Term
| what sites in the body are usually sterile? |
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Definition
| blood, urinary tract, sinus tract, uterus, prostate glad, CSF |
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Term
| what bacteria are usually found in the skin? |
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Definition
| staphylococcus, propionibacterium, yeasts, micrococcus, corynebacterium |
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Term
| what bacteria are usually found in the oropharynx? |
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Definition
| staphylococcus, streptococcus, haemophilus, neisseria |
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Term
| what bacteria are usually found in the intestinal tract? |
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Definition
| streptococcus, e. coli, bacteriodes, clostridium |
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Term
| what bacteria are usually found in the genitourinary tract? |
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Definition
| staphylococcus, streptococcus, lactobacillus, corynebacterium |
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Term
| what is the definition of a pathogen? |
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Definition
| an organism able to evade the normal immune defenses of an organism to cause infection, they can be either opportunistic or primary |
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Term
| what are opportunisitic pathogens? what are some examples from normal flora and the environment? |
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Definition
| organisms that rarely cause disease in healthy hosts, but regularly cause disease in compromised hosts. staphylococcus epidermidis, (post sx, catheter-related), and e. coli are normal flora that do this. pseuodomonas aeruginoasa are environmental organisms that can affect pts w/burns and CF |
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Term
| what are primary pathogens? what are some examples? |
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Definition
| primary pathogens are capable of establishing infection and causing disease in previously healthy individuals. mycobacterium tuberculosis, and bacillus anthracis are examples |
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Term
| does infection always lead to disease when normal flora or contaminating bacteria reach areas they are normally not found? |
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Definition
| no, it may be eliminated by host defenses, brought into normal flora, held in a carrier state, or disease, (damage to host tissue), can occur |
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Term
| what are two main determinants in whether infection will lead to disease? what are two other factors? |
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Definition
| infection becoming disease mainly depends on the pathogenicity, (virulence), of the pathogen and the immune status of the host. it can also depend on the route of entry and the number of infectious bacteria |
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Term
| what are virulence determinants? structurally, biochemically, genetically? can bacteria have more than one? |
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Definition
| virulence determinant are traits that promote colonization and survival of infecting bacteria. structurally, the capsule, LPS, and pili do this. biochemically, exotosins, proteases, and siderophores play a part. genetically, variation in surface antigens can be a virulence determinant. bacteria can have one or many virulence determinants. |
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Term
| what are the stages of infectious disease? |
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Definition
| encounter, entry, colonization, multiplication, invasion/dissemination |
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Term
| what are the three ways that the encounter phase of infectious disease can take place? |
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Definition
| endogenously, via normal flora. exogenously, via respiration, fecal-oral contact, venereal, other species as vectors, or vertebrate reserviors. congenitally, like if the mother transmits an infection to the fetus. |
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Term
| what are the two ways that the entry phase of infectious disease can take place? |
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Definition
| bacteria can enter via mucosal surfaces, (respiratory, urinary, genital, GI tracts, and conjunctiva), or through the skin, (via trauma, sx, ecxzema). these usually correlate with the organim's method of getting out of the body as well. |
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Term
| what are the two ways that the colonization phase of infectious disease can take place? are there different kinds of specific adherence? |
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Definition
| colonization or establishment of a pathogen in its host, can happen through receptor mediated, specific adherence to host cells, or through no receptor, non-specific binding. specific, receptor mediated adherence can be host specific or tissue specific. |
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Term
| in terms of the colonization phase of infection, what are some examples of receptor mediated adherence being host specific or tissue specific? |
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Definition
| host-specific receptor adherence: e. coli CFA/1 only binds to GM2 ganglioside in humans tissue-specific receptor adherence: e. coli P pili mediate colonizatoin of the urinary tract. |
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Term
| in terms of the colonization phase of infection, what are some examples of adherence being non-specific? |
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Definition
| P. aeruginosa's alginate capsule promotes adherence in lungs of CF pts, and S. epidermidis's polysaccharide slime promotes biofilm formation |
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Term
| how does the invasion phase of infectious disease can take place? what mediates this? |
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Definition
| invasion can refer to entrance into a cell or dissemination into the bloodstream, via molecules called invasins. thus invasion: localized or disseminate. |
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Term
| in terms of the invasive/dissemination phase of infection are there enzymes that certain bacteria use to facilitate their actions? |
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Definition
| streptococci+staphylococci use hyaluronidase, clostridium perfinges uses collagenase, shigella dysenteriae uses neuraminidase, and other bacteria use lecthinases |
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Term
| what are ways that the multiplication phase of infectious disease can take place? |
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Definition
| bacteria that have colonized need to fight off the immune system and grow at the same time, they need food, (co-factors for enzymes/sugars). they make siderophore that scavenges iron from lactoferrin/transferrin, (iron can be used for ETC enzymes) |
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Term
| what are ways that the multiplication phase of infectious disease can take place? |
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Definition
| bacteria that have colonized need to fight off the immune system and grow at the same time, they need food, (co-factors for enzymes/sugars). they make siderophore that scavenges iron from lactoferrin/transferrin, (iron can be used for ETC enzymes) |
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Term
| how do bacteria actually cause disease/tissue injury? in terms of their growth, secretions, host immune response? |
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Definition
| the byproducts of bacterial growth, (acids and gasses), secretion of enzymes that break down host cells/intracellular matrices, bacterial toxins, or host-damage by the immune respose that bacteria elict |
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Term
| what are exotoxins? what kinds of bacteria secrete them? are they antigenic? what kind of release can they achieve in the body? |
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Definition
| EXOtoxins are proteins SECRETED by both gram +/-. they can resemble enzymes, (many are very specific/denaturable), they are antigenic or superantigenic, (induce uncontrolled T cell cytokine release), and can be locally released, (vibrio cholerae), or systemically released, (clostridium tetani) |
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Term
| what does it mean to convert exotoxins to toxoids? |
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Definition
| purified exotoxins are treated to inactivate its action via formadehyde/formalin, but it retains its shape, so pts can be immunized. DTP is an example |
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Term
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Definition
| endotoxins are usually integral parts of the bacteria, such as the Lipid A core polysaccharide found in gram - bacteria. the O polysaccharide is the antigenic determinant that undergoes variation, but Lipid A is released during growth, death, and antibiotic tx and can induce acute phase response and inflammation -> endotoxic shock. |
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Term
| how can endotoxin be good in small, localized amounts? |
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Definition
| it can direct the immune system where to focus it's efforts, (via fever, vasodilation, increased antibody synth, and inflammation) -> on a systemic level though, this can keep the immune system from being able to respond, leading to endotoxic shock |
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Term
| what are some differences between exo- and endotoxins in terms of chemical composition, membrane integration, gram+/- involvement, kind of genetic coding, antigenicity, ability to be converted to a toxoid |
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Definition
| exotoxins are usually peptides, endotoxins are usually lipids. exotoxins are sometimes integral to the membrane, endotoxins are always part of gram - membrane. gram + only produce exotoxin, while gram - makes both exo- and endotoxin. only exotoxins are found expressed in phage or plasmids, (endotoxins are essential to gram -, therefore coded in chromosome). exotoxins can be antigenic, endotoxins are weakly antigenic. |
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Term
| what are some differences between exo- and endotoxins in terms of conversion to toxoid, neutralization by antibody, pharmacologic specificity, stability w/boiling, and clinical manifestation? |
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Definition
| only exotoxins can be coverted to toxoids so far. exotoxins can be neutralized by antibody, (unsure about endotoxins). exotoxins have differing pharmacological specificities, while endotoxins do not. exotoxins are rarely stable w/boiling, but endotoxins are. exotoxins have many clinical manifestations, while endotoxins are just shock+fever, (lipid A) |
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Term
| what are 2 examples of the host-mediated immune response causing pathogenesis? |
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Definition
| gram - sepsis, (LPS endotoxin incites a host damaging immune response), and infection with mycobacterium tuberculosis, (this bacteria is resistant to phagocytosis in the lungs, and the secretions by phagocytes attempting to remedy this are what cause necrosis) |
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Term
| what is one of the most important virulence factors bacteria have in terms of immune evasion? how does this help in terms of their composition and particular host immune response? |
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Definition
| capsules, which are made of polysaccharides, (poor immunogens), their slimy texture is hard to grasp by phagocytosis, it promotes survival inside phagosomes, and the biofilm helps prevent antibody and complement from reaching bacteria. |
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Term
| how can bacteria evade phagocytic killing? |
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Definition
| avoidance of contact (C5a pepsidase of strep), inhibition of phagocytic engulfment (S. pneumoniae capsule), survival inside phagocytes (M. tuberculosis), and production of toxins that kill or damage phagocytes |
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Term
| how do bacteria evade complement in terms of the capsule's function, C5a/C3a, opsonization, complement binding, or dealing with IgA |
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Definition
| masking of activating substances by capsule, C5a/C3a inactivation, prevention of opsonization-C3 deposited but no communication w/complement receptors, block binding or activation of complement, and coating themsleves with IgA antibodies, (which don't bind complement) |
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Term
| how do bacteria evade antibodies? |
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Definition
| intracellular residence (antibody can't get into cells), antigenic/phase variation, bind antibody inappropriately, IgA protease, and molecular mimicry, (makes the bacteria look like host cells). |
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Term
| what are some characteristics of bacterial toxins? |
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Definition
| rather than enzymes that simply help the bacteria proliferate, these enzymes themselves cause disease by altering the processes of host cells, (purified and outside of the bacteria, they would still cause disease). they are also are divided up into endo- and exotoxins. |
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Term
| what portion of LPS has endotoxic activity? |
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Definition
|
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Term
| how is LPS released from gram - cell walls? |
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Definition
| either soluble membrane blebs from growing bacteria or from bacterial lysis caused by complement, phagocytosis, or antibiotics |
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Term
| what is the mechanism of endotoxin activation? |
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Definition
| soluble LPS is bound by LBP, (LPS-binding protein, an acute phase protein), and then the resulting complex transfers LPS to CD14 on the surface of phagocytes. When CD14 binds LPS, it interacts with TLR-4, (toll-like receptor), which activates NFxB in the nucleus, (change in gene expression = cytokine production) |
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Term
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Definition
| toll-like receptor 4 is one of the innate immune system pattern recognition receptors, it responds to LPS, while TLR-2 responds to TCA, (teichoic acid) and TLR-5 responds to flagella |
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Term
| as a result of LPS stimulating TLR-4, and thus NFxB in the nucleus, what effects systemically can occur once cytokines are produced and released? |
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Definition
| TNF and IL-1 are released which cause a host of issues in the body, one of the more important being hypotension and vascular permeability, (decrease of blood flow results in shock) |
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Term
| what does septic shock refer to? what is an example of this happening? |
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Definition
| shock caused by bacterial infection, for example, endotoxemia, (or endogenous pyrogens/fever), is mediated by TNF, (tumor necrosis factor) and Il-1, (interleukin-1) if systemically relased. |
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Term
| what happens if TNF and Il-1 are released locally vs systemically? |
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Definition
| TNF and Il-1 released locally will result in containment and removal of the infection, but systemic release can result in hypotension, DIC, and systemic shock |
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Term
| what other things beyond LPS can also function as endotoxins? |
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Definition
| peptidoglycan, lipoteichoic acid, and parts of microbacterium tuberculosis |
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Term
| what are characteristics of exotoxins relating to their release, specificity, enzymatic activity? |
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Definition
| they are secreted or membrane bound and released upon lysis. they specifically destroy or inhibit cellular functions or tissue components. they vary in specificity, (neuro/cyto/enterotoxin), and many, but not all possess enzymatic activity. |
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Term
| what are routes of entry for exotoxins? |
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Definition
| mucosal infections, wound infections, intestinal infections, and food poisoning, (intoxication - bacteria is dead, but toxin is still active) |
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Term
| what are A-B subunit internalized exotoxins? |
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Definition
| exotoxins that have a B binding subunit that mediates binding to a specific receptor on the cell as well as translocation of the A subunit into the cell. the A active subunit possesses toxic enzymatic activity, though not all of its activity is enzymatic. |
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Term
| what are the two ways that AB subunit exotoxins enter cells? |
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Definition
| AB exotoxins can enter via direct entry, where the B subunuit binds to the a receptor and induces pore formation for A entry. in receptor mediated entry (RME), the entire toxin is internalized in an endosome and then A+B separate, w/A's release into the cytoplasm |
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Term
| what is an example of a an exotoxin that has an A+B subunit? where is it encoded? when is it expressed? what do the A+B subunits do? |
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Definition
| corynebacterium diphtheriae produces an AB toxin that is encoded on prophage and is expressed under low iron. the B subunit binds heparin, and A catalyzes ADP-ribosylation of a histidine molecule on EF2, (elongation factor 2 of eukaryotic cells = no protein synthesis). this is toxic to many cell types, and acts mainly locally, but the toxin can spread. this happens via RME. |
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Term
| how does the exotoxin produced by vibrio cholera function? where is it encoded? what is the result in bodily function? |
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Definition
| it is encoded on the chromosome. 2As and 5Bs subunits make up this exotoxin. the B binds to GM1 in the small intestine, and the A ribosylates and activates adenylate cyclase causing cAMP levels to go up, leading to secretion of fluid and electrolytes into the intestine, resulting in very watery diarrhea |
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Term
| how does the exotoxin produced by bacillus anthracis function? |
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Definition
| the B subunit acts as a protective antigen, while one of the A subunits, a calmodulin-activated adenylate cyclase causes edema, the other, a protease of MAP kinase is lethal |
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Term
| what are examples of single subunit internalized exotoxins? |
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Definition
| adenylate cyclase toxin, cytotoxins A+B, ST toxin, (from ETEC, enterotoxic e. coli), and streptolysin S |
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Term
| what is the adeylate cylase toxin? what kind of exotoxin is it? |
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Definition
| produced by bordetella pertussis, the adenylate cyclase toxin is activated by calmodulin which converts ATP to cAMP. its action is to inhibit leukocyte chemotaxis, phagocytosis and killing. it is a single subunit internalized exotoxin |
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Term
| what are cytotoxins A and B? what do they do in the cells? to the entire body? |
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Definition
| cytotoxin A, (enterotoxin) is chemotoxic for neutrophils, PMNs, causing the release of cytokines, hypersecretion of fluid into ileum of gut. cytotoxin B, (cytotoxin), causes disorganization of the cytoskeleton and disrupts protein synthesis. these can cause mild diarrhea to life-threatening pseudomembranous colitis. both are single subunit internalized exotoxins and produced by clostridium difficile. |
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Term
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Definition
| membrane active toxins that oligomerize, forming membrane pores, causing the cell to lyse. this can happen to red and white blood cells. various bacteria do this in different ways, enabling them to be classified accordingly |
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Term
| what is another way that membrane active exotoxins can create pores in cell membranes beyond oligomerizing? |
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Definition
| exotoxins can also destroy lipids in cell membranes, like the alpha toxin of clostridium perfringes. this causes vascular permeability, massive hemolysis and bleeding and tissue destruction. myonecrosis, a necrotizing activity is also seen in conjunction. |
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Term
| what does exfoliative exotoxin do? what bacteria produces it? is it membrane active? |
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Definition
| staphylococcus aureus produces exfoliative exotoxin, a protease that causes erythema and intradermal desquamation by disrupting epidermal cell-cell junctions, (skin-peeling) |
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Term
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Definition
| ST toxin is a single subunit exotoxin that is produced by ETEC, (enterotoxic e. coli), it binds to a receptor on the cell surface and causes watery diarrhea |
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Term
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Definition
| a single subunit exotoxin acting on surface receptors |
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Term
| what are superantigens? how do they interact with the immune system and what is the result? |
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Definition
| antigens that don't bind in the MHC class pocket and then interact with T cells, they bind on the outside so they can mediate the interaction between an APC and CD4+ T cell with any specificity. this can lead to and excess of cytokines and mimics endotoxic shock, (this is how gram + bacteria can mimic endotoxic shock) |
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Term
| what are 3 medically important superantigens? (def know these) |
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Definition
| staphylococcus aureus: toxic shock syndrome toxin, (TSST-1, toxic shock-like syndrome, responsible for rash seen in scarlet fever). staphylococcus: enterotoxins, (A-G)-act as superantigens in the bloodstream. streptococcus pyogenes: pyrogenic exotoxins, (A,B,C) |
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Term
| how are toxins encoded in the bacterial genome? |
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Definition
| toxins can generally be in the chromosom, plasmid, transposons, or prophage, but endotoxins have to be in the chromosome, (as well as lipoteichoic acid, peptidoglycan for gram +) |
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Term
| how is genetic toxin expression regulated? |
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Definition
| expression is governed by environmental conditions, like pH, temp, ionic conditions, (low iron, Ca++ etc) |
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Term
| what are treatments for exotoxin-mediated disease? |
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Definition
| antibiotic therapy, toxin antibodies that neutralize some such as those produced by diptheria, botulism, tetanus, and gangrene. endotoxic shock can be treated with monoclonal anti-TNF antibody |
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Term
| how can pts be immunized to toxins? do toxins change much over time? |
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Definition
| toxins can be mildly denatures by treatment with formaldehyde/formalin or heat inactivation, and the resulting toxoids are used to immunize pts. this works well because there is not much variation in toxins. current toxiods include diptheria, tetanus, and pertussis |
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