The immunobiology of muscle

Skeletal muscle can be both the site and target of immune reactions. Here, Reinhard Hohlfeld and Andrew Engel consider the role of muscle as an immunological microenvironment and discuss the immunological properties of human muscle cells. Furthermore, they provide a brief overview of autoimmune diseases of muscle and of other conditions in which intramuscular immune reactions play a role. Finally, they discuss the immunological problems of novel gene therapies that rely on muscle cells as vehicles for gene transfer.     

The immunobiology of Chlamydia

Bacteria of the genus Chlamydia cause a wide variety of disorders in animals and people worldwide. The immune response to chlamydiae is poorly understood and, as Daniel Levitt shows here, there is recent evidence that these organisms induce perturbations in immune function that may assist their own survival in infected hosts and that of co-infecting microbes.     

The immunobiology of zinc

Zinc is required for range of immune functions, including T-cell activity, Here, Lothar Rink and colleagues review its roles, and discuss the implications for its therapeutic use.     

The immunobiology of human gliomas

Conclusions The finding that glioma cells can express HLA-DR antigens and that their expression can be modulated by human recombinant -interferon should stimulate new ways to consider the immunotherapy of human gliomas. The presence of HLA-DR antigens might enhance the immunogenicity of the glioma cells. This hypothesis can be tested in vitro by mixed lymphocyte-tumor cell culture. Furthermore, the use of interleukin-2 may allow one to maintain for a relatively long term the proliferation of any cytotoxic T cell clone which should be obtained in vitro. It is even conceivable that some of these strategies could be used for adoptive immunotherapy. Since the present treatment modalities, in particular chemotherapy, have failed to improve the prognosis of malignant gliomas, it is of the utmost importance to investigate new forms of therapy.     

The immunobiology of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease.     

The immunobiology of primary sclerosing cholangitis

An understanding of the immunobiology of primary sclerosing cholangitis (PSC) is essential to improving both diagnosis and treatment. There have been significant gains in the discovery of genetic polymorphisms that generate susceptibility to disease, but only limited data on etiologic events that may initiate the inflammatory response. Colonic inflammation produces memory T cells that have the ability to bind both biliary and colonic endothelial cells. One possible mechanism for the development of PSC is the homing of these memory T cells to the biliary tree. In addition, TNF(alpha) may contribute to the oxidative damage of the biliary system. Finally, although speculative, mononuclear cell responses against biliary epithelial cells may create a persistent inflammatory response, eventually leading to fibrosis.     

Evolutionary immunobiology

Identifying the evolutionary origin of inducible, specific immune recognition represents a major objective in developmental immunology. In order to address this issue from an overall phylogenetic perspective, major studies of cellular and humoral immune function are being undertaken using lower vertebrate and invertebrate models. Here, C. Reinisch and G. Litman discuss the application of new technologies, particularly molecular genetic approaches, that is providing important new insights into the genetic mechanisms that have influenced the evolutionary diversification of immunological function.     

Tumour immunobiology

A hypothesis for the interactional mechanism between tumour cells and the lymphopoeitic system, with its resulting sequence of immune depression is outlined, along with a review of the current literature relating to this area. The concept that the tumour cell surface is responsible not only for loss of cell surface contact inhibition, but also protecting itself from the lymphopoeitic elements that come into contact with it by infecting them with nucleic acid particles produced by its excessive nuclear turnover, is espoused, with a variety of supporting data.A review of recent information is also presented on blocking factors, their nature, and how they relate to the above “infected” lymphopoeitic cells.     

Liver immunobiology

Tle liver has a number of important functions in innate and adaptive immunity. Contributions to the innate (nonspecific) immune system include production of acute phase proteins, nonspecific phagocytosis of particles, nonspecific pinocytosis of molecules, and nonspecific cell killing. Hepatic involvement in innate immunity contributes to the systemic response to local inflammation, clearance of particles and soluble molecules from the circulation, and killing of invading cells such as neoplastic cells. Liver involvement in the adaptive (specific) immune system includes deletion of activated T cells, induction of tolerance to ingested and self-antigens, extrathymic proliferation of T cells, and deletion of many of the signaling and effector molecules. Hepatic involvement in adaptive immunity allows clearance of activated T cells and signaling molecules following inflammatory reactions, and promotes immunologic tolerance toward potentially antigenic proteins that are absorbed from the intestinal tract. The liver is a major site of extrathymic T cell development, which assumes increasing significance with aging in mammals. Perturbations in hepatic structure or function can result in significant ramifications in both the innate and adaptive immune systems.     

The immunobiology of respiratory syncytial virus infection

There is increasing evidence that young children with severe respiratory syncytial virus (RSV)-induced bronchiolitis are at high risk of developing allergy and asthma during their later life. The determinants for this association are not well understood. Current studies suggest that both genetic backgrounds and unique characteristics of the virus play critical roles in determining the type of immune responses to RSV infection, leading to altered regulation of airway tone associated with wheezing. In susceptible subjects, RSV may either enhance the Th2 immune response or decrease the Th1 immune response. This altered Th1/Th2 cytokine response associated with RSV infection is not commonly observed among other RNA viruses, suggesting that RSV may have unique characteristics. Multiple clinical studies support the link between severe RSV bronchiolitis and the subsequent development of allergy and asthma. This link will be further tested by the ongoing large studies on the effect of early RSV intervention on the development of allergy. The administration of palivizumab, an anti-RSV monoclonal antibody, seems to be helpful for RSV prevention and treatment at early stage. There are no effective RSV vaccines available, and this is, at least in part, because of the poorly understood immunology and pathogenesis of RSV disease. The use of experimental animal models has led to a better, but not sufficient, understanding of the immunologic basis of RSV-induced disease, particularly asthma. Further studies on the immunopathology of RSV infection with animal models, including the nonhuman primate models, may help develop effective RSV vaccines.     

The immunobiology of cancer immunosurveillance and immunoediting

The last fifteen years have seen a reemergence of interest in cancer immunosurveillance and a broadening of this concept into one termed cancer immunoediting. The latter, supported by strong experimental data derived from murine tumor models and provocative correlative data obtained by studying human cancer, holds that the immune system not only protects the host against development of primary nonviral cancers but also sculpts tumor immunogenicity. Cancer immunoediting is a process consisting of three phases: elimination (i.e., cancer immunosurveillance), equilibrium, and escape. Herein, we summarize the data supporting the existence of each of the three cancer immunoediting phases. The full understanding of the immunobiology of cancer immunosurveillance and immunoediting will hopefully stimulate development of more effective immunotherapeutic approaches to control and/or eliminate human cancers.