Micro 2/2 Flashcards

Question

Differentiate between sexual and asexual life cycles of fungi

Answer 1

sexual: Produce sexual spores (meiospores such as basidiospores and ascospores) in sexual fruiting bodies asexual: Produce asexual spores (mitospores; formed through mitosis, such as conidiospores and sporangiospores) in asexual fruiting bodies

Answer 2

- and + mating type; plasmogamy take place: organisms meet and fuse (cytosols and nuclei mix: dikaryotic (2 different types of nuclei, where they haven’t fused yet), form ascus; within spore-forming structure creates karyogamy - +/- mating: haploid: dikaryotic: spore-forming dikaryotic structure: karyogamy, nuceli fuse and nucleus is diploid (2 copies of genetic material)

Answer 3

- Sexual ascospores are endospores; form within a sac-like meiocyte that form an ascus (pl. asci) - Sexual fruiting body = ascoma - Different kinds; shown here are the open cup-like apothecium

Answer 4

* Unicellular organisms, 3-10μm * Grows via budding * Some can form strings of connected budding cells (pseudohyphae), or hyphae * ex: saccharomyces cerevisiae, dimorphic patogen candida albicans

Answer 5

- nodule that cells grow together - shmoos grow towards each other and fuse - diploid gros vegatively, grows through sporulation, making spores with ascus, which can be disseminated

Answer 6

- pathogen: cryptococcus neoformans

Answer 7

- "to live together" - organisms adapt to the presence of others; they do not live alone - range of positive to negative replationships; partners evolve in response - organisms (usually 2) in association called symbiont

Answer 8

commensalism, parasitism, mutualism

Answer 9

One partner benefits, while the other is unaffected

Answer 10

intimate association where one partner benefits, while harming a specific host

Answer 11

- Emerging, globally important invasive pathogens (in immunosuppressed patients) with very high mortality rates - candida, cryptococcus, aspergillus

Answer 12

Each partner gains benefits from the other (in some cases, may not grow independently) - 2+ microbial partners - 1+ microbial partners with plant/animal host - removal of microbial partner leads to death or decreased growth of host - microbial genome shows extensive degeneration (reduction) of normally essential genes for metabolism and protective structures. - ex: lichens, gut microbiomes, mycorrhizae...

Answer 13

multiple fungal species and algae/cyanobacteria - cannot survive independently (reduced genomes) - grow almost anywhere - algae/cyanobacteria: photobiont (receives water and minerals/nutrients from fungi) - fungi recieves carbs produced by algae - fungi protects photobiont - nutrient exchange @ photobiont layer

Answer 14

- acellular entities (cannot replicate on its own) - obligate intracellular parasites (cannot replicate by itself) - hijacks host cellular machinery to replicate - displays tropism (interacts with specific hosts/host ranges) - interacts with host cell surfaces (specificity of interaction determines host range)

Answer 15

narrow: cold and influenza viruses infect human respiratory epithelial cells wide: rabies virus- dogs, foxes, raccoons, humans

Answer 16

become viruses when the host becomes infected

Answer 17

innocuous to lethal - most devastating impacts on human society

Answer 18

risk group 4: high individual and community risk: often untreatable, readily transmittable - filoviridae: ebola

Answer 19

- control infections as an alternative to antibiotics or disinfectants - Viruses can be modified as delivery vehicles for gene therapy - Bacteriophage can be used in molecular cloning, as cloning vectors

Answer 20

- Insertion of virus into host genome can impact gene expression at insertion site - Excision of viral genome from host and subsequent packaging impacts gene movement (e.g., horizontal gene transfer) - genes may be regulated or down-regulated because of viruses - viruses can be both pos and neg

Answer 21

- protein coat (capsid): surrounds nucleic acid - enclosed in a protein-containing membrane (enveloped), or not (naked or unenveloped) - nucleic acid either RNA or DNA; encodes viral proteins

Answer 22

complex: origin and evolutionary history largely uncharacterized - based on: nature of genome, ALL cells/viruses need to make mRNA to make protein, viral mRNA produced from viral genome inside host - genome can vary in size to accomodate varying lengths of genomic material - r/s between genome and mRNA produced is central to baltimore virus classification system

Answer 23

1- double-stranded DNA (uses its own or host DNA polymerase for replication) 2- single-stranded DNA (req. DNA polymerase to generate complementary strand) 3- double-stranded RNA (req. RNA-dependent RNA polymerase to make mRNA and genomic RNA) 4- + single-stranded RNA (req. RNA-dependent RNA polymerase to make template for mRNA and genomic RNA) 5- - single-stranded RNA (req. RNA-dependent RNA polymerase to make mRNA and replicate genome) 6- retrovirus (packages its own reverse transcriptase to make dsDNA) 7- double-stranded DNA pararetrovirus (req. plant host reverse transcriptase to make DNA)

Answer 24

- infects E. coli - chloroviruses infect algae - herpesviruses cause chickenpox, genital infections, birth defects - poxviruses cause smallpox and monkeypox - papillomavirus strains cause warts and tumors

Answer 25

- coronavirus; cause severe respiratory disease - flavivirus; cause hepatitus C, Zika fever, West Nile disease, yellow fever, dengue fever

Answer 26

filovirus: Ebola, causes severe hemorrhagic disease orthomyxoviruses: cause influenza

Answer 27

- Lentivirus: HIV,AIDS

Answer 28

attachment penetration uncoating release assembly biosynthesis *know to spot step

Answer 29

filamentous capsid, icosahedral capsid, complex viruses; bacteriophages - phage binds to trail sheath

Answer 30

viral RNA enters nucleus, where it is replicated by viral RNA polymerase - released into cell - complicated by the presence of an envelope and the nature of the genome

Answer 31

- Phage genome is injected through the cell wall and membrane and the capsid is shed

Answer 32

lytic cycle (T2, T4, ebola) - rapid phage replication - host cell lyses/ruptures lysogenic cycle - phage infects and inserts its DNA into host chromosome as a prophage - don't initially destroy host cell - amplifies amount of viruses that can be produced - activated to excise and follow lytic life cycle by certain triggers

Answer 33

1) One species benefits 2) The other species is harmed by the interaction 3) The interaction is non-specific EX: streptomyces and other soil bacteria

Answer 34

mutualism, synergism, commensalism, amensalism, parasitism

Answer 35

1) Each partner benefits from the other 2) Partners can be easily (?) separated and grown independently of each other EX: cow rumen microbiome

Answer 36

partner species may require each other – an example of extreme coevolution 1) Removal of one partner leads to death or reduced growth of the other 2) The genomes of each species show advanced degeneration 3) Products produced by one partner are utilized by the other – often both ways EX: LICHENS

Answer 37

1) One species benefits 2) The other species is neither harmed nor benefitted by the interaction EX: beggiatoa and other sulfur spring microbes

Answer 38

1) One species benefits 2) The other species is harmed by the interaction 3) The interaction is specific, and usually obligatory for the parasite EX: legionella pneumophila, amebas and human lung macrophages

Answer 39

endosymbionts: many insect species infected by intracellular bacteria - hard to tell type of relationships: parasitic or mutualistic

Answer 40

- microbes usually found as microbiomes, rarely as single species ecosystems - microbes form foundation of all Earth's ecosystems

Answer 41

- use of high-throughput methods to look at molecular signatures of microbes - genomics, transcriptomics, metabolomics, proteomics

Answer 42

WHO is there? WHAT are they doing? HOW do they respond to different conditions * we can use DNA, RNA, proteins, metabolites to figure this out

Answer 43

culture, DNA and RNA sequencing

Answer 44

- petri dishes with agar - not supportive of many bacterial species - developed by Petri and Hesse

Answer 45

* Many bacterial species from the environment find lab conditions so alien that they cannot survive * Some bacterial cells in an ecosystem may be oligotrophic , or otherwise fastidious * Some may depend directly on other species, or be inhibited by them * Some may be non-viable, or ‘viable but not culturable’ (VBNC)

Answer 46

- Reduces labour intensity by using AI & robots - Allows culture under hundreds of different conditions - Allows picking of thousands of colonies into multi-well plates

Answer 47

- An ecosystem is sampled, gDNA is extracted and subjected to either: amplicon or metagenomic sequencing * Both methods can reveal ‘alpha diversity’, or the species richness (# of species present), evenness (close together) and dominance

Answer 48

* A target gene is amplified, barcoded and sequenced * Most common method amplifies regions from the 16S rRNA gene from bacteria, a taxonomic marker - cheaper and quicker

Answer 49

* The extracted gDNA is broken up into bits (or not, depending on sequencing method), barcoded and directly sequenced * A powerful computer is used to pull out signature genes from the sequenced pool - better: tells us much more about what's in the system

Answer 50

* Extract the RNA (ideally, mRNA) from a community * Transcribe to DNA (using a viral reverse transcriptase (gene being transcribed) enzyme) - not all genes always being transcribed: will tell you what the RNA was doing at the exact time of transcription * (or not, depending on the sequence method) * Barcode and sequence * Match transcripts to known genomes - access to what is alive and actively transcribing at the moment; unalive cells do not transcribe

Answer 51

1- predictive 2- direct (proteomics, metabolomics, metatranscriptomics)

Answer 52

- powerful computer to assemble MAGs - software to annotate genes and predict possible functions

Answer 53

- Extract all the proteins in the sample, sequence peptide fragments using mass-spectrometry * Use a (powerful!) computer to match peptides to proteins, and then proteins to genes (ideally, from the metagenome) - pros: lots of info, seeing trancribed proteins - cons: not all of mRNA will get processed into proteins (regulation of metabolism, done outside essential dogma)

Answer 54

* Extract all the molecules in the sample * Subject directly to mass-spectrometry or NMR spectroscopy * Use a (powerful!) computer to match compound signatures from obtained spectra to standards pros: seeing all things being produced, small molecules may not br proteins (couldn’t predict from looking at genome)

Answer 55

metabolomics: looking at all metabolites from given organism metabonomics: looking at all metabolites from given ecosystem

Answer 56

* mRNA content reflects active transcription – what the cells are doing/making in response to their environment

Answer 57

lipidome, secretome, resistome, phenome

Answer 58

* If you take a single sample and carry out all of the so-far mentioned ‘omics analysis on it, will you get a full picture of what is going on? * You have taken a ‘snapshot’ of the microbiome in time * Microbiomes are dynamic systems – they change in response to their environment and/or what you do to them experimentally

Answer 59

relatively new development in field - multiple omics studies on given sample longitudinally - integrate metadata - computer to combine datasets - can also integrate host genomics, transcriptomics, metabolomics, epigenomics

Answer 60

- develop and carry out complex computational pipelines to interpret and understand enormous amounts of data

Answer 61

- leftover of what has been all been broken down - very N2 rich - good at holding moisture - will hold soil together - product of digestion

Answer 62

- support miniature colonies, biofilms, filaments of bacteria and fungi - interact with each other and plant roots - diverse ecosystem

Answer 63

a major genus of soil bacteria, notable for the diversity of antibiotics they make

Answer 64

- help protect plants from pathogens - may fix nitrogen (diazotrophs) - they feed on nutrients provided by the plant (root secretes nutrients)

Answer 65

- colonize the rhizoplane - form a thick, protective mantle around the root - extend outwards to absorb nutrients - good for agriculture: allowing the plant to extend its root to intake more nutrients

Answer 66

- Grow inside plant cells - Dependent on their hosts - Lack sexual cycles - Exist entirely underground - Relatively small number of endomycorrhizae species – but they are extremely important to the ecosystem - endosymbiosis (can't live without each other very well)

Answer 67

- grow within plant tissues - can be bacterial or fungal

Answer 68

endophytic - bacterial cells adapt to life within nodules to form a nitrogen fixing ‘organ’ for the host plant (leguminous plants) - nodules are pink: hemoglobin, due to oxygen carriers

Answer 69

- human body teems with them - majority are bacterial, harmless - many are beneficial to host

Answer 70

- non specific defenses - adaptive and non-adaptive immune defenses

Answer 71

- Microbes normally found at various non-sterile body sites are called - may be incorrect: commensal means they are not doing anything, yet they are

Answer 72

- consortium of colonizing microbes microbiota: cell consortium microbiome: genetic potential of consortium

Answer 73

* Vary with type of tissue, condition * Can cause a disease if they reach an abnormal location

Answer 74

rely on microbes for digestion of cellulose

Answer 75

allow digestion of their dietary substrates - termites - demodex mites: efficient gut microbiota, once thought they have no anus (most have them on face, they have sex and poop on your face every night)

Answer 76

1 : 1.3 - approximately 200 bacterial species per person

Answer 77

* Bacterial cells are far smaller than human cells * On average 1/100 to 1/1000 of the size * Each gram of feces contains ~ 1011 bacterial cells - 10 trillion cells in the average bowel movement!

Answer 78

autism, colorectal cancer, type 1 juvenile diabetes, chronic depression, parkinson's disease

Answer 79

epidermis, dermis, subcutaneous tissue

Answer 80

dry, salty, acidic, protective oils

Answer 81

10^12 microbes in moist areas - mostly gram positive bacteria (more resistant to salt and dryness)

Answer 82

- staphyloccocus epidermis - cutibacterium acnes (degrades skin oil, inflames sebaceous glands; also affected by human hormonal changes)

Answer 83

- non-pathogenic Neisseria spp. - streptococcous and lactobacillus spp.

Answer 84

Prevotella and Fusobacterium spp.: between gums and teeth *Streptococcus mutans: tooth enamel * Many oral bacteria are strict anaerobes

Answer 85

- oral and respiratory tract - when bacteria are on the surface, they make biofilms which restrict oxygen, beneficial for anaerobic growth

Answer 86

- bacillota and actinomycetota - one species or even genus dominates over the other

Answer 87

staphylcoccus aureus and staph. epidermis - some strains are better than others at keeping us healthy

Answer 88

- similar composition of microbes to saliva - Neisseria meningitids lives as commensal in 10% all adults and normally doesn't cause issues

Answer 89

- surface area 75m2 - once thought to be sterile: actually community of microbes present, mainly anaerobes

Answer 90

- Microbiota in diseases such as COPD, cystic fibrosis and asthma seems to be distinct for each condition

Answer 91

- constantly sweeps inhaled particles up towards throat - whooping cough: caused by toxin from bacteria

Answer 92

kidneys and urinary bladder: normally sterile or near-sterile

Answer 93

- changes with menstrual cycle - acidic: favour lactobacillus spp. - lactobacillus spp. presence appears to protect from STIs and improve reproductive success - rare; having a diverse microbial community is not good, lactobacillus will present diversity

Answer 94

S. epidermidis and some members of the Enterobacteriaceae - can cause UTIs

Answer 95

- very low pH (usual lethal to microbes) - few microbes survive

Answer 96

- present in stomach - survives at pH 1 - burrows into protective mucus - can cause gastric ulcers

Answer 97

hypochlorhydria - caused by malnourishment * Also now caused deliberately e.g. through PPI use * Can lead to intestinal disease stomach is a barrier between mouth and intestines

Answer 98

contains 10^9-10^11 per gm of feces * Ratio of 1000 anaerobes to 1 facultative anaerobe

Answer 99

- colon: where most important microbial ecosystem in the human body intestine: - community does as much metabolic work for us as the average liver; hence recently has become to be regarded as the ‘forgotten organ' - most human microbiome research focuses on gut microbiome

Answer 100

- the species' metabolic potentials, not the species themselves - lots of microbes share genes

Answer 101

* Regulate the immune system * Help to extract energy from foods * Control potential pathogens * Make some essential metabolites, including vitamins and cofactors * Improve intestinal function * Remove toxins and carcinogens * As important to us as a liver

Answer 102

- block pain receptors - IBS: if you’re missing particular microbes that modulate receptors in the gut

Answer 103

- fetus is sterile - vaginal delivery (fetus exposed to environment, baby swallowing microbes as it passes down body) - breastfeeding as a newborn - interaction with environment as an infant (putting things on lips; pick up microbes from environment; evolutionary theory)

Answer 104

- colon most heavily colonized by microbes - microbes can break down foods well to release calories

Answer 105

- good at breaking down compounds - comes from food; toxic if not broken down - same for drugs

Answer 106

- C-section delivery - maternal antibiotics - formula feeding (do not contain human oligosaccharides) - indoor living (seasonal) - excessive sanitation - chemical preservation of food - window for proper gut microbiota development is narrow ! (0-5 years old)

Answer 107

* Healthy ecosystem * Balance * Functional redundancy * High gene count * Resistance to damage

Answer 108

* Sick ecosystem * Imbalance * Functional disability * Low gene count * Susceptibility to damage

Answer 109

- missing microbiota hypothesis: we are removing microbes faster than replaced - Loss of microbiota generally compounds over generations, and recent changes in lifestyle have greatly exacerbated this loss - Yanomami (remote hunter-gatherers) have a more diverse microbiome than industrial: reflective of ancestral microbiome

Answer 110

robogut: RoBeeGut - reps what a bumble bee or honey bee eats

Answer 111

- grow, isolate microbes; how they behave in nature - bioreactors can be used to emulate the human colonic environment

Answer 112

* microbiota kept in check by physical barriers and immune system * Accidental penetration of the barrier, or damage in immune system: microbiota behaves badly * The microbes that breach the barriers: opportunistic pathogens or pathobionts * patient may be repeatedly infected by normal microbiota

Answer 113

* Seeded with fresh feces or defined communities and set to model the ecosystem of the colon * Host-free system * Can be used to ‘culture the unculturable’ * Can support whole gut microbial ecosystems for several weeks at a time * We can model the gut microbiota under different perturbation conditions * We can learn how to protect against the effects of these perturbations

Answer 114

- competitive exclusion: colonization of a niche to prevent pathogen from growing there - environment modification: lactobacillus in vagina - host stimulation: bacteroides fragilis using host cytokine - direct pacification: secreted factors from members of microbiome can prevent virulence gene expression

Answer 115

- brain and the gut (microbiota) signal to each other - full of neurons - types of microbes you have in your gut, and the metabolites they make, can affect your mood and behaviour

Answer 116

brain -> microbiome motility, secretion, nutrient delivery, microbiota balance microbiome -> brain neurotransmitter release, stress/anxiety, mood behaviour

Answer 117

containment breaches, niche disturbance, extinction events less bifido bacteria (lactic acid) in hunter gatherers: do not drink milk - beneficial microbes - adapted to industrial lifestyle

Answer 118

no frame reference for a healthy microbiome, everyone’s is different

Answer 119

- Gut microbiota influences nutrient acquisition and regulation of energy metabolism and fat storage - microbiome balance is different from that of healthy people for obesity - less diverse microbiome (but differs per person) - obesity associated with low-grade intestinal microbiome - insight from mouse experiments (high fat diet at first, can switch to a lean microbiome and lose weight)

Answer 120

- Potential loss of microbes increasing them - cells that line your gut, thin layer: has to maintain barrier and produces proteins that helps epithelial cells stick together and prevent things form crossing

Answer 121

- mice - animal where the associated microbiota is known and defined: bred/raised in environment devoid of microbes - germ free animals - expensive to manage, valuable for microbiome research

Answer 122

* Poorly developed immune systems * Lower cardiac output * Requirement for more calories to maintain body weight * Thin, poorly developed intestinal walls, including stunted villi * Abnormal, enlarged ceca * Odd behaviour * Misshapen mitochondria (crescents in germ free)

Answer 123

- boy in the bubble - SCID: impaired immune system, lived in a sterile environment for 12 years

Answer 124

Not all microbes are pathogens * We have various physical and chemical barriers: mucus, skin, stomach acid * The immune system comes into play when barriers are breached * A highly complex system of organs, tissues, cells and cell products that work in concert to recognize and neutralize potentially pathogenic threats

Answer 125

- highly complex system of organs, tissues, cells and cell products that work in concert to recognize and neutralize potentially pathogenic threats - complex collection of cells and soluble proteins is capable of responding to almost any foreign molecular structure

Answer 126

innate and adaptive

Answer 127

* Ancient – evolved early in invertebrates and carried over to vertebrates, including (eventually) humans * A ‘Rapid Response system’ Includes: physical barriers, chemical and cellular responses * ‘hardwired’ into the body * Present at birth

Answer 128

- Contact with an infectious agent does not guarantee that a person will get sick * If number of infecting organisms is small and/or the immune system is effective, disease will not normally follow infection

Answer 129

* Breach host defenses * Survive innate defense mechanisms * Begin to multiply

Answer 130

- Skin (difficult to penetrate when intact) - Mucous membranes (selectively permeable; epithelial cells tightly connected to support strong barrier function) - lungs (mucociliatory escalator, large microbes -100um trapped by cilia and hair in nose; sneezing to remove foreign material from respiratory tract)

Answer 131

- physical barriers are tightly connected to lymphoid tissue - Specialized cells monitor and sample these sites continuously, present antigens to immune cells in lymph nodes PRIMARY (factory for lymphoid cells): bone marrow and thymus SECONDARY (stations for antigen encounters): mechanisms to enable encounters to happen in limited areas

Answer 132

SALT: Skin Associated Lymphoid Tissue GALT: Gut Associated Lymphoid Tissue

Answer 133

the complement system 1. cripples 2. activates 3. kills by puncturing holes

Answer 134

"complement": set of proteins made by liver - named because they "complement" antibodies in the killing of bacteria - proteins circulate in blood and enter tissues all over the body: inactive forms, proteolytically cleaved to make them active - ~30 soluble and membrane bound protein components of the complement system (as of now) - C1-C9

Answer 135

* The classical pathway * The lectin pathway * The alternative pathway: only one associate with innate immune system * converge on lytic pathway

Answer 136

- C3 splits into two smaller proteins (C3a smaller than C3b) - C3b: opsonin (marker for other parts of immune system) - C3a C5a: anaphylotoxins (signals) direct immune cell traffic to where it is most needed, very reactive and unstable - Membrane Attack Complex – punches holes in target bacterial cells, killing them

Answer 137

- molecules secreted by cells which have an effect on other cells ex: interferon (intruder alert cytokine) - cell is infected by a virus, secretes interferons helping other cells nearby to fend off virus, to limit the spread of infection * The neighbouring cells step up their defense systems, ex by inhibiting viral entry

Answer 138

- natural antimicrobial peptides - act as antimicrobial elements produced in close proximity to cell - Small molecules able to lyse most microbial cells and some enveloped viruses (produced at all times, short half-life and produced in high concentration)

Answer 139

- natural antimicrobial peptide - affects our own host cells: producing strategically over quantitatively ! - high concentration in gut - Higher in close proximity to the crypts of the epithelium * Secretion is from crypts * Keeps out even the normal microbiota

Answer 140

cells in blood: - red blood cells - white blood cells **: part of immune system - platelets

Answer 141

* Polymorphonuclear leukocytes (PMNs, granulocytes or polys) * Monocytes & macrophages * Dendritic cells * Mast cells * Lymphocytes - "white": white blood cells and platelets, excreted from blood as well as plasma and red blood cells - useful indicator of state of health

Answer 142

lymphoid: natural killer cell myeloid: mast cell, neutrophil, monocyte, macrophage, dendritic cell

Answer 143

- phagocyte cells : cells that eat - takes up bacterium and encases it in “prison” (phagosome) which merges with lysosome and kills bacterium, breaking it up into many small parts

Answer 144

- carry a negative charge, like phagocytes do - C3b binds non-specifically to the surface of bacterial cells and makes it easier for phagocytes to stick to and ingest them

Answer 145

- neutrophil extracellular trap - NETosis: unusual form of cell death by the neutrophil - neutrophil senses invader, spews latticework of chromatin and antimicrobial compounds into vicinity (prevents pathogen spread, allowing rapid phagocytosis) - inappropriate NETosis thought to underlie lupus

Answer 146

- macrophages - monocytes circulate in blood stream - like neutrophils: attracted by chemical signals (cytokines) to needed sites - sticky: they roll on surface towards signal - as they travel through blood vessels (extravasation), they differentiate into macrophages (secretes more cytokines to attract other phagocytes)

Answer 147

- large structures that can ingest many microbes at one time - many body organs also contain patrolling resident macrophages (kuppfer cells in liver, langerhans in skin, microglia in brain, alveolar in lung)

Answer 148

- macrophages secrete cytokines which would be dangerous in blood vessels

Answer 149

- use electrons, wavelength used is less than wavelength of light

Answer 150

- dynamic cells (constantly moving) - possess long protrusions that can squeeze through tight spaces to sample microbes - very thin: can squeeze through tight junctions of epithelial layer in gut to directly sample gut content

Answer 151

- cytokines, chemokines, interferons - Close-range acting ‘hormone’ system - Allows cells of the body to communicate with each other * Particularly effective at signaling ‘danger’ * some cytokines are important for anti-inflammatory signals after danger has passed (Reset the homeostasis)

Answer 152

1) Heat at the site (loss of extravasation) 2) Edema (swelling) 3) Redness 4) Pain 5) Altered function (cell trying to deal with an infection won’t deal with a pimple)

Answer 153

- white blood cells; dead neutrophils

Answer 154

- Mycobacterium TB (slow growing, microbes hard for macrophages to kill as their cell wall is very waxy) - fish tank and liver granuloma - crohn's disease (ulcers)

Answer 155

- can be part of an inflammatory response, and heightens the activity of components of the innate immune system

Answer 156

- mainly phagocytes, can also be macrophages and dendrocytes - Process the antigens they ingest and display them on their surfaces for T cells - Form a link between the innate and adaptive immune system - when they digest their prey, they work to break them up into component parts, excreting waste, also taking some and posting them on their surface like a marker

Answer 157

- Peyer's patches: specialist sites within small intestine - rich in M-cells: specialist sites of uptake of antigens in the gut for presentation to macrophages - Help the body differentiate between friend and foe when faced with a complex microbiome

Answer 158

- hide major components, slippery, can be decoys - form halo around bacterial cells: keeping dye away from them - Many pathogens are encapsulated to help them evade the innate immune system - best way to deal with: filter through blood: spleen)

Answer 159

- innate immune system ! - Cells of the innate immune system have specialized sets of receptors to recognize invariant and essential microbial factors unique to the microbe: Pattern Recognition Receptors (PRRs) = PRRs recognize MAMPs (Microbe Associated Molecular Patterns): they don’t discriminate between ‘good’ and ‘bad’ microbes

Answer 160

- toll-like receptors (TLRs) - Transmembrane receptors on some immune cells that recognize viral and bacterial products On binding to ligand: * Stimulate cytokines to signal inflammatory response * Induce macrophages to produce antimicrobial proteins and peptides

Answer 161

- NODs and NOD-like receptors (NLRs) - TLRs monitor the outside of a host cell, so cannot sense them internal (cytoplasmic) NOD like receptors (NLRs) bind MAMPs and: * Activate cytokine production * Form a complex called an inflammasome that activates the adaptive immune response, and triggers apoptosis (‘good’ cell death!)

Answer 162

NODs - similar host defense proteins found in plants

Answer 163

bad: necrosis - enzymatic digestion and leakage of cellular components good: apoptosis - neat "suicide" - phagocytis of apoptotic cells and fragments

Answer 164

TLR- mostly outside of cell NLR- inside of cell

Answer 165

- a protein complex that allows rapid secretion of certain cytokines

Answer 166

"specialized hit squad" - not phagocytic - lymphocytic cell (distinct from T and B cells) - large and granular * Make up ~2% of lymphocytes in the body * main role is in innate defense (bridge between adaptive and immune) * Don’t attack pathogens themselves, but instead attack host cells that have become overwhelmed by pathogens - defense against cancerous cells

Answer 167

- infected cell signals altered self response - needs to alert body that there is a pathogen or it will hide in the body - adaptive immune system labels infected cell with antibodies - when it finds altered cells it kills them very quickly

Answer 168

- alerted by interferons ( itself) or macrophage-generated cytokines (other cells) - infected host cell signals altered self response - NK cell binds to infected cell (always patrolling bloodstream) - porforin kept in membrane bound granule so it doesnt kill itself - granzyme move through pores, induces infected cell to undergo apoptosis

Answer 169

- induces cells to undergo a good cell death (apoptosis) to keep inflammation at a minimum

Answer 170

- dying cell neatly packages itself up for disposal (apoptotic bodies) - small enough for neutrophils to consume through efferocytosis - neutrophils dispose of apoptotic cell bodies along with intruder microbes - minimum inflammation - after apoptosis

Answer 171

- branch of immune sys. with memory - develops when needed - 2 intertwined types (cell-mediated and humoral) - "weapons cache", defends body against any foreign invader

Answer 172

Cell-mediated immunity * Teams of T-cells (T-lymphocytes) and cells from thymus work together to recognize antigens displayed on infected cells * Target infections in the body’s cells Humoral immunity * Antibodies directly target microbial invaders (B-cell response) * Target infections in the body’s fluids (humors)

Answer 173

- usually lethal mutation: SCID - boy in the bubble

Answer 174

* Develops over ~3-4 day period following exposure to an invading microbe * Immune system recognizes small pieces of a given antigen antigen, called antigenic determinants or epitopes (May be 2- or 3-dimensional) * Phagocytosis produces many epitopes to show the adaptive immune system (APCs display surface of the cell with broken down microbes so they can recognize them)

Answer 175

- bacterial cells made of antigens (every surface/cytoplasmic structure) - each can have 1+ epitopes - most epitopes are immunogens (some haptens) - each immunogen can generate immune response by itself (large enough), haptens cannot

Answer 176

- small molecule that is too small to elicit an immune response on its own, but when bound to a larger molecule it can act as an antigen - ex: nickel ions, or urushiol. - innate immune systems can only see antigens at specific size (haptens are too small) - must be bound to larger molecule

Answer 177

immunogenicity: effectiveness by which an antigen elicits an immune respons worse->best antigen: nucleic acids and lipids (conserved), carbs, proteins (large 3D) - proteins are best as they have different shapes that are 3D

Answer 178

- T cells are born from hematopoietic stem cells found in the bone marrow - As these cells mature, each will develop a unique T cell receptor (TCR); each TCR reacts to a different random epitope. - thymus gland: where T cells learn what to do - This organ is fully developed in utero but shrinks as you grow older - T cell education begins before birth

Answer 179

* Audition for their ability to identify self Major Histocompatibility Complex peptides 1. “Positive selection” – can they understand commands? * Are tested for reactivity against self antigens in the thymus 2. “negative selection” – are they well-disciplined? - killed if they fail (98%)

Answer 180

- most T cell education occurs before and just after time of birth - reserves of educated T cells maintained by body and reproduce at balanced rate

Answer 181

- cytotoxic T cells / CD8+ cells - helper T cells / CD4+ cells

Answer 182

‘assassins’ * Trained to seek and destroy cells presenting noxious antigens (indicating they may be infected) - indicates they may be infected just like NK cellsi

Answer 183

‘intelligence officers’ * Trained to memorize databanks of antigens and to alert B-cells if circulating antigen is detected

Answer 184

- effector T cells and TH cells differentiate into memory TH cells - some naive T cells differentiate to regulatory T cells (do not promote an immune response but help to restore homeostasis after infection; limit collateral damage) - lack of Treg cells = chronic inflammation

Answer 185

* Retain antigen affinity of the originally activated T cell * used to act as later effector cells during reinfection * Don’t have a particularly long lifecycle, but are able to clonally replicate and pass traits to the next generation (imperfect) * Overtime, memory gets hazy - if pathogen returns much later, there may not be a strong immune response as T cell does not recognize as strongly (reason for boosters)

Answer 186

Major Histocompatibility Complex glycoproteins * These are the proteins onto which infected cells or APCs place antigens for display to the immune system * Two main types: MHCI and MHCII (so they are not attacked, immune system has to know difference between the antigens so they use MHCs)

Answer 187

- display antigens on the surface of an infected cell (i.e. the infected cell signals that it is infected) * Cytotoxic T cell assassins will promptly dispatch the infected cells

Answer 188

display antigens on the surface of APCs * Helper T cells will use this intelligence to alert the army and take further steps to neutralize infection

Answer 189

- lymph nodes of body (armpits, neck, lower back) (garrisons for army) - approx. 4x10^11 T cells in body - up to 10 T cells will recognize same pattern: clonotype

Answer 190

* APCs that have phagocytosed a pathogen travel to the lymph nodes to display their captured antigens to T cells * The binding of antigen-loaded MHCI or MHCII to T cell receptors (TCRs) activates the T cells, and the cell-mediated adaptive immune response begins * Remember, activated cytotoxic T cells can directly kill an infected host cell (using methods similar to those of NK cells) * They produce cytokines that initiate a macrophage feeding frenzy at the site of infection

Answer 191

- body contains ~10 billion B cells, each recognizes a particular epitope * Response to an infection by a microbe involves thousands of different B-cells, each recognizes a different part of the threat * Plasma cells are short-lived (4-5 days) but can produce 2000 antibodies per second! * Some activated B cells differentiate into long-lived memory B cells (can survive decade +, linger to speed immune response to same invader) * Basis for immunization

Answer 192

- some help to activate cytotoxic T cells, but others interact with B cells - B cells also in lymph nodes (born in bone marrow, but educated and selected there, not thymus college) * Each B cell is programmed to recognize only 1 antigen epitope - helper T cells: conduit b/w APCs and B cells - B cells are agents of humoral immune response - Free-floating antigens from the microbe bind to B cell receptors that are specific for an epitope of that antigen * If a helper T cell presents the same antigen to a B cell as the one already on its B cell receptor, the B cell becomes activated * Differentiates into a plasma cell, a factory for antibodies

Answer 193

- antigen dose is important - If antigen dose is over a threshold value, then B- and T-cells become over- stimulated - T-cells become non-functional - B-cells do not respond to subsequent antigen exposures to make antibodies This is partly why we don’t respond to the antigens of the microbes of a healthy microbiome - T-cells are extensively trained in the thymus and tested for lack of sensitivity to self-antigens-

Answer 194

- antibodies (immunoglobulins) - know/understand shape

Answer 195

- 4 polypeptide chains - 2 large heavy chains - 2 smaller light chains - Bound together by disulfide bonds

Answer 196

- some can help B cells respond to T-cell dependent antigens

Answer 197

* APCs engulf a pathogen and travel to the nearest lymph node * In transit, they digest the pathogen and display its antigens on their surface * At the lymph node garrison, the APCs activate T cells and B cells * Plasma cells, memory cells and cytotoxic T cells leave the garrison and enter the circulation * Cytotoxic T cells travel directly to the site of infection (fight) * Plasma cells and memory cells travel to the bone marrow * Plasma cells soon die off, but memory cells persist

Answer 198

- constant and variable - Defined by ‘constant’ regions of conserved aa sequences * 5 heavy chain types: α, μ, γ, δ, ε * 2 light chain types: κ, λ * Heavy chain defines the antibody class * α=IgA,μ=IgM,γ=IgG;δ=IgD;ε=IgE * Each class is common to a species (called an isotype) * For example, IgE is the same for all humans but different from that of monkeys

Answer 199

defines the various heavy chains of a species (e.g. human)

Answer 200

differences in the constant region shared by some but not all members of a species

Answer 201

differences in the hypervariable region within an individual

Answer 202

* Simplest, smallest and most abundant antibody in blood and tissue fluids * A monomer, with 4 classes (IgG1-4) * Each class varies in aa sequence and interchain cross-linking * Binds and opsonizes microbes (allowing phagocytes to grab them more easily) * Binds and neutralizes viruses * Activates the classical complement pathway

Answer 203

* Major secreted antibody of mucosal surfaces * Most commonly found as a dimer, linked by disulfide bonds to the J (joining)-chain protein * Secretory piece is wrapped around both molecules during secretion * “secretory IgA” (sIgA) is found in tears, breast milk and on mucosal surfaces - slgA can bind 4 antigens

Answer 204

* Can be found as monomers on the surface of B-cells (part of the B cell receptor) * But is most commonly found as a pentamer held together by J-protein (large monomer) * First antibody isotype detected during the course of an infection - can bind 10 antigens

Answer 205

* Present in trace amounts in the blood * Exists in monomeric form on surface of B-cells * Does not bind complement * Plays a role in B-cell activation * Function not well understood * Recent work suggests that IgD enhances mucosal homeostasis and immune surveillance by arming basophils and mast cells against mucosal antigens, including microbiota members

Answer 206

* Present in trace amounts in the blood * Found more prominently on the surfaces of mast cells and basophils * These cells are loaded with inflammatory mediators (histamine) (held in granules) * When 2 molecules of IgE on mast cells or basophils are cross- linked by antigen, cells degranulate and act to quickly amplify the immune response * Primary role of IgE is to amplify the body’s response to invaders * They help orchestrate the acute response to invasion, early during infection

Answer 207

- antigens which are harmless to most people are perceived as threats * Anti-allergen IgE triggers release of chemicals such as histamine from mast cells, or leukotrienes from eosinophils * Leukotrienes are the major chemical mediators of asthma * Causes itching, swelling, wheezing (if in the lungs) - immune system not getting feedback it needs from environment

Answer 208

- large amount of IgE made after first encounter, attaching to mast cells - cross-linking occurs on second encounter, mast cells triggers release of histamine - immune response: sneezing, runny nose, itchiness, etc

Answer 209

- very severe allergy form * Excess histamine triggers smooth muscle contraction - Contraction of lung smooth muscles interferes with breathing * Excess histamine also weakens junctions between cells lining blood vessels * Causes them to leak * Fluid forced from circulation into tissues * fluid contains histamine and the reaction spreads rapidly

Answer 210

- pumps epinephrine, dilating blood vessels and opens airways - quickly increases levels of cyclic AMP, stopping mast cells from dumping histamine to stop reaction

Answer 211

* alternative complement pathway: (C3b binds to bacteria and initiates the formation of the Membrane Attack Complex) - Antibodies made as part of the adaptive response activate complement through the ‘classical’ pathway * Requires a few additional proteins, but C3 is again the major player

Answer 212

- similar to classical - Lectins are produced by the liver and bind sugars on bacterial cells (target for immune system) - Allow complement proteins to bind and trigger the formation of C3 convertase, then the pathway is the same as the classical pathway (converges)

Answer 213

- C1 complex cleaves C4 and C2, fragments re-join to make C3 convertase (cleaves C3 to C3a+C3b) - C5 made with C3b, C5 convertase cleaves C5 to C5a+C5b; C5b forms membrane attack complex

Answer 214

- Patients who have deficiencies in complement are extremely susceptible to certain blood-borne pathogens that display ‘phase variation’ * These are ‘shapeshifting pathogens’ - virulence strategy: change their antigens regularly to elude the immune system - New antigens are not recognized by antibodies and are thus invisible to cytotoxic T cells

Answer 215

* Epithelial barrier is studded with T cells that have encountered antigens * Dendritic cells reach between epithelial cells to sample antigens from the microbiota * Specialized cells called M cells (found in ‘Peyer’s patches) also sample antigens - Sampled antigens are constantly presented to a rich supply of macrophages, B and T cells in the layer under the epithelial cells

Answer 216

* Secreted into the lumen of the gut * Coats microbiota components considered to be threats * Prevents bound microbes from penetrating the barrier * May promote the colonization of certain important beneficial microbes by adhering to them

Answer 217

- TLRs on the epithelial cell side facing the gut lumen (many antigens), some also on basal side of layer (fewer antigens, only from invasive pathogens) - TLRs on basal side are much more reactive than luminal side * beneficial microbes have evolved to dampen TLR signaling

Answer 218

- immune system can have access to all the energy that it can get hold of - most complex biological system other than brain

Answer 219

- degree to which an antibody recognizes an antigen - can distinguish between several similar-looking antigens - earliest clues: smallopox

Answer 220

- pick off scabs, put them in a bowl with herbs and grind them, let it dry - take powder and shoot up noise, rub into skin, would cause a milder form of disease (2% would die)

Answer 221

- extremely painful, lasts 2 weeks - doesn’t exist anymore (besides in 2 labs) - risk: children and pregnant women - killed 1/3 of infected, scarred others - variola major:same class as monkeypox

Answer 222

- cold viruses (many, approx 200 viruses) evolve very quickly - boosters: COVID drifts antigenically, changes the proteins on its surface (similar to influenza: better)

Answer 223

- first to put into practice that milkmaids contracted cowpox (closely related), but causes less prominent disease - if milkmaid came into contact, they may get small lesions, but it provided immunity for smallpox and was much less severe - cross-protection: the major antigen cowpox and smallpox produce is the same

Answer 224

cows; vacca- latin

Answer 225

- Suffering an infection with a pathogen gives immune response to the pathogen and (usually) acquired immunity-driven protection against subsequent infection * high morbidity and sometimes mortality for nasty pathogens * risk of infecting others nearby (epi/pandemics)

Answer 226

- trick the body into seeing a pathogen and raising an immune response without the risk of pathogen-mediated disease - ex: vaccination; works because of our adaptive immune response (needs to be primed against specific antigen)

Answer 227

1. killed whole organisms 2. live attenuated organisms 3. subunit vaccines 4. nucleic acid vaccines (mRNA, viral vector)

Answer 228

- take pathogen, kill it and administer killed pathogen to patient, providing antigens that immune system needs to respond (no infection as organism is dead) - vaccines for hep. A, polio (salK) BENEFITS: easy to produce, many antigens are presented to the immune system for a robust response DRAWBACKS: Complete inactivation of the organism difficult to achieve

Answer 229

- cutter lab manufactured salk vaccine * batches incorrectly tested/passed, contained live virus - 250+ polio cases, many paralysis cases - legislation introduced to stop this happening again

Answer 230

- organisms weakened (not dead) before administration, to give the immune system the upper hand EX: BCG, sabin polio vaccine BENEFITS: pathogen infection process is appropriate, many antigens are presented to the immune system for a robust response DRAWBACKS: difficult to produce; Contraindicated for those who are immunocompromised; cold chain distribution usually required

Answer 231

- selected, purified antigenic components of pathogens (have to be very aware of pathogen) EX: toxoid vaccine, S. pneumoniae, viral capsids from human papillomavirus BENEFITS: easy to produce; no chance of infection DRAWBACKS: hard to find protective antigen - some subunit vaccines contain subunits of antigens from multiple pathogens

Answer 232

- many pathogens produce them, they give you the infection; virulence component - protect against what is actually causing the disease - if you change stuff on its surface, you don’t change toxin shape, but it no longer acts as a toxi

Answer 233

- mRNA vaccines contain mRNA that codes for a specific antigen, that is wrapped in a lipid layer and injected EX: covid vaccines BENEFITS: super-easy to manufacture, and relatively quick to get to market; no chance of infection DRAWBACKS: Cold chain distribution required; very poor public understanding/excessive fearmongering, mRNA very unstable

Answer 234

- your immune system is the most open to infection - immunity from breast milk and placenta wanes after 6 months

Answer 235

- better response * first dose leads to early synthesis of IgM followed by IgG * second shot is ‘booster’ shot; a rapid response because memory B cells formed during first response * booster shot ensures sufficient antibodies with sufficient reactivity towards antigen will be circulating in the body, protecting against reinfection

Answer 236

- vaccine primes the body against an antigen that may be lost/changed into something else within short space of time - ex: influenza, SARS-CoV-2; - need a slightly different vaccine to fit the new antigens, as soon as the virus mutates (which is often)

Answer 237

* Memory T cells and memory B cells have long lifespans, but not indefinite * As they replicate, they can lose specificity for their cognate antigen * Eventually they become unprotective

Answer 238

- live pathogen activates the immune system appropriately

Answer 239

- polio transmitted through fecal-oral route - replicates in gut mucosa, moves to regional lymph nodes + induces viremia; some replicated virus can attack nervous system and cause paralysis - salk vaccine is injected; antibody response is protective against paralysis, does not elicit mucosal response - a person can later get mild form of disease through fecal-oral route; they can then pass this on to unvaccinated people - may get transient infection, body can get over it quickly but can be passed on before body clears it

Answer 240

- antibody response is protective against severe disease, but does not elicit the typical lung mucosal response - respiratory disease, but gets injected into arm (prevents more severe forms of disease) - person can still get a mild form of disease through natural infection - "breakthrough infection"; they can pass it on to others

Answer 241

- No–vaccinating a large part of the community effectively interrupts the transmission of the disease

Answer 242

- large community is immune - depends upon many factors including transmission rate, population density - only works for diseases transmitted person-to-person

Answer 243

- protects immunocompromised people who cannot tolerate, or do not respond to vaccinations * vaccination is not an option, and they rely on the vaccination of others

Answer 244

- problem at the moment (largely because of the social media megaphone, and lack of fact-checking) * Not new – Jenner’s work promoted public hysteria in the 18th century * People believed cowpox would turn them into cows

Answer 245

- alternative: serious infectious disease and the potential to cause an epidemic - no medical procedure is without risk, but social media has blown risk way out of proportion to benefit

Answer 246

- would not be alive today had antibiotics not been available to save you * Infections we consider minor today often killed their victims even just 80 or 90 years ago

Answer 247

- people used molds and soil microbes as home remedies for centuries prior to the discovery of penicillin - Ernst Duchesne originally discovered the antibiotic properties of Penicillium molds (not credited) - Fleming rediscovered it; didnt garner much interest as it was very unstable - 'Howard Florey and Ernst Chain are credited with purification of penicillin (kept it stable for use)

Answer 248

- German physician (1895-1964) who worked at Bayer - daughter had serious infection after pinprick - injected her with dye; Prontosil (was being investigated as possible antimicrobial, no activity on plates)

Answer 249

- saved hundreds of thousands of lives - prontosil and sulfanilamide -

Answer 250

- screened 10,000 strains of soil bacteria for antimicrobial activity; discovered streptomycin

Answer 251

- used to be innovative that a drug should be selectively toxic against a pathogen and leave host alone - possible because there are key elements of microbial physiology that eukaryotic cells do not share - ex: peptidoglycan, ribosomes

Answer 252

- archaea have similar ribosomal structure/processes to eukaryotes - no archaeal vaccines, we don't necessarily know of archaeal pathogens

Answer 253

- according to activity * Antifungal, antibacterial, antiprotozoan, antiviral * "antibiotic" usually reserved for compounds that affect bacteria

Answer 254

narrow: agents affect few target organisms broad: agents affect a much larger number of target organisms

Answer 255

bactericidal: antibiotics kill bacterium bacteriostatic: antibiotics prevent growth of bacterium, but do not kill it (can be narrow or broad spectrums, choice depends on infection and its site, and health state)

Answer 256

- prevents reproduction of microbe - suspends growth, buys time for immune system to take over

Answer 257

* The organism being treated * The attainable tissue levels of the drug * The route of administration (oral, topical, injected)

Answer 258

* Serial dilution in a 96-well plate * E-strips (MIC strip tests) * Kirby-Bauer disk diffusion assay *downside of these tests: it takes time, not possible for time-sensitive situations

Answer 259

* Cell wall synthesis * Cell membrane integrity * DNA synthesis * RNA synthesis * Protein synthesis * Metabolism

Answer 260

- penicillins - cephalosporins - vancvomycin - bacitracin - monobactams

Answer 261

- polymyxins - daptomycin - gramicidin

Answer 262

1. Sugar molecules N-acetylmuramic acid (NAM) and N-acetyl glucosamine (NAG) are made in the cytosol 2. Linked together by a transglycosylase enzyme at the cell wall 3. side chains of adjacent NAM molecules are cross- linked by transpeptidase to provide rigidity to the cell wall - each step is a separate target for different antibiotic classes

Answer 263

1. AA add to NAM 3. NAM pentapeptide transfers to bactoprenol 4. NAG links to NAM

Answer 264

- bactoprenol flips; moving NAM-NAG to outer side of cytoplasmic membrane - transglycosylace attaches new disaccharide unit to chain - pentaglycine connects L-Lys on one side chain and D-Ala on other - one phosphate on liberated bactoprenol removed, lipid moves back to cytoplasmic side of membrane

Answer 265

- Derived from fungi, consist of a beta lactam ring structure to which a number of R groups can be added - each R group provides different properties (stability, spectrum of activity) - work by making the cell wall fall apart

Answer 266

- transpeptidase and transglycosylase enzymes - involved in cell wall building

Answer 267

1. inheritance of a gene that codes for beta-lactamase gene (can be overcome by its inhibitors; clavulanic acid) 2. inheritance of a gene that codes for an altered PBP that does not bind antibiotic (mutations)

Answer 268

- type of beta-lactam antibiotic - continuously synthetically altered to combat the development of resistance - microbes are quick to adapt - some only used in worst-case scenarios, to slow does resistance development

Answer 269

- binds to the bactoprenol lipid carrier and inhibits transport of the peptidoglycan monomers to the growing chain * Very toxic and can only be used topically

Answer 270

- inhibits the two enzymes that make a precursor peptide of the NAM side-chain * Useful for the treatment of tuberculosis

Answer 271

- binds to the D-Ala-D-Ala terminal end of the disaccharide unit & prevents bindings of transglycosylases and transpeptidases * Some bacteria have incorporated D-lactate into the D-Ala terminus to develop resistance

Answer 272

gramicidin, polymyxin, daptomycin

Answer 273

- cyclic peptide that inserts into the bacterial membrane - only used topically (activity towards mammalian cell membranes)

Answer 274

- Binds to both outer and inner membranes of G- bacteria, disrupting the inner membrane like a detergent - only used topically (activity towards mammalian cell membranes)

Answer 275

- aggregates in G+ bacterial membranes to form channels * Very effective against MRSA (for now)

Answer 276

- sulfonamides - trimethoprim - metronidazole

Answer 277

- quinolones

Answer 278

- rifampin - pyronins

Answer 279

- sulfa drugs (antimetabolites) - quinolones

Answer 280

- interfere with nucleic acid synthesis by preventing the synthesis of tetrahydrofolic acid (THF), an important cofactor in the synthesis of nucleic acid precursors - selectively toxic to bacteria as bacteria are the only ones that can make it, due to their biochemical pathway

Answer 281

- target microbial topoisomerases, enzymes that are essential for catalyzing changes in DNA topology to allow replication and transcription - toxic to mitochondria as they are also bacteria: they use the same mechanisms and enzymes to replicate their genomes; mitochondria replicately separately from human genome

Answer 282

- pro-druge * Activated on reduction by microbial flavodoxin or ferrodoxin, found in microaerophilic and anaerobic bacteria * Nicks DNA at random once activated * Not effective against aerobic bacteria

Answer 283

- rifampicin (used clinically) and actinomycin D

Answer 284

* Binds to the exit tunnel of bacterial RNA polymerase, blocking RNA from exiting the polymerase structure * Halts transcription

Answer 285

- chloramphenicol - macrolides (erythromycin) - clindamycin - oxazolidinones (linezolid) - streptogrammins (synercid)

Answer 286

- aminoglycosides (gentamicin) - tetracyclines (doxycycline)

Answer 287

* Bind and interfere with the function of bacterial rRNA * Bacterial ribosomes and eukaryotic ribosomes have fundamentally different properties – bacterial ribosomes are useful antibiotic targets * ribosomes catalyze linkage of amino acids during translation, using mRNA as the code and tRNAs as the source of amino acids * Bacterial ribosomes are made up of small (30S) and large (50S) subunits

Answer 288

* Aminoglycosides: Bind 16S ribosomal RNA (part of the 30S ribosome) and causes translation misreading of mRNA (jumbled peptides) * Tetracyclines: Bind to and distort the ribosomal A site (that accepts incoming tRNAs) (interferes with bone development in children)

Answer 289

- inhibit translocation of the growing peptide chain

Answer 290

- inhibits peptidyltransferase activity - Can depress production of blood cells in the bone marrow

Answer 291

- Bind to the 23S rRNA component of the 50S ribosome and prevent formation of the protein synthesis 70S initiation complex

Answer 292

- 2 types; both bind to the peptidyltransferase site - types A and B are used together and act synergistically

Answer 293

- binds to bacterial enzymes that attach amino acids to end of tRNA molecules, halting protein synthesis * Used topically in creams to treat infections caused by G+ bacteria * Cannot be used internally because it is rapidly degraded in the bloodstream

Answer 294

- many derived from nature - we have used high concentrations of antibiotics for long periods (exerts selective pressure on bacteria to evolve)

Answer 295

- keep antibiotics out of cell ! Destroy the antibiotic before it can enter the cell * Decrease membrane permeability across the outer membrane (express narrower pores) * Pump the antibiotic out of the cell using specific transporters

Answer 296

- Prevent antibiotics from binding their target! - Modify the target so that it no longer binds the antibiotic - Add modifying groups to the antibiotic so that the antibiotic is inactivated

Answer 297

- Dislodge an antibiotic bound to its target! - Ribosome protection or rescue (some G+ make proteins that bind to ribosomes to prevent antibiotic binding near peptidyltransferase site)

Answer 298

- intrinsic (natural resistance) - genetic mutations - through receipt of antibiotic resistance gene (carried on mobile genetic element; plasmid, transposon, integron)

Answer 299

- many genes originate in environment - human activity and travel amplified and disseminated them

Answer 300

* Collateral damage * A huge number of diseases are now recognized to be associated with a lack of diversity in the gut microbiome - still should take; lifesaving drugs if used correctly!

Answer 301

- have not used antibiotics appropriately since their development - used in enormous quantities in agriculture - often prescribed inappropriately - taken inappropriately - bacteria can exist in biofilms where resistant strains can persist - pharmaceutical companies have no desire to develop new antibiotics

Answer 302

- never use to treat viral infections - Do not use an antibiotic to treat an infection if the patient’s microbiome has resistant strains - know which antibiotic resistant strains are prevalent within community before prescription - consider length needed to take antibiotic - use narrow-spectrum antibiotics when possible - screen infectious agents for AMR genes - ensure those with chronic infections maintain antibiotic regiment until infection is cleared

Answer 303

- a negative strand RNA virus

Answer 304

- most common life-threatening viruses of the western world - 10% of north america infected - pregnant women and elderly

Answer 305

* Narrower host range than influenza A * Can cause serious disease but mutates much more slowly - no current circulating strands

Answer 306

* Narrower host range than influenza A * Causes mostly mild disease and does not spread easily

Answer 307

* never been detected in humans. Associated with swine and cattle. * Relatively rare; emerged in 2011

Answer 308

- usually influenza A - cyclic appearance of extremely virulent strains that cause pandemic mortality - Spanish flu, Asian flue, Hong Kong flu

Answer 309

- H7N9 – causes very serious disease in a high proportion of infected people - not currently transmissible person-person

Answer 310

- influenza: severe headache and extreme, longer duration, some GI symptoms

Answer 311

- no geometrical capsid - shell of matrix proteins (M1) that surround the 8 RNA chromosome fragments - matrix surrounded by membrane envelope (derived from host cell during budding; originates from last person's cells who was infected) - Viral envelope proteins hemagglutinin (HA) and neuraminidase (NA) stud the surface of the virus

Answer 312

- block activity - does not work for COVID - antiviral drugs are very specific for the viruses they affect

Answer 313

* Each is coated with nucleocapsid proteins (NPs) * Each encodes 1 protein * 2 segments undergo splicing to encode 2 further proteins - genome segments line up precisely

Answer 314

- if you make your own viral RNA polymerase and pack it with genome, as soon as it gets released, you can get to start genome - quickly replicating genome (race against time)

Answer 315

* They link to each other in order as they arrange themselves * Each segment lines up like a bundle of sticks * Tiny molecular extensions seem to connect these sticks

Answer 316

- most dangerous aspects of influenza virus is its ability to continually change its antigenic determinants - Segmented genomes allow for re-assortment of genetic information, generating drastically new strains more quickly than viruses with non-segmented genomes

Answer 317

- hemagglutinin (18 HA subtypes) - genome out of cytoplasm to work effectively; due to hemagglutinin - allows fusion of the viral membrane with the host cell membrane

Answer 318

* 1) HA C-terminal domain recognizes and binds to host cell sialic acid receptor * 2) Triggers uptake of virion by endocytosis * 3) Endocytic vesicle acidifies and produces a conformational change that exposes the N-terminal fusion peptide * 4) Fusion of host and viral membranes can now take place (pH sensitive) * 5) Triggers release of the genome cargo into the host cytosol

Answer 319

- birds are the natural infleunza A virus reservoir - pigs have both types receptors and they get infected with 2 strains simultaneously; providing an opportunity for reassortment - emergence of a dangerous pandemic strain - influenza A binds to sialic acid glycoprotein (found on epithelial cells lining lungs and intestines) - host determinant: nature of the cell-surface glycoproteins on host cells that bind the HA and allow endocytosis

Answer 320

1) Viral segments travel to nucleus and enter nuclear pores 2) Attached viral RNA polymerase synthesizes (+) strand RNA (used as mRNA or as templates for generating progeny (-)RNA) 3) mRNA travels to cytoplasm for translation to viral proteins – these are processed by the ER/Golgi & sent to the host cell membrane

Answer 321

- Envelope proteins and viral genome packages travel to cell membrane for packaging into new virions - 11 neuraminidase N variants * Within the cell membrane, envelope proteins assemble around the genome and matrix proteins * Virion then buds out of the host cell * Neuraminidase cuts the virion loose from host glycoproteins to release it to the extracellular space

Answer 322

- ability of influenza virus (A and B) to mutate and change slightly - RNA replication errors in HA and NA genes

Answer 323

- big change in the structure of the ‘flu virus - Can be caused by jumping of the virus into a new species - caused by re-assortment of the genes from 2 different viruses mixing in a single host (usually a pig)

Answer 324

- WHO provides data on current season's circulating strains - for northern hemisphere, meeting takes place in february (recommendations about which viruses to include are made) - begins in early spring; 6 months to produce enough - strain can arrive late in season, predicting can be challenging

Answer 325

- annual ’flu shots is a drag, and community uptake is never optimal enough to prevent outbreaks - Several groups are working in developing vaccines to more conserved regions of the influenza virus * don’t change between viral strains * Best candidate: the stalk region of the HA * body’s attention is diverted towards the head part of HA and antibodies are not made to the stalk region (a viral defense tactic) *directing the immune system to recognize the stalk region may be the key

Micro 2/2 Flashcards

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