nester19 - Important Point: Basically every surface (except...

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Unformatted text preview: Important Point: Basically every surface (except deep lungs and, perhaps, the stomach). Note that much of those locations not mentioned are sterile in healthy individuals. Normal flora are helpful to us for a number of reasons including supplying nutrients, priming our adaptive immunity, and protecting us from pathogens. Normal Flora “Relatively few microbes are able to inflict any noticeable damage, invading tissues or producing toxic substances,” which is fortunate considering that microbial cells living on the human body, our Normal Flora, outnumber our own cells. “Those minority of microorganisms that can cause us harm we call Pathogens.” To immunocompromised individuals the subset of microbes that are potentially pathogenic is larger than for those whose defenses are fully intact. Host compromised or not, pathogens “have distinct patterns of interaction with the host that enable them to have the upper hand in the relationship and elude at least some of the body’s defenses.” “This chapter will explore some of the ways in which microbes colonize the human host, living either as members of the normal flora in harmony with the host or subverting the host defences and causing disease.” Normal flora may be differentiated in terms of the duration of their residence in/on our bodies. Resident Flora persists with us for relatively long times, often colonizing us early in life and persisting until death (plus passing on from parent to offspring). Transient Flora, on the other hand, persists for only relatively short periods. Among transient flora are those organisms that come into contact with us but never successfully colonize. One reason for this transience is that resident flora already occupy niches (space, food) that consequently are denied to transients. Antibiotic-Associated Superinfection Normal Flora Locations & Species Host-Microbe Interactions Chapter 19: Host-Microbe Interactions Among those flora denied residence by normal flora are potential pathogens. Thus normal flora can play a protective role by preventing pathogen colonization. Circumstances where normal flora are disrupted, such as following antibiotic treatment, therefore can result in disease (a superinfection). One common superinfection is the overgrowth of the yeast Candida albicans following the antibioticmediate destruction of vaginal Lactobacilli. Another common superinfection is antibioticassociated colitis caused by Clostridium difficile. In both cases the pathogens are considered Opportunistic since normally these organisms can come into contact with us without causing disease. 1 More Terms Infectious Disease Terms Symptom = indications of disease that cannot be objectively measured, e.g., “It hurts!” Sign = indications of disease that can be objectively measured, e.g., body temperature. Syndrome = a collection of signs and symptoms that typically are associated with a given cause. Subclinical or Inapparent Infection = symptoms are sufficiently mild that they go unnoticed. Opportunistic Pathogen or Opportunist = flora that do not normally cause disease except under unusual circumstances or in unusual locations. Virulence = relative level of symptoms associated with a given pathogen. Course of Infectious Disease Pathogen Communicability Infectious Disease Terms Infection = colonization by a pathogenic organism. Bacteremia dose not necessarily imply disease. Contrast with “Localized.” An infectious disease is caused by a microorganism, but is not necessarily communicable. A Communicable Disease can be passed from person to person. A Contagious Disease (contrary to what your text says) is a communicable disease that is easily passed from person to person (i.e., highly communicable). We can measure the potential for infection associated with a pathogen in terms of its Infectious Dose. Infectious dose typically is expressed as ID50 which is the number of organisms that must be applied to establish infection in 50% of recipients. An individual who is asymptomatic but still contagious is described as a carrier. Course of Infectious Disease Convalescence is a time of recuperation and recovery from illness. Incubation period is the interval between exposure and illness onset. Depending on various factors an individual may still be infectious during either incubation or convalescence. 2 Inactivation or alteration of this gene leads to measurable decrease in virulence or pathogenicity (e.g., inactivation via antibody therapy, chemotherapy, or genetic engineering). Restoration of gene or factor restore virulence. In other words, the gene or factor must be shown to be associated with a given pathogenic condition in a causative manner. Caveat: Just because causation cannot be shown using Koch’s or these molecular postulations does not prove lack of causation (i.e., these postulates are how one proves causation, not lack of causation). For most pathogens, cells must adhere to tissues (and then colonize) before infection can take place, even if ultimately damage results from invasion or exotoxin production. Bacteria typically employ proteins known as Adhesins to attach to host tissues, which usually are located on ends of fimbriae. Alternatively, adhesins can consist of glycocalyx. 3. Pure organism causes same disease. Together these indicate infectiousdisease causation. 2. Organism grown in pure culture. 4. Same organism recovered. Mechanisms of Pathogenicity Gene or factor is expressed and/or present during pathogenic condition. 1. Same organism present in each case. Individual pathogens display Virulence Determinants that give rise to characteristic Mechanisms of Pathogenicity. “The innate and adaptive immune systems do not need to be overcome indefinitely, simply long enough for the pathogen to multiply and then successfully exit the host.” “A pathogen that is too adept at overcoming the host defenses and causing damage is actually at a disadvantage because its opportunity to be transmitted may be limited and it loses an exclusive source of nutrients if the host dies.” We can describe four mechanisms of pathogenicity: Toxin ingestion following production. Toxin production following colonization. Invasion of host tissues without toxin production. Tissue invasion followed by toxin production. Food Poisoning Adhesion to Host Tissues Molecular Postulates Koch’s Postulates Variation in Incubation Periods With food poisoning the pathogen doesn’t need to be ingested to cause disease, only the toxins it produces need to be injested. Another name for food poisoning consequently is Foodborne Intoxication. Common causes of food poisoning are Staphylococcus aureus and Clostridium botulinum. These cause Staphylococcal Food Poisoning and Botulism, respectively. Botulism is associated with non-acidic canned food and the toxin can be inactivated with 10 min of boiling (at sea level). The toxin associated with staphylococcal food poisoning, on the other hand, cannot be inactivated with boiling (nor would you want to boil your potato salad that’s been sitting out in the sun all day). 3 Invasion, no Toxin Colonization then Toxin Invasion Then Toxin Certain diseases are associated with pathogens that are non-invasive but which produce toxins that damage body tissues. In this case, disease does not occur unless sufficient pathogen numbers are present to produce sufficient quantities of toxin. Since they are non-invasive, growth occurs on tissue surfaces, i.e., on mucous membranes, and therefore is considered to be colonization. Vibrio cholerae and Escherichia coli O157 are examples of gastrointestinal pathogens with this mechanism of pathogenicity. Corynebacterium diphtheriae causes respiratory infections via a similar mechanism. It is perhaps of interest that the primary toxins produced by all three of these pathogens (Shiga, vibrio, and diptheria toxins, respectively) are phage encoded. The virulence factors associated with a number of pathogens are not so much exotoxins that directly damage body tissues as factors that allow tissue invasion and immune-system inactivation. In many cases, these organisms avoid immunesystem control by surviving and replicating within body cells, e.g., as following phagocytosis. In the process of invasion, however, tissue damage does occur, and sufficient organism numbers therefore can result in significant illness. Mycobacterium tuberculosis, Yersinia pestis, and various Salmonella species are examples tissueinvading bacterial pathogens. Avoidance of Phagocytosis Organisms such as Shigella dysenteriae and Streptococcus pyogenes are both invasive and are producers of exotoxins. Another good example is certain strains of Staphylococcus aureus: Endotoxin is LPS (a heat-stable molecule) and the toxin portion of LPS is the Lipid A portion. Avoidance of Phagocytosis Capsules are Involved in avoidance of phagocyte-mediated recognition and attachment. Endotoxin As such, Endotoxin is a characteristic of Gramnegative bacteria rather than Gram-positive. Endotoxin is released mostly upon bacterial death (e.g., following antibiotic treatment). Endotoxin serves as a signal to the body, especially during localized infections, that the body has been invaded by a Gram-negative organism. Problems arise when the body is exposed to larger quantities of endotoxin systemically as during Gramnegative septicemias. In such cases the body displays what essentially is a systemic inflammatory response that results, among other things, in a dramatic drop in blood pressure as vessels dilate and otherwise leak fluids. This consequence, known as Septic Shock, is deadly and is the great concern given Gram-neg septicemia. 4 Exotoxins vs. Endotoxins Exotoxins Exotoxins are proteins that are exported out of cells and which can damage body tissues. Endotoxin is LPS Link to Next Presentation Exotoxins (along with exoenzymes) are more associated with Gram-positive bacteria than Gramnegative, though pathogens of both Gram types display Exotoxins. Vaccination against exotoxins can be accomplished via toxoid vaccines, though infection typically is not sufficient to induce immunity against exotoxins owing to the relatively small quantities of toxin produced. Passive immunization against certain exotoxins is also possible. We can describe some toxins in terms of their sites of action: Neurotoxins affect neurons. Enterotoxins affect the gastrointestine. Cytotoxins damage cells. 5 Infectious Disease Terms 19 Exotoxins vs. Endotoxins 19 ...
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This note was uploaded on 06/03/2011 for the course MCB 205 taught by Professor Abedon during the Spring '11 term at Ohio State.

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