Cytokines in the Treatment and Prevention of Autoimmune Responses

Xin Xiao Zheng, Wlodzmierz Maslinski, Sylvie Ferrari-Lacraz and Terry B. Strom

Cytokines are important protein mediators of immunity, inflammation, cell prolifer- ation, differentiation, and fibrosis.¹ These are the major biological processes un-derlying autoimmunity. Hence, it is not surprising that there is now convincing evidence that the dysregulatio...

Cytokines, Chemokines and their Receptors

Mark J. Cameron and David J. Kelvin

The immune system is skilled in communication and designed to respond quickly, specifically and globally to protect an organism against foreign invaders and disease. The cytokine superfamily of proteins is an integral part of the signaling network between cells and is essential in genera...

Cytokines, Lymphocyte Homeostasis and Self Tolerance

Yiguang Chen and Youhai Chen

Cytokines play pivotal roles in maintaining lymphocyte homeostasis and self tolerance. Cytokines are required for activating and inactivating as well as deleting cells of the immune system during immune responses. Mutations in cytokine genes in humans and animals can lead to the break...

DNA Vaccination Against Autoimmune Diseases

Gerald J. Prud’homme, Yelena Glinka, Yigang Chang and Xiaoying Li

The ultimate goal in the treatment of autoimmune diseases is to restore immune toler ance to the relevant target antigen(s). Short of this ideal, the attenuation of pathogenic immune responses is a highly desirable end. Many forms of immunotherapy are being studied with these objectives in mind, ...

Endocrine Diseases II: Graves’ and Hashimoto’s Diseases

Yoshiyuki Ban and Yaron Tomer

The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic suscepti bility in combination with external factors (e.g., dietary iodine) are believed to initiate the autoimmune response to thyroid a...

Endocrine Diseases: Type I Diabetes Mellitus

Regine Bergholdt, Michael F. McDermott and Flemming Pociot

Type 1 diabetes (T1D) [MIM 222100] is the third most prevalent chronic disease of childhood, affecting up to 0.4% of individuals in some populations by age 30 years, with an overall lifetime risk of nearly 1%.1,2 T1D is caused by absolute insulin deficiency due to destruction of the pancreatic &#...

Etiopathogenesis of Myasthenia Gravis (MG)

Jean-François Bach, Ana Maria Yamamoto, Farid Djabiri and Henri-Jean Garchon

Myasthenia gravis (MG) is not one of the most common autoimmune disease (approximate prevalence of 0.1 per thousand in Western Europe) but it is certainly one of the most thoroughly studied autoimmune diseases. There is a very useful experimental animal model, induced by sensitization ag...

Experimental Models of Mucosal Inflammation

Warren Strober and Ivan J. Fuss

While studies of models of mucosal inflammation has been a mainstay of IBD research for the past half century, it is only in the last 10-15 years that this kind of study has taken its place as primus inter pares among the many approaches to studying these diseases. The reason this has come about is ...

From Immunogenic Mechanisms to Novel Therapeutic Approaches in Inflammatory Bowel Disease

Martin H. Holtmann and Markus F. Neurath

Crohn’s disease (CD) and ulcerative colitis (UC) are the two most common forms of chronic inflammatory bowel disease (IBD). The etiology of IBD is still unclear and should be considered as multi-factorial according to recent studies.1 Genetic factors seem to play a pathogenetic role as well as envir...

Functional Aspects of the Mucosal Immune System

Cathryn Nagler-Anderson

The mucosal immune system is faced with a daunting challenge. It must quickly and efficiently protect the epithelial barrier from invasion by microbes while avoiding a response to antigenic stimuli from the commensal bacteria or food proteins that constantly bombard it.1 It meets this challenge thro...

Gastroenterologic and Hepatic Diseases

Marcela K. Tello-Ruiz, Emily C. Walsh and John D. Rioux

Celiac disease, autoimmune hepatitis (AIH), and the inflammatory bowel diseases (IBDs), Crohn’s disease and ulcerative colitis (UC), are chronic inflammatory diseases of unknown etiology. They are considered complex genetic diseases because both inherited and environmental influences appear to be...

Gene Therapeutics in Autoimmune Diabetes

Jon D. Piganelli, Massimo Trucco and Nick Giannoukakis*

A significant amount of resources has recently been devoted to the restoration of normal glycemic regulation in type 1 diabetic patients by transplantation of allogeneic islets of Langerhans. Despite the promise offered by this approach, logistical hurdles necessitate a comprehensive strategy aim...

Gene Therapy Approaches for Autoimmune Diseases of the Central Nervous System and Other Tissues

Roberto Furlan, Erica Butti, Stefano Pluchino and Gianvito Martino

Autoimmune disorders are the result of an aberrant immune reaction against self-components of the organism. Genetic traits, conferring predisposition to break immunological tolerance to self-antigens, are thought to concur, together with environmental factors, in the aetiology of this large, grow...

Gene Therapy-Based Approach for Immune Tolerance Induction Using Recombinant Immunoglobulin Carriers

Moustapha El-Amine, Mary Litzinger, Marco E. F. Melo and David W. Scott

The mechanisms of tolerance induction and its breakdown are important to explore because of its involvement in the pathogenesis of many known autoimmune diseases. Tolerance to “self ” is not absolute and can be overcome by the immune system after a foreign stimuli caused by pathogens, allergens o...

Genetics of Autoimmune Myocarditis

Mehmet L. Guler, Davinna Ligons and Noel R. Rose

Autoimmune heart diseases in humans are multifactorial and genetically complex. Fortunately a great deal has been learned from animal models. They have established that a variety of infectious or toxic insults can lead to autoimmune heart disease in genetically susceptible animals. These animal m...

Genomic Variation and Autoimmune Disease

Silke Schmidt, Lisa F. Barcellos

Genetic epidemiology is the study of the relationship between genomic and phenotypic variation with a goal to uncover the genetic basis of monogenic or complex disorders. A variety of study designs are available, and the importance of choosing an approach that is appropriate for the goals of the ...

Hematologic Diseases: Autoimmune Hemolytic Anemia and Immune Thrombocytopenic Purpura

Mattias Olsson, Sven Hagnerud, David U.R. Hedelius and Per-Arne Oldenborg

Autoimmune destruction of circulating blood cells in autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) is often seen in autoimmune diseases and lymhoid malignancies. Erythrocytes or platelets that are recognized by autoantibodies are rapidly phagocytosed by macrophages....

HLA and Autoimmunity Structural Basis of Immune Recognition

The MHC region on human chromosome 6p21 is a critical susceptibility locus for many human autoimmune diseases. Susceptibility to a number of these diseases, including rheumatoid arthritis, multiple sclerosis and type 1 diabetes, is associated with particular alleles of HLA-DR or HLA-DQ genes. Crysta...

Immunobiology of Autoimmunity

Donald Bellgrau and George S. Eisenbarth

Autoimmunity can be defined as immune responses directed against selfantigens and an autoimmune disorder as a disease which results from autoimmunity.^1,2 The cells of the immune system with "antigenic specificity" are B and T lymphocytes.³ An essential fea...

Immunogene Therapy with Nonviral Vectors

Ciriaco A. Piccirillo, Argyrios N. Theofilopoulos and Gerald J. Prud’homme*

The majority of gene therapy studies have been performed with viral vectors that present important limitations in terms of immunogenicity and pathogenicity. Nonviral (usually plasmid-based) gene therapy is not hampered by these limitations and, although gene transfer is generally less efficient, ...

Immunogenetics of Rheumatoid Arthritis, Systemic Sclerosis and Systemic Lupus Erythematosus

Allison Porter, J. Lee Nelson

The autoimmune rheumatologic diseases discussed in this chapter include rheumatoid arthritis (RA), systemic sclerosis (SSc), also called scleroderma, and systemic lupus erythe matosus (SLE). Historically the terms connective-tissue diseases or collagen-vascular diseases have sometimes been used i...

Immunoregulation by Cytokines in Autoimmune Diabetes

Alex Rabinovitch

In the previous Chapter, Meagher and colleagues discuss the role of a number of cytokines and chemokines in the pathogenesis of murine type 1 (insulin dependent) diabetes mellitus. Here I provide an integrated view of type 1 diabetes as a disorder of immunoregulation. T cells specific for panc...

Inflammatory Myopathies: Dermatomyositis, Polymyositis and Inclusion Body Myositis

Renato Mantegazza and Pia Bernasconi

Dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM) belong to the heterogeneous group of the inflammatory myopathies and are characterized by muscle cell infiltrations and specific alterations of the muscle fibers. In DM it is evident a perifascicular atrophy of muscle tissu...

Insights into the Molecular Mechanisms of the Autoimmune Thyroid Diseases

Horia Vlase and Terry F. Davies

The human AITDs¹ include hyperthyroid Graves' disease (classical Graves' disease with thyrotoxicosis), euthyroid Graves' disease (without thyrotoxicosis), both with or without Graves' orbitopathy, and autoimmune thyroiditis (Hashimoto's disease), including the goitrous form (c...

Insulin Autoimmune Syndrome (IAS, Hirata Disease)

Yasuko Uchigata and Yukimasa Hirata

Although HLA and disease association has been studied for many diseases, only four dis- eases have been identified in which almost all patients have the same HLA antigen; B27 in 88% of ankylosing spondylitis,¹ DR4 in 91% of patients with pemphigus vulgaris,² DR2 in ...