course of an immune response and suppress effector cells. Our simulations show that this feedback mechanism responds robustly over a range of at least four orders of magnitude of precursor frequencies. We conclude that the proliferation program paradigm does not entirely capture the observed robustness of T cell responses to variations in precursor frequency. We propose an alternative mechanism by which the primary T cell response is governed by an emergent group dynamic and not by individual T cell programs. [ABSTRACT FROM AUTHOR]

Abstract  Previous diagnosing methods based on agglutination have a limitation in view of emergency and point-of-care diagnoses due to the requirement of large scale equipments and much agglutination time. In this paper, we propose a low cost microfluidic lab-on-a-chip for more efficient detection of agglutination. In the present lab-on-a-chip, two inlet microwells, flow guiding microchannels, chaotic micromixer and reaction microwell are fully integrated. Mold inserts for the lab-on-a-chip were manufactured by UV photolithography and nickel electroplating process. The complete lab-on-a-chip was realized by the microinjection molding of cyclic olefin copolymer and the subsequent thermal bonding. The improved serpentine laminating micromixer, developed by our group, integrated in the lab-on-a-chip showed the high-level of chaotic mixing, thereby enabling us to get a reliable mixing of sample and reagent. The performance of the fabricated lab-on-a-chip was demonstrated by agglutination experiments with simulated bloods of 10 μl and simulated sera of 10 μl. The results of agglutination inside the reaction microwell were clearly read by means of the level of light transmission. The present microfluidic lab-on-a-chip could be widely applied to various clinical diagnostics based on agglutination tests. [ABSTRACT FROM AUTHOR]

The identification of pathogen-associated molecular patterns, conserved microbial structures that act on Toll-like receptors, has led to a novel avenue of investigation aimed at developing a new generation of cancer immunotherapies. Ligation of Toll-like receptors results in the induction of robust immune responses that may be directed against tumor-associated antigens. Recent data suggest that such strategies may result in enhanced antitumor immunity. Nonetheless, as clinically effective immunotherapy for cancer remains a somewhat distant goal, attention has shifted toward multimodality approaches to cancer therapy, sometimes combining novel immune interventions and conventional treatments. The traditional view of radiation therapy as immunosuppressive has now been challenged, prompting a re-evaluation of its potential as an adjunct to immunotherapy. Radiation therapy can enhance the expression of tumor-associated antigens, induce immune-mediated targeting of tumor stroma, and diminish regulatory T cell activity. Recent evidence suggests that radiation therapy may also activate effectors of innate immunity through TLR-dependent mechanisms, thereby augmenting the adaptive immune response to cancer. In this paper, we will review evidence for enhanced tumor-directed immunity resulting from radiation exposure and early promising data suggesting synergistic effects of radiation and TLR-targeted immunotherapies.Oncogene (2008) 27, 200–207; doi:10.1038/sj.onc.1210909 [ABSTRACT FROM AUTHOR]

The article presents research highlights from the field of T cell memory based on the original research paper "Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow," by K. Tokoyoda et al. that was published in the May 7, 2009 issue of "Immunity." Subjects discussed include antigen-specific memory T cells in mice, immune responses, and the role of interleukin-7 (IL-7) in expressing stromal cells.