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Chapter 6 – Diseases of the Immune System The Normal Immune Response Innate Immunity Adaptive Immunity Components of the Immune System: Cells, Tissues, and Selected Molecules Cells of the Immune System Tissues of the Immune System MHC Molecules: Peptide Display System of Adaptive Immunity Cytokines: Messenger Molecules of the Immune System Overview of Lymphocyte Activation and Immune Responses The Display and Recognition of Antigens Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes Decline of Immune Responses and Immunological Memory
Hypersensitivity and Autoimmune Disorders Mechanisms of Hypersensitivity Reactions Immediate (Type I) Hypersensitivity Antibody-Mediated (Type II) Hypersensitivity Immune Complex–Mediated (Type III) Hypersensitivity T Cell–Mediated (Type IV) Hypersensitivity Autoimmune Diseases Immunological Tolerance Mechanisms of Autoimmunity: General Principles General Features of Autoimmune Diseases Systemic Lupus Erythematosus (SLE) Spectrum of Autoantibodies in SLE Etiology and Pathogenesis of SLE Drug-Induced Lupus Erythematosus Rheumatoid Arthritis Sjögren Syndrome Etiology and Pathogenesis Systemic Sclerosis (Scleroderma) Etiology and Pathogenesis Inflammatory Myopathies Mixed Connective Tissue Disease Polyarteritis Nodosa and Other Vasculitides
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Rejection of Tissue Transplants Mechanisms of Recognition and Rejection of Allografts Rejection of Kidney Grafts Transplantation of Other Solid Organs Transplantation of Hematopoietic Cells Immunodeficiency Syndromes Primary Immunodeficiencies X-Linked Agammaglobulinemia (Bruton's Agammaglobulinemia) Common Variable Immunodeficieny Isolated IgA Deficiency Hyper-IgM Syndrome DiGeorge Syndrome (Thymic Hypoplasia) Severe Combined Immunodeficiency Immunodeficiency with Thrombocytopenia and Eczema (Wiskott-Aldrich Syndrome) Genetic Deficiencies of the Complement System Secondary Immunodeficiencies Acquired Immunodeficiency Syndrome (AIDS) Epidemiology Etiology: The Properties of HIV Pathogenesis of HIV Infection and AIDS Natural History of HIV Infection Clinical Features of AIDS
Amyloidosis Properties of Amyloid Proteins Pathogenesis of Amyloidosis Classification of Amyloidosis The immune system is vital for survival, because our environment is teeming with potentially deadly microbes and the immune system protects us from infectious pathogens. Predictably, immune deficiencies render individuals easy prey to infections. But the immune system is similar to the proverbial double-edged sword. Although it normally defends us against infections, a hyperactive immune system may cause diseases that can sometimes be fatal. Examples of disorders caused by immune responses include allergic reactions and reactions against an individual's own tissues and cells (autoimmunity). This chapter is devoted to diseases caused by too little immunity or too much immunologic reactivity. We also consider amyloidosis, a disease in which an abnormal protein, derived in some cases from fragments of immunoglobulins, is deposited in tissues. First, we review some of the important features of normal immune responses, to provide a foundation for understanding the abnormalities that give rise to immunological diseases.
The Normal Immune Response The normal immune response is best understood in the context of defense against infectious pathogens, the classical definition of immunity. The mechanisms of protection against infections fall into two broad categories. Innate immunity (also called natural, or native, immunity) refers to defense mechanisms that are present even before infection and that have evolved to specifically recognize microbes and protect individuals against infections. Adaptive immunity (also called acquired, or specific, immunity) consists of mechanisms that are stimulated by (“adapt to”) microbes and are capable of recognizing microbial and nonmicrobial substances. Innate immunity is the first line of defense, because it is always ready to prevent and eradicate infections. Adaptive immunity develops later, after exposure to microbes, and is even more
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powerful than innate immunity in combating infections. By convention, the term “immune response” refers to adaptive immunity.
INNATE IMMUNITY The major components of innate immunity are epithelial barriers that block entry of microbes, phagocytic cells (mainly neutrophils and macrophages), dendritic cells, natural killer (NK) cells, and several plasma proteins, including the proteins of the complement system. The two most important cellular reactions of innate immunity are: inflammation, the process in which phagocytic leukocytes are recruited and activated to kill microbes, and anti-viral defense, mediated by dendritic cells and NK cells. Leukocytes and epithelial cells that participate in innate immunity are capable of recognizing components of microbes that are shared among related microbes and are often essential for the infectivity of these pathogens (and thus cannot be mutated to allow the microbes to evade the defense mechanisms). These microbial structures are called pathogenassociated molecular patterns. Leukocytes also recognize molecules released by injured and necrotic cells, which are sometimes called danger-associated molecular patterns. The cellular receptors that recognize these molecules are often called pattern recognition receptors. The best-defined pattern recognition receptors are a family of proteins called Toll-like receptors (TLRs)[1] that are homologous to the Drosophila protein Toll. Different TLRs are specific for components of different bacteria and viruses. TLRs are located on the cell surface and in endosomes, so they are able to recognize and initiate cellular responses to extracellular and ingested microbes. Other microbial sensors are located in the cytoplasm, where they recognize bacteria and viruses that may have colonized cells. Upon recognition of microbes, the TLRs and other sensors signal by a common pathway that leads to the activation of transcription factors, notably NF-κB (nuclear factor κB). NF-κB turns on the production of cytokines and proteins that stimulate the microbicidal activities of various cells, notably the phagocytes. Other cellular receptors bind microbes for phagocytosis; these include receptors for mannose residues, which are typical of microbial but not host glycoproteins, and receptors for opsonins such as antibodies and complement proteins that coat microbes. Epithelia of the skin and gastrointestinal and respiratory tracts provide mechanical barriers to the entry of microbes from the external environment. Epithelial cells also produce anti-microbial molecules such as defensins, and lymphocytes located in the epithelia combat microbes at these sites. If microbes do breach epithelial boundaries, other defense mechanisms are called in. Monocytes and neutrophils are phagocytes in the blood that can rapidly be recruited to any site of infection; monocytes that enter the tissues and mature are called macrophages (Chapter 2). Dendritic cells produce type I interferons, anti-viral cytokines that inhibit viral infection and replication; these cells are described below, in the context of antigen display to lymphocytes. Natural killer cells provide early protection against many viruses and intracellular bacteria; their properties and functions are also described below. The proteins of the complement system, which were described in Chapter 2, are some of the most important plasma proteins of the innate immune system. Recall that in innate immunity the complement system is activated by microbes using the alternative and lectin pathways; in adaptive immunity it is activated by antibodies using the classical pathway. Other circulating proteins of innate immunity are mannose-binding lectin and C-reactive protein, both of which coat microbes for phagocytosis. Lung surfactant is also a component of innate immunity, providing protection against inhaled microbes. The early innate immune response not only provides the initial defense against infections but is also involved in triggering the subsequent, more powerful adaptive immune response. Copyright © 2011 Elsevier Inc. All rights reserved. Read our Terms and Conditions of Use and our Privacy Policy. For problems or suggestions concerning this service, please contact:
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