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Cytolytic immune lymphocytes of the Human Host Products of the Evolving Universal Immune System
by Joseph G. Sinkovics
The Monograph: “Cytotoxic Lymphocytes of the Human Host Products of the Evolving Universal Immune System.”
Part I is devoted to molecular cell biology re-capitulating the formation of the first cells, their vertical and horizontal acquisition of new genes, using for examples extant archaea and primitive prokaryotes. A bold proposal is elaborated on the formation of the first eukaryotic nucleated cells from ancient virally mediated fusions of archaeal and prokaryotic spheroplasts. A detailed account on the evolution of viruses follows. The well preserved innate immune faculties (TLRs, chemokines, cytokines, complement, opsonins and bactericidal substances) include a detailed description of the interferons, and interfering iRNAs. The first multicellular organisms in the Cambrian sea already possessed dendritic cells and natural killer (NK) cells.
Part II traces back the origin of the RAG, RSS and V(D)J genomic sequences to ancient retrotransposons entering the genomes of ancient sharks. Another original proposal is that an ancestral herpesvirus transduced the RAG genes from sea urchins to sharks; the extant EBV still operates RAG-like genomic sequences. The entire adaptive immune system consisting of NKT, CD4 and CD8 T cells and antibody-secreting plasma cells becomes functional at this level. On one side, there is a fine-tuned cooperation between the innate and adaptive immune systems. On the other side, the mammalian placenta compromised the united innate and adaptive immune system by forcing it to accept the semi-allogeneic fetus. In terms of molecular immunobiology, both the placenta (temporarily), and the malignant tumor (permanently) utilize the same mechanisms of immunosuppression in order to achieve acceptance and nurturing by the host.
Part III is devoted to human tumor immunology/immunotherapy (vaccines; adoptive immune lymphocyte therapy and monoclonal antibodies). In an extraordinary chapter, the author describes the formation of a natural hybridoma between an antibody-secreting plasma cell and a lymphoma cell in the mouse; the description of this well documented and understood natural hybridoma predated by 5 years the Nobel-Prize winning discovery of Köhler & Milstein. Now the author proposes that the Sézary cell is a natural T cell hybridoma formed by the malignant mycosis fungoides T cell and a regulatory T cell.
Part IV is devoted to molecular immunobiology of human autoimmune diseases. The reactivation of HER occurring during somatic hypermutations of lymphoid cells receives great attention, as budding HER particles appear in lymphoid cell involved both in lymphomagenesis and autoimmunity.
Part V compares the generation of Th1- and Th2-type immune reactions of the host to exogenous pathogens (viruses, bacteria, fungi, parasites and worms) and to endogenous tumor cells. The comparison yields fascinating results.
Part VI is a Concise Synopsis summarizing the most recent data from 2007-8 of molecular cell biology and immunology, epigenetic tumor cell biology, the newest results with tumor vaccines, oncolytic viruses, and adoptive therapy with immune lymphocytes. There are 16 summary Tables and 12 large illustrations (figures, plates and graphs); and the number of selected and explained up-to-date references reaches 2370.
TLR = Toll-like receptors RAG = recombination activating genes RSS = recombination signal sequences V(D)J = variable, diversity, joining EBV = Epstein-Barr virus HER =human endogenous retroviruses
416 Seiten, Hardcover, 16,5 x 24 cm
ISBN 978-3-939337-57-7
Inhalt
CYTOTOXIC LYMPHOCYTES IN THE ARMAMENTARIUM OF THE HUMAN HOST PRODUCTS OF THE EVOLVING UNIVERSAL IMMUNE SYSTEM
Joseph G. Sinkovics
MD St. Joseph’s Hospital Cancer Institute Affiliated with the H. L. Moffitt Comprehensive Cancer Center at the University of South Florida; Department of Medical Microbiology and Immunology and Department of Molecular Medicine, The University of South Florida College of Medicine, Tampa, Florida, USA
1. The Innate Immune System
1.1 The Universal Ancestor(s)
1.2 Chemokines and Toll-like Receptors Make Their Appearance
1.3 Nod
1.4 Viral Evolution
1.5 Interferons and RNAi
1.6 The Ascidian Haemocyte and Its Followers
1.7 Programmed Cell Death
1.8 Bactericidal Substances
1.9 Some Simple Interactions
1.10. Oncogenic Mutations
2. The Adaptive Immune System
2.1 Primordial Adaptive Elements
2.2 Retrotransposons
2.3 Host and Viral Genetic Refinements
2.4 The Placenta
2.5 The Thymus, Bursa of Fabricius, and MALT
2.6 The Host Confronts Mutagenes and Pathogenes Attacking Lymphoid Tissues
2.7 T, B, NK, and TREG Cells
2.8 Humoral and Cell-Mediated Immunity
3. Tumor Immunology and Immunotherapy
3.1 Cancer Vaccines
3.2 Natural Lymphoid-Cell Hybridoma Formation by Cell Fusions
3.3 Lymphocytes Cytotoxic to Human Tumor Cells
3.4 Adoptive Immunotherapy with Cytotoxic Lymphocytes
4. Autoimmunity and Lymphomagenesis
4.1 Hashimoto’s Thyroiditis
4.2 Systemic Lupus Erythematosus
4.3 Autoimmunity and Malignant Thymoma
5. Cytotoxic Lymphocytes against Cellular and Viral Infectious Agents
5.1 Complex Eukaryotic Pathogens
5.2 Septic Shock
5.3 Interactions with Intracellular Bacteria
5.4 Anti-Oncoviral Immunity
6. Concise Synopsis 2007-8
6.1 From RNA Nucleotide Concentrates to Syntrophus and Upward
6.2 Innate Immune Faculties Regulate the Lymphocytes
6.3 Innate and Adaptive Interactions in Infections and Malignancies
6.4 Latest Events in Human Cancer Immunology and Immunotherapy
Summary
References over 2270 plus single-spaced small type Figures (Plates) 1 - 12; and Tables 1-14
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