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The subject of immune deficiency has become of special importance for two reasons. First, conditions with well defined defects in the immune system could be analyzed as "experiments of nature" in terms of finding out the accurate biological relevance of the defective link in the immune system. Secondly, the recognition of immune deficiency states has become important in order to provide the patients with the treatment necessary to remedy these defects. With regard to immune deficiency states in patients, these have been instrumental as "experiments of nature" in the revelation by Drs. Good and Cooper and their associates of the two-component structure of the immune system, a discovery which can be consi dered as a major breakthrough in the history of immunopathology. Today's research allows us to go far beyond this basic two component structure with the assessment of disorders affecting either cell to cell interactions or regarding subsets of lymphocyte populations. Furthermore, the association of immune deficiency with distinct enzymatic defects of purine metabolism is opening the door to the molecular level of immune deficiency. Dr. Cooper and Dr. Lawton have succeeded in obtaining the collaboration of the leaders in the field of immune deficiency. In view of the importance of their contributions in scientific and clinical terms, we decided to prepare a book version of the two issues of Seminars in Immunopathology devoted to this subject.
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The discovery of specifically acquired immunity which followed the major contributions of Louis Pasteur completely over-shadowed the first studies of the host's natural resistance. Later, the exquisite sensitivity and precision of antigen-antibody reactions made the study of immunochemistry much more attractive than the rather primitive and ambiguous field of non-specific immunity. Neverthe less, during the last three decades, a considerable body of informa tion was developed and also means by which natural resistance could be enhanced or depressed by exogenous agents such as lipopolysaccharides or BCG. An important advance was the chemical recognition of the biologically active components of these agents which in turn allowed the synthesis or" analogues. More recently, endogenous host products which can play a role in nonspecific immunity, such as thymic hormones, have also been identified, produced and used both experimentally and clinically. It therefore seemed worthwile to Drs. Miescher and Mueller-Eberhard to devote two volumes of Seminars in Immunopathology to the topic of Immunostimuhltion. Because of the good response obtai ned from readers, Springer Verlag decided to issue a hard cover book and asked their guest editor to make a preface. Prefaces, although they are found in the opening pages, are always written after the first issue has been completed.
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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. .
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Peter A. Miescher The skin has always been one of the major targets to clinicians interested in immunology. Initially, the main focus was centred on allergic conditions such as contact hypersensitivity and urticeria. Gradually, the spectrum of immunological conditions involving the skin increased, encompassing diseases such as Dermatitis Herpetiformis, Erythema Muitiforme, Cutaneous Bullous Disorders and Photo toxic Reactions. It has been the intention of the editors of Springer Seminars in Immu nopathology to cover the broad spectrum of immune phenomena encountered in dermatological diseases with special emphasis to newer developments in Immunopathology. Dr. 1. N. Gigli has managed to assemble a series of important contributions within two issues of the Journal which are of such an interest to dermatologists that we decided to publish this topic as a separate volume for all dermatologists who do not have access to Seminars in Immunopathology. 3 Immunologically Mediated Epidermal Cell Injury Richard D. Sontheimer* and James N. Gilliam Division of Dermatology, University of Texas Health Science Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235, USA Introduction The epidermis is a functional unit of different cell types that has the critical role of protecting man from his environment. The three major cell types that make up the epidermis (keratinocytes, melanocytes, and Langerhans cells) serve different protective functions. The vast majority of epidermal cells are keratinocytes (Fig. 1).
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Activation of the complement system gives rise to a number of molecular species which can interact with host-derived cells and regulate their function. This interaction is mediated through distinct cell surface complement receptors, and receptor engagement produces biologic responses which can either modulate host defense reactions or enhance inflammation. Although the first complement receptor was recognized more than 30 years ago [80J, detailed biochemical information concerning the receptors has only recently become available. Currently, eight distinct complement receptors are recognized. Five receptors (CRl, CR2, CR3, C3a receptor, and C3e receptor) react with various regions on C3 while the other receptors display specificity for Clq, C5a, or Factor H. This chapter focusses on the chemistry of the various ligands and receptors and discusses the biologic activities which arise as a result of receptor-ligand interaction. II. CIQ Receptor A. The Ligand Clq is the recognition molecule of the classical complement pathway [reviewed in 20, 130].In serum, it is part of a calcium-dependent penta molecular complex containing one molecule ofClq and two molecules each of the pro enzymes Clr and CIs. During classical pathway activation, the macromolecular complex becomes associated with the activator through the Clq subcomponent. Bound Clq undergoes a conformational change and induces the proteolytic autoactivation of Clr which in turn effects the proteolytic activation of CIs. This process is controlled by the Cl inhibitor (ClINH) which binds irreversibly to activated Clr and CIs, and inhibits their enzymatic activities.