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This magni fication is achieved when light rays from an illuminator diabetes prevention drug generic pioglitazone 30 mg without prescription, the light source, pass through a condenser, which has lenses that direct the light rays through the specimen. From here, light rays pass into the objective lenses, the lenses closest to the specimen. We can calculate the total magnification of a specimen by multiplying the objective lens magnification (power) by the ocular lens magnification (power). Most microscopes used in microbiology have several objective lenses, including 10* (low power), 40* (high power), and 100* (oil immersion). Multi plying the magnification of a specific objective lens with that of the ocular, we see that the total magnifications would be 100* for low power, 400* for high power, and 1000* for oil immersion. She jokes her husband should buy stock in Pepto-Bismol, because she buys so much of it. After hearing that Maryanne feels better immediately after taking Pepto-Bismol, the doctor suspects Maryanne may have 5 mm a peptic ulcer associated with Helicobacter pylori. Because different microscopes have different resolution ranges, the size of a specimen determines which microscopes can be used to view the specimen effectively. Most micrographs shown in this textbook (like the ones above) have size bars and symbols to help you identify the actual size of the specimen and the type of microscope used for that image. Resolution (also called resolving power) is the ability of the lenses to distinguish fine detail and structure. Specifi cally, it refers to the ability of the lenses to distinguish two points that are a specified distance apart. A general principle of microscopy is that the shorter the wavelength of light used in the instrument, the greater the resolution. The white light used in a compound light microscope has a relatively long wavelength and cannot resolve structures smaller than about 0. This and other considerations limit the magnification achieved by the best compound 54 light microscopes to about 1500 *. To obtain a clear, finely detailed image under a com pound light microscope, specimens must contrast sharply with their medium (the substance in which they are sus pended). To attain such contrast, we must change the refrac tive index of specimens from that of their medium. We change the refractive index of specimens by staining them, a procedure we will discuss shortly. After the specimen is stained, the specimen and its medium have different refractive indexes. When light rays pass through the two materials (the specimen and its medium), the rays change direction (refract) from a straight path by bending or changing angle at the boundary between the materials. As the light rays travel away from the specimen, they spread out and enter the objective lens, and the image is thereby magnified. To achieve high magnification (1000*) with good reso lution, the objective lens must be small. Although we want light traveling through the specimen and medium to refract differently, we do not want to lose light rays after they have passed through the stained specimen. The immersion oil has the same refractive index as glass, so the oil becomes part of the optics of the glass of the microscope. Unless immersion oil is used, light rays are refracted as they enter the air from the slide, and the objective lens would have to be increased in diam eter to capture most of them. The oil has the same effect as increasing the objective lens diameter; therefore, it improves the resolving power of the lenses. If oil is not used with an oil immersion objective lens, the image has poor resolution and becomes fuzzy. Under usual operating conditions, the field of vision in a compound light microscope is brightly illuminated. It is not always desirable to stain a specimen, but an unstained cell has little contrast with its surroundings and is therefore difficult to see. Unstained cells are more easily observed with the modified compound microscopes described in the next section. Unrefracted light Oil immersion objective lens Without immersion oil, most light is refracted and lost Immersion oil Air Glass slide Condenser lenses Condenser Darkfield Microscopy A darkfield microscope is used to examine live microorgan isms that either are invisible in the ordinary light microscope, cannot be stained by standard methods, or are so distorted by staining that their characteristics are obscured. Only light that is reflected off (turned away from) the specimen enters the objective lens. This tech nique is frequently used to examine unstained microorgan isms suspended in liquid. Phase-Contrast Microscopy Another way to observe microorganisms is with a phasecontrast microscope. Phasecontrast microscopy is especially useful because the internal structures of a cell become more sharply defined, permitting detailed examination of living microorganisms. In a phasecontrast microscope, one set of light rays comes directly from the light source. The other set comes from light that is reflected or diffracted from a particular structure in the specimen. Because the refractive indexes of the glass microscope slide and immersion oil are the same, the light rays do not refract when passing from one to the other when an oil immersion objective lens is used. Q Why is immersion oil necessary at 10003 but not with the lower power objectives The only light that reaches the specimen comes in at an angle; thus, only light reflected by the specimen (blue lines) reaches the objective lens. Direct light rays (unaltered by the specimen) travel a different path from light rays that are reflected or diffracted as they pass through the specimen. The photographs compare the protozoan Paramecium using these three different microscopy techniques. Q What are the advantages of brightfield, darkfield, and phase-contrast microscopy The diffracted rays are bent away from the parallel light rays that pass farther from the speci men. In addition, prisms split each light beam, adding contrasting colors to the specimen. The colors in the image are produced by prisms that split the two light beams used in this process. Some organisms fluoresce naturally under ultraviolet light; if the specimen to be viewed does not naturally fluoresce, it is stained with one of a group of fluorescent dyes called fluorochromes. When microorganisms stained with a fluorochrome are examined under a fluorescence microscope with an ultra violet or nearultraviolet light source, they appear as lumines cent, bright objects against a dark background. For example, the fluorochrome auramine O, which glows yellow when exposed to ultraviolet light, is strongly absorbed by Mycobacterium tuberculosis, the bacterium that causes tuberculosis. When the dye is applied to a sample of material suspected of containing the bacterium, the bacterium can be detected by the appearance of bright yellow organ isms against a dark background. Antibodies are natural defense mol ecules that are produced by humans and many animals in reac tion to a foreign substance, or antigen. Fluorescent antibodies for a particular antigen are obtained as follows: an animal is injected with a specific antigen, such as a bacterium, and the animal then begins to produce antibodies against that anti gen. These fluorescent antibodies are then added to a microscope slide containing an unknown bacterium. If this unknown bacterium is the same bacterium that was injected into the animal, the fluorescent antibodies bind to antigens on the surface of the bacterium, causing it to fluoresce. When the preparation is added to bacterial cells on a microscope slide, the antibodies attach to the bacterial cells, and the cells fluoresce when illuminated with ultraviolet light. Twophoton microscopy uses longwavelength (red) light, and therefore two photons, instead of one, are needed to excite the fluoro chrome to emit light. Confocal microscopy can image cells in detail only to a depth of less than 100 mm. Additionally, the longer wavelength is less likely to generate singlet oxygen, which damages cells (see page 156). For example, cells of the immune system have been observed responding to an antigen. Confocal microscopy produces three-dimensional images and can be used to look inside cells.

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If a particular disease occurs only occasionally diabetes medications help cheap pioglitazone 15 mg with amex, it is called a sporadic disease; typhoid fever in the United States is such a disease. A disease constantly present in a population is called an endemic disease; an example of such a disease is the common cold. If many people in a given area acquire a certain disease in a relatively short period, it is called an epidemic disease; influenza is an example of a disease that often achieves epidemic status. Severity or Duration of a Disease Another useful way of defining the scope of a disease is in terms of its severity or duration. An acute disease is one that develops rapidly but lasts only a short time; a good example is influenza. A disease that is intermediate between acute and chronic is described as a subacute disease; an example is subacute sclerosing panencephalitis, a rare brain disease characterized by diminished intellectual function and loss of nervous function. A latent disease is one in which the causative agent remains inactive for a time but then becomes active to produce symptoms of the disease; an example is shingles, one of the diseases caused by Varicellovirus. Another example of a latent disease is cold sores, which are caused by Simplexvirus. The virus resides in the nerve cells of the body but causes no damage until it is activated by a stimulus such as sunburn or fever. The rate at which a disease or an epidemic spreads and the number of individuals involved are determined in part by the immunity of the population. Vaccination can provide longlasting and sometimes lifelong protection of an individual against certain diseases. People who are immune to an infectious disease may carry the pathogen but not have the disease, thereby reducing the occurrence of the disease. Even though a highly communicable disease may cause an epidemic, many nonimmune people will be protected because of the unlikelihood of their coming into contact with an infected person. If most people in a population (herd) are immune to a particular disease, this form of immunity is referred to as herd immunity. Where there is herd immunity, outbreaks are limited to sporadic cases because there are not enough susceptible individuals to support the spread of the disease to epidemic proportions. Susceptible individuals include children who are too young to be vaccinated or whose parents refuse to vaccinate them, people with immune disorders, and those who are too ill to be vaccinated (for example, some cancer patients). An example of a disease that has been eradicated by vaccination and herd immunity is smallpox. The World Health Organization hopes to eradicate other diseases, such as measles and polio, as well. A local infection is one in which the invading microorganisms are limited to a relatively small area of the body. In a systemic (generalized) infection, microorganisms or their products are spread throughout the body by the blood or lymph. Very often, agents of a local infection enter a blood or lymphatic vessel and spread to other specific parts of the body, where they are confined to specific areas of the body. Focal infections can arise from infections in areas such as the teeth, tonsils, or sinuses. Sepsis is a toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection. Septicemia, also called blood poisoning, is a systemic infection arising from the multiplication of pathogens in the blood. Toxemia refers to the presence of toxins in the blood (as occurs in tetanus), and viremia refers to the presence of viruses in blood. Secondary infections of the skin and respiratory tract are common and are sometimes more dangerous than the primary infections. Poliovirus and hepatitis A virus, for example, can be carried by people who never develop the illness. As you will learn shortly, for an infectious disease to occur, there must be a reservoir of infection as a source of pathogens. Next, the pathogen must be transmitted to a susceptible host by direct contact, by indirect contact, or by vectors. Transmission is followed by invasion, in which the microorganism enters the host and multiplies. Following invasion, the microorganism injures the host through a process called pathogenesis (discussed further in the next chapter). The extent of injury depends on the degree to which host cells are damaged, either directly or by toxins. Despite the effects of all these factors, the occurrence of disease ultimately depends on the resistance of the host to the activities of the pathogen. Predisposing Factors Certain predisposing factors also affect the occurrence of disease. A predisposing factor makes the body more susceptible to a disease and may alter the course of the disease. Gender is sometimes a predisposing factor; for example, females have a higher incidence of urinary tract infections than males, whereas males have higher rates of pneumonia and meningitis. For example, sickle cell disease is a severe, life-threatening form of anemia that occurs when the genes for the disease are inherited from both parents. Individuals who carry only one sickle cell gene have a condition called sickle cell trait and appear normal unless specially tested. The potential that individuals in a population might inherit life-threatening sickle cell disease is more than counterbalanced by protection from malaria among carriers of the gene for sickle cell trait. Climate and weather seem to have some effect on the incidence of infectious diseases. In temperate regions, the incidence of respiratory diseases increases during the winter. This increase may be related to the fact that when people stay indoors, the closer contact with one another facilitates the spread of respiratory pathogens. Other predisposing factors include vaccination and herd immunity in decreasing the spread of diseases, age (the very young and elderly are more susceptible to infections), antigenic variants and antigenic drift, behavioral and religious practices, inadequate nutrition, environment, habits, lifestyle, fatigue, occupation, preexisting illness, and chemotherapy. During the period of illness, the number of white blood cells may increase or decrease. If the disease is not successfully overcome (or successfully treated), the patient dies during this period. Most severe signs and symptoms Signs and symptoms Time Period of Decline During the period of decline, the signs and symptoms subside. During this phase, which may take from less than 24 hours to several days, the patient is vulnerable to secondary infections. Period of Convalescence During the period of convalescence, the person regains strength and the body returns to its prediseased state. We all know that during the period of illness, people can serve as reservoirs of disease and can easily spread infections to other people. However, you should also know that people can spread infection during incubation and prodrome as well. This is especially true of diseases such as typhoid fever and cholera, in which the convalescing person carries the pathogenic microorganism for months or even years. Incubation Period the incubation period is the interval between the initial infection and the first appearance of any signs or symptoms. In some diseases, the incubation period is always the same; in others, it is quite variable. The time of incubation depends on the specific microorganism involved, its growth rate, the number of infecting microorganisms, and the resistance of the host. Whether a disease can be transmitted during the incubation period depends on the specific pathogen. The prodromal period is characterized by early, mild symptoms of disease, such as general aches and malaise. It is often difficult to differentiate the common cold from the prodromal symptoms related to other diseases such as measles, chickenpox, or cytomegalovirus infection. The person exhibits overt signs and symptoms of disease, such as 14-10 What is a predisposing factor If the person next to you has a cold, when will you know whether you contracted it

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This is used for postexposure prophylaxis from diseases such as rabies or in immunotherapy (discussed in Chapters 18 and 19) blood sugar problems quality 45mg pioglitazone. When an individual is given artificially acquired passive immunity, it confers an immediate passive protection against the disease. However, although artificially acquired passive immunity is immediate, it is short-lived because antibodies are degraded by the recipient. The half-life of an injected antibody (the time required for half of the antibodies to disappear) is typically about 3 weeks. Plasma cell Memory cells Some T and B cells differentiate into memory cells that respond rapidly to any secondary encounter with an antigen. Humoral immunity, also called antibody-mediated immunity, is directed at freely circulating pathogens and depends on B cells. Cellular immunity, also called cell-mediated immunity, depends on T cells to eliminate intracellular pathogens, reject foreign tissue recognized as nonself, and destroy tumor cells. Humoral immunity involves antibodies, which are found in serum and lymph and are produced by B cells. Cellular immunity responds to intracellular antigens; humoral immunity responds to antigens in body fluids. Typical monomers consist of four polypeptide chains: two heavy chains and two light chains. Within each chain is a variable (V) region that binds the epitope and a constant (C) region that distinguishes the different classes of antibodies. An antibody monomer is Y-shaped or T-shaped: the V regions form the tips, and the C regions form the base and Fc (stem) region. IgG antibodies are the most prevalent in serum; they provide naturally acquired passive immunity, neutralize bacterial toxins, participate in complement fixation, and enhance phagocytosis. IgM antibodies consist of five monomers held by a joining chain; they are involved in agglutination and complement fixation. Serum IgA antibodies are monomers; secretory IgA antibodies are dimers that protect mucosal surfaces from invasion by pathogens. IgE antibodies bind to mast cells and basophils and are involved in allergic reactions. Cells of the immune system communicate with each other by means of chemicals called cytokines. Overproduction of cytokines leads to a cytokine storm, which results in tissue damage. Immunoglobulin genes in B cells recombine so that mature B cells each have different genes for the V region of their antibodies. An antigen (or immunogen) is a chemical substance that causes the body to produce specific antibodies. Antibodies are formed against specific regions on antigens called epitopes, or antigenic determinants. A hapten is a low-molecular-mass substance that cannot cause the formation of antibodies unless combined with a carrier molecule; haptens react with their antibodies independently of the carrier molecule. Agglutination results when an antibody combines with epitopes on two different cells. Antibodies that attach to microbes or toxins and prevent them gaining access to the host or performing their action cause neutralization. An antibody, or immunoglobulin, is a protein produced by B cells in response to an antigen and is capable of combining specifically with that antigen. Immunity resulting from infection is called naturally acquired active immunity; this type of immunity may be long-lasting. Antibodies transferred from a mother to a fetus (transplacental transfer) or to a newborn in colostrum results in naturally acquired passive immunity in the newborn; this type of immunity can last up to a few months. Immunity resulting from vaccination is called artificially acquired active immunity and can be long-lasting. Artificially acquired passive immunity refers to humoral antibodies acquired by injection; this type of immunity can last for a few weeks. Draw the antibody response of this same individual to exposure to a new antigen at time B. How can a human make over 10 billion different antibodies with only 25,000 different genes Explain why a person who recovers from a disease can attend others with the disease without fear of contracting it. Why is dietary protein deficiency associated with increased susceptibility to infections A positive tuberculin skin test shows cellular immunity to Mycobacterium tuberculosis. She survived because the emergency department physician injected her with antivenin to neutralize the toxin. A woman had life-threatening salmonellosis that was successfully treated with anti-Salmonella. A patient with chronic diarrhea was found to lack IgA in his secretions, although he had a normal level of serum IgA. Newborns (under 1 year) who contract dengue have a higher chance of dying from it if their mothers had dengue prior to pregnancy. Practical Applications of Immunology n Chapters 16 and 17, we learned the basics of how the immune system enables the body to recognize and defend against foreign microbes, toxins, and altered cells. In this article, we discuss some useful applications that have been developed from knowledge of the immune system. These include vaccines as well as tests that help identify infections by specific organisms. In addition, we will explore some of the disciplines-such as serology and diagnostic immunology-that have been developed from our understanding of antibody production and its interaction with antigens. Pertussis (whooping cough) is on the rise-see the Clinical Case of this chapter for discussion on pertussis vaccination. In the Clinic As the nurse in a vaccine clinic, you meet Eric, a healthy infant in for his 2-month appointment. His mother asks what vaccinations are due, and you explain that today Eric should receive his second dose of the hepatitis B vaccine, along with first doses of vaccinations designed to protect against rotavirus, diphtheria, tetanus, pertussis, Haemophilus influenzae type b, pneumococcus, and polio. Principles and Effects of Vaccination Development of vaccines based on the model of the smallpox vaccine is the single most important application of immunology. It prevents the targeted disease from ever occurring, thereby ceasing suffering before it ever begins. Costs of prevention and treatment are especially important in the developing world. The injection, by skin scratches, provoked a primary immune response that led to formation of antibodies and long-term memory cells. This response mimics the immunity the person gained by recovering from the disease. The cowpox vaccine was later replaced by a vaccinia virus vaccine, a related poxvirus. Many communicable diseases can be controlled by behavioral and environmental methods. For example, proper sanitation can prevent the spread of cholera, and the use of latex condoms can slow spread of sexually transmitted infections. Therefore, vaccination is frequently the only feasible method of controlling viral disease. If a high percentage of the population is immune, a phenomenon called herd immunity, outbreaks are limited to sporadic cases because there are not enough susceptible individuals to support the spread of epidemics. It is remarkable that there are still no widespread, useful vaccines against a number of pathogenic microbes, including chlamydias, fungi, protozoa, or helminthic parasites of humans. To create effective vaccines, the developers need to overcome a number of hurdles: understanding the most effective antigens that will cause an immune response, fully understanding the life cycle or stages of a microorganism, finding effective animal models to test efficacy, and funding and coordinated research on a particular vaccine. The principal vaccines used to prevent bacterial and viral diseases in the Long before vaccines existed, it was known that people who recovered from certain diseases were immune to the same infections thereafter. Chinese physicians were the first to try to prevent disease by exploiting this phenomenon.

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Infections that cause mild or moderate illness in adults can have catastrophic effects when they pass from mother to child during pregnancy or birth diabetes mellitus hemoglobin a1c buy generic pioglitazone from india. In 2016, some athletes did not participate in the Summer Olympics in Brazil because of fears surrounding an outbreak of Zika virus disease there. In 2016, 41 of the 875 babies born to Zika-infected mothers in the United States had birth defects. Zika virus disease crosses the placenta during pregnancy and targets nerve stem cells. It is linked to microcephaly, calcium deposits in the brain, and other brain and eye abnormalities. It has a mortality rate of 60%, and survivors have central nervous system disorders such as seizures. Transmission to the fetus is highest if the mother acquires the infection during the first half of pregnancy. However, a select group of pathogens possesses the ability to cross the placenta and enter a fetus. Congenital Listeria monocytogenes infection results in premature delivery, miscarriage, or stillbirth. Elizabethkingia, a newly discovered pathogen, can cross the placenta and cause meningitis in newborns. Since prevention is almost always better than treatment after the fact, women who plan to become pregnant should be up to date on their recommended vaccinations, including those for measles, mumps, and rubella-all of which can cause serious congenital problems. On September 30, Yolanda, a 10-year-old girl, has pain and stiffness in her right arm and temperature of 38. In mid-June, Yolanda had awakened during the night and said a bat had flown into her bedroom window and bitten her. Rabies is confirmed by direct fluorescent-antibody staining of a skin biopsy for rabies virus antigens. Human rabies is preventable with proper wound care and timely, appropriate administration of human rabies immune globulin and rabies vaccine before onset of clinical symptoms. There are reasons why bats make good disease reservoirs: there are more than a thousand species to occupy various niches; they are long-lived (5 to 50 years), which lends them stability as a reservoir; they tend to roost in close assemblies, which facilitate viral spread; and they fly relatively long distances as they forage for food-some are even migratory. Finally, bats seem to be able to carry viruses for long periods without clearing the infection or becoming ill. Classic rabies is caused by one of 11 known genotypes of the genus Lyssavirus and is widespread worldwide. Other, nonrabies, lyssaviruses causing encephalitis are indigenous to Europe, Australia, Africa, and the Philippines, most commonly in bats. Different species of bats are infected with distinct variants of the rabies-related lyssaviruses. This terminology represents a functional grouping; it is not a formal taxonomic term. Sentinel animals, such as caged chickens, are tested periodically for antibodies to arboviruses. This gives health officials information on the incidence and types of viruses in their area. A number of clinical types of arboviral encephalitis have been identified; all can cause symptoms ranging from subclinical to severe, including rapid death. Fewer than 1% of people infected exhibit symptoms; it can, however, be a severe disease with a mortality rate in symptomatic patients of about 20%. The primary mosquito is a species of Culex, which can overwinter as adults in temperate climates. Birds serve as amplifying hosts; some species, such as house sparrows, can have high levels of viremia without dying. But mortality of infected crows, ravens, and blue jays is high, and public health officials sometimes request reports of dead birds of these species. As of 2017, 30 cases of Heartland virus disease (a member of the Bunyaviridae) have occurred in the United States is unknown. Japanese encephalitis is the best known; it is a serious public health problem, especially in Japan, Thailand, Korea, China, and India. Vaccines are used to control the disease in these countries and are often recommended for visitors. Zika virus may also be transmitted sexually, from mother to child during pregnancy and delivery, and through blood transfusions. It was subsequently identified in humans in 1952 in the United Republic of Tanzania. They are usually mild and include fever, headache, muscle and joint pain, malaise, skin rash, and conjunctivitis. Because people usually do not become ill enough to require hospitalization, they may not even realize that they are infected. As with arboviral encephalitis, the best prevention is reducing mosquito-breeding sites and reducing contact between mosquitoes and humans. Local transmission has occurred around Miami Beach, Florida, and Brownsville, Texas. These organisms are widely distributed, especially in areas contaminated by bird droppings most notably from pigeons, which excrete an estimated 25 pounds a year. The disease is transmitted mainly by the inhalation of dried, contaminated droppings. However, an association has now been observed with trees native to subtropical and temperate regions, as well; the fungus inhabits an ecological niche in decayed hollows of mature trees. From there the basidiospores (see page 330) can contaminate surrounding soils or be spread with the distribution of wood products. This species has now been isolated in cases of cryptococcosis, even in otherwise healthy individuals, in several areas of western North America as far north as Vancouver Island in Canada. This disease is likely to continue to spread southward and may eventually affect areas as far as Florida. The best serological diagnostic test is a latex agglutination test to detect cryptococcal antigens in serum or cerebrospinal fluid. The drugs of choice for treatment are amphotericin B and flucytosine in combination. African Trypanosomiasis African trypanosomiasis, or sleeping sickness, is a protozoan disease that affects the nervous system. In 1907, Winston Churchill described Uganda during an epidemic of sleeping sickness as a "beautiful garden of death. The disease is caused by two subspecies of Trypanosoma brucei that infect humans: Trypanosoma brucei gambiense and T. They are morphologically indistinguishable but differ significantly in their epidemiology-that is, in their ability to infect nonhuman hosts. It is distributed throughout west and central Africa and is sometimes termed West African trypanosomiasis. Wild animals inhabiting these areas are well adapted to the parasite and are little affected, but humans and domestic animals become acutely ill. This has had a profound effect on sub-Saharan Africa, an area nearly the size of the United States. In this photomicrograph, the capsule is made visible by suspending the cells in dilute India ink. Q What is the significance of the extremely heavy polysaccharide capsule found in C. Amebic Meningoencephalitis There are three species of free-living protozoa that cause amebic meningoencephalitis, a devastating disease of the nervous system. Human exposure to them is apparently widespread; many in the population carry antibodies-fortunately, symptomatic disease is rare. Although scattered cases are reported in most parts of the world, only a few cases are reported in the United States annually. The organism initially infects the nasal mucosa and later penetrates to the brain and proliferates, feeding on brain tissue. The fatality rate is nearly 100%, death occurring within a few days after symptoms appear.

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A waxy component of the cell diabetic diet sugar grams order genuine pioglitazone online, cord factor, is responsible for this ropelike arrangement. An injection of cord factor causes pathogenic effects exactly like those caused by tubercle bacilli. Other factors are the increasing populations of susceptible individuals in prisons and other crowded facilities, as well as the elderly or undernourished. Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis, a slender rod and an obligate aerobe. On the surface of liquid media, their growth appears moldlike, which suggested the genus name Mycobacterium (myco means fungus). It seldom spreads from human to human, but before the days of pasteurized milk and the development of control methods such as tuberculin testing of cattle herds, this disease was a frequent form of tuberculosis in humans. Mycobacteria stained with carbolfuchsin dye cannot be decolorized with acid-alcohol and are therefore classified as acid-fast (see page 66). This characteristic reflects the unusual composition of the cell wall, which contains large amounts of lipids. These lipids might also be responsible for the resistance of mycobacteria to environmental stresses, such as drying. In fact, these bacteria can survive for weeks in dried sputum and are very resistant to chemical antimicrobials used as antiseptics and disinfectants (see Table 7. Tuberculosis is a particularly good illustration of the ecological balance between host and parasite in infectious disease. A host is not usually aware of tuberculosis pathogens that invade the body and are defeated, which occurs 90% of the time. If immune defenses fail, however, the host becomes very much aware of the resulting disease. By error, 249 babies were inoculated with virulent tuberculosis bacteria instead of the attenuated vaccine strain. Even though all received the same inoculum, there were only 76 deaths, and the remainder did not become seriously ill. An important factor in the pathogenicity of the mycobacteria probably is that the mycolic acids of the cell wall strongly stimulate an inflammatory response in the host. However, most healthy people will defeat a potential infection with activated macrophages, especially if the infecting dose is low. Interior of alveolus 2 Infiltrating macrophage (not activated) Early tubercle Tubercle bacilli multiplying in macrophages cause a chemotactic response that brings additional macrophages and other defensive cells to the area. Most of the surrounding macrophages are not successful in destroying bacteria but release enzymes and cytokines that cause a lungdamaging inflammation. Tubercle bacillus Caseous center Activated macrophages Lymphocyte 3 After a few weeks, disease symptoms appear as many of the macrophages die, releasing tubercle bacilli and forming a caseous center in the tubercle. The disease progresses as the caseous center enlarges in the process called liquefaction. The caseous center now enlarges and forms an air-filled tuberculous cavity in which the aerobic bacilli multiply outside the macrophages. This figure represents the progression of the disease when the defenses of the body fail. In most otherwise healthy individuals, the infection is arrested, and fatal tuberculosis does not develop. Sputum may become bloodstained as tissues are damaged, and eventually blood vessels may become so eroded that they rupture, resulting in fatal hemorrhaging. The initial step in laboratory diagnosis of active cases is a microscopic examination of smears, such as sputum. According to recent medical opinion, the commonly used 125-year-old microscopic exam routinely misses half of all cases. A colony might take 3 to 6 weeks to form, and completing a reliable identification series may add another 3 to 6 weeks. Diagnosis of Tuberculosis People infected with tuberculosis respond with cell-mediated immunity against the bacterium. This form of immune response, rather than humoral immunity, develops because the pathogen is located mostly within macrophages. In this test, a purified protein derivative of the tuberculosis bacterium, derived by precipitation from broth cultures, is injected cutaneously. This reaction appears as an induration (hardening) and reddening of the area around the injection site. In older individuals, it might indicate only hypersensitivity resulting from a previous infection or vaccination, not a current active case. Streptomycin is still in use, and all of the currently used drugs were developed decades ago. The likelihood that resistance may develop is increased because many patients fail to faithfully follow such a prolonged regimen, which can involve 130 doses of the drugs. In addition to the first-line drugs, there are a number of second-line drugs that can be used, mainly if resistance develops to alternatives. These drugs are either less effective than first-line drugs, have toxic side effects, or may be unavailable in some countries. The prolonged treatment is necessary because the tubercle bacillus grows very slowly or is only dormant (the only drug effective against the dormant bacillus is pyrazinamide), and many antibiotics are effective only against growing cells. Also, the bacillus may be hidden for long periods in macrophages or other locations that are difficult to reach with antibiotics. These are defined as being resistant to the two most effective first-line drugs, isoniazid and rifampin. In addition, strains have arisen that are also resistant to the most effective second-line drugs, such as any fluoroquinolone, and to at least one of three injectable second-line drugs, such as the aminoglycosides amikacin or kanamycin, as well as the polypeptide capreomycin. In the United States, however, the vaccine is currently recommended only for certain children at high risk who have negative skin tests. People who have received the vaccine show a positive reaction to tuberculin skin tests. This has always been one argument against its widespread use in the United States. Experience has shown that it is fairly effective when given to young children, but for adolescents and adults it sometimes has an effectiveness approaching zero. A number of new vaccines are in the experimental pipeline, but they will require large numbers of human samples and several years of follow-up to evaluate. Estimates are that more than 10 million people develop active tuberculosis every year and that infections result in nearly 2 million deaths annually. Testing for Drug Susceptibility Solid-media culture-based methods for drug susceptibility testing can take as long as 4 to 8 weeks for finalized results. These assays are simultaneously useful for both diagnosis and determination of drug susceptibility. The determination of susceptibility for rifampin can be considered a marker for potential resistance to other drugs. The biggest problem is that most drug resistance, aside from resistance to Bacterial Pneumonias the term pneumonia is applied to many pulmonary infections, most of which are caused by bacteria. Pneumonias caused by other microorganisms, which can include fungi, protozoa, viruses, and other bacteria, especially mycoplasma, are termed atypical pneumonias. Pneumonias also are named after the portions of the lower respiratory tract they affect. For example, if the lobes of the lungs are infected, it is called lobar pneumonia; pneumonias caused by S. Pleurisy is often a complication of various pneumonias, in which the pleural membranes become painfully inflamed. The cell pairs are surrounded by a dense capsule that makes the pathogen resistant to phagocytosis.

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The atomic number is the number of protons in the nucleus; the total number of protons and neutrons is the atomic mass diabetes test during pregnancy fasting buy pioglitazone 15 mg on-line. A hydrogen bond exists when a hydrogen atom covalently bonded to one oxygen or nitrogen atom is attracted to another oxygen or nitrogen atom. Hydrogen bonds form weak links between different molecules or between parts of the same large molecule. Atoms with the same number of protons and the same chemical behavior are classified as the same chemical element. Atoms that have the same atomic number (are of the same element) but different atomic masses are called isotopes. The molecular mass is the sum of the atomic masses of all the atoms in a molecule. A mole of an atom, ion, or molecule is equal to its atomic or molecular mass expressed in grams. The chemical properties of an atom are due largely to the number of electrons in its outermost shell. Molecules are made up of two or more atoms; molecules consisting of at least two different kinds of atoms are called compounds. The combining capacity of an atom-the number of chemical bonds the atom can form with other atoms-is its valence. Endergonic reactions require more energy than they release; exergonic reactions release more energy. In a synthesis reaction, atoms, ions, or molecules are combined to form a larger molecule. In a decomposition reaction, a larger molecule is broken down into its component molecules, ions, or atoms. In an exchange reaction, two molecules are decomposed, and their subunits are used to synthesize two new molecules. The products of reversible reactions can readily revert to form the original reactants. Lipids are a diverse group of compounds distinguished by their insolubility in water. Simple lipids (fats) consist of a molecule of glycerol and three molecules of fatty acids. A saturated lipid has no double bonds between carbon atoms in the fatty acids; an unsaturated lipid has one or more double bonds. Phospholipids are complex lipids consisting of glycerol, two fatty acids, and a phosphate group. By linking amino acids, peptide bonds (formed by dehydration synthesis) allow the formation of polypeptide chains. Proteins have four levels of structure: primary (sequence of amino acids), secondary (helices or pleated), tertiary (overall threedimensional structure of a polypeptide), and quaternary (two or more polypeptide chains). Conjugated proteins consist of amino acids combined with inorganic or other organic compounds. A solution of pH 7 is neutral; a pH value below 7 indicates acidity; pH above 7 indicates alkalinity. A nucleotide is composed of a pentose, a phosphate group, and a nitrogen-containing base. Functional groups of atoms are responsible for most of the properties of organic molecules. Small organic molecules may combine into very large molecules called macromolecules. Monomers usually bond together by dehydration synthesis, or condensation reactions, that form water and a polymer. Organic molecules may be broken down by hydrolysis, a reaction involving the splitting of water molecules. Carbohydrates are compounds consisting of atoms of carbon, hydrogen, and oxygen, with hydrogen and oxygen in a 2:1 ratio. Isomers are two molecules with the same chemical formula but different structures and properties-for example, glucose (C6H12O6) and fructose (C6H12O6). Monosaccharides may form disaccharides and polysaccharides by dehydration synthesis. Classify the following as subunits of either a carbohydrate, lipid, protein, or nucleic acid. The optimum pH of Acidithiobacillus bacteria (pH 3,) is times more acid than blood (pH 7). What happens to the relative amount of unsaturated lipids in the plasma membrane when E. Because animals cannot digest cellulose, how do you suppose these animals get nutrition from the leaves and wood they eat Acidithiobacillus ferrooxidans was responsible for destroying buildings in the Midwest by causing changes in the earth. Individuals with this disease are missing an enzyme to convert phenylalanine (phe) to tyrosine; the resulting accumulation of phe can cause mental retardation, brain damage, and seizures. The antibiotic amphotericin B causes leaks into cells by combining with sterols in the plasma membrane. The word microscope is derived from the Latin word micro (small) and the Greek word skopos (to look at). This article describes how different types of microscopes function and why one type might be used in preference to another. The bacterium was largely ignored until the resolving ability of microscopes was improved. Some microbes are more readily visible than others because of their larger size or more easily observable features. Many microbes, however, must undergo several staining procedures before their cell walls, capsules, and other structures lose their colorless natural state. The last part of this chapter explains some of the more commonly used methods of preparing specimens for examination through a light microscope. You may wonder how we are going to sort, count, and measure the specimens we will study. To answer these questions, this chapter opens with a discussion of how to use the metric system for measuring microbes. In the Clinic Mike is one of your regular patients at the homeless clinic where you are a volunteer nurse. A major advantage of the metric system is that units relate to each other by factors of 10. Thus, 1 meter (m) equals 10 decimeters (dm) or 100 centimeters (cm) or 1000 millimeters (mm). Microorganisms are measured in even smaller units, such as micrometers and nanometers. The prefix micro indicates the unit following it should be divided by 1 million, or 106 (see the "Expo nential Notation" section in Appendix B). His lenses were ground with such preci sion that a single lens could magnify a microbe 300*. Contemporaries of van Leeuwenhoek, such as Robert Hooke, built compound microscopes, which have multiple lenses. In fact, a Dutch spectacle maker, Zaccharias Janssen, is credited with making the first compound microscope around 1600. However, these early compound microscopes were of poor quality and could not be used to see bacteria. It was not until about 1830 that a significantly better microscope was developed by Joseph Jackson Lister (the father of Joseph Lister). Microscopic studies of live specimens have revealed dramatic interactions between microbes. Light Microscopy Light microscopy refers to the use of any kind of microscope that uses visible light to observe specimens. Equivalents Metric Unit 1 kilometer (km) 1 meter (m) 1 decimeter (dm) 1 centimeter (cm) 1 millimeter (mm) 1 micrometer (mm) 1 nanometer (nm) 1 picometer (pm) deci = 1/10 centi = 1/100 milli = 1/1000 micro = 1/1,000,000 nano = 1/1,000,000,000 pico = 1/1,000,000,000,000 Meaning of Prefix kilo = 1000 Metric Equivalent 1000 m = 10 m Standard unit of length 0. Q What is the total magnification of a compound light microscope with objective lens magnification of 403 and ocular lens of 103 Super-Resolution Light Microscopy Until recently, the maximum resolution for light microscopes was 0.

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Surveys show that in endemic areas control diabetes home remedies buy pioglitazone 30 mg without prescription, perhaps 1 out of every 1000 ticks is infected. Mammals are not essential to survival of the pathogen, Rickettsia rickettsii, in the tick population; the bacteria may be passed by transovarian passage, so new ticks are infected upon hatching. A blood meal is required for ticks to advance to the next stage in the life cycle. Stupor and a rash of small red spots caused by subcutaneous hemorrhaging are characteristic, as the rickettsias invade blood vessel linings. Tetracycline and chloramphenicol are usually effective against typhus fever, but eliminating conditions in which the disease flourishes is more important. The microbe is considered especially hazardous, and attempts to culture it require extreme care. Vaccines are available for military populations, which historically have been highly susceptible to the disease. People with dark skin have a higher mortality rate because the rash is often not recognized early enough for effective treatment. Viruses cause a number of cardiovascular and lymphatic diseases, prevalent mostly in tropical areas. However, one viral disease of this type, infectious mononucleosis, is an especially familiar infectious disease among American college-aged individuals. At that time, there was no known virus that caused human cancer, although several viruses were clearly associated with animal cancers. Intrigued by this possibility, in 1964 British virologist Tony Epstein and his student, Yvonne Barr, performed biopsies on the tumors. Diagnosis before the typical rash appears is difficult because symptoms vary widely. A misdiagnosis can be costly; if treatment is not prompt and correct, the mortality rate is about 20%. Antibiotics such as tetracycline and chloramphenicol are very effective if administered early enough. Q To judge from this graph, which of these diseases is more likely to result from early-childhood infections The virus has, in fact, become so adapted to humans that it is one of our most effective parasites. In the United States, early treatment with anticancer drugs has a high success rate. A principal cause of the rare deaths is rupture of the enlarged spleen (a common response to a systemic infection) during vigorous activity. The usual route of infection is by the transfer of saliva by kissing or, for example, by sharing drinking vessels. The infected B cells produce heterophile antibodies, so called from the Greek hetero (different) and phile (affinity). These are weak antibodies with multispecific activities; their significance is that they are used in the diagnosis of mono. If this test is negative, the symptoms may be caused by cytomegalovirus (see page 670) or several other disease conditions. While on vacation, she contracted an infection characterized by fever, sore throat, swollen lymph nodes in the neck, and general weakness. It is not much affected by the immune system, replicating very slowly and escaping antibody action by moving between cells that are in contact. Carriers of the virus may shed it in body secretions such as saliva, semen, and breast milk. These inclusion bodies were first reported in 1905 in certain cells of newborn infants affected with congenital abnormalities. The cells were also enlarged, a condition known as cytomegaly, from which the virus eventually received its name. The inclusion bodies were originally thought to be stages in the life cycle of a protozoan, and a viral cause of the disease was not proposed until 1925. All non-immune women should be informed of the risks of infection during pregnancy. It can also be transmitted sexually, by transfused blood, and by transplanted tissue. Transmission by transfused blood can be eliminated by filtering out the white cells from the blood or by serological testing of the donor for the virus. Chikungunya Another tropical disease now causing concern is chikungunya (the name sounds like "chicken-gun-yah," but the disease is often referred to simply as chik). An outbreak has already occurred in Italy, and locally acquired cases have occurred in Florida and Texas. Chik is the most common disease acquired by travelers, and its local transmission demonstrates how modern air travel contributes to disease emergence. Well adapted to urban settlements, it also survives cold climates and will probably become established eventually even in the northern parts of the United States and the coastal areas of Scandinavia. Because it is an extremely aggressive daytime biter, it is a serious nuisance for outdoor activities. Classic Viral Hemorrhagic Fevers Yellow Fever Most hemorrhagic fevers are zoonotic diseases; they appear in humans only from infectious contact with their normal animal hosts. Some of them have been medically familiar for so long that they are considered "classic" hemorrhagic fevers. In the early stages of severe cases of the disease, the person experiences fever, chills, and headache, followed by nausea and vomiting. This stage is followed by jaundice, a yellowing of the skin that gave the disease its name. This coloration reflects liver damage, which results in the deposit of bile pigments in the skin and mucous membranes. At one time, the disease was endemic in the United States and occurred as far north as Philadelphia. Army surgeon Walter Reed were effective in eliminating yellow fever in the United States. Monkeys are a natural reservoir for the virus, but human-tohuman transmission can maintain the disease. Local control of mosquitoes and immunization of the exposed population are effective controls in urban areas. Diagnosis is usually by clinical signs, but it can be confirmed by a rise in antibody titer or isolation of the virus from the blood. The vaccine is an attenuated live viral strain and yields a very effective immunity. Globally, an estimated 400 million cases in at least 100 countries occur annually. The countries surrounding the Caribbean are reporting an increasing number of cases of dengue. In most years, more than 100 cases are imported into the United States, mostly by travelers from the Caribbean and South America. If the patient suffers from severe bleeding and organ impairment, the case is classified as severe dengue. Severe dengue occurs mostly in patients with their second dengue infection and in infants who have passive immunity from their mother. It appears that antibodies to the virus enhance its ability to enter cells, a development called antibody enhancement. Several cases of dengue acquired in Florida and Hawaii since 2010 have raised concern about the potential for emergence of dengue in the U. An efficient secondary vector, Aedes albopictus, has also expanded widely in range in recent years. However, the risk of antibody enhancement and severe dengue is proving difficult to overcome. When asked, Katie explains that the rash is from scratching the numerous mosquito bites she incurred while in Key West. The Asian tiger mosquito has been moving north and east since its introduction in 1987.

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Rabies is unique in that the incubation period is usually long enough to allow immunity to develop from postexposure vaccination diabetes diet type 1 menu purchase line pioglitazone. The natural immune response is ineffective because the viruses are introduced into the wound in numbers too low to provoke it; also, they do not travel through the bloodstream or lymphatic system, where the immune system could best respond. Initially, the virus multiplies in skeletal muscle and connective tissue, where it remains localized for periods ranging from days to months. In some extreme cases, incubation periods of as long as 6 years have been reported, but the average is 30 to 50 days. Bites in areas rich in nerve fibers, such as the hands and face, are especially dangerous, and the resulting incubation period tends to be short. At this time, a frequent symptom is spasms of the muscles of the mouth and pharynx that occur when the patient feels air drafts or swallows liquids. In fact, even the mere sight or thought of water can set off the spasms-thus the common name hydrophobia (fear of water). The final stages of the disease result from extensive damage to the nerve cells of the brain and the spinal cord. Animals with furious (classic) rabies are at first restless, then become highly excitable and snap at anything within reach. The biting behavior is essential to maintaining the virus in the animal population. When paralysis sets in, the flow of saliva increases as swallowing becomes difficult, and nervous control is progressively lost. Some animals suffer from paralytic (dumb or numb) rabies, in which there is only minimal excitability. The animal remains relatively quiet and even unaware of its surroundings, but it might snap irritably if handled. There is some speculation that the two forms of the disease may be caused by slightly different forms of the virus. Prevention of Rabies Only high-risk individuals, such as laboratory workers, animal control professionals, and veterinarians, are routinely vaccinated against rabies before known exposure. Another indication for antirabies treatment is any unprovoked bite by a skunk, bat, fox, coyote, bobcat, or raccoon not available for examination. Treatment after a dog or cat bite, if the animal cannot be found, is determined by the prevalence of rabies in the area. The bite of a bat may not be perceptible and may be impossible to rule out in cases where the bat had access to sleeping persons or small children. These vaccines are administered in a series of four injections at intervals during a 14-day period. In eastern states in which raccoons are the predominant rabies-infected animal, many cases were also reported in foxes and skunks. The primary treatment, which succeeds in a minority of cases, is to induce an extended coma to minimize excitability while administering antiviral drugs. This procedure was first used in the case of a Wisconsin girl bitten by a rabid cat and has come to be called the Milwaukee protocol. Distribution of Rabies Rabies occurs all over the world, mostly a result of dog bites. Vaccination of pets is prohibitively expensive in most of Africa, Latin America, and Asia. As many as 40,000 people are administered postexposure rabies vaccine each year, often as a precaution when the rabies status of the biting animal cannot be determined. In Europe and North America, there are ongoing efforts to immunize wild animals with live vaccinia virus, genetically modified to produce a rabies virus glycoprotein that is added to food left for the animals to find. This has been highly successful in Europe, and several countries have been declared free of rabies as a result. Skunks Foxes Cats Dogs Cattle 0% Wild Domestic Rabies cases in various wild and domestic animals in the United States. Rabies in domestic animals such as dogs and cats is uncommon because of high vaccination rates. Raccoons, skunks, and bats are the animals most likely to be infected with rabies. In the United States, 7000 to 8000 cases of rabies are diagnosed in animals each year, but in recent years, only one to six cases have been diagnosed in humans annually (see the Clinical Focus box on page 636). Related Lyssavirus Encephalitis In recent years, a few fatal cases of encephalitis that are clinically indistinguishable from classic rabies have occurred in Australia and Scotland-countries considered free of rabies. Because of the rarity of the disease, there is a low "index of suspicion"; also, the symptoms resemble those of encephalitis caused by other, more common, pathogens. The population of each trypanosome clone drops nearly to zero as the immune system suppresses its members, but a new clone with a different antigenic surface then replaces the previous clone. Q What viral disease that is causing a worldwide pandemic would make for a similar figure It requires an extended series of injections, but it is so dramatically effective against even late stages of T. The use of tentlike, insecticide-treated traps that mimic the color and odor of animal hosts of the insect, combined with large-scale releases of sterile males have eliminated the tsetse fly on the offshore island of Zanzibar. The suckerlike structures (called amebastomes) function in phagocytic feeding-usually on bacteria or assorted debris that may include host tissue. This protozoan also has a spherical cyst stage and an ovoid flagellated stage (which is most likely to be the infective form) that allows it to swim rapidly in its aquatic habitat. A rboviral encephalitis is usually characterized by fever, headache, and altered mental status ranging from confusion to coma. Vector control to decrease contacts between humans and mosquitoes is the best prevention. Mosquito control includes removing standing water and using insect repellent while outdoors. Distribution Epidemiology Affects mostly 4- to 18-year age groups in rural or suburban areas. The news is serious: Patricia has primary amebic meningoencephalitis, usually a rapidly fatal disease. The trophozoite encysts during cold or dry conditions and reemerges when conditions improve (see the figure). The ameba, present in soil, is probably transmitted by inhalation or through skin lesions. Approximately 150 cases of balamuthiasis have been reported worldwide since the disease was recognized in 1990; 10 of those cases were in the United States. Several fatal diseases affecting the human central nervous system are caused by prions. Its function is uncertain, but there is evidence that it may guide maturation of nerve cells. But this protein can assume two folded shapes, one normal and the other abnormal (there is no change in the amino acid sequence). Therefore, a single infective prion may lead to a cascade of new prions, which then clump together to form the fibril aggregations of misfolded proteins that are found in diseased brains. A typical prion disease in animals is sheep scrapie, which has been long known in Great Britain and made its first appearance in the United States in 1947. The infected animal scrapes itself against fences and walls until areas of its body are raw. During a period of several weeks or months, the animal gradually loses motor control and dies. The infection can be experimentally passed to other animals by injecting brain tissue from one animal to the next. A prion disease, chronic wasting disease, affects wild deer and elk in the western United States and Canada. It is invariably fatal, and there are concerns that it might infect humans who eat venison and might eventually infect domestic livestock. These diseases, caused by prions, include bovine spongiform encephalopathy, scrapie in sheep, and Creutzfeldt-Jakob disease in humans. Several cases have been traced to the injection of a growth hormone derived from human tissue. Boiling and irradiation have no effect, and even routine autoclaving is not reliable.

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Multiple large aggregations of lymphoid tissues are located in specific parts of the body diabetes mellitus medical management cheap pioglitazone online master card. The spleen contains lymphocytes and macrophages that monitor the blood for microbes and secreted products such as toxins, much like lymph nodes monitor lymph. Play Host Defenses: Overview It also contains dendritic @MasteringMicrobiology cells and macrophages. Fluid circulating between tissue cells (interstitial fluid) is picked up by lymphatic capillaries. Lymph nodes are the sites of activation of T cells and B cells, which destroy microbes by immune responses (Chapter 17). Also within lymph nodes are reticular fibers, which trap microbes, and macrophages and dendritic cells, which destroy microbes by phagocytosis. The lymphatic capillaries permit interstitial fluid derived from blood plasma to flow into them, but not out. These vessels, like veins, have one-way valves to keep lymph flowing in one direction only. All lymph eventually passes into the thoracic (left lymphatic) duct and right lymphatic duct and then into their respective subclavian veins, where the fluid is now called blood plasma. The blood plasma moves through the cardiovascular system and ultimately becomes interstitial fluid between tissue cells, and another cycle begins. Phagocytosis (from Greek words meaning eat and cell) is the ingestion of a microorganism or other substance by a cell. We have previously mentioned phagocytosis as the method of nutrition of certain protozoa. Phagocytosis is also involved in clearing away debris such as dead body cells and denatured proteins. In this article, phagocytosis is discussed as a means by which cells in the human body counter infection as part of the second line of defense. Actions of Phagocytic Cells Cells that perform phagocytosis are collectively called phagocytes. When an infection occurs, both granulocytes (especially neutrophils, but also eosinophils) and monocytes migrate to the infected area. These leave the blood and migrate into tissues where they enlarge and develop into macrophages. Some macrophages, called fixed macrophages, or histiocytes are resident in certain tissues and organs of the body. In some instances, adherence occurs easily, and the microorganism is readily phagocytized. Microorganisms can be more readily phagocytized if they are first coated with certain serum proteins that promote attachment of the microorganisms to the phagocyte. The proteins that act as opsonins include some components of the complement system and antibody molecules (described later in this chapter and in Chapter 17). Macrophages in the mononuclear phagocytic system remove microorganisms after the initial phase of infection. The various macrophages of the body constitute the mononuclear phagocytic (reticuloendothelial) system. During the course of an infection, a shift occurs in the type of white blood cell that predominates in the bloodstream. Granulocytes, especially neutrophils, dominate during the initial phase of bacterial infection, at which time they are actively phagocytic; this dominance is indicated by their increased number in a differential white blood cell count. The increased number of monocytes (which develop into macrophages) is also reflected in a 1 2 differential white blood cell count. The plasma membrane of the phagocyte extends projections called pseudopods that engulf the microorganism. The membrane of a phagosome has enzymes that pump protons (H+) into the phagosome, reducing the pH to about 4. Phagolysosome Formation and Digestion Next, the phagosome pinches off from the plasma membrane and enters the cytoplasm, where it contacts lysosomes that contain digestive enzymes and bactericidal substances (see Chapter 4, page 100). Lipases, proteases, ribonuclease, and deoxyribonuclease hydrolyze other macromolecular components of microorganisms. Chemotaxis allows phagocytes to migrate to infection sites and destroy invading bacteria. L eukocytes, including neutrophils and macrophages, are the cells listed in the test results that fight infections. The damage can be caused by microbial infection, physical agents (such as heat, radiant energy, electricity, or sharp objects), or chemical agents (acids, bases, and gases). Inflammation has the following functions: (1) to destroy the injurious agent, if possible, and to remove it and its byproducts from the body; (2) if destruction is not possible, to limit the effects on the body by confining or walling off the injurious agent and its by-products; and (3) to repair or replace tissue damaged by the injurious agent or its by-products. Inflammation can be classified as acute or chronic, depending on a number of factors. In acute inflammation, the signs and symptoms develop rapidly and usually last for a few days or even a few weeks. It is usually mild and self-limiting, and the principal defensive cells are neutrophils. Examples of acute inflammation are a sore throat, appendicitis, cold or flu, bacterial preumonia, and a scratch on the skin. In chronic inflammation, the signs and symptoms develop more slowly and can last for up to several months or years. It is often severe and progressive, and the principal defensive cells are monocytes and macrophages. Examples of chronic inflammation are mononucleosis, peptic ulcers, tuberculosis, rheumatoid arthritis, and ulcerative colitis. Acute-phase 449 455 459 463 469 470 Toxic oxygen products are produced by an oxidative burst. Other enzymes can make use of these toxic oxygen products in killing ingested microorganisms. Macrophages help T and B cells perform vital adaptive immune functions-this will be discussed in Chapter 17. In the next section, we will see how phagocytosis often occurs as part of another innate mechanism of resistance: inflammation. For purposes of our discussion, we will divide the process of inflammation into three stages: vasodilation and increased permeability of blood vessels, phagocyte migration and phagocytosis, and tissue repair. Dilation of blood vessels, called vasodilation, is responsible for the redness (erythema) and heat associated with inflammation. Increased permeability permits defensive substances normally retained in the blood to pass through the walls of the blood vessels and enter the injured area. The increase in permeability, which permits fluid to move from the blood into tissue spaces, is responsible for the edema (accumulation of fluid) of inflammation. The pain of inflammation can be caused by nerve damage, irritation by toxins, or the pressure of edema. One such substance is histamine, a chemical present in many cells of the body, especially in mast cells in connective tissue, circulating basophils, and blood platelets. Histamine is released in direct response to the injury of cells that contain it; it is also released in response to stimulation by certain components of the complement system (discussed later). Kinins are another group of substances that cause vasodilation and increased permeability of blood vessels. Kinins are present in blood plasma, and once activated, they play a role in chemotaxis by attracting phagocytic granulocytes, chiefly neutrophils, to the injured area. Prostaglandins, substances released by damaged cells, intensify the effects of histamine and kinins and help phagocytes move through capillary walls. Despite their positive role in the inflammatory process, prostaglandins are also associated with the pain related to inflammation.

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Q Why are viral infections generally difficult to treat with chemotherapeutic agents For influenza viruses blood sugar monitor walmart order pioglitazone with visa, this requires the enzyme neuraminidase Antiprotozoan Drugs Quinine is still used to control the protozoan disease malaria, but synthetic derivatives, such as chloroquine, have largely replaced it. For preventing malaria in areas where the disease has developed resistance to chloroquine, mefloquine is often recommended, although serious psychiatric side effects have been reported. Artemisinin was a traditional Chinese medicine long used for controlling fevers: Chinese scientists, following this lead, identified its antimalarial properties in 1971. Some of these contain enough of the genuine drug to evade simple tests, but these low dosages are accelerating development of resistance. Diiodohydroxyquin (iodoquinol) is an important drug prescribed for several intestinal amebic diseases, but its dosage must be carefully controlled to avoid optic nerve damage. Tinidazole, a drug similar to metronidazole, is effective in treating giardiasis, amebiasis, and trichomoniasis. Another antiprotozoan agent, and the first to be approved for the chemotherapy of diarrhea caused by Cryptosporidium hominis, is nitazoxanide. Because it interferes with an enzyme used in the anaerobic conversion of pyruvic acid to acetyl-CoA, it is also used to treat some bacterial infections. Praziquantel has a broad spectrum of activity and is highly recommended for treating several fluke-caused diseases, especially schistosomiasis. It causes the helminths to undergo muscular spasms and also makes them susceptible to attack by the immune system. Mebendazole and albendazole are broad-spectrum antihelminthics that have few side effects and have become the drugs of choice for treating many intestinal helminthic infections. Both drugs inhibit the formation of microtubules in the cytoplasm, which interferes with the absorption of nutrients by the parasite. These drugs are also widely used in the livestock industry; for veterinary applications, they are relatively more effective in ruminant animals. Its exact mode of action is uncertain, but the final result is paralysis and death of the helminth without affecting mammalian hosts. Antihelminthic Drugs Tapeworm infections have decreased in developing countries because of improved sewage treatment. Praziquantel is about equally effective for treating tapeworms; it kills worms by altering the Different microbial species and strains have different degrees of susceptibility to chemotherapeutic agents. Moreover, the susceptibility of a microorganism can change with time, even during therapy with a specific drug. Thus, a physician must know the sensitivities of the pathogen before treatment can be started. Several tests can be used to indicate which chemotherapeutic agent is most likely to combat a specific pathogen. However, if the organisms have been identified-for example, Pseudomonas aeruginosa, beta-hemolytic streptococci, or gonococci- certain drugs can be selected without specific testing for susceptibility. The drugs are purchased already diluted into broth in wells formed in a plastic tray. A suspension of the test organism is prepared and inoculated into all the wells simultaneously by a special inoculating device. Each disk contains a different chemotherapeutic agent, which diffuses into the surrounding agar. The clear zones indicate inhibition of growth of the microorganism swabbed onto the agar surface. A Petri plate containing an agar medium is inoculated ("seeded") uniformly over its entire surface with a standardized amount of a test organism. Next, filter paper disks impregnated with known concentrations of chemotherapeutic agents are placed on the solidified agar surface. During incubation, the chemotherapeutic agents diffuse from the disks into the agar. If the chemotherapeutic agent is effective, a zone of inhibition forms around the disk after a standardized incubation. The diameter of the zone can be measured; in general, the larger the zone, the more sensitive the microbe is to the antibiotic. For a drug with poor solubility, however, the zone of inhibition indicating that the microbe is sensitive will be smaller than for another drug that is more soluble and has diffused more widely. The zone diameter is compared to a standard table for that drug and concentration, and the organism is reported as sensitive, intermediate, or resistant. Results obtained by the disk-diffusion method are often inadequate for many clinical purposes. The plastic strip, which is placed on an agar surface inoculated with test bacteria, contains an increasing gradient of the antibiotic. Such plates contain as many as 96 shallow wells that contain measured concentrations of antibiotics. The test microbe is added simultaneously, with a special dispenser, to all the wells in a row of test antibiotics. To ensure that the microbe is capable of growth in the absence of the antibiotic, wells that contain no antibiotic are also inoculated (positive control). To ensure against contamination by unwanted microbes, wells that contain nutrient broth but no antibiotics or inoculum are included (negative control). One popular, rapid method makes use of a cephalosporin that changes color when its -lactam ring is opened. In addition, a measurement of the serum concentration of an antimicrobial is especially important when toxic drugs are used. These assays tend to vary with the drug and may not always be suitable for smaller laboratories. The hospital personnel responsible for infection control prepare periodic reports called antibiograms that record the susceptibility of organisms encountered clinically. These reports are especially useful for detecting the emergence of strains of pathogens resistant to the antibiotics in use at the institution. But the development of resistance to them by the target microbes is a worldwide public health problem. When first exposed to a new antibiotic, the susceptibility of microbes tends Play Interactive to be high, and their mortalMicrobiology ity rate is also high; there may @MasteringMicrobiology be only a handful of survivors See how antibiotic-resistance from a population of billions. Once acquired, however, the mutation is transmitted vertically by normal reproduction, and the progeny carry the genetic characteristics of the parent microbe. Because of the rapid reproductive rate of bacteria, only a short time elapses before practically the entire population is resistant to the new antibiotic. Thousands of antibiotic-resistance genes and proteins against 240 antibiotics are known. These mutational differences can be spread horizontally among bacteria by processes such as conjugation (page 234) or transduction (page 235). Knowledge of these mechanisms is critical for understanding the limitations of antibiotic use. Efflux of antibiotic Bacteria that are resistant to large numbers of antibiotics are popularly designated as superbugs. Faced with infections by such pathogens, Play Antibiotic Resistance: Origins of Resistance medical science has only lim@MasteringMicrobiology ited treatment options. Mechanisms of Resistance There are only a few major mechanisms by which bacteria become resistant to chemotherapeutic agents. Totally synthetic chemical groups of antibiotics such as the fluoroquinolones are less likely to be affected in this manner, although they can be neutralized in other ways. This may simply reflect the fact that the microbes have had fewer years to adapt to these unfamiliar chemical structures. The penicillin/cephalosporin antibiotics, and also the carbapenems, share a structure, the -lactam ring, which is the target for -lactamase enzymes that selectively hydrolyze it. Nearly 200 variations of these enzymes are now known, each effective against minor variations in the -lactam ring structure. The first of these penicillinaseresistant drugs was methicillin (see page 568), but resistance to methicillin soon appeared. These highly adaptable bacteria have even developed resistance against antibiotic combinations that include clavulanic acid, specifically developed as an inhibitor of -lactamases (see page 568). These strains produce a toxin, a leukocidin, that destroys neutrophils, a primary innate defense against infection. This mechanism was originally observed with tetracycline antibiotics, but it confers resistance among practically all major classes of antibiotics.