Harrison's Internal Medicine Chapter 114. Molecular Mechanisms of Microbial Pathogenesis
Molecular Mechanisms of Microbial Pathogenesis: Introduction
Over the past three decades, molecular studies of the pathogenesis of microorganisms have yielded an explosion of information about the various microbial and host molecules that contribute to the processes of infection and disease.
Numerous virus–target cell interactions have been described, and it is now clear that different viruses can use similar host-cell receptors for entry. The list of certain and likely host receptors for viral pathogens is long. Among the host membrane components that can serve as receptors for viruses are sialic acids, gangliosides, glycosaminoglycans, integrins and other members of the immunoglobulin superfamily, histocompatibility antigens, and regulators and receptors for complement components.
Central to the development of glomerular inflammation and injury are alterations and
abnormalities of various cytokines and signaling systems. There are four chapters in
this book that deal with these aspects in the pathogenesis. The role of TGF-β in
progressive glomerular disease is discussed in great detail in a chapter well written by
Hyun Soon Lee, with particular reference to mesangial matrix accumulation, while the
role of STAT3 activation in glomerulonephritis is elaborated in the well written
chapter by Fumio Tsuji et al.
Reiko Inagi reviewed very lucidly the role of endoplasmic reticulum in the stress of
responses in glomeruli, while the pathogenic significance of dendritic cells in
autoimmune glomerulonephritis is elaborated by Yahuan Lou. Finally, the relevance
of urinary biomarkers in relation to pathogenesis of glomerulonephritis is put together
in a concise chapter written by Sophie Ohlsson.
Encounters with Epithelial Cells
Over the past decade, many bacterial pathogens have been shown to enter epithelial cells (Fig. 114-2); the bacteria often use specialized surface structures that bind to receptors, with consequent internalization. However, the exact role and the importance of this process in infection and disease are not well defined for most of these pathogens. Bacterial entry into host epithelial cells is seen as a means for dissemination to adjacent or deeper tissues or as a route to sanctuary to avoid ingestion and killing by professional phagocytes.
GPI-anchored receptors do not have intracellular signaling domains. Instead, the mammalian Toll-like receptors (TLRs) transduce signals for cellular activation due to LPS binding. It has recently been shown that binding of microbial factors to TLRs to activate signal transduction occurs not on the cell surface, but rather in the phagosome of cells that have internalized the microbe. This interaction is probably due to the release of the microbial surface factor from the cell in the environment of the phagosome, where the liberated factor can bind to its cognate TLRs.
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Glomerular matrix metalloproteinases and their regulators in the pathogenesis of lupus nephritis...
Tham khảo tài liệu 'báo cáo hóa học:" role of the vegf-flt-1-fak pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone"', luận văn - báo cáo phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả
(See also Chap. 161) All viral pathogens must bind to host cells, enter them, and replicate within them. Viral coat proteins serve as the ligands for cellular entry, and more than one ligand-receptor interaction may be needed; for example, HIV uses its envelope glycoprotein (gp) 120 to enter host cells by binding to both CD4 and one of two receptors for chemokines (designated CCR5 and CXCR4). Similarly, the measles virus H glycoprotein binds to both CD46 and the membrane-organizing protein moesin on host cells.
Encounters with Phagocytes
Phagocytosis and Inflammation Phagocytosis of microbes is a major innate host defense that limits the growth and spread of pathogens. Phagocytes appear rapidly at sites of infection in conjunction with the initiation of inflammation. Ingestion of microbes by both tissue-fixed macrophages and migrating phagocytes probably accounts for the limited ability of most microbial agents to cause disease.
Many diseases are caused primarily by pathogens growing in tissue sites that are normally sterile. Pneumococcal pneumonia is mostly attributable to the growth of S. pneumoniae in the lung and the attendant host inflammatory response, although specific factors that enhance this process (e.g., pneumolysin) may be responsible for some of the pathogenic potential of the pneumococcus. Disease that follows bacteremia and invasion of the meninges by meningitisproducing bacteria such as N. meningitidis, H. influenzae, E.
Transmission to New Hosts
As part of the pathogenic process, most microbes are shed from the host, often in a form infectious for susceptible individuals. However, the rate of transmissibility may not necessarily be high, even if the disease is severe in the infected individual, as transmissibility and virulence are not linked traits.
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: α The role of anti-α-actinin antibodies in the pathogenesis and monitoring of lupus nephritis...
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The second part of the book is dedicated to the pathogenesis of myocarditis. The
chapters in this part also discuss some clinical findings, but mostly focus on the
underlying mechanism of the disease, using in-depth data from mouse models. Some
of the chapters focus on host immune response. For example, one chapter reviews the
role of pattern-recognition receptors in myocarditis, and another chapter examines the
role of lymphocyte effectors in myocarditis pathogenesis.
Flagella are long appendages attached at either one or both ends of the bacterial cell (polar flagella) or distributed over the entire cell surface (peritrichous flagella). Flagella, like pili, are composed of a polymerized or aggregated basic protein. In flagella, the protein subunits form a tight helical structure and vary serologically with the species. Spirochetes such as T. pallidum and Borrelia burgdorferi have axial filaments similar to flagella running down the long axis of the center of the cell, and they "swim" by rotation around these filaments.
Tuyển tập các báo cáo nghiên cứu khoa học quốc tế về bệnh thú y đề tài: Effects of cyclosporin A treatment on the pathogenesis of avian leukosis virus subgroup J infection in broiler chickens with Marek’s disease virus exposure
Tuyển tập các báo cáo nghiên cứu khoa học quốc tế về bệnh thú y đề tài: The effects of cyclophosphamide treatment on the pathogenesis of subgroup J avian leukosis virus (ALV-J) infection in broiler chickens with Marek's disease virus exposure