Immunological Aspects Of The Liver And Gastrointestinal Tract

We have been privileged to start our academic careers at the begin ning of the decade in which the immunological roles and hypersensitivity diseases of the gastrointestinal tract and liver have been defined. In the early 1960s IgA was reported to be the main secretory immunoglobulin, immunoblasts were shown to home to the intestinal mucosa and certain serum autoantibodies were described in patients with chronic liver disease. Shortly thereafter IgE and Australia antigen were discovered. Parallel advances in clinical investigation, in particular closed biopsy techniques, facilitated correlation of morphological changes with im munological mechanisms in disease of the gastrointestinal tract and liver. Only 10 years later, the concepts of immunity and hypersensitivity are regularly applied to the pathogenesis, diagnosis, treatment and prog nosis of many chronic diseases in these organs. In designing this book we have attempted to integrate theorectical and clinical immunology as they pertain in 1975; our ultimate aim is aptly described by Brachet as quoted by Professor Paronetto (page 319). We would like to think that this review provides a basis for the next major advances in the fields of gastrointestinal and hepatic immunology. As we see it, the outstanding problem in both sites is how to produce protective immunity without hypersensitivity.

Howard C. Thomas In normal subjects the regulatory apparatus of the immune system permits responses to foreign antigens but suppresses those directed to "self' components. Autoimmune disease occurs as a failure ofthis system either as a result of a primary defect in the regulatory apparatus (primary autoimmunization) or because of a change in the antigenicity of the tissues (secondary autoimmunization). Autoaggressive reactions are characterised by the presence of autoantibodies. When these are directed to membrane displayed antigens (Fig. 1) they are probably of importance in the lysis of hepatocytes. Those directed to cytoplasmic antigens may be useful diagnostically but are of unknown pathogenic significance. When no extrinsic aetiological factor can be identified, the process is assumed to be the result of a failure ofthe regulatory system, allowing the spontaneous expansion of a clone of autoreactive lymphocytes. The defect may be generalised or specific to certain groups of self-antigens and thus the autoimmune disease may be either multi- or unisystemic. The recent development of techniques to enumerate and measure the functional activity of the suppressor lymphocytes which control the effector limbs of the immune system has enabled investigators to test whether the various purported autoimmune diseases do have as their basis a generalised defect in immunoregu lation. Assessment of antigen-specific immunoregulatory function is, however, not yet readily available. liver Membrane I Antigen (LIM) I Liver I HLA, A, B, C, Sensitisation to Specific -;::!IIIL. .

Diseases of the gastrointestinal tract are common. There is increasing appreciation of the importance of the immune system in the pathogenesis of a number of these diseases. This book covers basic aspects of innate and adaptive immunity in the gastrointestinal tract, oral tolerance, and cellular and molecular mechanisms of acute and chronic inflammation. Specific disease covered include bacterial infections, human immunodeficiency virus (HIV) infection, coeliac disease, and inflammatory bowel disease. Other topics include mucosal immunisation and intestinal transplantation immunology. The readership of this book includes clinicians, scientists, and students interested in the gastrointestinal tract.

This book is the proceedings of the Falk Symposium No. 135 held in Prague, Czech Republic, on September 12-13, 2003, and is dedicated to the important issue of immunological aspects of diseases of the liver and gut. Without any doubt, immunological pathways are among the most important and universal factors in the pathogenesis of all diseases. Their importance is also constantly increasing, because these principles have been adopted in clinical practice for both diagnostic and therapeutic procedures. Chapters by prominent experts will stimulate new ideas and set the scene for productive discussion on this topic.

This 1994 volume summarizes basic scientific advances in the area of the gut immune system and the immune abnormalities relevant to gastrointestinal and liver disease.