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Associate Professor, Loma Linda University School of Medicine
The bacterium is usually transmitted to humans through the inhalation of dried excrement medicine to stop runny nose discount 25mg antivert, urine symptoms after miscarriage best purchase for antivert, or respiratory secretions from psittacine birds medications given im antivert 25mg low price. Veterinarians medicine misuse definition buy cheap antivert 25mg line, zookeepers, pet shop workers, and employees of poultry-processing plants are at increased risk for this infection. The illness develops after an incubation of 5 to 14 days and usually manifests as headache, high fever, chills, malaise, and myalgias (see Figure 35-4). Central nervous system involvement is common, usually consisting of headache, but encephalitis, convulsions, coma, and death may occur in severe untreated cases. Patients may suffer gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea. Other systemic symptoms include carditis, hepatomegaly, splenomegaly, and follicular keratoconjunctivitis. Person-to-person transmission rarely occurs, so isolation of the patient and prophylactic treatment of contacts are not necessary. Psittacosis can be prevented only through the control of infections in domestic and imported pet birds. Such control can be achieved by treating birds with chlortetracycline hydrochloride for 45 days. E1 Case Study and Questions A 22-year-old man came to the emergency department with a history of urethral pain and purulent discharge that developed after he had sexual contact with a prostitute. Gram stain of the discharge revealed abundant gram-negative diplococci resembling Neisseria gonorrhoeae. Two days later, the patient returned to the emergency room with a complaint of persistent watery urethral discharge. Abundant white blood cells but no organisms were observed on Gram stain of the discharge. Describe the differences among the three Chlamydiaceae species that cause human disease. Describe the patient population most commonly infected and the epidemiology of these infections. It is likely that these antibiotics are ineffective because they cannot reach the peptidoglycan target. Three species of Chlamydiaceae are clinically important: Chlamydia trachomatis, Chlamydophila pneumoniae, and Chlamydophila psittaci. Unlike most bacteria, fungi, and parasites, viruses are obligate intracellular parasites that depend on the biochemical machinery of the host cell for replication. In addition, reproduction of viruses occurs by assembly of the individual components rather than by binary fission (Boxes 36-1 and 36-2). Viruses lack the capacity to make energy or substrates, cannot make their own proteins, and cannot replicate their genome independently of the host cell. The physical structure and genetics of viruses have been optimized by mutation and selection to infect humans and other hosts. To do this, the virus must be capable of transmission between hosts, must traverse the skin or other protective barriers of the host, must be adapted to the biochemical machinery of the host cell for replication, and must escape elimination by the host immune response. Knowledge of the structural (size and morphology) and genetic (type and structure of nucleic acid) features of a virus provides insight into how the virus replicates, spreads, and causes disease. The concepts presented in this chapter are repeated in greater detail in the discussions of specific viruses in later chapters. Norwalk virus is named for Norwalk, Ohio; coxsackievirus is named for Coxsackie, New York; and many of the togaviruses, arenaviruses, and bunyaviruses are named after African places where they were first isolated.
Transformation was the first mechanism of genetic transfer to be discovered in bacteria treatment yersinia pestis proven antivert 25mg. In 1928 treatment 7 february order on line antivert, Griffith observed that pneumococcal virulence was related to the presence of a polysaccharide capsule and that extracts of encapsulated bacteria producing smooth colonies could transmit this trait to nonencapsulated bacteria medicine 79 buy discount antivert 25mg line, normally appearing as rough colonies symptoms joint pain fatigue order antivert uk. Conjugation occurs with most, if not all, eubacteria, usually between members of the same or related species, but it has also been demonstrated to occur between prokaryotes and cells from plants, animals, and fungi. The mating type (sex) of the cell depends on the presence (male) or absence (female) of a conjugative plasmid, such as the F plasmid of E. When it transfers into the recipient cell, it carries that fragment with it and converts it into an F male. If the F plasmid sequence is integrated into the bacterial chromosome, the cell is designated an Hfr (high-frequency recombination) cell. Mobilization begins when a plasmid-encoded protein makes a singlestranded site-specific cleavage at the oriT. The nick initiates rolling circle replication, and the displaced linear strand is directed to the recipient cell. Because of the fragile connection between the mating pairs, the transfer is usually aborted before being completed, such that only the chromosomal sequences adjacent to the integrated F are transferred. Artificial interruption of a mating between an Hfr and an F- pair has been helpful in constructing a consistent map of the E. Box 13-2 GenerationofVancomycin-Resistant Staphylococcus aureusbyMultipleGeneticManipulations Until recently, vancomycin was the last-resort drug for Staphylococcus aureus strains resistant to -lactam (penicillin-related) antibiotics. The gene for vancomycin resistance was contained within a transposon (Tn1546) on a multiresistance conjugative plasmid. Generalized transducing particles are valuable in the genetic mapping of bacterial chromosomes. This process usually requires specialized (sometimes site-specific) recombination enzymes, such as those produced by many transposons and lysogenic bacteriophages. The use of genetic engineering and "cloning" has revolutionized biology and medicine. Bacteriophages, such as lambda, are used for larger fragments up to 25 kb, and cosmid vectors have combined some of the advantages of plasmids and phages for fragments up to 45 kb. Restriction enzymes recognize a specific palindromic sequence and make a staggered cut that generates sticky ends or a blunt cut that generates blunt ends (see Table 13-1). Genetic engineering has been used to isolate and express the genes for useful proteins such as insulin, interferon, growth hormones, and interleukin in bacteria, yeast, or even insect cells. Similarly, large amounts of pure immunogen for a vaccine can be prepared without the need to work with the intact disease organisms. The hepatitis B surface antigen is produced by the yeast Saccharomyces cerevisiae. Bibliography Alberts B: Molecular biology of the cell, ed 4, New York, 2002, Garland Science. What products of anaerobic fermentation would be detrimental to host (human) tissue. Which mechanisms may be used by a bacterial cell for the exchange of genetic material Discuss the applications of molecular biotechnology to medicine, including contributions and uses in diagnoses. Anaerobic conditions: Glycolysis occurs in a process called fermentation without respiration. Repression: A repressor protein binds to the promoter sequence and prevents the polymerase from binding. For the lac operon, the repressor prevents expression of the gene unless lactose is present.
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In the first part of this chapter we will describe the interactions of B cells with helper T cells that lead to the production of antibodies symptoms restless leg syndrome buy 25mg antivert fast delivery, the affinity maturation of this antibody response medicine education antivert 25 mg visa, the isotype switching that confers functional diversity medicine ball chair order antivert canada, and the generation of memory B cells that provide long-lasting immunity to reinfection medicine 5325 discount antivert 25mg with mastercard. In the rest of the chapter we will discuss in detail the mechanisms whereby antibodies contain and eliminate infections. The humoral immune response is mediated by antibody molecules that are secreted by plasma cells. Antigen that binds to the B-cell antigen receptor signals B cells and is, at the same time, internalized and processed into peptides that activate armed helper T cells. Signals from the bound antigen and from the helper T cell induce the B cell to proliferate and differentiate into a plasma cell secreting specific antibody (top two panels). They can inhibit the toxic effects or infectivity of pathogens by binding to them: this is termed neutralization (bottom left panel). By coating the pathogens, they can enable accessory cells that recognize the Fc portions of arrays of antibodies to ingest and kill the pathogen, a process called opsonization (bottom center panel). Complement proteins can strongly enhance opsonization, and can directly kill some bacterial cells (bottom right panel). Some microbial antigens can activate B cells directly in the absence of T-cell help. The ability of B cells to respond directly to these antigens provides a rapid response to many important bacterial pathogens. However, somatic hypermutation and switching to certain immunoglobulin isotypes depend on the interaction of antigen-stimulated B cells with helper T cells and other cells in the peripheral lymphoid organs. Antibodies induced by microbial antigens alone are therefore less variable and less functionally versatile than those induced with T-cell help. The humoral immune response is initiated when B cells that bind antigen are signaled by helper T cells or by certain microbial antigens alone. It is a general rule in adaptive immunity that naive antigen-specific lymphocytes are difficult to activate by antigen alone. Naive T cells require a co-stimulatory signal from professional antigen-presenting cells; naive B cells require accessory signals that can come either from an armed helper T cell or, in some cases, directly from microbial constituents. Thus, protein antigens binding to B cells both provide a specific signal to the B cell by cross-linking its antigen receptors and allow the B cell to attract antigenspecific T-cell help. A second signal is required for B-cell activation by either thymus-dependent or thymusindependent antigens. The first signal required for B-cell activation is delivered through its antigen receptor (top panel). For thymus-independent antigens, the second signal can be delivered by the antigen itself (lower panel), or by non-thymus-derived accessory cells (not shown). When mice are immunized with hen egg lysozyme coupled to three linked molecules of the complement fragment C3dg, the modified lysozyme induces antibody without added adjuvant at doses up to 10,000 times smaller than unmodified hen egg lysozyme. As we will see later in this chapter, antibodies already bound to antigens can activate the complement system, thus coating the antigen with C3d and producing a more potent antigen, which in turn leads to more efficient B-cell activation and antibody production. Although armed peptide-specific helper T cells are required for B-cell responses to protein antigens, many microbial constituents, such as bacterial polysaccharides, can induce antibody production in the absence of helper T cells. Thymus-independent antibody responses provide some protection against extracellular bacteria, and we will return to them later. T-cell dependent antibody responses require the activation of B cells by helper T cells that respond to the same antigen; this is called linked recognition. This presumably occurs by interaction with an antigen-presenting dendritic cell (see Section 8-1). Although the epitope recognized by the armed helper T cell must therefore be linked to that recognized by the B cell, the two cells need not recognize identical epitopes. Indeed, we saw in Chapter 5 that T cells can recognize internal peptides that are quite distinct from the surface epitopes on the same protein recognized by B cells. For more complex natural antigens, such as viruses, the T cell and the B cell might not even recognize the same protein. It is, however, crucial that the peptide recognized by the T cell be a physical part of the antigen recognized by the B cell, which can thus produce the appropriate peptide after internalization of the antigen bound to its B-cell receptors. For example, by recognizing an epitope on a viral protein coat, a B cell can internalize a complete virus particle. Helper T cells that have been primed earlier in an infection by macrophages or dendritic cells presenting these internal peptides can then activate the B cell to make antibodies that recognize the coat protein.
Enterotoxins Numerous distinct staphylococcal enterotoxins (A to X) have been identified medicine for vertigo order 25mg antivert fast delivery, with enterotoxin A most commonly associated with food poisoning 247 medications buy cheapest antivert. Enterotoxins C and D are found in contaminated milk products treatment xanthelasma eyelid buy antivert 25 mg low cost, and enterotoxin B causes staphylococcal pseudomembranous enterocolitis symptoms zinc overdose discount antivert 25mg with visa. Less is known about the prevalence or clinical importance of the other enterotoxins. Thus, once a food product has been contaminated with enterotoxin-producing staphylococci and the toxins have been produced, neither mild reheating of the food nor exposure to gastric acids will be protective. These toxins are superantigens capable of inducing nonspecific activation of T cells and massive cytokine release. Characteristic histologic changes in the stomach and jejunum include infiltration of neutrophils into the epithelium and underlying lamina propria, with loss of the brush border in the jejunum. Stimulation of release of inflammatory mediators from mast cells is believed to be responsible for the emesis that is characteristic of staphylococcal food poisoning. The cell-free coagulase accomplishes the same result by reacting with a globulin plasma factor (coagulase-reacting factor) to form staphylothrombin, a thrombin-like factor. The role of coagulase in the pathogenesis of disease is speculative, but coagulase may cause the formation of a fibrin layer around a staphylococcal abscess, thus localizing the infection and protecting the organisms from phagocytosis. Some other species of staphylococci produce coagulase, but these are primarily animal pathogens and uncommonly recovered in human infections. Staphylococci produce a variety of other enzymes that hydrolyze host tissue components and aid in bacterial spread. Hyaluronidase hydrolyzes hyaluronic acids, present in the acellular matrix of connective tissue. Interestingly, the strains were not related to strains circulating in hospitals, and strains isolated in each country were genetically unique. Unfortunately, the community strains have moved into hospitals in the last decade, complicating control measures previously established. Hospitalized patients are now susceptible to infections caused by strains they were colonized with in the community as well as strains acquired in the hospital. The clinical manifestations of some staphylococcal diseases are almost exclusively the result of toxin activity. Likewise, patients with congenital diseases associated with an impaired chemotactic or phagocytic response. All persons have coagulasenegative staphylococci on their skin, and transient colonization of moist skinfolds with S. Approximately 15% of normal healthy adults are persistent nasopharyngeal carriers of S. Adherence of the organism to the mucosal epithelium is regulated by the staphylococcal cell surface adhesins. Because staphylococci are found on the skin and in the nasopharynx, shedding of the bacteria is common and is responsible for many hospital-acquired infections. Staphylococci are susceptible to high temperatures and disinfectants and antiseptic solutions; however, the organisms can survive on dry surfaces for long periods. The organisms can be transferred to a susceptible person either through direct contact or through contact with fomites. Therefore, medical personnel must use proper hand-washing techniques to prevent transfer of staphylococci from themselves to patients or among patients. Slight pressure displaces the skin (a positive Nikolsky sign), and large bullae or cutaneous blisters form soon thereafter, followed by desquamation of the epithelium (Figure 18-3). The blisters contain clear fluid but no organisms or leukocytes, a finding consistent with the fact that the disease is caused by the bacterial toxin. The epithelium becomes intact again within 7 to 10 days, when antibodies against the toxin appear. This is a disease primarily of neonates and young children, with the mortality rate less than 5%. When death does occur, it is a result of secondary bacterial infection of the denuded skin areas. Infections in adults usually occur in immunocompromised hosts or patients with renal disease, and mortality is as high as 60%. The disease occurs primarily in infants and young children and is highly communicable.