Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 5)

The complement system (Chap. 308) consists of a group of serum proteins functioning as a cooperative, self-regulating cascade of enzymes that adhere to— and in some cases disrupt—the surface of invading organisms. Some of these surface-adherent proteins (e.g., C3b) can then act as opsonins for destruction of microbes by phagocytes. The later, "terminal" components (C7, C8, and C9) can directly kill some bacterial invaders (notably, many of the neisseriae) by forming a membrane attack complex and disrupting the integrity of the bacterial membrane, thus causing bacteriolysis. Other complement components, such as C5a, act as chemoattractants for PMNs (see below)....
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Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 5) Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 5) The complement system (Chap. 308) consists of a group of serum proteinsfunctioning as a cooperative, self-regulating cascade of enzymes that adhere to—and in some cases disrupt—the surface of invading organisms. Some of thesesurface-adherent proteins (e.g., C3b) can then act as opsonins for destruction ofmicrobes by phagocytes. The later, terminal components (C7, C8, and C9) candirectly kill some bacterial invaders (notably, many of the neisseriae) by forming amembrane attack complex and disrupting the integrity of the bacterial membrane,thus causing bacteriolysis. Other complement components, such as C5a, act aschemoattractants for PMNs (see below). Complement activation and depositionoccur by either or both of two pathways: the classic pathway is activated primarilyby immune complexes (i.e., antibody bound to antigen), and the alternativepathway is activated by microbial components, frequently in the absence ofantibody. PMNs have receptors for both antibody and C3b, and antibody andcomplement function together to aid in the clearance of infectious agents. PMNs, short-lived white blood cells that engulf and kill invading microbes,are first attracted to inflammatory sites by chemoattractants such as C5a, which isa product of complement activation at the site of infection. PMNs localize to thesite of infection by adhering to cellular adhesion molecules expressed byendothelial cells. Endothelial cells express these receptors, called selectins (CD-62, ELAM-1), in response to inflammatory cytokines such as tumor necrosisfactor α and interleukin 1. The binding of these selectin molecules to specificreceptors on PMNs results in the adherence of the PMNs to the endothelium.Cytokine-mediated upregulation and expression of intercellular adhesion molecule1 (ICAM 1) on endothelial cells then take place, and this latter receptor binds to β 2integrins on PMNs, thereby facilitating diapedesis into the extravascularcompartment. Once the PMNs are in the extravascular compartment, variousmolecules (e.g., arachidonic acids) further enhance the inflammatory process. Approach to the Patient: Infectious Diseases The clinical manifestations of infectious diseases at presentation aremyriad, varying from fulminant life-threatening processes to brief and self-limitedconditions to indolent chronic maladies. A careful history is essential and mustinclude details on underlying chronic diseases, medications, occupation, andtravel. Risk factors for exposure to certain types of pathogens may give importantclues to diagnosis. A sexual history may reveal risks for exposure to HIV andother sexually transmitted pathogens. A history of contact with animals maysuggest numerous diagnoses, including rabies, Q fever, bartonellosis, Escherichiacoli O157 infection, or cryptococcosis. Blood transfusions have been linked todiseases ranging from viral hepatitis to malaria to prion disease. A history ofexposure to insect vectors (coupled with information about the season andgeographic site of exposure) may lead to consideration of such diseases as RockyMountain spotted fever, other rickettsial diseases, tularemia, Lyme disease,babesiosis, malaria, trypanosomiasis, and numerous arboviral infections. Ingestionof contaminated liquids or foods may lead to enteric infection with Salmonella,Listeria, Campylobacter, amebas, cryptosporidia, or helminths. Since infectiousdiseases may involve many organ systems, a careful review of systems may elicitimportant clues as to the disease process. The physical examination must be thorough, and attention must be paid toseemingly minor details, such as a soft heart murmur that might indicate bacterialendocarditis or a retinal lesion that suggests disseminated candidiasis orcytomegalovirus (CMV) infection. Rashes are extremely important clues toinfectious diagnoses and may be the only sign pointing to a specific etiology(Chap. 18; Chap. e5). Certain rashes are so specific as to be pathognomonic—e.g.,the childhood exanthems (measles, rubella, varicella), the target lesion oferythema migrans (Lyme disease), ecthyma gangrenosum (Pseudomonasaeruginosa), and eschars (rickettsial diseases). Other rashes, although lessspecific, may be exceedingly important diagnostic indicators. The promptrecognition of the early scarlatiniform and later petechial rashes of meningococcalinfection or of the subtle embolic lesions of disseminated fungal infections inimmunosuppressed patients can hasten life-saving therapy. Fever (Chaps. 17, 18,and 19) is a common manifestation of infection and may be its sole apparentindication. Sometimes the pattern of fever or its temporally associated findingsmay help refine the differential diagnosis. For example, fever occurring every 48–72 h is suggestive of malaria (Chap. 203). The elevation in body temperature infever (through resetting of the hypothalamic setpoint mediated by cytokines) mustbe distinguished from elevations in body temperature from other causes such asdrug toxicity (Chap. 19) or heat stroke (Chap. 17). Laboratory Investigations Laboratory studies must be carefully considered and directed towardestablishing an etiologic diagnosis in the shortest possible time, at the lowestpossible cost, and with the least possible discomfort to the patient. Since mucosalsurfaces and the skin are colonized with many harmless or beneficialmicroorganisms, cultures must be performed in a manner that minimizes thelikelihood of contamination with this normal flora while maximizing the yield ofpathogens. A sputum sample is ...