Chapter 10 - Host Microbe Interactions PDF

Chapter 10: Host Microbe interactions and Pathogenesis  Host–microbe interactions may be benign or cause disease 3 Microbes have __________of interactions with a host: Normal microbiota colonize our skin, areas of the digestive, genital, urina...

Chapter 10: Host Microbe interactions and Pathogenesis  Host–microbe interactions may be benign or cause disease 3 Microbes have __________of interactions with a host: Normal microbiota colonize our skin, areas of the digestive, genital, urinary, and respiratory systems Opportunistic pathogens are agents of disease under certain circumstances Pathogens: disease-causing microbes Dysbiosis ___________: microbiota disruption  Tropism All microbes typically require specific host features to establish infection Loading… tropsom but this factor can Most microbes exhibit some level of __________, change over time Most emerging pathogens expanded host or tissue range to become able to infect reassortment antigenic shift humans;______________, Can invade preferred host and enter favored tissue but still not cause disease Age, gender, overall health, life habits, impact whether disease develops Host–microbe interactions influence virulence Pathogenicity: ability of a microbe to cause disease Virulence __________: describes the degree or extent of disease that a pathogen causes Virulence factors: ways pathogens overcome host defenses Host–microbe interactions influence virulence Classic virulence factors include pathogen toxicity, aggressiveness, and transmission Loading… Virulence is also associated with hotf _____ properties (e.g. immune fitness, normal microbiota balance) Pathogens develop new virulence factors in response to the host and selective pressures Virulence factors damage host cells by: Directly damaging host alls _________________________ Provoking dangerous immune responses Not all pathogens are equally virulent For a pathogen to persist in a population… It must endure over time It must find a balance between breaking down defenses and living within an individual host Agents that are transmitted from person to person and kill hosts quickly usually… high-mortality outbreaks Cause _______________ Are short in duration rolated Are geographically ___________ Virulence factors are often logically linked to transmission Most STI associated pathogens are infectious but minimally symptomatic  Virulent versus Attenuated Pathogens Making virulence factors requires an energy investment Pathogens only develop and keep a particular virulence factor when it bestows a benefit Randomn mutators natural selection ______________& Environment heavily influences production of virulence factors alternated when Pathogens often become ____________ grown in cell culture Can happen randomly in nature Lose virulence factors needed to cause disease Still infectious but weakened Do not cause disease in an immunocompetent  host Infectious Dose For a pathogen to establish disease it must first infect the host Infectious dose-50 (ID50) 50 %to of Number of cells or virions needed to establish an infection in _____ exposed hosts More infectious ________________pathogens have a lower ID50 Just because a pathogen is highly infectious doesn’t mean it is especially dangerous Lethal Dose Lethal dose-50 (LD50) kill Amount of toxin needed to ______ 50% of affected hosts that are not treated ID50 and LD50 can change based on: Species affected immune fitness Host’s _____________ Route of exposure Note: LD50 and ID50 measures usually come from animal studies, so they are not a perfect predictor of what would occur in people Toxins Toxins: molecules that generate a range of adverse host effects such as tissue damage and suppressed immune response ________: Toxgenic microbes that make toxins Toxemiko toxins in the ________: bloodstream Two classes of toxins: Endotoxins Exotoxins Endotoxin gram negative _________________bacteria have an outer membrane rich in lipopolysaccharide (LPS) LPS consists of: Loading… Lipid portion (Lipid A) Sugars ____________ Lipid A region of LPS is called endotoxin Toxic to us and other animals  LPS _____________________ Conserved Endotoxin Endotoxin Mainly released when gram-neg bacteria di ___ The immune system and/or antibiotics kill Gram-negative pathogens, which causes… _________ Encrous in circulating endotoxin levels Leads symptoms to including fever, chills, body aches, hypotension, tachycardia, increased respiratory rate, inflammation, a feeling of disorientation, nausea, and vomiting If present in sufficient quantities, endotoxin septic shock causes _______________ May kill the host as organs fail In the U.S., septic shock affects 1 million people per year (deadly in up ½ Endotoxin Treating lipid-based endotoxins… Not readily neutralized No vaccines _____________to protect against them Necessary to ensure that endotoxins don’t contaminate anything used in patient care (e.g., drugs, implanted devices, etc.) Exotoxins Exotoxins Toxic Soluble proteins wide range of Affect a _____ cells both Gram- Made by _____ positive and Gram-negative bacteria  Exotoxins Exotoxins Exotoxins are named based on the organism that makes it or the type of cells it targets _____________ – affect the nervous system Enterotoxins – target the GI Exotoxins are named based on the organism that tract _____________ – affect the liver makes it or the type of cells it targets Nephrotoxins – damage the kidneys Neurotoxing – affect the nervous system _____________ To date, >200 exotoxins have been described Exotoxins are often classified into Enterotoxins – target the GI tract three main families based on their hepatoxus – affect the liver _____________ mode of action Nephrotoxins – damage the kidneys To date, >200 exotoxins have been described Exotoxins are often classified into three main families based on their mode of action  Exotoxins Type I exotoxins Ambrane acting _______________ extracellular toxins Bind to target via receptors on the surface Propagate a signaling cascade via the receptor Evokes changes in _____ ganz _________ expression Leads to diverse outcomes Range from temporarily altered cell physiology to cell death  Exotoxins Type II exotoxins Membrane-damaging toxins Disrupt the host cell plasma membrane ___________________ Forms pores or removes phosphate head groups from phospholipids Destabilizes the membrane alllisis Cause _________  Exotoxins Type III exotoxins Intracellular toxins Bind to a receptor and enter the cell Most exotoxins in this group are AB toxins B (______) binding region A (______) Actul portion exerts effects inside  Not all Toxins are Bad Katridim Botulinum exotoxin from _________ betulen causes botulism __________ Exotoxin interferes with neural transmission by blocking the release aufylcholine of ______________ Many antigenically distinguishable serotypes of the exotoxin A, B, C1, C2, D, E, F and G “Miracle Poison” Botox Intramuscular injection results in muscle paralysis Dystonin _________= overactive muscles Parkinson’s, Huntington’s, multiple sclerosis, cerebral palsy, epilepsy  FIVE STEPS TO INFECTION To establish an infection, a successful pathogen must complete five general tasks: 1. Enter the host 2. Adhere ________ to host tissues 3. Invade tissues and obtain __________ 4. Replicate _________ while warding off immune defenses 5. Transmit to a new host Step 1. Entry Portal entryany site that a ___________: of pathogen uses to enter the host Mucous membranes are most common portal the ___________ of entry Site where disease develops (but not necessarily the only or the main site affected) Some pathogens have >1 portals of entry Skin, Ocular, Otic, and Parenteral Entry integumentary _______________ system Based on overall weight and surface area is the largest body system Consists of skin, hair, nails, and associated glands Blocks most microbes _____ Pathogens have developed virulence factors that penetrate the integumentary system  Respiratory Tract Entry most Respiratory tract is the _____ _______ common portal of entry Coughing and sneezing suspends pathogens in the air as respiratory droplets Infectious agents stirred up from dust or soil However, a pathogen that enters through the respiratory tract does not necessary infection establish an ____________ there  Gastrointestinal (GI) Tract Entry Digitis _____________ system pathogens Local Frequently have a _____ ______ transmission oral Invade the mucosal surfaces of the GI tract Route of entry may be the first tissue affected, but it isn’t necessarily the only tissue affected  Urogenital Tract and Transplacental Entry Most sexually transmitted pathogens enter through the mucosal lining of the uaging _________ or________ cervix in women or the urethra ______ in men Some can invade through the skin of the genitalia Pathogens that cause urinary tract infections invade the urethra in men and women Some pathogens exhibit ________ * transmission by transplacental entry Step 2. Adherence After entering a host, the pathogen must next adhere to host tissues Loading… hydrophobic nonspecific such as through _____________ Initial adhesion is often ____________, interactions After nonspecific anchoring, the agent may target an exact surface molecule on the host cell tropism is due to specificity for a particular host Species and tissue __________ cell surface marker  Adhesion Factors Adhesio ____________ are virulence factors used to stick to host cells in a specific or nonspecific manner Bacterial adhesins include cell wall components, capsules _________, fimbriae and pili, a variety of plasma membrane–associated molecules  Fimbriae and Pili Fimbriae and pili are thin, protein tubes originating from the cytoplasmic membrane Both stick bacteria to surfaces biotics Contribute to ________ 60086 of human infections ________ feuer longe Pili are typically _________ and ______in number than fimbriae. They are found in virtually all Gram-negative bacteria but not in many Gram-positive bacteria  Binding Factors Sialic Acid Binding Factors Surface molecules that bind to sialic acid Acid found on host cell membrane inflenza _________ Plasmodium falciparum Heparin and HeparinSulfate ________ Binding Factors Factors that target heparin and heparin sulfate in hosts cells and tissues Lyme ____ disease – bacterial infection HIV and herpes simplex virus Fibronectin Binding Factors __________ Fibronectin in epithelial tissues Streptococcus pyogenes Yeast infection – Candida Leishmania  Step 3. Invasion Following adhesion, the pathogen has several options:. _______the Stay on surface of the host cell. Pass through cells to invade deeper tissues. Enter cells to reside as an _________ intracellular pathogen As pathogens invade, they tend to damage host tissues and cytopathic effects generate __________ Structural changes to cell  Invasins Allow pathogens to inval ______ host tissues Local ______-acting factors Usually membrane-associated or secreted enzymes Mechanism of action: Break down host tissues Form blood clots or break down clots Induce the host to uptake the pathogen motcht, _________ Invasion and Nutrient Acquisition Most cellular pathogens require iron to survive In humans, very little iron freely circulates in tissues and blood Transfer nin binds to iron and shuttles it to tissues ___________ Many bacteria produceschrophe ___________ that snatch iron from transferrin Many bacteria and fungi also make extracellular enzymes Break down nutrients in the local environment Allows pathogens to scavenge nutrients as they damage host tissues Lipases – break down lipids _________ Proteases – break down proteins  Step 4. Evasion of Host Immune System A pathogen must evade the immune system so it can safely replicate hid inderming _____ from the immune system or ________ the hosts immune system Intracellular pathogens Include viruses, many protozoans, and some bacterial pathogens Spend majority their time inside host cells Examples of intracellular bacteria include: Listeria monocytogenes Mycobacterium tuberculosis  Hiding from Host Immune Defenses Latency _______________ Ability of a pathogen to quietly exist inside a host Usually causes persistent or recurrent disease Examples: Herpes viruses (intermittent flare-ups) HIV __________(genetic hitchhikers) Can confer protection from drug therapies  Hiding from Host Immune Defenses Antigmatic marking ________________ Upon entering the host, the pathogen may conceal antigenic features Coats itself with host molecules Antigenetze ________________ mimig Emulating host molecules Capsules can resemble host carbohydrates Antigenetic ________________ variation Periodically altering the surface molecules Prevents a rapid immune response Causes include: Mutations in the genome Change in protein expression Undermining the Host Immune Response phago wo Interference of ________________ Some pathogens avoid phagocytosis by: Making a ___________ Capsul Bursting free of the phagosome Blocking fusion of the phagosome with the ___________ lysts Onl Neutralizing enzymes of the phagocytes Damaging phagocytic cells using toxins Pathogen may have evolved to thrive inside the harsh environment of the phagolysosome Undermining the Host Immune Response Immune _________________ Supressiest Pathogens suppress immune function by: Directly targeting immune system cells Making proteases that break down host antibodas ___________ Interfering with transcription of interleukins – responsible for immune responses Interfering with the molecular signaling that activates parts of the immune response Evasion of Host Immune System Step 5. Exiting the host to find a new one The last crucial step in a pathogen’s success is new host transmission to ______________________ a Sometimes the symptoms a pathogen generates facilitate transmission to others Itchiness greezing __________ Coughing Diarrhea Any route a pathogen uses to exit its portal of ext host is a ____________ Feces, urine, and bodily fluids such as blood or fluids drained from wounds, vomit, saliva, mucus, or semen offe  Concept Questions 1. Travis Kelce and Taylor Swift are spending time together at a local bar in close proximity with a few other friends. Both Travis and Taylor have their own drinks and keep their hands to themselves at the bar. However, a few days later Travis checks in with his team’s physician with signs and symptoms of a fever, cough, and shortness of breath. The doctor confirms Travis has a respiratory infection caused by a bacteria. To try to rid Travis of the infection as quickly as possible, the doctor prescribes a microbiocidal drug (Drug A) without further testing. Soon after taking the drug, Travis’ health vastly declines. The doctor quickly realizes the bacteria likely has an endotoxin and stops the original treatment and opts for a microbiostatic drug instead (Drug B). Travis recovers and is able to catch a touchdown for Kansas City on Sunday in front of his adoring fan, Taylor. What portal of entry is most likely for this bacterial infection? Why? Explain why Drug A caused more health problems because of the endotoxin? Why wouldn’t Drug B cause those same health problems? Is this bacteria gram negative or gram positive? Why?  Explain in your own words, the five steps to infection. Concept Questions 2. Explain in your own words what LD50 and ID50 are. If Disease A has a ID50 of 5 bacterial cells and Disease B has a ID50 of 20 bacterial cells, which of these diseases is more dangerous and why? 3. Explain in your own words the three types of exotoxins. 4. Why might it beneficial for a bacteria infecting the respiratory tract to cause the host to cough? Why might it be beneficial for a bacteria infecting the digestive system to cause spontaneous diarrhea instead of a cough? 5. Virulence factors are ways the pathogens have evolved to increase it’s virulence. These are features that assist in adherence to host cells, invading hosts cells/tissues,