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Microbio Final Exam
| Question | Answer |
|---|---|
| what is an infectious disease | - diseases caused by bacteria, viruses, fungi, or parasites - diseases that can be passed directly or indirectly from person to person |
| what are pathogens | microbes that cause disease |
| bacterial pathogens can cause what | diseases in otherwise healthy individuals |
| in what situations are bacterial pathogens observed more frequently and cause more severe diseases | - when immune system is weakened - if breach of mechanical barriers - during long term antibiotic use |
| what are examples of things that cause the immune system to get weakened | - genetic deficiency - immunosuppressive therapy - HIV/AIDS |
| what are examples of ways to breach mechanical barriers | - surgery - wounds, cuts, burns |
| environmental microorganisms and normal microbiota are what | opportunistic pathogens |
| what method is used to identify the causative agent of a particular infectious disease | Koch's Postulate |
| what is the Koch's Postulate | - microbe is found in all cases of the disease - microbe is isolated from diseased host and grown in pure culture - when microbe is introduced into healthy susceptible host same disease occurs - same strain is obtained from the newly diseased host |
| gastritis | inflammation of the inside lining of the stomach |
| peptic ulcers | open sores on the protective lining and the upper portion of the small intestine |
| what may gastric inflammation lead to | duodenal or gastric ulcer with severe complications including bleeding ulcer and perforated ulcer |
| where is duodenal ulcers located | at transitional part between stomach and intestine |
| where is gastric ulcer located | in the stomach lining |
| what do proton pump (acid secretion) inhibitors do and what can it lead to | - decrease acid in the stomach by blocking proton (H+) pump causing an increase in pH which aids in healing of ulcers - can lead to high relapse rate |
| what did Dr. Warren find in gastric biopsies | curved bacilli later identified as Helicobacter pylori |
| how did Marshall eventually grow the pathogen in pure culture after isolating from diseased host | - tried lots of different agars and growth conditions yet still no colonies - threw out plates after overnight incubation - left plates over long weekend and eventually plates had small colony growths |
| how did Marshall test the next part of the Koch's Postulate (pathogen from pure culture must cause disease when inoculated into healthy susceptible host) | - couldn't get human volunteers so he tested it in himself - he drank a culture of H. pylori and about a week later, he started vomiting and suffering other painful symptoms of gastritis - endoscopy indicated gastric inflammation |
| how did Marhsall satisfy the final part of Koch's postulates | Gastric biopsy recovered the same species --> H. pylori causes gastric inflammation |
| what were other supporting evidence that H. pylori caused gastritis | clinical trials: antibiotics eliminated inflammation and peptic ulcer disease and reduced relapse rate |
| what was the relapse rate when only using acid secretion inhibitors | >60% |
| what was the relapse rate when using a acid secretion inhibitor and antibiotics | <10% |
| where does H. pyloric colonize in the body | the stomach despite low pH |
| what enzyme does H. pylori produce | urease |
| what does urease do | generates ammonia and carbon dioxide from urea and water which neutralizes the stomach acid causing an increase in pH |
| what does ammonia also reduce | viscosity of mucus (which is gel like at low pH) making it easier to penetrate |
| what other factors of H. pylori makes it beneficial to colonize the stomach | flagella and its helical shape |
| what happens when H. Pylori bacteria penetrate and attach | they secrete toxins causing bacterial protein damage and kill cells |
| what does the toxin damage epithelial cells and inflammation lead to | decrease in mucus production --> there's no protection from stomach acids so acidic stomach juices damage expose tissues causing formation of ulcers |
| what are some weaknesses of the Koch's Postulate | - some infected people/animals don't show signs of disease (they're asymptomatic) - not all pathogens can be cultured in lab (some only grow in host cells) - some pathogens only infect humans (experimental animal models not available) |
| what are in vivo animal models | mice (most common), rats, rabbits, guinea pigs, pigs, (non-human primates) |
| what are some in vitro models | cells in culture, organoid (3D culture) |
| what are alternative animal models that can be used | insect, nematode, fish |
| what are some pros to using alternative animal models | no/less ethical concerns, lower costs, larger number of hosts generating better statistics, easier maintenance |
| what are cons to using alternative animal models | not as closely related to people as non-human mammals |
| what are ways to determine the effect of pathogens in model systems | symptoms (doesn't really work since you can't really ask the model about it) and signs - LD50 - histology - determining the number (CFU) of bacteria in different organs |
| what is LD50 | does of pathogen required to kill 50% of experimentally infected animals |
| how to test for LD50 | - divide mice into several groups - inoculate each group with different dose (number) of bacteria - determine the number of dead mice for each group |
| how do you determine what strain causes a more severe disease | it takes a lower dose of that strain to kill half the animals infected |
| what is histology | staining of tissue and determine alteration by microscopy and bacteria present |
| molecular mechs of bacterial pathogenesis | adherence, colonization, motility, invasion, avoiding host defense, causing damage to host |
| what is adherenence | attaching/binding to a surface |
| what is colonization | establishment of bacteria at a particular site (expansion in the number of bacteria at that site) |
| what is motility | ability to move and reach a new environment, leave hostile environment |
| what is invasion | - gaining access to new niches - crossing the epithelial barrier - trait of some bacteria |
| what is the mech of avoiding host defenses | - surviving in the face of anti-microbial defenses - mech to avoid recognition and destruction by phagocytes |
| what does it mean by causing damage to host | killing/modifying host cells |
| what does adherence enable the microbe to do | avoid host clearance mechanisms such as tears, saliva, mucus or even in UTI infections where the urine "washes" away the bacteria |
| What are signs and symptoms of UTI | frequent, painful urination, burning with urination, discharge, lower belly discomfort |
| UTi | - most often in women - 80% caused by E. coli - Treatment: antibiotics - can re-occur - recurrent infections often caused by the same strain |
| adhesins do what | - attach to host cell receptor - binding is highly specific |
| what are examples of adhesins | - pili (fimbriae) - other surface proteins or capsule |
| host cell receptors are often what | often glycolipids or glycoproteins |
| what can host cell receptors dictate | the tissue or host tropism of the pathogen |
| what does colonization involve | adherence and growth |
| what do bacteria undergo to adapt to new environments | changes in gene expression and metabolism |
| what does bacterial growth often occur as during colonization | biofilm |
| what component of a bacteria is often invovled in motility | flagella |
| what is a flagella | - long helical surface appendages - spin like propellers to move cell |
| what is the term when bacteria can sense chemical signals and respond by moving accordingly | chemotaxis |
| what type of signals may attract or repel bacteria from moving in that direction | - nutrients may attract - toxic components may repel |
| what does the flagella allow the bacteria to do to ascend UTIs | allows bacteria to travel from urethra and bladder to kidneys |
| what can an ascending UTI lead to if not treated | pyelonephritis (kidney infection) and bacteremia (presence of bacteria in the bloodstream_ |
| what are signs and symptoms of pyelonephritis | back or side pain, fever, nausea, vomiting |
| what is the most common entry point for invasion | mucus membrane |
| why is the mech of invasion a trait for some bacteria | - allows access to other nutrients - avoid some anti-microbial mechs (complement system, antibodies, phagocytes) - avoid competing mircobes |
| what are the mechanisms of invasion | - uptake of bacteria by microfold (M) cells at mucosal surfaces (passive) - bacteria induces the host cells to engulf them (active) |
| host cell cytoskeleton consists of what major parts and is can be described as what | - actin filament, intermediate filament, and microtubules - dynamic (always changing, rearranging) |
| receptor mediated endocytosis is what type of invasion mech | active |
| what is an example of receptor mediated endocytosis by a bacteria | internalin on surface of gram pos pathogen Listeria monocytogenes bind to receptors on host cell initiating signaling cascades |
| what does the signaling cascade from Listeria monocytogenes binding to host cell receptors cause to occur | promotes actin recruitment and assembly, remodeling of the plasma membrane (zipper like mech) and bacterial engulfment through endocytosis |
| what is another example of an active invasion mech | secretion systems |
| what is involved in the Type III secretion system in gram neg pathogen Salmonella | - needle complex (injectisome) delivers proteins (effectors) into host cells - these effectors target host signaling pathways that alter cytoskeleton (actin) structure to allow bacterial cell entry |
| what does rearrangement of host actin cause | - membrane "ruffling" and cell engulfs the microbe via endocytosis - "induced uptake" |
| what happens when microbe is inside the cell | microbe is inside of an endosome and may escape it or remain in it |
| what is involved in the passive uptake by microfold (M) cells | some bacteria hitchhike M cells to get to the basolateral side of the epithelium |
| what is an example of a bacteria that uses M cells to get into cells | shigella |
| what are M cells | - specialized epithelial cells - sample intestinal lumen contents - delivers samples including bacteria to dendritic cells, macrophages through transcytosis - if pathogens survive/disrupt macrophage function, they escape and desseminate |
| how does Shigella induce cells to engulf them | - macrophages in Peyer's patches engulf material that passes through M cells. Shigella cells survive and replicate causing phagocytosis to undergo apoptosis - shigella cells attach to base of epithelial cells and induce these cells to engulf them |
| how do bacteria avoid host defenses | - hide within host cells - spread cell to cell intracellularly - results in avoidance of phagocytes, complement and antibodies |
| what are the steps involved in intracellular replication and spreading from cell to cell | - enter host cell - break out of vacuole - replicate in cytosol - assemble host actin - use energy from actin assembly/disassembly to move - eventually encounter new cell, become engulfed, escape new vacuole |
| Listeria/Shigella's characterized process of intracellular replication and cell to cell spread (first couple of steps) | - uses internalin (InIA, InIB) to trigger endocytosis - once inside it gets trapped in vacuoles and to escape it produces listeriolysisn (LLO) which forms pores in the membrane and phospholipases (PIcA, PIcB) which breaks down lipids |
| what happens once Listeria/Shigella escapes from vacoules | nutrients in cytoplasm allows cells to replicate rapidly |
| how does Listeria/Shigella use host actin to move through cell | uses actin assembly inducing protein (ActA) to hijack host actin and form "actin tails" to propel bacteria through cells |
| how does the Listeria/Shigella cell spread from cell to cell | - they push into neighboring cells forming protrusions and is engulfed by them - forms a double membrane vacuole (one membrane is from original cell and one from new cell) - escapes using Listeriolysin and phospholipases (cycle repeats) |
| what do complement systems do | sense the presence of microbe and activates a cascade of enzymatic reactions and create membrane attach complex for forms pores in bacterial cell membrane killing the bacterium |
| what molecules do complement systems generate | - peptides that promote chemotaxis of phagocytic cells - opsonins (proteins generated that decorate bacteria and tag them for destruction/phagocytosis) --> Ex: C3b |
| what are methods to avoid host defenses | - prevent encounters with phagocytes - avoid destructions by phagocytes - avoid recognition and uptake by phagocytes |
| what are ways for bacterial cells to prevent encounters with phagocytes | - use of proteases to destroy chemoattractant such as C5a - secrete pore forming toxin to cause lysis of phagocytes |
| how might bacterial cells avoid destruction by phagocytes | - escape from phagosome by producing a toxin that forms pores in the phagosome membrane --> lysis - prevent phagosome-lysosome fusion by producing proteins that block fusion or interfere with signaling |
| how do bacterial cells avoid recognition and uptake by phagocytes | - mimicking or adding host molecules - cover surface with molecules similar to those found in host cell or bind host molecules |
| how does having a capsule help in avoiding recognition and uptake by phagocytes | it's made of polysaccharides that are the same or similar to host sugars helping to prevent phagocytosis |
| what are other ways for bacterial cells to avoid being recognized and taken up by phagocytes | - have surface localized proteins that bind host proteins such as fibrinogen (helps blend in) - express Fc receptor (Fc receptor on bacterium binds the Fc region of an antibody reducing the effect of phagocytes) |
| an antibody is made up of what two regions and what do these regions do | - Fab region: binds to antigen (bacterium) - Fc region: binds to receptor on phagocytes which is the initial step of phagocytosis |
| can proteases be used to avoid recognition and uptake by phagocytes | yes, specific proteases can be produced and secreted to destroy antibodies |
| what are toxins | wide range of molecules (mostly proteins) that damage the host cells, tissue, and organs |
| extracellular toxins are | surfaced localized, fully secreted to the extracellular environment or directly injected into host cells |
| toxins can act in what locations | locally (at site of infection) or systematically |
| what are the major toxin types | AB toxins, membrane damaging toxins, superantigens, proteases and other enzymes |
| what do the two components of AB toxins do? | - protein B: binds the toxin to cells before entry (binds to host cell receptor) - protein A: usually has some specific enzymatic activity damaging to cells or tissues (causes toxicity in or on host cells) |
| what are examples of AB toxins | - tetanus toxin, anthrax toxin, diphtheria toxin, cholera toxin, shiga toxin |
| what are the receptors that AB toxin often binds to | glycoproteins or glycolipids |
| what do pore forming toxins do | insert into membranes and make holes, disrupting and lysing the cell |
| what do phospholipases do | enzymes that cleave phospholipids, damaging the membrane |
| what do superantigens do | protein/peptide that simultaneously bind MHC class II (APC) and T cell receptors nonspecifically (randomly activates T cells) |
| what does the random activation of T cells by superantigens cause | - massive cytokine release from helper T cells causing a surge in proinflammatory response which can lead to fever, rash, shock, and death - important cause of S. aureus toxic shock syndrome toxin (TSST) |
| what do hydrolytic enzymes (another toxic protein) do | proteases and lipases can break down cells and tissues including muscles and skin (breakdown provides bacteria with nutrients and help them spread) |
| what do the pathogen toolbox consist of | virulence factors that contribute to adhesion, colonization, avoiding host defense mechs, causing damage |
| can the pathogen toolbox vary between different strains of pathogens, if so, what is an example | yes, E coli has several pathogenic strains and strains differ in adhesion, invasiveness, and toxins which can make them intestinal pathogen or extra-intestinal pathogenic |
| skin | - complex organ - prevents entry of microbes, restricts fluid loss, regulates body temp, and senses environment - ecological habitat |
| what consists of the skin microbiota | bacteria and fungi which are adapted to dry, acidic, salty, and cool habitats |
| what does the members of the skin microbiota use as nutrients | - substances in sweat and sebum (oily matter; lipids) as nutrients |
| what products can inhibit growth of other microbes | degradation products |
| what type of environment/area has the most inhabitants in the skin microbiome | moister areas |
| Cutibacterium acnes | - member of skin microbiota - aerotolerant anaerobe (grows only in absence of oxygen but can live in oxygen) - associated with acne (plugged pores) |
| where does Cutibacterium acnes grow and use as nutrients | - grows and uses sebum as nutrients in the sebaceous glands (lipases) |
| what does cutibacterium acnes cause | increase production of sebum --> increased bacterial growth --> inflammation resulting in a pimple (localized collection of pus made of living and dead neutrophils, bacteria, and cell debris) |
| what is used to treat severe acne | drugs that reduce sebum production and antibiotics |
| Staphylococcus Aureus | - gram positive --> grows in clumps - survives well in the environment; can grow in salty conditions such as skin - common inhabitant of nostrils (spread of hands) - usually harmless |
| what is S. Aureus responsible for | considerable morbidity (mild to severe) in many different ways - associated with skin infection (hair follicle; boils), food poisoning, pneumonia, wound infection, blood stream infection |
| what are examples of ways that the skin barrier is broken and allows entry of what | wounds, cuts, punctures, bug bits, burns, and chemical injury which provides entry for pathogens |
| what happens if a wound becomes infected | - delayed healing - formation of abscesses - spread of bacteria OR their toxins to other areas |
| what bacteria is the leading cause of wound infection | S. aureus |
| what is food poisoning mediated by | - toxins - toxin (superantigen) is resistant to heat (symptoms develop fast; within hours and involves vomiting, stomach cramps, and diarrhea; over in 1/2-2 days) |
| what treatment is involved with food poisoning | rehydration |
| what are the variety of surface and secreted proteins that S. aureus has | - capsule - Fc receptor - Coagulase (clumping factor) which binds fibrinogen hiding them from phagocytes - proteases |
| S aureus has what virulence factors | Toxins (pore forming toxins, superantigens, protease) |
| what are the pore forming toxins S. aureus has | leukocidin and alpha toxin |
| what do the superantigens that S. aureus has cause | food poisoning (toxin in food), toxic shock syndrome (if in blood) |
| what do the protease of S. aureus cause and lead to | - cleaves protein that connects cells to skin leading to blistering and skin peeling, sun burn like rashes, loss of body fluids - staphylococcal scalded skin syndrome (mostly infants, rare) - can lead to secondary infections |
| why is S. aureus difficult to treat | - greater than 90% of strains are penicillin resistant mostly due to enzyme, beta-lactamase, that destroy penicillin - resistance to methicillin has been increasing rapidly which was effective against penicillin resistant S. aureus --> MRSA |
| what does MRSA stand for and where is it acquired | - methicillin resistant S. aureus - in hospitals and more recently in the community |
| streptococcus pyogenes | - group A streptococcus or group A strep - gram positive chain forming - superficial skin infection - impetigo (blisters that break, releasing pus, crusts) |
| what other infections can S. pyogenes cause | - strep throat which can lead to scarlet fever if not treated - rheumatic fever; bacteremia; necrotizing fasciitis (more serious but rare infections) |
| what treatments are used for S. pyogenes | antibiotics (Still sensitive to it) |
| what cell wall structures does S. pyogenes have that contribute to its pathogenicity | - capsule: some contain hyaluronic acid (mimic host molecule) - Fc receptor (called protein G): binds Fc portion of antibodies - M protein: anti-phagocytic protein; prevents opsonization by C3b |
| what secreted toxins do S. pyogenes produce | pore forming toxins, superantigens, C5a peptidase, tissue degrading enzymes such as proteases, hyaluronidase, DNase |
| necrotizing fasciitis | - flesh eating disease - combination of toxins including pore forming toxins and enzymes --> destroys tissues - requires antibiotic treatment AND removal of dead tissue (debridement); amputation |
| zoonotic diseases may be transmitted from animals to people via what ways | either directly or via vectors (insects or arthropods) |
| what bacteria causes Lyme disease and how is it transmitted | - Borrelia burgdorferi which is present in small mammals like mice - transmitted via black legged ticks (Ixodes) |
| Borrelia burgdorferi | - long, thin spirochete (structure good for burrowing thru tissue) - gram negative like (double membrane) - instead of LPS, it has glycolipids, lipoproteins, and cholesterol - incorporates host lipids in membrane |
| where is the axial filament and what does it help B. burgdorferi do | - between the two membranes and is several floating flagella - helps it swim in a corkscrew like motion and bore its way through tissues |
| Stage I of B. burgdorferi infection | - days-weeks after tick bite; localized - influenza like symptoms; fatigue - erythema migrans (skin rash); bacteria migrate away from infection site, casing inflammation as they go ("bullseye" lesion) |
| Stage II of B. burgdorferi infection | - several weeks, months later; disseminated) if not treated - damage to heart and nervous system - dizziness, facial paralysis, severe headaches, fatigue, impairment of nerves in the extremities, etc. |
| stage II of B. burgdorferi infection | - years after tick bite - chronic arthritis; joint swelling and pain, tenderness in the joints |
| is B. burgdorferi treatable | yes, with antibiotics if given early |
| strep throat | - streptococcal pharyngitis - caused by Group A streptococcus - rapid onset; painful sore throat; red and swollen tonsils (sometimes with white patches/streaks of pus); fever; swollen neck lymph nodes; generally no runny nose or cough |
| scarlet fever | - superantigen - high fever, nasty rash (head, neck, chest, thighs); roughening of the skin; " strawberry" tongue |
| how is strep throat /tested for | - throat swab: rapid strep test for presence of cell wall carbohydrate antigen A (group A) - blood agar culture: beta-hemolysis due to pore forming toxin |
| what treatment is used for strep throat | antibiotic treatment to prevent sequelae (complications following primary infection) |
| what complications can develop after S. pyogenes infection | Rheumatic fever which occurs weeks after primary infection |
| what is rheumatic fever | - severe inflammatory disease affecting heart, brain, and connective tissues; may be autoimmune - symptoms: fever, painful tender joints - damage to heart valves; heart failure |
| is there a vaccine for Group A strep | No vaccine available |
| Corynebacterium diphtheriae | - aerobic gram positive pathogen - responsible for very difficult sore throat, neck swelling, fever - toxin mediated oozing of fluid in throat |
| where does the toxin mediated oozing of fluid in the throat caused by C. diphtheriae contain and where can it thicken and get into | - dead epithelial cells, RBCs, leukocytes, fibrin, and bacteria - thicken into thick pseudomembrane on tonsils and throat; can make it difficult to breathe - toxin can get into bloodstream; damage to heart and nerve |
| diphtheria toxin is a virulence factor secreted by what type of toxin | AB toxin |
| what does each subunit of the Diphtheria toxin cause | - B chain binds to cell receptor allowing molecule to be taken up by endocytosis (Cells lacking receptor --> unaffected) - A chain (enzymatically active): inactivates ribosomal protein which is required for protein synthesis resulting in cell death |
| what are toxoid vaccines and what does it do | - chemically modified form of the toxin used as a vaccine - toxicity is suppressed; immunogenicity is maintained - vaccine generates antibodies to toxin |
| what treatments are there for Diphtheria | antibiotics and antitoxin (antibodies against toxin) |
| how was diphtheria effectively eliminated in the US | - diphtheria toxoid was given as part of DTaP vaccine (diphtheria, tetanus, pertussis) - given to the young in most countries |
| Respiratory tract | - mechanical defense - particles are handled nonspecifically through mucociliary clearance or "mucociliary escalator" - ciliated cells and mucus producing goblet cells - propels mucus with trapped microbes and other particles |
| what can impair the respiratory tract | viral infection, smoke, alcohol |
| what bacteria causes Pertussis (whooping cough) | Bordetella pertussis (gram neg) |
| Pertussis | - highly contagious - major symptom: frequent bursts of violent, uncontrollable coughing spells followed by forceful attempts to inhale (high pitched intake of air) - serious for babies; stop breathing |
| what do the multiple toxins (tracheal cytotoxin, pertussis toxin, adenylate cyclase toxin) in Bordetella pertussis cause | - inflammation and local cell injury (necrosis) - killing of ciliated cells - disruption of phagocytic functions including chemotaxis, engulfment and killing of bacteria |
| Pertussis Vaccine Success | - earlier vaccine (DTP) killed bacterial (several antigens, elicited "multivalent" protection) - very effective (rapid rate of decrease in cases over 30 yrs) - occasionally severe side effects (drove development of an "acellular" vaccine > DTaP) |
| classic symptoms and signs of pneumococcal pneumonia | cough with fever, severe chest pain, shortness of breath, "rust" sputum (phlegm) |
| streptococcus pneumoniae | - heavily encapsulated with surface polysaccharides which makes it anti-phagocytic (prevents opsonization) - multiple capsular types |
| what is pneumolysin | potent pore forming toxin which damages many host cell types including ciliated epithelial cells and phagocytes |
| what does loss of microbe clearance cause | inflammation |
| what happens if inflammatory cells, plasma, and blood fill the alveoli (air sacs) | causes difficulty in breathing |
| what does imagery of pneumococcus show | - fluid accumulation - sputum contains pus, blood and lots of penumococci |
| what is the treatment for penumococci | antibiotics |
| when do cases of pneumococcus increase | - following influenza - in people with impaired mucociliary escalator |
| since pneumococcus is carried in high frequency in healthy people why doesn't it cause disease | bacteria seldom reach the lungs because of mucociliary escalator (self-clearing mech in the respiratory system that traps and moves inhaled particles and pathogens out of airways to protect the lungs) |
| what are some complications that can occur with pneumococci | - may enter bloodstream and result in fatal infections - bacteremia (bacteria in bloodstream) - meningitis (infection of membranes over brain and spinal cord) |
| pneumococcal capsule | - each capsular type stimulates production of a different antibody - multivalent vaccines are needed |
| what bacterial cell component/structure is a virulence trait and a basis for effective vaccinology | the capsule |
| mycobacterium tuberculosis | - slow growing; 16-20 hr generation time - rod shaped aerobe - unusual cell envelope |
| what is the mycobacterium surface like | - unique highly hydrophobic impermeable cell wall - mycolic acids (long fatty acids) --> "waxy coat"; nearly waterproof - does not take up gram stain or counterstain - resistance to drying, disinfectants, antibiotics |
| in a primary TB infection is the initial infection asymptomatic or symptomatic | asymptomatic (no or mild flu-like symptoms) |
| what cells take up M. tuberculosis (TB) in a primary infection | lung macrophages |
| how does M. TB avoid macrophage killing | - blocks phagosome-lysosome fusion, enters cytosol and multiplies - more macrophages swarm in and are infected - repeated cycles of phagocytosis, bacterial replication and cell lysis - dead tissue accumulates |
| there is a delay in what type of cell response after infection with M. TB | T cell response |
| how is M. TB infection eventually controlled resulting in latent TB infection | - lymphocytes infiltrate and "wall off" the area resulting in granuloma formation - mycobacteria can't multiple (too low pH and anoxic environment in the granulomas) --> infection controlled but not eliminated |
| in what situations can Latent TB be reactivated (<5% of cases) | - HIV/AIDS - aging and natural waning of immunity - other immunocompromised states |
| how does Latent TB get reactivated | - granulomas ruptures forming lesion and M. TB multiplies and is released into airways, continues to destroy the lung tissue and can spread to other organs including brain |
| reactivated TB is _____ TB disease that is ______ | active, infectious |
| what are symptoms/signs of ACTIVE TB disease | - progressive decline in health (slight fever, night sweating, persistent cough, often blood streaked sputum, weight loss) - without treatment: 50% die within 5 yrs |
| how does Tuberculin skin test work | - injection of TB antigens intradermally - a hypersensitivity response is seen 2-3 days in people infected with M. TB - positive response = firm, red, raised bump of about 15 mm or bigger |
| what is the positive response of TB skin test caused by | activation of T cells, cytokine production, infiltration of other immune cells, edema |
| what does the Tuberculin skin test not distinguish between | latent and active infections |
| what are additional tests that can be used to test for TB | - heath exams, chest X-ray, examination of sputum for presence of M. TB - treatment regimens: combination of 2-4 different antibiotics; 4-6 months course |
| summary: a person with latent TB infection has what characteristics | - no symptoms/signs - doesn't feel sick - doesn't spread TB bacteria to others - pos test indicating TB infection - treatment for latent TB infection to prevent active TB disease |
| Summary: a person with active TB disease has what characteristics | - symptoms/signs occur slowly and gradually with a progressive decline in general health - usually feels sick - can spread TB bacteria to others - pos test indicating TB infection - needs treatment to treat active TB disease |
| GI tract | - harbors an extensive and rich normal microbiota (warm protected environment for microbes; digested food ready source of nutrients for microbial growth) - prone to pathogen exposure throughout its length |
| what does dental plaque (polymicrobial biofilm) consist of | - consists of microorganisms encased in extracellular matrix - bacteria attach to both tooth surface and each other (consist of both anaerobes and aerobes, cooperative behavior) - soft and sticky |
| what accumulates in dental plaque | mineral salts deposits, crusty substances; tartar |
| what can occur if dental plaque is not removed | tooth decay and gum disease |
| what bacteria is a significant cause of dental caries | streptococcus mutans |
| how does S. mutans cause dental caries | - sugar fermentation results in acid production which leads to a drop in pH causing calcium phosphate of the teeth to dissolve |
| what is dental caries | - cavities, tooth decay - biofilm on teeth (much less on gums and tongue) |
| what does fluoride treatment aimed at | hardening tooth enamel --> acid resistance --> less tooth decay |
| what does bacterial products release from plaque trigger | inflammation of the gums (swelling, red gums that may bleed; gingivitis) |
| irritated gums that recede from the tooth root allow what to enter | allows for bacterial entry and further plaque development |
| what happens as plaque develops | gram neg anaerobic bacteria such as Porphyromonas gingivalis are enriched and produce proteases and toxins that destroy supporting tissue around the teeth (periodontitis) --. can result in tooth loss |
| how does diarrheal disease cause human suffering and what is it caused by | - caused by a variety of microbes - contributes to malnutrition, growth retardation, and permanent disability - increased risk for other infections |
| infection of the small intestine leads to what kind of diarrheal disease | - infection of small intestine copious watery diarrhea |
| infection of the colon leads to what diarrheal disease caused by bacteria | smaller amounts containing mucus, pus, sometimes blood (dysentery) |
| the toxins released by bacteria that cause diarrheal disease do what | - enterotoxin: cause electrolyte and water flow from intestinal cells - cytotoxins: cause cell death |
| what can intestinal cell invasion and alterations from diarrheal disease-causing bacteria cause | inflammatory responses |
| how are bacteria that cause diarrheal diseases transmitted | - through the oral-fecal route (water or food contaminated by human or animal feces) |
| do acid sensitive pathogens require high infecting dose or low infecting dose; what about acid resistant pathogens | - acid sensitive pathogens require high infecting dose - acid resistant pathogens have low infecting dose |
| what treatment is for diarrheal diseases caused by bacteria | - oral rehydration therapy (ORT) that counteracts loss of fluid and electrolytes - antibiotics usually not helpful |
| how can we prevent diarrheal diseases caused by bacteria | - clean water, sewage treatment, hand washing, cooking and storing food properly - drink bottled water and avoid food from street vendors when traveling in low income countries |
| cholera | - waterborne acute diarrheal disease - one of the most rapid and fatal of all diarrheal diseases (20 liters/day --> dehydration --> organ failure --> death) - disease of poverty, natural disasters, and political violence |
| in what areas is cholera most widespread | in areas with poor sanitary conditions such as disaster areas, water zones, refugee camps |
| Vibrio cholerae is a gram neg or gram pos bacteria | gram neg pathogen |
| what is the major virulence factor of Vibrio Cholerae | Cholera toxin |
| Cholera toxin is what type of toxin | AB toxin/enterotoxin |
| what does Cholera toxin do | - activate adenylate cyclase resulting in high cAMP levels - cAMP activates ion transport channels resulting in release of electrolytes and water causing watery diarrhea |
| are there vaccines for protection against cholera | - vaccines available but incomplete and provides short lived protection - used to reduce size of outbreak - used for travelers |
| what are some clinical outcomes of E. coli that express virulence factors | depending on the factor it can cause different diarrheal diseases, UTI, or meningitis |
| what does EHEC stand for | Enterohemorrhagic E. coli |
| what does STEC stand for | Shiga toxin producing E. coli |
| what are the two principle virulence mech for Shig toxin producing E. coli (STEC) | T3SS and Shiga toxin (Stx) |
| what does the virulence mech of T3SS do | - inject proteins including Tir (receptor) - Intimin on bacterial surface binds to Tir on host cell surface - induces intestinal cell alterations (pedestal formation) --> inflammation, abdominal cramping, diarrhea |
| what does the Shiga toxin do | - AB toxin - targets epithelial and endothelial cells - a subunit cleaves RNA of the host ribosome - inhibits protein synthesis leading to cell death, bloody diarrhea |
| what is dysentery | hemorrhagic colitis (i.e. bloody inflammation) |
| what happens if Shiga toxin gets into the bloodstream | - it can cause severe, life threatening complications --> Hemolytic Uremic Syndrome (HUS) |
| what is Hemolytic Uremic Syndrome (HUS) | - damage and inflammation of small blood vessels - can cause clot formation in blood vessels throughout body - damage of kidneys --> kidney failure |
| what treatment does HUS require | blood transfusion and kidney dialysis |
| where is Shiga toxin producing E. coli acquired from | undercooked contaminated beef, unpasteurized milk, green leafy vegetables - Cattle: main reservoir; runoff from cattle farms |
| is there a vaccine available for STEC | none available |
| Shigellosis | - Shigella - severe inflammation; inflammatory colitis; dysenteric (mucus, pus, blood); fever |
| how does shigellosis spread | avoids detection by immune system and replicates and spreads intracellularly |
| what is the reservoir for shigella | human only reservoir (only human to human spread) |
| how many species are there of Shigella and which one is the most virulent and common in US | - four species - S. dysenteriae most virulent (produces Shiga toxin; often fatal for infants in low-income countries; rare in the US) - S. sonnei most common in US |
| what is the pathogenesis of Shigella | - taken up by antigen sampling M cells - multiply inside macrophages; escape following macrophage death - induce uptake by epithelial cells using T3SS - multiply cause acting polymerization to move around and into other cells |
| what is the outcome of infected epithelial cells from Shigella | - infected epithelial cells die and slough off - an intense inflammatory response leads to bleeding and abscess formation - cell death |
| Clostridioides difficile is the leading cause of what | - leading cause of hospital acquired diarrhea - symptoms and signs ranging from mild diarrhea to life threatening inflammation of the colon (watery diarrhea and mild abdominal cramping; dehydration) |
| when do symptoms start developing after C. diff infection | - develops within 5-10 days after starting a course of antibiotics but may occur up to 2 months later |
| in severe cases what does C. difficile induces | colon inflammation (colitis) and may also induce formation of patches that bleed or produce pus (pseudomembranous colitis) |
| in rare cases what can C. diff cause | toxic megacolon which is a serious swelling of the colon, leaving it incapable of expelling gas and stool; rupture of colon; potentially lethal |
| what mechanisms causes C. diff to cause infection after antibiotic treatment | - spore forming bacterium (dormant, non-reproductive) |
| what are benefits to spore forming bacterium like C. diff | - surrounded by a tough and highly impermeable coating - resistant to damaging conditions or agents (heating, freezing, drying, radiation, disinfectants, antibiotics) |
| C. diff infection | - spore contamination in hospitals - present as spores in intestine; not growing; not killed by antibiotics - only able to grow to high numbers when normal microbiota disrupted - production of two toxins --> inflammation |
| what treatments are used for C. diff | - antibiotic treatment to kill growing C. diff (but 20% recurrence) - fecal microbiota transplant (stool transplantation) from healthy person (80-90% successful) |
| what are ways that bacterial diseases spread | - direct or indirect contact; sharing saliva and bodily fluids - air borne droplets (coughing, sneezing, shouting, singing) - fecal-oral route - vector transmission (ex: thru ticks) - introduction of our own microbiota to sites they don't belong |
| how is salmonella most commonly spread through | foodborne, but pets (hedgehogs, turtles, geckos, etc.) can also carry the pathogen |
| what are methods to treat bacterial infections | - rehydration therapy blood transfusion, kidney dialysis, antitoxin therapy, debridement, fecal microbiota transplant, antibiotics |
| what does rehydration therapy do and what is it used for | - restore fluid and electrolytes; oral or IV therapy - used for diarrheal diseases such as cholera, but also toxin induced non-bacterial food poisoning |
| what is blood transfusion and kidney dialysis used for | if STEC or shigellosis lead to HUS |
| what does antitoxin therapy do and what is it used to treat | - antibodies that neutralize the toxin that is circulating in the body - used to treat Diphtheria |
| what is debridement and what is it used to treat | - surgical removal of dead and infected tissue - used to treat necrotizing fasciitis |
| what is fecal microbiota transplant used to treat | recurrent C. diff infection |
| what do antibiotics do | kill or prevent growth of bacteria BUT bacteria develop resistance |
| what are some efforts to identify and synthesize new antibiotics | - continue modification of existing antibiotics -continue screening of soil isolate and organisms from other locations/environments - screen synthetic chemical library for molecules with antibacterial activities - identify ways to boost immune system |
| what does isolating and identifying bacteriophages for therapy in new antibiotics synthesize involve | - to specifically target the pathogen without disturbing the normal microbiota - requires the identification of the pathogen - isolation of a phage that specifically target the pathogenic strain |
| how does phages kill bacteria | 1. phage first lands on bacteria 2. it injects its DNA inside bacteria 3. DNA is copied and used to make packaging for new gen of phages 4. new phages assemble and burst bacteria killing it in the process |
| what are new possibilities/mechs for developing new antibiotics | have them target virulence properties (adhesion, gene regulation; quorum sensing, invasion, toxins (secretion, receptor binding, activity)) |
| what is pathogenesis | process of producing a disease |
| what are the two components of viral disease | - effects of virus replication on the host - effects of host immune responses on the virus and host |
| do all virus causes diseases | no the same virus may have very different effects in different hosts (viral infections span the range from benign to lethal) |
| what might asymptomatic infections contribute to | seroprevalence and virus transmission |
| what is seroprevalence | the frequency of individuals who are positive for a pathogen based on serologic measurements (antibodies) |
| is EBV seroprevalence high? | high |
| can the same virus have different symptoms? | yes |
| in what case is infection prevented or abortive | when virion never finds a living cell to infect, is inactivated by the host, or never infects more than a cell or two at site of infection |
| in what case is a virus a disease cofactor | virus replication contributes to an environment in which another microbe/factor causes disease (2nd degree influenza pneumonia) |
| when does a viral disease require a co-factor | viral diseases require an environment generated by another microbe/factor (ex: Kaposi's sarcoma) |
| barriers associated with organisms often make infectious does ______ than pfu and give examples of these physical barriers | - higher - skin, mucous layers, and other physical barriers in the host organism |
| how many virions does it take to infect a host | answers varies for every host/virus interaction |
| infection is multifactorial; what are these variables | host genetics, host antiviral defenses, viral virulence, host social behavior, host age, weather and environment |
| what are the primary replication sites within the host | skin, respiratory tract, GI tract, urogenital tract |
| give examples of how an viral infection might spread within a host | upper RT --> lower RT; lung --> gut; blood --> brain |
| at any stage, a viral infection can.... | - fail/be aborted - can cause disease - can be asymptomatic |
| what are the stages of the infection process that eventually leads to systematic spread | - primary viremia - replication at secondary sites (virus leaves blood and infects target organs/tissues and replicates extensively) - secondary viremia - further dissemination |
| what is primary viremia | first time the virus enters the bloodstream (usually comes from first site of replication) |
| what is secondary viremia | virus re-enters bloodstream after replicating in those organs (have much higher viral load) |
| what are effects of viral replication on host cells | - alter metabolism - commandeer transcription and/or translation machinery - stimulate quiescent cells to divide (can lead to cancer) - kill cells (often an inflammatory even) |
| enough virus induced cell death can cause what kind of damage | major tissue damage |
| _____ killing is a major aspect of pathogenesis for some virus | cell |
| Measles | - acute infection - kills B cells - virus that promotes pathogenesis via cell killing |
| immune amnesia can occur after what | recovering from measles |
| reduced antibody repertoire can leave a person susceptible to what | previous vaccine or infection mediated immunity (diseases your body was already immune to) |
| what are the effects of host response on the virus | - some viruses/dsRNA trigger interferon - virus spread is halted and can lead to inflammation |
| what is an interferon | a general inhibitor of translation; leads to cell death |
| what does the inflammatory response from infection result from | increased blood flow, increased capillary permeability, influx of phagocytic cells, tissue damage |
| why might the IFN system be dangerous | - IFN induces the expression of many deleterious gene products - large quantities of IFN have dramatic physiological consequences: fever, chills, nausea, malaise - every viral infection results in IFN production |
| why are flu-like symptoms so common | every viral infection results in IFN production |
| what are acute infections | - virus enters a body cell, replicates, and causes disease (or not) - virus is either cleared from the body (or the person dies) - ends with no infectious virus remaining in the person |
| what are persistent infections | - virus enters a body cell, replicates and causes disease (or not) - virus is NOT cleared from the body (or the person dies) - virus remains in body after disease resolves |
| what is the process of acute infection | - virus enters a body cell and replicates - progeny virions infect adjacent cells - replication may stay localized or spread in body - virus is either cleared from body or person dies - ends with no infectious virus, often immunologic memory |
| how does CoV2 enter a cell | entry is driven by interactions between Spike and angiotensin converting enzyme 2 (ACE2); subsequent protease cleavage drives fusion. (cell surface receptor = TMPRSS2) |
| what are the newly recognized/possible host variables that may affect initiation of infection | - cold/stress - cigarette smoking - ACE inhibitors taken up by patients |
| how does cold/stress affect initiation of infection | increases cell surface density of the receptor for some common cold viruses |
| how does smoking affect iniation of infection | may trigger the expansion of a respiratory epithelial cell subpopulation that expresses ACE2 which is the SARS/SARS CoV2 receptor |
| how does taking ACE inhibitors affect initiation of infection | may upregulate ACE2 |
| the timing and nature of the immune response is shaped by what | viral and host genetics, environmental factors, etc. |
| what is required by persistent viruses | host immune evasion which helps "buy time" and allow virus to complete a replication cycle(s) |
| what does innate immune defense entail | - cytokines, pattern detectors, sentinel cells, complement - takes care of most infections before we know what's going on |
| viral patterns | patterns viruses carry that healthy host cells don't have that allows the immune system to detect non-self from self |
| what are examples of viral patterns | dsRNA, uncapped 5' triphosphate RNA, viral DNA in the cytoplasm (detected by cGAS), unusual replication intermediates (ex: RNA:DNA hybrids or long stretches of repetitive nucleic acids) |
| pattern sensing | specialized receptors detect viral molecular patterns and launch an interferon response |
| what are some examples of viral pattern sensing receptors | - Toll like receptors (TLR3 detect dsRNA in endosomes) - RIG-I-Like receptors (cytosolic sensors for viral RNA) |
| what happens have sensing a viral pattern | sensors converge on signaling hubs that activate interferon production and inflammatory cytokines and chemokine production |
| viral evasion | viruses survive by sabotaging detection, signaling, or interferon response |
| how do viruses evade detection | hide their nucleic acids, block sensors, block interferon signaling |
| what are some ways that viruses might hide their nucleic acids | - cap their RNA to look like hosts - replicate inside membrane compartments - bind dsRNA with viral proteins to mask it |
| what are ways that viruses block sensors to evade detection | - viral proteins that bind RIG-I or MDA5 - use proteases that cleave MAVS or TRIF - inhibit cGAS or STING |
| how might viruses block interferon signaling | - degrade interferon receptors - shut down host transcription globally - prevent activation of molecules (STAT1/STAT2) |
| cytoplasmic DNA leads to interferon production via what signaling pathway | cGAS-STING signaling (STING signaling can also activate chemokine expression via NF-kB) |
| _____ features can limit the extent to which interferon is trigger | physical |
| what are accessory genes | genera/species-specific are usually dispensable for viral replication in vitro but required in vivo |
| SARS immune evasion results in what | higher virus titers |
| what might suggest that antivirals are effective only at earlier stages when it comes to SARS-CoV2 infection | - virus titers highest before disease symptoms occur (easier to detect virus before patient is sick) - virus titers are lower as disease progresses |
| SARS-CoV1 and SARS-CoV2 are what type of virus | acute virus making COVID19 an acute viral disease |
| what is the course of infection for Polio | 1. initial replication at site of infection 2. dissemination to secondary sites 3. disease symptoms (90-95% of patients have none detectable symptoms) 4. residual virus shedding ~3 months then one 5. immunity |
| Dengue virus infection (DENV) and disease | - RNA virus (flavivirus) - most common vector born viral disease - often asymptomatic (sometimes headache, muscle pain, rash) - on re-infection dengue hemorrhagic fever - antibody dependent enhancement of infection |
| how might antibody enhancement of infection occur | via Abs against antigens from other prior flavivirus infections (related but different serotype) |
| what is the process of persistent infection | - virus enters body cell and replicates - progeny virions infect adjacent cells - replication may stay localized or spread in body - virus somehow evades immune clearance - virus replication continues - can last months to yrs or for lifetime |
| chronic vs. latent infection | - Chronic: infectious virus is released from host with no symptoms (continuous virus replication, often at reduced levels) - latent: virus is maintained in neurons in non-infectious state. Virus is activated to produce new disease symptoms |
| persistent infections are further subdivided into what kind of infections | chronic and latent infections |
| systemic spread can occur for what kinds of infections | both acute and persistent viruses |
| do acute viruses have persistent and acute phases or just acute phases? what about persistent viruses? | acute viruses do NOT have persistent phases, but persistent viruses have acute AND persistent phases |
| what factor is critical for infection and immune response | the timing |
| what are the two paths to long COVID | 1. severe covid ---> discharge --> post severe cov19 syndrome (fibrosis, tissue and organ damage) 2. mild/asymptomatic covid --> virus no longer detected --> post covid fatigue syndrome (PCFS) (fatigue, brain fog, poster exertional malaise, dysautonomia) |
| EBV disease/symptoms by timing and infection phase | - early/primary: asymptomatic, infectious mono, or oncogenesis (with co-factors) - Late/reactivation (viremia, CAEBV, cancers, MS? other autoimmune diseases? |
| VZV disease/symptoms by timing and infection phase | - early/primary: asymptomatic, chicken pox - late/reactivation: shingles |
| HSV-1 disease/symptoms by timing and infection phase | - early/primary: ulcers, fevers, swollen lymph nodes - late/reactivation: cold sores, neural complications |
| what are the two oncogenic herpes viruses that are gammas herpes virus | EBV and KSHV (Kaposi's sarcoma herpes virus) |
| Hep A (HAV) | - acute virus - causative agent: naked, ssRNA picornavirus - transmission: fecal- oral - incubation period: 3-5 weeks (range 2-7 weeks) - Prevention: inactivated vaccine; immune globulin - comments: usually mild symptoms, but often prolonged |
| Hep B and C cause what type of infection | chronic infection (virions are continuously detectable) |
| what is the leading cause of liver transplants | Hep B and C --> cause 80% of liver cancers |
| what is a characteristic of resolved acute infections | anti-viral antibodies can generally be detected |
| Hep B (HBV) | - causative agent: enveloped, dsDNA hepadnavirus - transmission: blood, semen - incubation period: 10-15 weeks (range 6-23 weeks) - prevention: subunit vaccine; immune globulin - comments: acute symptoms; can cross the placenta |
| Hep C (HCV) | - causative agent: enveloped, ssRNA favivirus - transmission: blood, possibly semen - incubation period: 6-7 weeks (range 2-24 weeks) - prevention: no vaccine - comments: usually few/no symptoms, liver damage can lead to cirrhosis and cancer |
| what percentage of infected children become chronic carriers of Hep B | 25-50% |
| what type of antigen can be detected throughout chronic HVC infection | HBsAg |
| Dane particle | functional infectious HBV particle/virion that can infect subsequent cells |
| HBV infected cells produced both Dane particles and what other type of particles | - defective particles (don't contain capsid or genome) --> viral envelope particles containing HBsAg) - can't replicate or invade other cells - more abundant |
| how do defective particles contribute to pathogenesis | The defective HBV particles form crosslinking with antibodies to form large macromolecular immune complexes that eventually lead to tissue injury by clogging up vessels (ex: clog kidney glomeruli; blood vessels) |
| Hep B surface antigen (HBsAg) | - surface protein of HBV; can be detected in high levels in serum during acute or chronic infection - presence indicates person is infectious - body normally produces Ab to it as part of normal immune response to infection - used to make HBV vaccine |
| Hep B surface antibody (anti-HBs) | - presence generally interpreted as indicating recovery and immunity from HBV infection - also develops in person who has been successfully vaccinated against Hep B |
| Total Hep B core antibody (anti-HBc) | - appears at onset of symptoms in acute Hep B and persists for life - presence indicates previous or ongoing infection with HBV in an undefined time frame |
| IgM antibody to Hep B core antigen (IgM anti-HBc) | - positivity indicates recent infection with HBV (less than or equal to 6 months) - presence indicates acute infection |
| what do these test results mean: - HBsAg: neg - anti-HBc: neg - anti-HBs: neg | susceptible --> good candidate that will benefit with vaccine |
| what do these test results mean: - HBsAg: neg - anti-HBc: pos - anti-HBs: pos | immune due to natural infection |
| what do these test results mean: - HBsAg: neg - anti-HBc: neg - anti-HBs: pos | immune due to hep B vaccination (anti-HBs is protective) |
| what do these test results mean: - HBsAg: pos - anti-HBc: pos - IgM and anti-HBc: pos - anti-HBs: neg | acutely infected indicated by IgM anti-HBc pos and anti-HBs neg |
| what do these test results mean: - HBsAg: pos - anti-HBc: pos - IgM and anti-HBc: neg - anti-HBs: neg | chronically infected --> fail to develop anti-HBs |
| chronic HBV infection symptoms/signs can lead to what | - activation of processes similar to wound healing leads to deposition of extracellular matrix causing fibrosis or cirrhosis - chronic liver injury, inflammation, and regeneration can lead to malignancy |
| what is a method that is able to fight against cancers caused by viruses | vaccines |
| antibodies to HBsAg are sufficient to confer ____ immunity | protective |
| using what type of vaccine has reduced hepatocellular carcinoma rates | recombinant HBsAg vaccine |
| what type of inhibitors are effective against Hep B's reverse transcriptase | non-nucleoside RT inhibitors |
| what is the increase in Hep B and C infections being influenced by? | opioid and heroin use epidemics --> use of needles |
| is there a treatment for HCV | yes, effective combined antiviral inhibitors have been developed that can cure chronic infection but are very expensive |
| why is it dangerous that people don't know they are infected with Hepatitis | puts them at risk for life threatening liver disease and cancer and unknowingly transmitting the virus |
| what is the hallmark of herpesviruses infection | latency |
| in latency, replication is delayed after what step of the virus infection process | entry |
| Herpes simplex virus type I (HSV-1) | - acute phase disease at site of infection - goes latent into trigeminal nerve cells (no circulating virus or virus replication, very little virus gene expression) - subsequent reactivation repeats lesions |
| HSV-1 causes what kinds of lesions | oral |
| HSV-2 causes what kinds of lesions | genital |
| what are the different types of human herpes viruses: | herpes simplex virus (HSV 1 and 2); Varicella zoster virus (VZV); Epstein Barr Virus (EBV), cytomegalovirus (CMV), HHV-6A, 6B, HHV-7, Kaposi's sarcoma herpes virus (KSHV) |
| Burkitt's lymphoma generally results form what | chromosomal translocations, such as ones that fuse Ig loci with the myc oncogene |
| how does EBV infect the body | activates B cells --> undergo genetic rearrangement chronic malaria infection affect T cell checkpoint & produce inflammatory environment for B cell response create co-pathogenic context for DNA damage & accidental chromosomal rearrangement upon repair |
| EBV is a primary cause of what | infectious mononucleosis (IM) |
| what is multiple sclerosis (MS) | - autoimmune demyelination syndrome that causes neurologic disease - onset is gradual, disease severity varies among individuals and increases over time |
| what is the correlation between EBV and MS | antibodies against EBV protein EBNA1 can cross react with GlialCAM (CNS protein) involved in cell adhesion --> strengthens link between EBV and MS |
| how might persistent viruses avoid adaptive immune recognition | one example is CMV (cytomegalovirus-immune cell interaction) |
| how does cytomegalovirus immune cell interaction (CMV) work | viruses in infected cells direct cells to make fake MHC class I proteins that cannot display an antigen so that neither Tc cells nor NK cells can recognize it leading to virus infected cell survival |
| why might a virus still be recognized and kill if they suppress expression of MHC | NK cells can recognize abnormal cells that don't express MHC or have few MHC molecules and induce them to undergo apoptosis |
| in infected cells, many viruses inhibit what presentation to evade immunity | canonical antigen presentation |
| HIV infection is split into 3 stages what are they? | acute retroviral syndrome, asymptomatic interval, AIDS |
| what are the characteristics of acute retroviral syndrome | - flu-like symptoms may occur, HIV infection spreads throughout the body - virus load and viral RNA increases, CD4 T cells drops sharply then partially recovers |
| what are the characteristics of asymptomatic interval (latency) | - period of wellbeing and very low "viral load" which normalizes at "HIV set point" - CD4 T cells gradually decline, viral load drops to a set point, virus actively replicates but at low levels (viral RNA gradually increases) |
| AIDS | - after variable time (untreated infection) progresses with virus increases, patient susceptible to opportunistic infections that can cause death - viral load rises, CD4 cells collapse |
| the asymptomatic interval is a time of what type of persistence and what do drugs do to that interval | chronic persistence and drugs prolong that interval |
| antiretroviral drugs (HAART) are capable of doing what to HIV | suppressing HIV even to undetectable levels but virus rebounds after cessation of therapy (HIV persists for yrs) |
| true or false: early trials revealed ongoing virus replication in asymptomatic interval | true |
| what is special about Hep D (HDV) infection | it can't replicate on its own and requires cells to previously be infected with Hep B (needs to use HBV HBsAg to form its viral particle) |
| sometimes a host cell may only be permissive to a viral infection if it's already infected with a _____ virus | "helper" virus |
| what viruses are helper viruses for AAV | adenoviruses |
| AAV has been engineered to be used as what | gene delivery "vector" (recombinant AAVs in which the viral replication and capsid genes are removed and replaced with gene of interest) |
| what virus caused vaccinations to get developed | smallpox |
| what is the goal of vaccination | to establish a protective immune response (to a virus) without causing disease |
| what do effective vaccines do | provide disease protection |
| what are the different degrees of protection provided by vaccines | - some vaccines reliably produce sterilizing immunity (functional resistance to infection) - others do not but can reduce disease severity from infection |
| live attenuated virus | - virulent in a different species - attenuated: infectious but not disease causing (loss virulence mutants, genetically manipulated) |
| when viruses lose their virulence mutant it makes them what to temperature | cold adapted/temperature sensitive |
| inactivated virus | heat, UV, or chemical treatment makes virus particles become incapable of infection |
| factors of live attenuated vaccines | - duration of immunity: long term - thermostability: low (need cold chain) - breadth of immunity (cell mediated or mucosal): good - reversion to virulence: occasional - production costs: low |
| factors of inactivated vaccines | - duration of immunity: shorter - thermostability: higher - breadth of immunity (cell mediated or mucosal): poor - reversion to virulence: none - production costs: low |
| what are the two polio vaccines | - IPV: inactivated polio vaccine ("Salk Vaccine") - OPV: Oral Polio Vaccine ("Sabin Vaccine") |
| Inactivated Polio Vaccine (IPV) | - trivalent, inactivated, given intramuscularly - serological immunity - protects against disease not infection |
| Oral Polio Vaccine (OPV) | - trivalent, live, attenuated, orally administered - stable (with cold chain) - mucosal immunity - protects against infection |
| what is the significant of these Polio vaccines being trivalent | it protects against multiple strains of poliovirus (Types 1, 2, and 3) |
| what are the two consequences of live attenuated vaccines against Polio | 1. live vaccines can occasionally revert to virulent forms (can get mutations for replication) 2. fecal oral route can lead to unintentional spread (can cause "herd immunity" but if there's a mutation that causes replication it can also cause infection) |
| what are some other problems associated with vaccine use | - vaccination of immunocompromised person with live virus can be life threatening - side effects such as allergic reactions - development and liability insurance = very expensive - organisms with many serotypes are difficult to control |
| what defines what immune responses are needed | immunologic correlates of protection |
| subunit vaccines | - purified viral protein, not a whole virus - used in cases when immune response to a single viral protein confers protective immunity - Ex: Hep B surface antigen |
| what is virus like particles (VLP) | a particle coated with viral proteins that can be recognized by the host immune system |
| what is a chimeric virus | use a different non-virulent virus engineered to express one or more antigens of a virulent virus |
| recombinant viruses | virus whose genetic material has been altered by combining DNA or RNA from different sources, either naturally or in a laboratory, to create a new viral genome |
| what cases are recombinant viruses used and what are some examples of ones | - used in cases when multi target immune responses are needed for protection - ex: HPV vaccine (VLP), J&J COVID vaccine (Chimeric virus) |
| nucleic acid vaccines (DNA or RNA) | vaccines that introduce either DNA or RNA that encodes a specific pathogen's antigen into host cells. Once inside body it gets translated into proteins and antibodies are made against it |
| in what cases are nucleic acid vaccines used | numerous; advantageous in terms of production speed, scale, and minimizing risks associated with traditional vaccines (ex: moderna COVID vaccine --> lipid nanoparticles containing mRNA encoding target viral protein translated by host ribosome) |
| true or false: a danger of subunit vaccines is that the vaccine revert to replication competence and cause disease | false, no genome for which viral product can express |
| "old school" vaccines characteristics | - may provide broader immunity (multiple antigens) - usually easier to manufacture (use of eggs) - may be better for resource limited settings |
| what are some advantages and disadvantages of viral vectors | Pros: less expensive to manufacture, more stable than RNA vaccines cons: immunity to the vaccine virus (adenovirus serotype) may limit repeated use |
| what are viral vectors | uses a harmless virus which is altered to contain part of a virus's genetic code |
| how does the adenovirus vaccine work | genetic instructions are given to human cells to make part of the virus |
| what are advantages of mRNA vaccines | - translated in cell; can stimulate antibody responses and T cell responses - easy to change (engineer) sequences (fastest vaccine development ever; potential use for any situation where it's desirable to express protein in cells) |
| what are disadvantages to mRNA vaccines | - expensive to manufacture - needs cold chain/has short shelf life |
| what are major advances in delivery for mRNA vaccines | lipid nanoparticles are used instead of virion which helps enhances fusion with cells and makes it more stable (good for manufacturing), also less immunogenic than viruses |
| what can we change about the delivered RNA itself for mRNA vaccines | delivered RNA can be engineered to include pseudo-uridine instead of uridine making it more stable and has less innate immune detection |
| what is herd immunity | a phenomenon that occurs when a critical concentration of immune hosts prevents the spread of an infectious agent thereby protecting the entire population (viruses need hosts) --> need 95% compliance |
| why are vaccines that protect from disease but not infection less successful at providing herd immunity | vaccines that protect from disease reduces the severity of it but you can still get infected and transmit that to other people. You're not inhibiting the virus from establishing itself (e.g. covid) |
| what factors contribute to a successful vaccination campaign | 1. humans are the sole reservoir for the virus 2. rates of asymptomatic infection and/or pre-symptomatic infectivity are low 3. adverse effects/outcomes of infection are more visible (not just symptoms in an individual; also public awareness) |
| what are other factors that contribute to a successful vaccination campaign | 4. virus modes of transmission are limited 5. there are few strains of the virus (related to virus evaluation) 6. virus replication and/or disease progression are very slow |
| having more strain variation in a virus requires what | broader immune response coverage to protect against infection |
| what are the two components of Rabies post exposure prophylaxis (PEP) | 1. HRIG (human rabies immune globulin) 2. vaccine schedule (4-5 doses over 2-4 weeks) |
| how does post-exposure prophylaxis (PEP) help prevent rabies | if vaccine is provided early, protective humoral immunity develops before virus can build up in the CNS |
| how does having economics of vaccine development being favorable contribute to success of a vaccination campaign | challenging to develop and don't always work; may only be used once in a lifetime --> not profitable for companies thus vaccines require buy in from governments or large nonprofits |
| vaccination campaigns are often more successful when immunization compliance is high or low | high |
| what shapes vaccine compliance | individuals' attitudes and behaviors en masse which is in turn shaped by messaging. Messaging about vaccines should be informed by empirical evidence |
| what is one of the major public responsibilities of science | to establish rigorous, reproducible data to advance knowledge and inform decisions |
| epidemiological studies search for causes of diseases based on what | associations with various risk factors that are measured in the study |
| what are confounding factors | factors that differ between groups being compared and will distort the observed association between the disease and exposure under study |
| what are some factors beyond confounded correlations | sample size (limited case reports vs. systematic study), doubt, frustration, and confusion about disease/medical conditions with unclear etiology can all be exploited and capitalized |
| measle rates in the US | was declared eliminated in the US in 2000 but with current MMR vaccine rates in US being ~92% there has been a rise in cases |
| HIV mortality rates are decreasing but people living with HIV (PLWH) are increasing or decreasing | increasing |
| what percentage of the population and gender have a higher percentage of new HIV infections | gay men and other men who have sex with men and males |
| what are some challenges with antiretroviral therapy (ART) | - treatments prolong life but some drug complications (metabolic effects of older drugs esp protease inhibitors) - compliance: need to take daily but better/more tolerable drugs are being developed like Lenacapavir (take 2 times a yr) |
| why isn't ART good enough | - viral suppression doesn't cure (infection complications are abundant) |
| what are some examples of infection complications that occur with HIV even with taking ART | - tolerance/compliance issues - CMV/EBV/KSHV tumors, others - opportunistic infections - poorer outcomes with secondary infections - neurologic effects - other organ system complications |
| what does the immune system see with HIV latency | essentially nothing because HIV DNA is integrated into the genome but transcription is shut down or extremely low so no viral proteins are being made or virions produced making it look "normal" to the immune system |
| why is latency a barrier to curing HIV | ART blocks new replication but can't eliminate latent cells and these cells can persist for years or decades and may increase by cell division and eventually get reactivated if ART stops |
| what are therapeutic approaches to purge latent HIV reservoir | - "shock": treat with drug to activate latent HIV - "kill": immune response to activated HIV cells - block: ART to prevent new infection events within hosts |
| thus far has shock and kill treatments been successful | no |
| there are some instances where people have been cured of HIV how was that so | was donated hematopoietic stem cells from a donor with a 32 base pair deletion in the CCR5 gene --> stem cell transplant |
| HIV infection prevention: PReP | Taken BEFORE HIV exposure - Taken before sex, drug use, or other HIV exposure - For people who don’t have HIV and are at risk of getting HIV - Consistent use can reduce risk of getting HIV |
| reservoir host | host in which virus can persist within the population (differs from persistence within an individual) |
| dead end host | infected directly or indirectly (environmentally or via vector) from reservoir host but does not ordinarily transmit to others in same species and does not serve as a reservoir |
| humans are a dead-end host to what virus | rabies |
| vector | agent (generally an arthropod) that transmits virus between hosts |
| zoonosis | when a virus jumps from an animal host to humans |
| why do viruses evolve to limit pathogenic potentials in a natural host and host populations evolve to reduce pathology | viruses co-evolve to be less virulent because they don't want to kill hosts |
| what is the most common viral vector | arthropods (ex: mosquitos, ticks) |
| what is the genome of dengue virus | (+)ssRNA genome |
| arboviruses | - arthropod-borne viruses - classification based on vector that transmit them into host - not a genetic taxonomic group |
| what does ADE stand for | antibody dependent enhancement |
| Current DENV vaccines | - one shows increased risk of hospitalization for seronegative vaccinated people who are infected with serotype 3 - another is only recommended for people with previous cases of DENV to avoid ADE on natural infection |
| what can drive vector borne viruses to spread and distribute further | changes in vector habitats where climate change can allow vector species to spread to warmer areas where they can survive and live (ex: Dengue virus) |
| Zika virus | - arbovirus - from Flaviviridae family - can cause severe diseases including microcephaly in utero - concern for pregnant individuals because it can be transmitted to the fetus - ~80% of infected individuals show no disease symptoms |
| how is Zika virus transmitted | by Aedes aegypti mosquitoes (primary vector) and can also be transmitted by Aedes albopictus |
| what type of travelers are known to have brough Zika to nearly every US state | pregnant travelers |
| Does the Zika virus have the potential to spread | yes as local mosquitoes pick up the virus from infected travelers and reach regions of the US in which 60% of our population lives |
| what is antibody dependent enhancement (ADE) of infection and replication | antibodies against one viral antigen may cross react with antigens from another virus without neutralizing infection. Instead, the bound antibodies may in fact facilitate virus entry into hosts |
| symptoms of Zika infection tend to be worse in patients who live in tropical areas than in Europeans who become infected while vacationing in tropical areas. Why might that be? | people in the tropics are more likely to have been exposed to Dengue which displays some Zika cross reactivity |
| Ebola virus (EBOV) | - filovirus --> (-)ssRNA genome - human infection via spillover - can spread human to human |
| Ebola virus pathogenesis can cause what | systemic failure and hemorrhagic fever |
| what is one reason why there is a growing frequency of outbreaks in recent years esp with multiple outbreaks in African countries | deforestation --> it concentrates species in a smaller area that leads to higher chance of spillover events to humans if animals carry pathogenic viruses |
| why were the last decade's Ebola outbreaks worse? | there might be a genetic mutation that may have made Ebola more deadly by improving the virus's ability to enter human cells |
| what are effective vaccines that have been approved for Ebola | - rVSV-ZEBOV (for Zaire Ebola) --> recombinant vesicular stomatitis virus - replication competent vesicular stomatitis virus/Ebola glycoprotein recombinant (chimeric vaccine based on multiple viruses) |
| what virus infects a broad range of animals | influenza |
| what is special about Ebola virus | although its an acute viral infection, infectious virus continues to be shed from individuals who have recovered for unclear durations |
| why are bats a reservoir for many viruses | they have an immune system that seems to select for robustness in viruses (virus has to evolve really well so they aren't cleared by the bat's immune system) --> they have rapid interferon response (due to stress of flight) but not viral clearance |
| what are the three layers of host defense that a virus must overcome in order for spillover to occur | acquired immunity, innate immunity, intrinsic immunity, |
| why is host dependency factor important for spillover to occur | the host cells need to have the right receptors in order for the virus to bind and be able to replicate in our cells |
| can zoonotic transmission affect animals other than humans | yes |
| why can generate a pandemic virus (ex: HIV-1) | a single rare event like a change in genome that can cause a virus to spillover to humans from animals |
| what's the reason that debunks the lab leak theory that SARS CoV2 originated from a Wuhan lab that was studying bat coronavirus | - FCS (furin cleavage site) is often lost through mutation in lab adapted strains and early CoV-2 isolates contain FCS - subsequent searching for origins shows natural occurring FCS in many non bat CoVs |
| when is a virus variant of concern | it is more contagious, causes more severe disease, or blunts the immune system |
| omicron virus (covid) | contained many "new" mutations and recent (2022) subvariants appear driven by immune evasion like seasonal influenza |
| what properties are some covid variants shifting towards | using only cleaved ACE2 which is common in GI tract and rare in lungs |
| what does endemic mean and does it equal harmless | - regularly occurring within an area or community - it does NOT equal harmlesss |
| Even though Polio is close to being eradicated why is it a re-emerging concern | it's a non-zoonotic virus but there as been setbacks due to political instability/wars, distrust in vaccines, and covid |
| what is the name of the Polio vaccine that is a more genetically stable vaccine that is being researched and developed | nOPV2 |
| what is the sixth most common type of cancer worldwide | head and neck squamous cell carcinoma (HNSCC) |
| what can reovirus infection cause | infection triggers inflammatory responses to dietary antigens and development of celiac diseases --> lead to gluten intolerance |
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rach6774