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by Anil Dasgupta
This book aims to trace the history of the discovery of antigen as a primer and give an overview on the development of immunology, which has undergone an evolution of stellar proportions, over the last two hundred years, particularly in the last six decades. 1. Immunology is the science that developed alongside its twin science microbiology. Its history goes back to 1798, when the discovery of antigen, a substance that generates an anti-substance as a molecule or a cell and that protects the host against infection, was made. It displays the state of specificity to an antigenic determinant, memory to a determinant to which it has previously been exposed and diversity in generating multiple binding specificities during clonal selection or antigen independent gene reshuffling and antigen dependent genetic reprogramming by the lymphocytes. Immunology deals with the Immune system and it developed in the process of evolution of man, enabling him to respond to non-self or foreign antigens and tolerate self or his own antigens limit infections from microbial agents and protect him from autoimmune diseases respectively and enable him to monitor neoplastic changes by the mechanism termed immune surveillance. 2. The immune system is a physiological system and a collection of cells and molecules, spread throughout the body, that constitute the anatomy, physiology and pathology of the immune system. The immune system is not an island. It does not work in isolation. It may also engage in cross-talk with others, for example MHC/HLA gene which is a part of immunogenetics, to guide protein antigen and maintain a steady state of homeostasis and integrity of the body as a whole. It would be appropriate to note that the cells, that protect us from infections, are the same cells that cause allograft rejections or tissue damage in hypersensitivity reactions. Furthermore, when a part of the immune system suffers, other parts of the body may be affected and vice versa, such as a person affected by adrenal hypertrophy, also called Cushing’s Syndrome, in which cortisone is increasingly released, may make the host susceptible to infection, perhaps as a result of stabilization of lysosomal membrane. It is hard today to find a disease which does not have a link with immunology. It is also hard to find an expert, in biomedical science, who does not take interest in immunology. 3. Cells of the immune system, that protect us from infections, originate mostly from pleuripotent haemopoietic stem cells—giving rise to the cells of the myeloid and lymphoid series, such as phagocytic cells, natural killer (NK) cells, accessory cells and lymphocytes— that have been extensively studied over the last more than six decades, in particular, B cells, subset of T cells and antigen presenting cells. Most of these cells are organized into lymphoid tissues and they are divided into: (i) Primary or central, such as bone marrow and thymus—a major site of lymphopoiesis and clonal selection (positive or negative) or induction of tolerance (i.e. central), involving antigen independent gene reshuffling, such as construction and expression of cell surface antigen receptor and (ii) Secondary or peripheral, such as unencapsulated lymphoid tissues and encapsulated lymph nodes spread all over the body—a major site of multifaceted immune reactivity involving antigen dependent genetic reprogramming, such as isotype switching, T cell differentiation and maintenance of tolerance (i.e. peripheral), together with lymphocyte traffic, antigen recognition, activation of lymphocytes and regulation of the immune response, that constitute the anatomy and physiology of the immune system. Peripheral tolerance or T regulatory cells (e.g. CD4+CD25+Foxp3+) may suppress T cell responses to self, even non-self, and limit the activation of mature self reactive T cells, that may have crossed through the barrier or passed the checkpoint, during clonal selection or lymphopoiesis. 4. Molecules of the immune system, that protect us from infection, are largely the products of the cells of myeloid and lymphoid series that too have been extensively studied over a period of time. Antibody, a best known molecule, that agglutinates bacteria, precipitates antigen, neutralizes toxin, activates complement and facilitates phagocytosis, is one together with the antigens, MHC/HLA gene products, receptor molecules, Cluster of Differentiation (CD) molecules, transduction molecules, transcription factors, complement and its activation products, chemokines, adhesion molecules, cytokines, interferons, pharmacological mediators, lysozymes, Toll receptors, mannose binding proteins and pattern recognition receptor molecules for defense of the host or immunity. 5. Immunity, traditionally defined as a state of protection against infection, is divided for convenience into two: innate and acquired. It consists of cellular and molecular elements of the immunity that may discriminate self from non-self and act singly, in combination or in continuum, and be expressed as: appropriate immunity, primary or secondary, such as immunity to infection. Infectious agents, that surround us, may cause diseases, but a great majority usually leave no pathology, perhaps as a result of eveready elements of innate immunity and booster or memory response of acquired immunity. Immunity is subject to a complex regulatory mechanism—involving astronomical number of different factors that may breakdown— giving rise to diseases of immunity and be expressed as: (i) impaired immunity, such as immunodeficiency disorders, congenital or acquired, and (ii) inappropriate immunity or altered reactivity to antigen to which it has previously been exposed, such as allergen in allergy, auto-antigen in autoimmunity, allo-antigen in transplantation reaction and neo-antigen in cancer, that constitute the pathology of the immune system, and that may be investigated routinely by immune-molecular techniques in the clinical laboratory for the diagnosis of diseases and the management of the patients. It may also be worthwhile to note that the random creation of cell surface receptors by gene rearrangement prior to antigen contact for immune response and the million fold range in binding affinities for a particular type of recognition, make the immune system intrinsically difficult to regulate. 6. In short, the book covers an introduction to immunology, with a brief description on the anatomy of the immune system. The immune system is a physiological system and it is a collection of cell and molecules which are deplored in certain strategies of the immune system, such as clonal selection or immunological tolerance or a antigen independent gene reshuffling, antigen dependent process of reprogramming, together with recognition of antigen, cells that process and present antigen with MHC molecules, activation of lymphocytes and regulation of the immune response. It also covers topics on innate and acquired immunity or immunity to infection, diseases of immunity and investigations relevant to the diagnosis of diseases and management of the patients. It would be appropriate to note that a reference of one or some knowledge of one side is essential for understanding another in immunology, such as (a) the reference of antibody of define antigen, (b) the reference of T cells for differentiation of antigenically activated B cells into antibody producing plasma cells in linked recognition for immunity, (c) the knowledge of immunity for immune tolerance, (d) the knowledge of immune for its mirror image autoimmune diseases and (e) the knowledge of the details of lymphoid tissues for immunodeficiencies.
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