Basic Immunological Principles Research Articles

Design and evaluation of an immunology and pathology course that is tailored to today's dentistry students.

Curricular reform provides new opportunities to renovate important pillars of the dentistry curriculum, such as immunology and pathology, with novel approaches that appeal to new generations of students. When redesigning a course that integrates both immunology and pathology at the level that provides dentistry students with sustainable knowledge that is useful for their entire career, several challenges must be met. The objective of the present study was to describe the considerations involved in the design phase of such a new course. First, the course should be compatible with the new view on the incorporation of more active learning and teaching methods. Practically, this means that the course design should contain fewer lectures and more seminars and tutorials, where the students have fewer contact hours and actively engage in using recently acquired knowledge within a contextual background. A mandatory session of team-based learning provides opportunities to apply knowledge in combination with academic reasoning skills, teamwork, and communication. Second, for a 4-week course, choices must be made: students will not become immunologists nor pathologists in such a short period. A governing principle for this course's design is that it should be based on understanding the basic principles of immunology and pathology. The ultimate goal for the students is to make the course immuno-logical and patho-logical, challenging them to reach a next level but clearly without oversimplification. Part of the course design should allow room for students to further study an immunological topic of their own choice, thereby contributing to their immunological curiosity and to their academic development. Third, to make it tailored to a new generation of dentists, examples from the field of dentistry are actively integrated in all aspects of the course. Finally, the era of ChatGPT provides novel opportunities to use generative artificial intelligence (AI) tools in the learning process, but it demands critical thinking of how to use it in a newly designed course. A mid-course evaluation revealed that students acknowledged that immunology and pathology were presented as an integrated course. The final course evaluation endorsed the use of these various educational methods. These methods proved to be appropriate and logical choices for reaching the learning goals of the course.

An Introduction to Relevant Immunology Principles with Respect to Oral Vaccines in Aquaculture.

Vaccines continue to play an enormous role in the progression of aquaculture industries worldwide. Though preventable diseases cause massive economic losses, injection-based vaccine delivery is cost-prohibitive or otherwise impractical for many producers. Most oral vaccines, which are much cheaper to administer, do not provide adequate protection relative to traditional injection or even immersion formulas. Research has focused on determining why there appears to be a lack of protection afforded by oral vaccines. Here, we review the basic immunological principles associated with oral vaccination before discussing the recent progress and current status of oral vaccine research. This knowledge is critical for the development and advancement of efficacious oral vaccines for the aquaculture industry.

Uveitis: Molecular Pathogenesis and Emerging Therapies.

The profound impact that vision loss has on human activities and quality of life necessitates understanding the etiology of potentially blinding diseases and their clinical management. The unique anatomic features of the eye and its sequestration from peripheral immune system also provides a framework for studying other diseases in immune privileged sites and validating basic immunological principles. Thus, early studies of intraocular inflammatory diseases (uveitis) were at the forefront of research on organ transplantation. These studies laid the groundwork for foundational discoveries on how immune system distinguishes self from non-self and established current concepts of acquired immune tolerance and autoimmunity. Our charge in this review is to examine how advances in molecular cell biology and immunology over the past 3 decades have contributed to the understanding of mechanisms that underlie immunopathogenesis of uveitis. Particular emphasis is on how advances in biotechnology have been leveraged in developing biologics and cell-based immunotherapies for uveitis and other neuroinflammatory diseases.

Erratum to: Basic principles of replication and immunology of SARS-CoV-2

Erratum to: Basic principles of replication and immunology of SARS-CoV-2

How Basic Immunological Principles May Instruct the Design of a Successful HIV-Type 1 Vaccine.

This article is dedicated to Dr. Peter Doherty. While Peter continues to make groundbreaking discoveries in the field of immunology, he also provides outstanding scientific mentorship to his trainees. Here we contemplate our past training with Peter, Peter's teachings of basic immunological principles, and how basic principles may instruct the design of a successful human immunodeficiency virus-type 1 vaccine.

Elispots and Ex Vivo Expansion of FVIII-Specific T-Cell Clones Confirm Specificity of CD4+ T-Cell Responses to Self-FVIII in Healthy Non-Hemophilic Blood Donors

The existence of natural antibodies recognizing endogenous factor VIII (FVIII) and of FVIII-specific CD4+ T-cell responses in some healthy, non-hemophilic blood donors has been appreciated for >20 years. The Conti-Fine group measured CD4+ T-cell proliferation following in vitro stimulation with FVIII protein or synthetic FVIII peptides. More recently, FVIII-specific CD4+ T-cell lines were expanded from PBMCs isolated from large blood volumes donated by healthy individuals, and estimates of specific precursor frequency (~2/million CD4+ T cells) were calculated on the basis of interferon (IFN)-gamma ELISPOT assays of FVIII-stimulated cells (Meuniere et al., Blood Advances 1(21): 1842-7). Escape of these self-reactive precursor cells from thymic editing via deletion or anergy and their subsequent persistence in the periphery may contribute to the rare but potentially severe autoimmune reactions to FVIII ("acquired hemophilia A") and to the unusual immunogenicity of therapeutic FVIII administered i.v. to hemophilia A patients. The present study sought to further characterize CD4+ T-cell responses to endogenous FVIII and to map epitopes recognized by these self-reactive cells. We were particularly interested to learn if these cells recognize multiple epitopes in FVIII or if they respond to only several immunodominant epitopes. Accordingly, IFN-gamma ELISPOT assays were carried out by stimulating CD4+ T cells with 15-mer FVIII peptides having 12-residue overlaps and spanning the FVIII A1, A2, A3, C1 and C2 domains. For efficient mapping, initial assays utilized large pools of peptides, and positive responses were then "decoded" by ELISPOTs using smaller peptide pools or individual peptides. Blood samples were obtained from healthy controls under approved IRB protocols. The ELISPOT assays utilized CD4+ T cells isolated by negative selection, with irradiated autologous PBMCs as antigen presenting cells. Anti-CD49d/CD28 monoclonal antibodies were added for co-stimulation to increase the sensitivity of the assay and cells were cultured with IL-7 to improve cell viability. As a result, this assay required smaller blood volumes, but it should be noted that lower-avidity T-cell responses were likely detected that might be missed in ELISPOT assays without these modifications. Relevance of such low-avidity self-reactive cells is provided by the clinical observation, consistent with basic immunological principles, that risk factors for autoimmune responses to FVIII include old age (pro-inflammatory), trauma, surgery and postpartum status, all of which up-regulate T-cell co-stimulatory factors. The first subject had HLA-DRB1*01:01 and HLA-DRB1*08:04 alleles. Stimulation with large peptide pools and rFVIII protein indicated recognition of epitopes in at least 3 FVIII domains. Additional ELISPOTs tested the immunogenicity of 15 peptides corresponding to FVIII peptides previously demonstrated to be presented on dendritic cells from 2 individuals with an HLA-DRB1*01:01 allele (van Haren et al., Mol Cell Proteomics. 2011;10(6)), ensuring that our assays included tests of naturally processed FVIII peptides. Two of these peptides, both from the FVIII A1 domain, produced ELISPOT readings above background levels. T cells were then stimulated with these peptides for 19 days, stained with peptide-loaded MHC Class II (HLA-DRB1*01:01) tetramers, sorted and expanded for another 14 days. Tetramer staining then confirmed isolation of CD4+ T-cell clones recognizing one of these peptides. T cells that recognize their cognate antigen with high avidity are significant drivers of allo- and autoimmune responses. Lower-avidity T cells, however, can play significant roles in pro-inflammatory settings. Tetramer staining validated our ELISPOT-based identification of specific epitopes in FVIII. We are now carrying out ELISPOT assays using pooled peptides followed by individual FVIII peptides as stimulants, to estimate the repertoire of FVIII-specific CD4+ T cells in healthy non-hemophilic individuals. Mapping of HLA-restricted T-cell epitopes will also enable future tetramer-based isolation and phenotypic characterization of these rare T cells without expanding them in culture. This will allow us to investigate the interesting question of what peripheral tolerance mechanisms prevent expansion of these self-reactive cells in vivo, except in rare cases of FVIII autoimmunity. . Disclosures Pratt: Bloodworks NW: Patents & Royalties: inventor on patents related to FVIII immunogenicity; Grifols, Inc: Research Funding.

Principi di immunobiologia del trapianto ed attivazione della risposta immune

To achieve an effective immune response it is important that T cells can recognize a wide variety of non-self antigens; this allows for restrained immune activation and subsequent antigen-specific killing. This task is accomplished through the generation of a repertoire of T cells in a single individual with specificity for an enormous number of potential foreign antigens presented as peptides on the surface of major histocompatibility complex (MHC) molecules. Variations in MHC structure among individuals increase the variety of peptides that can be presented to T cells; this mechanism protects the species as a whole by ensuring adequate T-cell responses to a given foreign organism. Although slightly different, these MHC polymorphisms expressed in the donor kidney are recognized after kidney transplantation between non genetically-identical humans, and induce alloresponses that in the absence of immunosuppression result in rejection of the allograft. In this chapter, we review basic immunological principles important to the field of kidney transplantation.

Liver Transplant Immunology 2: Application to Liver Allograft Immunity

The liver is a multifunctional organ responsible for complex metabolic and immune functions. Although not a classic lymphoid organ, the liver is enriched with traditional immune cells as well as parenchymal and nonparenchymal cells that play a key role in immune homeostasis. Due to its location and unique anatomic structure, the liver must finely balance immunity and tolerance to avoid undue inflammation in the setting of constant antigenic exposure from portal blood flow while maintaining appropriate immunity against pathogens. Since the first successful liver transplantation in humans in 1967 at the University of Colorado, our knowledge of hepatic immunity and tolerance, in the context of both liver disease and liver transplantation, has evolved dramatically. With these advancements, therapeutic modalities have been developed that have revolutionized the care of liver transplant recipients. In Part 2: Application to Liver Allograft Immunity, we apply the basic principles of liver immunology and allorecognition to our current management of liver transplant recipients in the context of both immunosuppression and the holy grail of transplantation, operational tolerance. This review contains 4 figures, 3 tables, and 32 references Key Words: adaptive immunity; allograft rejection; allograft tolerance; allorecognition; antigen presenting cells; immunosuppression; innate immunity; liver transplantation; T lymphocytes

An Extraperitoneal Technique for Murine Heterotopic Cardiac Transplantation

The mouse heterotopic cardiac transplantation model has been used extensively by investigators in the field of organ transplantation to study the rejection process, test new antirejection treatments, tolerance induction protocols or to understand basic immunological principles. Due to its extensive use, any small refinement of the technique would have a major impact on replacement, reduction and refinement (commonly known as the 3Rs). Here, we describe a novel approach to refine this model. The donor aorta and pulmonary artery are anastomosed peripherally to the femoral artery and vein of the recipient, respectively. The technical success rate is comparable to the conventional abdominal site, but it avoids a laparotomy and handling of the bowels making it less invasive method. As a result, recipients recover faster and require less postoperative analgesia. It is a major refinement under one of the 3Rs and would represent an advance in animal welfare in scientific research.

Emerging Immunotherapies for Cancer and Their Potential for Application in Pediatric Oncology.

After decades of basic research, immune-based therapeutics for the treatment of cancer are showing evidence of efficacy in clinical trials; several immunotherapeutics already incorporated into standard treatment regimens. Intensive research is underway to improve the efficacy of immunotherapeutics and to expand the application of immunotherapy to a wider array of cancers. The therapeutic options that comprise immunotherapy for cancer are vast and span monoclonal antibodies, tumor vaccines, adoptive cellular therapies, as well as therapies aimed at reversing immunosuppression and enhancing immune reactivity globally and/or locally within the tumor microenvironment. In pediatric cancer, monoclonal antibodies have demonstrated efficacy in hematologic malignancies, and neuroblastoma and bispecific antibodies that activate resident T cells, as well as adoptive cell therapy, have shown recent exciting results for the treatment of acute lymphoblastic leukemia in childhood. This review discusses the basic principles of tumor immunology driving clinical development of new immunotherapies, describes immunotherapeutics with demonstrated efficacy and several currently in clinical trials, and highlight agents that seem to be most promising for the treatment of pediatric cancer.

The role of dendritic cells in immunity against primary herpes simplex virus infections

Herpes simplex virus (HSV) is a DNA virus with tropism for infecting skin and mucosal epithelia during the lytic stages of its complex life cycle. The immune system has evolved a multitude of strategies to respond to primary HSV infections. These include rapid innate immune responses largely driven by pattern recognition systems and protective anti-viral immunity. Dendritic cells (DC) represent a versatile and heterogenic group of antigen presenting cells that are important for pathogen recognition at sites of infection and for priming of protective HSV-specific T cells. Here we will review the current knowledge on the role of DCs in the host immune response to primary HSV infection. We will discuss how DCs integrate viral cues into effective innate immune responses, will dissect how HSV infection of DCs interferes with their capacity to migrate from sites of infection to the draining lymph nodes and will outline how migratory DCs can make antigens available to lymph node resident DCs. The role of distinct DC subsets and their relevant contribution to antigen presentation on MHC class I and MHC class II molecules will be detailed in the context of T cell priming in the lymph node and the elicitation of effector function in infected tissues. An improved understanding of the fundamental mechanisms of how DCs recognize HSV, process and present its antigens to naïve and effector T cells will not only assist in the improvement of vaccine-based preventions of this important viral disease, but also serves as a paradigm to resolve basic immunological principles.

Cancer cell technology as a tool for teaching basic principles of immunology (EDU1P.248)

Abstract Testicular cancer mainly affects men between the ages of 20 and 39, but it is the most common neoplasm in men between the ages of 15 and 34. The National Cancer Institute states that localized testicular cancer has a recurrence rate of 15-20%, and those tumors, including Sertoli or Leydig cell derived, do not respond well to chemotherapy or radiation treatment. My summer research was centered on the effort to better characterize the immune response to a testicular tumor. This was accomplished through the use of different immunology techniques such as proliferation assays, immunohistochemistry, ELISA, and ELISPOT. My lab experience inspired me to design a unit curriculum which will help elucidate the various physiognomies of tumor growth. Students first learn and apply the essential techniques of cancer cell culture. The testicular cancer cell line I-10 (CCL-83, ATCC) is used to familiarize students with routine feeding and maintenance, subculturing, counting, and cryopreservation. I-10 cell RNA is converted to cDNA and qualitatively analyzed for inhibin-alpha gene expression, which serves as a tumor marker, using RT-PCR. Then, they analyze previously formalin-fixed, paraffin embedded murine testes (normal and cancerous) using H&E staining and immunohistochemical staining for CD3, inhibin-alpha, and IgG. Upon completion of this unit, students demonstrate these learned skills in a combined written and practical examination.

Immunology primer for neurosurgeons and neurologists part I: Basic principles of immunology

Our knowledge concerning the workings of the immune system has evolved considerably over the past 20 years, with great strides being made as regard to complex interactions and repertoire of effector reactions under a host of conditions. Many of our previous understandings have been challenged, especially concerning tumor immunology and autoimmunity. Also of critical importance is our understanding of how the immune system terminates its attacks and the mechanisms used to regulate the balance between proinflammatory and antiinflammatory mechanisms, so as to prevent excessive immune bystander damage. I will discuss in part I the basic physiology of innate immune function and the immune systems reactions to invasion by microorganisms.

Book review

This book is the ideal text for anyone wishing to develop a broad understanding of the subject of neuroimmunology. It is small enough to carry on the train, yet manages to cover a broad range of related topics with a surprising degree of detail. In the first few chapters, it offers an introduction to the basic principles of immunology, neurology and neuroimmunology, instantly making the book accessible to all comers to the field. It uses clever analogies to illustrate basic principles of how the immune and nervous systems interact to maintain health, and to describe how inappropriate levels of regulation can lead to disease.

Exploring Immunology - Concepts and Evidence Gordon MacPherson & Jon Austyn Wiley-Blackwell 2012 http://eu.wiley.com/WileyCDA/Wiley Title/productCd-3527324127.html Price 39,90€, paper back, 372 pages Published April 2012

It was very inspiring to start reading this immunology textbook, as it is dedicated to the memory of the late Ralph Steinman, Nobel Laureate in Physiology or Medicine 2011 “for his discovery of the dendritic cell and its role in adaptive immunity”. He co-shared the Nobel Prize in 2011 with Jules Hoffmann and Bruce Beutler who were awarded “for their discoveries concerning the activation of innate immunity”. This fair dedication to an outstanding scientist should remind us of the importance immunology has had in biomedical research in the past decades and the therapeutical resources that are reaching clinical practice as a consequence of basic and clinical research in this field. This new book, ‘Exploring Immunology — Concepts and Evidence’, must be welcomed as a new resource for the study of a subject that is essential in all biological sciences. It is a concise book with 7 chapters; however, it nonetheless includes all the up-to-date relevant information that one would expect to find in a general immunology book. The sequence of chapters chosen by the authors was creative and original — the novice reader can have a good general overview of immunology by reading the first chapter, ‘The Immune System’. Those who wish to read about the clash between microbes and the immune system, and about immune-mediated diseases and treatments have two separate chapters, ‘Infection and Immunity’, and ‘Immunity, Disease and Therapy’, respectively. More detailed information about how the immune system works is described in the remaining four chapters which cover, in turn, the ‘Functional Anatomy of the Immune System’, ‘Innate Immunity’, ‘T Cell-Mediated Immunity’ and ‘Antibody-Mediated Immunity’. This book is very pleasant and easy to read, reflecting the authors’ long experience in immunology teaching and research. It has been written using clear language and in a straightforward manner, while also raising and discussing unresolved and controversial issues. With beautiful colored illustrations (you'll hardly find two sequential pages without a single figure!), it is well suited for undergraduate students in the biological and health sciences in the early years of their college or university studies. Undergraduate students taking a microbiology course will also find helpful information, particularly in the chapter about ‘Infection and Immunity’. Graduate students studying areas involving immunology would also benefit from reading this book before delving into the more specialized literature. Furthermore, any health professional who wishes to refresh and update his or her knowledge on immunology will also find this book useful. Questions are included throughout the book to stimulate reflection and critical thinking. Some of these questions are more direct, while others are intriguing and thought-provoking. Some of them may not have definitive answers, as acknowledged by the authors, and this reminds us that our understanding of immunological processes, despite having increased tremendously over past decades and still increasing rapidly is nonetheless incomplete. Although the primary aim of these questions is educational, they could also be used to help formulate research questions. Case studies are particularly stimulating and helpful as resources to teach immunology, and many of them can be found in this book, portraying different immune-mediated and infectious diseases. They are described in accessible language with few technical medical terms, reinforcing the principles explained and providing an indication of the participation of the immune system in many different illnesses. Another point to be praised in this book is the regular use of scientific evidence supporting the knowledge about immunology — this compliment really goes to the authors. There are citations of animal research and human studies that describe early discoveries and recent findings regarding basic immunologic principles and also infectious diseases, allergies, vaccines, primary immunodeficiencies, autoimmunity and transplantation. Although the authors opted not to cite the detailed bibliographic references from these scientific studies, maybe their citation would really have given an evidence-based ‘taste’ to this textbook. I was very pleased to read ‘Exploring Immunology’ and would be more so if it became widely available to students and in libraries’ collections throughout the world. I cannot do less than to honestly recommend it.

Intracellular sensors of microbes and danger

2011 John Wiley & Sons A/S Immunological Reviews 0105-2896 The editors of this volume of Immunological Reviews respectfully acknowledge the passing of Jurg Tschopp, who died suddenly on March 22, 2011. A towering figure in the field, Jurg made many important contributions to our understanding of cell death and inflammation signaling pathways. His seminal description of the inflammasome has not only had major impact on scientists working in innate immunity but also influenced many interested in related fields. The impact of Jurg’s work was immense, ranging from improving our understanding of basic immunologic principles to providing novel insights leading to new modes of therapy for important human diseases. Jurg was not only a colleague but also a friend of several contributors to this volume. He will be missed.

The hen model of human ovarian cancer develops anti-mesothelin autoantibodies in response to mesothelin expressing tumors

ObjectiveStudy of the hen immune system led to seminal contributions to basic immunological principles. Recent studies of spontaneous ovarian cancer in the laying hen show strikingly similar tumor types and antigen expression compared to human ovarian cancer, suggesting hens would be valuable for studies of tumor immunology and pre-clinical vaccine development. Circulating mesothelin is a relatively specific marker for human ovarian cancer and autoantibodies to mesothelin were reported. We hypothesized that hen tumors express mesothelin and that circulating anti-mesothelin antibodies occur in response to tumors.MethodsMesothelin mRNA expression was analyzed by RT-PCR in hen ovarian tumors and normal ovaries. Mesothelin protein expression was evaluated by immunohistochemistry (IHC) and two-dimensional SDS-PAGE Western blots. Anti-mesothelin antibodies were assessed by immunoassay of sera from hens with normal ovaries and with ovarian tumors.ResultsSignificant mesothelin mRNA expression was observed in 57% (12/21) of hen ovarian tumors but not in normal ovaries and was found predominantly in serous tumors as in humans. Mesothelin protein was detected in tumors with mesothelin mRNA by IHC and 2D Western blots, but not in normal ovaries or tumors without mesothelin mRNA. Circulating anti-mesothelin antibodies occurred in 44% (n = 4/9) of hens with ovarian tumors which express mesothelin mRNA and were not found in hens with tumors that did not express mesothelin (n = 0/5) or normal ovaries (n = 0/5).ConclusionThe results support the utility of the hen as a novel model for preclinical studies of mesothelin as a biomarker and a target for immunotherapy.

State of the union between metabolism and the immune system in type 2 diabetes

Lymphocytes and myeloid cells (monocyte/macrophages) have important roles in multiple types of diseases characterized by unresolved inflammation. The relatively recent appreciation of obesity, insulin resistance and type 2 diabetes (T2D) as chronic inflammatory diseases has stimulated interest in understanding the role of immune cells in metabolic imbalance. Myeloid cells regulate inflammation through cytokine production and the adipose tissue remodeling that accompanies hyper-nutrition, thus are critical players in metabolic homeostasis. More recently, multiple studies have indicated a role for T cells in obesity-associated inflammation and insulin resistance in model organisms, with parallel work indicating that pro-inflammatory changes in T cells also associate with human T2D. Furthermore, the expansion of T cells with similar antigen-binding sites in obesity and T2D indicates these diseases share characteristics previously attributed to inflammatory autoimmune disorders. Parallel pro-inflammatory changes in the B-cell compartment of T2D patients have also been identified. Taken together, these studies indicate that in addition to accepted pro-inflammatory roles of myeloid cells in T2D, pro-inflammatory skewing of both major lymphocyte subsets has an important role in T2D disease pathogenesis. Basic immunological principles suggest that alterations in lymphocyte function in obesity and T2D patients are an integral part of a feed-forward pro-inflammatory loop involving additional cell types. Importantly, the pro-inflammatory loop almost inevitably includes adipocytes, known to respond to pro-inflammatory, pro-diabetogenic cytokines originating from the myeloid and lymphoid compartments. We propose a model for inflammation in T2D that functionally links lymphocyte, myeloid and adipocyte contributions, and importantly proposes that tools for B-cell ablation or regulation of T-cell subset balance may have a place in the endocrinologist's limited arsenal.

Basic Transport Phenomena in Biomedical Engineering, 2nd Edition, by Ronald L. Fournier, Taylor & Francis, New York, 2006

In the words of the author, the second edition of this text “brings together fundamental engineering and life science principles to provide a focused coverage of key transport concepts in biomedical engineering.” The book is focused toward the beginning student of biomedical engineering as well as its already-established engineers and scientists. The second edition has been substantially augmented and reorganized over the first edition. The new text starts with an introductory chapter covering units, dimensions, and several basic approaches and principles applied to solving biomedical transport problems. Before delving into transport processes, the revised text also includes, as Chapter 2, a useful summary on the thermodynamic principles of chemical systems. This chapter will be especially useful for students of biomedical engineering, who sometimes begin the study of transport processes without having had sufficient background in principles of chemical equilibrium. After all, a “transport process” describes a system disrupted from equilibrium that is attempting to regain equilibrium. More practically, the conditions that apply at the boundary of biomedical transport systems stem from various principles of chemical equilibrium at interfaces between various subcellular, cellular, tissue, or organ components (or “compartments”). The remaining chapters in the book appeared in the first edition but have been reorganized, augmented, and reordered. As in other texts on biomedical transport phenomena, momentum transport is addressed before mass transport. Chapter 4 covers the flow dynamics of blood flow with emphasis given to paradigmatic relationships such as the Hagen-Poiseuille equation, as well as the non-Newtonian characteristics of blood rheology and blood rheological models. The chapter also provides coverage and analysis relative to the “particulate effects” of blood flow in the microcirculation, the Fahraeus and FahraeusLindqvist effects describing hematocrit and viscosity reductions in microvessels. Chapters 5 and 6 cover solute and oxygen transport in blood and tissue as well as transcapillary exchange. The breadth of coverage in these chapters is extensive, with many important paradigms covered, including convective mass transport, capillary filtration, membrane transport, transcapillary solute exchange, oxygen carriage in blood, oxygen transport within tissue (Krogh model), and characteristics of artificial blood. A strong point of the original text and revised text is coverage of several areas of interest in applied biomedical transport phenomena, which will garner significant interest from beginning students in biomedical engineering. Chapters 7 through 10 cover pharmacokinetics, extracorporeal medical devices, tissue engineering, and biohybrid artificial organs. These are some of the more interesting applications in the biomedical area for implementing transport design principles. The presentation of extracorporeal devices focuses mainly on membranebased devices such as hemodialyzers and blood oxygenators. The tissue engineering chapter focuses mainly on general principles related to extracellular matrix, cellular receptors, and transport within polymeric matrices. The coverage of biohybrid artificial organs reviews basic principles of immunology and immunological isolation and describes encapsulated cellular systems such as the artificial pancreas. Recent advances in the biohybrid liver and kidney systems are also briefly described. Consistent with the philosophy put forward for this book, the text does not pursue a comprehensive review of contemporary developments in all these areas but instead intends to teach and illustrate principles and applications of biomedical transport phenomena within the context of important technologies currently in clinical use or close to clinical reality. The suitability of this book as a text for an undergraduate or graduate course in biomedical transport phenomena will largely depend on the style of the instructor. This is not necessarily a textbook that derives important relationships from first principles, nor does it follow a Bird, Stewart, and Lightfoot approach to the development of transport principles. Important concepts in biomedical transport phenomena are introduced, but the pace may seem too rapid for a beginning engineering student. However, the student or practitioner who has already been exposed to some of the engineering principles covered in this text will appreciate the efficiency and breadth with which biomedical applications of classic transport principles are presented. Transport or mechanics faculty working in the bioengineering area will find this book an excellent addition to their bookshelves. From the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Submitted for consideration December 2006; accepted for publication in revised form January 2007. Reprint Requests: William J. Federspiel, PhD, Room 215, McGowan Building, McGowan Institute of Regenerative Medicine, University of Pittsburgh, 3025 East Carson Street, Pittsburgh, PA 15203.

Pox Viral Vaccine Approaches

Recent advances in understanding tumor-specific immunity have introduced new excitement in the clinical development of vaccines for the treatment of cancer. A better understanding of basic immunologic principles has led to a variety of techniques for enhancing tumor-specific immunity through vaccination. Approaches to antigen-specific immunotherapy have included: (1) peptides, usually in combination with various immunological adjuvants; (2) soluble proteins; (3) dendritic cells pulsed with specific antigens; (4) monoclonal antibodies; (5) recombinant plasmid DNA; (6) autologous and allogeneic tumor cells; and (7) recombinant viral vectors. This review will focus on the use of viral vectors, which offer unique advantages as both gene delivery vectors and as agents supplying additional adjuvant activity for vaccination. Viral vectors are particularly attractive for immunotherapy since they mimic natural infection and can induce potent immune responses. Replicating and nonreplicating members of the poxvirus family have been widely studied for expression of tumor antigens and other immunomodulatory genes, such as cytokines and costimulatory molecules. Although a large number of TAAs are available for insertion into viral vectors, this review will discuss the preclinical and clinical development of prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA) poxviral vaccines, as models of the pox viral vaccine approach.