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MICR 2420 > Second half > Flashcards

Second half Flashcards

1
Q

what condition is required to count microbes/bacteria

A

must be suspended in liquid

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2
Q

3 ways to count microbes/bacteria (suspended in a liquid)

A
  1. direct microscopic counts via haemocytometry
  2. plate counts (dilution plating)
  3. optical density
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3
Q

what is haemocytometry

A
  • direct microscopic counts of bacteria
  • can also distinguish between dead and live cells
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4
Q

what is optical density

A

an indirect measurement of light scattered by the suspension at a specific wavelength to determine the concentration of microbial cells in liquid suspension
- higher the concentration of cells = the more turbid the suspension = more scattered light

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5
Q

how is the microbial growth cycle analyzed

A

as cells density as a function of time

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6
Q

what are the 4 phases of microbial growth in a batch liquid culture

A
  1. lag phase
  2. exponential/log phase
  3. stationary phase
  4. death
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7
Q

Phase 1 of microbial growth: Lag phase

A

Bactria adapt themselves to growth conditions - maturation and synthesis of RNA, enzymes and other molecules

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8
Q

Phase 2 of microbial growth: Exponential/log phase

A

characterized by cell doubling, number of cell divisions per unit time
can be split int 2 phases
1. early phase: cell growth is at maximum rate possible based on growth conditions
2. late phase: slowing of growth due to cell density, competition for nutrients, accumulating waste, etc.

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9
Q

Phase 3 of microbial growth: Stationary phase

A

overall population growth plateaus due to a growth-limiting factor such as depletion of nutrients or formation of an inhibitory product

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10
Q

Phase 4 of microbial growth: Death phase

A

without any new nutrients (and production of toxic byproducts) all cells eventually die off

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11
Q

chemostat and continuous culture systems

A
  • ensures continuous growth by adding and removing equal amounts of culture medium
  • conditions of the culture approximate that of the native environment
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12
Q

what is metagenomics

A

the study of metagenomes - collections of genetic material from a diverse group of organisms (microbial communities)

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13
Q

overview of steps in metagenomic analysis

A
  1. gDNA isolation from environment/sample
  2. gDNA library construction
  3. sequencing
  4. analysis
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14
Q

a more complicated way to identify species: ribosomal based

A
  • 16S rRNA in prokaryotes and 18S rRNA in eukaryotes
  • rRNA sequencing allows for identification of operational taxonomic units (OTUs)
  • OTU can define a species when only DNA sequence data is available
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15
Q

viral metagenomics is difficult as they…

A
  • lack a unique rRNA-like region
  • may be incorporated into the bacterial genome
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16
Q

what are biofilms

A

specialized structures of microbes growing in communities/consortiums of different species that stick together on surfaces

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17
Q

Extracellular polysaccharide (EPS) matrix of biofilms

A
  • EPS is secreted by microbial cells and is a sticky adhesive that surrounds biofilms
  • trapped within the EPS matrix are bacterial secreted proteins and extracellular DNA fragments
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18
Q

how are biofilms formed (5 steps)

A
  1. attachment of planktonic bacteria
  2. attached bacteria form microcolonies
  3. EPS secretion
  4. biofilm elaboration and maturation
  5. dissolution and dispersal
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19
Q

Life cycle of biofilms

A
  • form when and where nutrients are plentiful
  • bacteria attach to cell surfaces via cell envelop/appendages
  • once nutrients are depleted microbes detach and look for new sources of nutrients
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20
Q

true or false: biofilms can consist of multiple species or just one individual species

A

true

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21
Q

what regulates biofilm formation

A

quorum sequencing

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22
Q

what is quorum sequencing

A

the process of assessing bacterial density by secreting autoinducers into the surrounding environment
- QS is a mechanism for regulating density-dependent community behaviours - e.g. biofilm dissolution, expression of virulence factors, etc.

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23
Q

how does quorum sequencing result in a co-ordinated response by ALL cells in the community

A
  • autoinducer binds to a cytoplasmic receptor protein (transcription factor)
  • at a certain “quorum” (aka inducer concentration) the transcription factor is activated and binds to DNA activating quorum-sensing regulated genes
  • ONLY occurs when cell density (quorum) is high
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24
Q

benefits of biofilms

A
  • allows microbes to work together
  • normal microbiota biofilms of plants/animals are essential
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25
Q

cons of biofilms

A
  • may damage/degrade infrastructure
  • colonize abiotic surface put into the body
  • biofilms of pathogenic bacteria are a problem in medicine
  • bacteria are highly resistant to antimicrobials and killing by the immune response defences
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26
Q

general information about viruses

A
  • acellular entities
  • obligate intracellular parasites
  • display tropism (have specific hosts/ranges)
  • interacts with host cell surfaces
  • more viruses on the planet than any other organism
  • impacts range from innocuous to lethal
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27
Q

narrow vs wide host range of viruses

A

narrow: binds to specific type of cell, e.g. cold and influenza infect human respiratory epithelial cells
wide: can bind to a wide variety of cells, e.g. rabies virus binds to dogs, foxes, racoons and humans

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28
Q

Risk group 4 viruses

A
  • often untreatable, high individual and community risk
  • include viruses such as filoviridae (e.g. Ebola virus)
  • only viruses make it to risk level 4 (no bacteria, yeasts or fungi)
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29
Q

how can viruses be beneficial?

A
  • bacteriophages can be used to control infections as an alternative to antibiotics or disinfectants
  • viruses can be modified as delivery vehicles for gene therapy
  • bacteriophages can be used in molecular cloning, as cloning vectors
  • evolution: insertion and excision of viral genome
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30
Q

what is the general structure of viruses

A

capsid: protein coat that surrounds nucleic acid
envelope: if enclosed in a protein-containing membrane or nor
nucleic acid: either DNA or RNA encodes viral proteins

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31
Q

what are the 7 groups of viruses

A

I: double-stranded DNA virus
II: single-stranded DNA virus
III: double-stranded RNA virus
IV: (+) single-stranded RNA virus
V: (-) single-stranded RNA virus
VI: retrovirus
VII: double-stranded DNA pararetrovirus

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32
Q

group I: double-stranded DNA virus

A
  • uses its own or host DNA polymerase for replication
  • Bacteriophage lambda
  • herpes virus: chicken pox, genital infections
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33
Q

group II: single-stranded DNA virus

A
  • requires DNA polymerase to generate complementary strand
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34
Q

group III: double-stranded RNA virus

A
  • requires RNA-dependent RNA polymerase to make mRNA and gRNA
  • reoviruses: rotavirus
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35
Q

group IV: (+) single-stranded RNA virus

A
  • requires RNA-dependent RNA polymerase to make a template for mRNA and genome replication
  • flaviviruses: HepC, yellow fever
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36
Q

group V: (-) single-stranded RNA virus

A

-requires RNA-dependent RNA polymerase to make mRNA and replicate its genome
- orthomyxoviruses: influenza

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37
Q

group VI: retrovirus

A
  • packages its own reverse transcriptase to make dsDNA
  • lentiviruses: HIV (the cause of AIDS)
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38
Q

group VII: double-stranded DNA pararetrovirus

A
  • requires plant host reverse transcriptase to make dsDNA
  • caulimoviruses: infects vegetables
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39
Q

Classification of viruses is based on a combination of criteria…

A
  1. nature of the genome (most important)
  2. Viral structure
  3. presence/absence of an envelope
  4. size of viral particle
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40
Q

Structures of viruses

A
  1. Filamentous: helical capsid symmetry - genome is coiled
  2. Icosahedral capsid: rotational symmetry
  3. Multiple helical packages: collection of several helical genome segments enables rapid evolution of new strains
  4. Complex viruses: bacteriophages
  5. Asymmetric: no capsid, DNA is enclosed by a core envelope surrounded by an OM
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41
Q

example of filamentous capsid virus

A

ebola virus

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42
Q

example of icosahedral capsid virus

A

human papilloma virus

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43
Q

example of multiple helical packages virus

A

influenza virus

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44
Q

examples of complex viruses

A

bacteriophages: T2, T4, and lambda phage

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45
Q

example of asymmetric viruses

A

vaccinia poxvirus

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46
Q

Basic process of viral infection and reproduction

A
  1. Attach to the host cell
  2. penetration of the host via endocytosis
  3. Uncoating and release of viral contents
  4. Biosynthesis of viral RNA
  5. Assembly of new phages
  6. Release of new viral particles
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47
Q

what makes biosynthesis of new viruses complicated

A

the presence of an envelope and the nature of the genome (especially RNA viruses and retrovirus)

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48
Q

how does phage genome get into the cell

A
  • the virus attached to specific host cell receptors
  • phage genome is injected through the cell wall and membrane and the capsid is shed
  • phage structure becomes waste in the environment
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49
Q

2 types of bacteriophage life cycle

A
  1. Lytic cycle
    - rapid phage replication and lyses host cell
    - lytic phages include T2, T4 and Ebola virus
  2. Lysogenic cycle
    - temperate phage infects and inserts the DNA into host chromosome
    - activated to excise and follow lytic life cycle by certain triggers
    - lysogenic phages include phage lambda
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50
Q

Mutualism example: lichen

A
  • fungus provides minerals and protection from UV
  • cyanobacteria/algae provide photosynthetic nutrients
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51
Q

synergism example: cow rumen microbiome

A
  • rumen bacteria ferment complex polysaccharides from grass, making H2 and CO2
  • methanogens convert these gases to methane
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52
Q

commensalism example: Beggiatoa and other sulfur spring microbes

A
  • toxic H2S microbial mats contain Beggiatoa (a sulfur oxidizer).
  • Beggiatoa reduce ecosystem toxicity and allows growth of other species
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53
Q

Amensalism example: Streptomyces and other soil bacteria

A
  • streptomyces produce antibiotics and use these molecules to kill and lyse bacteria in soil, releasing their nutrients for consumption by streptomyces
  • interaction is NON-specific
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54
Q

Parasitism example: legionella affecting amebas and human lung macrophages

A
  • The causative agent of Legionnaire’s disease
  • can infect freshwater amebas and lung macrophages
  • usually contaminate via air conditioning systems
  • interaction is specific and usually obligatory for the parasite
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55
Q

what are endosymbionts

A
  • intracellular bacteria that infect species (mostly insects)
  • like “helpful parasites” (mutualism + parasitism)
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56
Q

endosymbiosis example: Wolbachia

A
  • have symbiosis with 50% of insects
  • can be transferred from mother to progeny
  • useful to fight malaria - compete with viruses for colonization to lessen the viral load
  • infections are localized to ovarian germ cells and testes
  • females have an advantage for reproduction
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57
Q

Mutualism example: Photorhabdus luminescent and nematode worm

A
  • the bacterium are bioluminescent and collectively make nematodes glow
  • this attracts insect larvae predators to consume the worm
  • once inside the insect, the bacteria are released from the nematode and use potent toxins to rapidly kill the insect
  • both the worm and bacteria use the released nutrients from the dead insect and then reassociate to start the cycle again
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58
Q

parasitism and synergism example: helicobacter pylori and gastrointestinal tract

A
  • the bacterial pathogen is the main causative agent of gastric ulcers and gastric cancer
  • the bacteria utilize host cell energy stores for growth
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59
Q

commensalism example: staphylococcus epidermidis and skin cells

A
  • the bacteria lives on human skin and used dead skin cells as nutrients
  • unless you are immunocompromised in some way, they won’t effect your body
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60
Q

mitochondria and chloroplasts have what type of symbiosis?

A

endosymbiosis (form of mutualism)

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61
Q

what are the 3 main questions of microbial ecosystems

A
  1. who is there
  2. what are they doing
  3. how do microbiomes vary under different conditions
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62
Q

question 1: who is there? - determine using culture

A
  • only supportive of a handful of bacterial species
  • “the great plate count anomaly” states that many bacterial species int the lab conditions foreign and they cannot survive
  • using “culturomics” can reside labor intensity with AI and robots, allows culture under many different conditions and picking of thousands of colonies into multi-well plates
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63
Q

question 1: who is there - determine using DNA sequencing

A

gDNA is extracted and subjected to either…
A) Amplicon sequencing - target gene is amplified, barcoded and sequenced (most common to amplify regions from 16S rRNA gene)
B) Metagenomic “shotgun” sequencing - gDNA is broken up into bits, barcoded and directly sequenced, computer is used to match genes to sequenced pool
- both methods reveal alpha diversity (species richness)
- amplicon sequencing is better and more accessible

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64
Q

question 1: who is there - determine using RNA sequencing

A
  • extract mRNA from a community
  • transcribe to DNA (using viral reverse transcriptase)
  • barcode and sequence
  • match transcripts to known genomes
    key benefit = know the microbe is alive
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65
Q

question 2: what are they doing - predictive method

A
  • a powerful computer assembles MAGs
  • use the software to annote genes and predict their possible functions
  • most famous program = pie crust
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66
Q

question 2: what are they doing - direct proteomics

A
  • extract all the proteins in the sample, sequence peptide fragments using mass spectrometry
  • use a computer to match peptides to proteins and proteins to genes
  • pro: protein shows the genes are useful
  • con: expensive
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67
Q

question 2: what are they doing - direct metabolomics

A
  • extract all the molecules in a sample
  • subject directly to mass-spectrometry or NMP spectroscopy
  • use computer to match compound signatures to standards
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68
Q

question 2: what are they doing - direct metatranscriptomics (RNA-seq)

A
  • mRNA content reflects active transcription - what the cells are doing/making in response to the environemt
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69
Q

question 3: how do microbes vary under different conditions

A
  • microbes are dynamic systems - change in response to the environment
  • sample longitudinally - at multiple points in time (multi-omics integration)
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70
Q

primary producers in oceans and freshwater ecosystems

A

bacteria and algae

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71
Q

which region of marine habitats contains the highest concentration of microbes

A

the neuston layer (surface layer)
- because of photosynthesis by primary producers

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72
Q

what extremophile category do most ocean microbes fall into

A

oligotrophs - do not need a lot of nutrients

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73
Q

major findings of tara oceans and tara pacific

A
  • in the upper ocean layers temperature is that main determinant of microbiome composition
  • in an era of climate change this could have major ramifications
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74
Q

mutualism within the ocean microbiome: Prochlorococcus and Alteromonas

A
  • Prochlorococcus lost the catalyst in its genome to allow it to grow
  • Altheromonas produce a catalayse for them
  • Prochlorococcus removes H2O2 making a better environment for altheromonas
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75
Q

which extremophiles are found on the open ocean floor

A

barophiles - extreme pressure
psychrophiles - extreme cold
oligotrophs - extreme nutrient depletion
- these microbes have extremely slow metabolic rates and high concentration of heavy metal resistance genes

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76
Q

hydrothermal vent

A
  • a deep ocean oasis with extreme pressure end extreme heat
  • barophiles can live here
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77
Q

other carbon-rich sources that fuel marine microbiomes

A
  • cold seeps
  • whale fall
  • ship wrecks
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78
Q

what is the most harmful treatment to soil microbes

A
  • manufactured fertilizer pellets - introduce nitrogen into the soil
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79
Q

microbes found in the top layers of soil…

A

topmost = fungi, actinomycetes, slime molds
below = mycorrhizae (plan roots), aerobic bacterial biofilms and filaments

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80
Q

soil food web

A

producers: plants - leaves and roots, lithographs
consumers: protists and fungi
secondary consumers (predators): protists, nematodes, arthropods
decomposers: bacteria and fungi

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81
Q

each particle of soil supports miniature colonies, biofilms and filaments of bacteria and fungi that…

A

interact with each other and with plant roots

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82
Q

what are the streptomyces

A
  • a major genus of soil bacteria notable for diversity of antibiotics they make
  • also responsible for soil “smell”
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83
Q

microbes in the rhizosphere…

A
  • help to protect plants from pathogens
  • may fix nitrogen (diazotrophs)
  • feed off nutrients provided by the plant
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84
Q

what are ectomycorrhizae

A
  • grow outside plant cells
  • colonize the rhizoplane
  • form a thick, protective mantle around the root
  • extend outward to absorb nutrients
  • ectomycorrhizal hyphae do not penetrate cells
  • eventually want to get into a cell and become an “endo”
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85
Q

what are endomycorrhizae

A
  • grow inside plant cells
  • dependent on their host
  • lack sexual cycles
  • exist entirely underground (e.g. root cells)
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86
Q

specialist endophytic relationship: plant roots and rhizobia

A
  • bacterial cells adapt to life within nodules to form a nitrogen-fixing “organ” for the host plant
  • leguminous plant
  • leghemoglobin makes nodules pink and is there to allow O2 to be taken away (anaerobic environment)
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87
Q

what are commensal organisms

A
  • microbes that are normally found at various non-sterile body sites
  • can cause disease if they reach abnormal places
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88
Q

microbiota vs microbiome

A

microbiota = cell consortism
microbiome = the genetic potential of the consortium

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89
Q

some insects require microbes to allow digestion of their dietary substrates…

A

termites and demoted mites

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90
Q

how human are we?

A

1 : 1.3
human : bacteria

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91
Q

what are the most common bacteria found at various parts of the body

A

actinobacteria and firmicutes

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92
Q

which parts of the body can only host bacteria (as opposed to viruses and fungi)

A

nose and stomach

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93
Q

microbiome of the skin

A
  • the skin is difficult to colonize because it is dry, salty, acidic and has protective oils
  • most microbes found in moist areas such as scalp, ears, armpits, genitals and anal areas
  • mostly gram-positive bacteria (more resistant to salt and dryness)
  • e.g. S. epidermidis and C. acnes
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94
Q

microbiome of the mouth

A
  • infants mouth is colonized by non-pathogenic Neisseria (gram-negative) + Streptococcus and Lactobacillus (gram-positive)
  • as teeth emerge other bacteria start growing between gums and teeth and on tooth enamel
  • oral respiratory tract = most common site of infection
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95
Q

microbiome of the nose and oropharynx

A
  • nostrils and nasopharynx are dominated by bacillota and actinomycetota (one dominates over other)
  • Nasopharynx dominated by S. aureus and S. epidermidis
  • oropharynx has similar composition to saliva
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96
Q

microbiome of the lungs

A
  • not sterile, microbes are present here as biofilms
  • many are anaerobes
  • microbiota in diseases such as COPD, cystic fibrosis and asthma are distinct for each condition and different to that of a healthy lung
  • the mucocilliatory escalator constantly sweeps inhaled particles up toward the throat
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97
Q

microbiome of the urogenital tract

A
  • the kidneys and urinary bladder ate STERILE
  • the urethra contains S. epidermidis which can cause UTIs
  • composition of vaginal microbiota changes with the menstrual cycle - acidic secretions favour Lactobacillus (low pH in vagina) which is protective from STIs and improve reproduction
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98
Q

microbiome of the stomach

A
  • stomach has very low pH
  • helicobacter pylori survives at pH , burrows into mucus and causes gastric ulcers
  • hypochlorydia can be caused by malnourishment or PPI use
  • stomach acid is a key defensive barrier
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99
Q

microbiome of the intestine

A
  • ratio of 1000 anaerobes to 1 facultative aerobe in feces
  • the most important microbial ecosystem in the human body lives in the colon
  • does as much metabolic work as the liver, regarded to as the forgotten organ
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100
Q

true or false : it is the metabolic potential of the gut microbiome that is important, not its specific species

A

true

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101
Q

what do our gut microbes do for us?

A
  • regulate the immune system
  • extract energy from food
  • control potential pathogens
  • make some essential metabolites, including vitamins and cofactors
  • improve intestine function
  • remove toxins and carcinogens
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102
Q

what is considered a “virtual organ” that is as important to us as our liver

A

the gut microbiome

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103
Q

how do we acquire our microbes

A
  • vaginal delivery
  • breast feeding
  • interaction with the environment
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104
Q

how do we lose our microbes

A
  • C-section delivery
  • maternal antibiotics
  • formula feeding
  • indoor living
  • excessive sanitation
  • chemical preservation of food
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105
Q

a high diversity of species in our gut microbiome leads to…

A
  • healthy ecosystem
  • balance
  • functional redundancy (high gene count)
  • resistance to damage
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106
Q

a low diversity of species in out gut microbiome leads to…

A
  • sick ecosystem
  • imbalance
  • functional disability (low gene count)
  • susceptibility to damage
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107
Q

what does the AV lab research on “missing microbes” focus on

A
  • studying the gut microbiome of remote hunter-gatherer people
  • they have a far more diverse microbiome than we do
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108
Q

what is a robogut

A
  • a bioreactor model used to emulate the gut environment
  • bioreactors model of the human colic environment evaluates the gut microbial community ecology and functions
  • a “host free” system used to culture the unculturable
  • can support whole gut microbial ecosystems for several weeks
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109
Q

what happens when we have accidental penetration of physical barriers or damage in the immune system

A
  • the microbiota behaves badly
  • microbes that breach barriers are opportunistic pathogens
  • the patient may be infected by the normal microbiota (e.g. inflammatory bowel disease)
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110
Q

how is the microbiota protective

A
  • competitive exclusion: prevents pathogen from growing there
  • environment modification: makes it hostile for the pathogen
  • host stimulation: e.g. host cytokines regulate the immune system
  • direct pacification: secreted factors from microbiome members can prevent expression of virulence genes
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111
Q

the microbiome-gut-brain axis

A
  • the brain and gut microbiota signal to each other
  • the metabolites made by gut microbes can affect your moos and behaviour
  • signalling pathway = vagus nerve
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112
Q

what happens when microbial balance is compromised

A
  • containment breaches
  • niche disturbance
  • extinction events
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113
Q

Obesity and dysbiosis - microbiome imbalance example

A
  • gut microbiome influences nutrient acquisition and regulation of energy metabolism and fat storage
  • obesity is associated with a less diverse microbiome
  • obesity is also associated with low-grade intestinal inflammation
  • loss of microbes that increase tight junctions
  • increase of microbes that make pro-inflammatory molecules such as LPS
114
Q

abnormal physiology of germ-free animals

A
  • poorly developed immune system
  • lower cardiac output
  • require more calories
  • thin, poorly developed intestinal walls with stunted villi
  • enlarged ceca
  • odd behaviour
  • misshapen mitochondria
115
Q

what is the innate immune system

A
  • “non-specific”
  • a rapid response system
  • includes physical barriers + cellular and chemical responses (if physical barriers are breached)
  • present since birth
116
Q

for an infectious agent to cause disease, the pathogen needs to…

A
  1. breach host defenses
  2. survive innate defence mechanisms
  3. begin to multiply
117
Q

physical barriers to infection

A

Skin: difficult to penetrate when intact
Mucous membranes: selective permeability allows absorption of nutrients
Lungs: have a mucociliatory escalator to remove small particles, larger molecules are trapped by hair in the nose and cilia lining of upper airway

118
Q

primary vs secondary lymphoid organs

A

primary: factory for lymphoid cells, include thymus and bone marrow
secondary: stations for antigen encounters, include lymph nodes, appendix, spleen, peyer’s patches, tonsils

119
Q

what is the complement system

A
  • a surveillance system of proteins that circulate the blood in their inactive forms and are cleaved to become activated
  • they compliment antibodies in the killing of bacteria by forming a MAC complex
120
Q

Important components of the alternative complement pathway

A
  • C3b acts as an opsonin
  • C3a and C5a act as anaphylotoxins, directing immune cell traffic
  • membrane attack complex (MAC) punches holes in target bacterial cells, killing them
121
Q

what are cytokines

A

molecules secreted by cells which have an effect on other cells
- e.g. interferon: when a cell is infected by a virus the cell secretes interferons to call nearby cells to fend off the virus and limit spread of infection

122
Q

what are defensins

A

small molecules able to lyse most microbial cells and some enveloped viruses
- in the gut, there is a concentration gradient of defensins - higher near the crypts of the epithelium

123
Q

what are types of white blood cells

A
  • leukocytes (PMNs)
  • monocytes and macrophages
  • dendritic cells (minor in innate)
  • mast cells (minor in innate)
124
Q

MYELOID bone marrow stem cells differentiate into…

A

phagocyte cells

125
Q

why are bacterial cells difficult to catch by phagocytes? how does this get resolved?

A
  • bacteria and phagocytes both carry a negative charge
  • C3b binds non-specifically to the surface of bacterial cells and makes it easier for phagocytes to ingest them
126
Q

NETs: neutrophil extracellular traps

A
  • an unusual form of cell death by neutrophils called NETosis
  • neutrophil senses invader and spews a latticework of chromatin and antimicrobial compounds to allow rapid phagocytosis of pathogen
  • inappropriate netosis is thought to underlie an autoimmune disease called lupus
127
Q

what bacterial structure might interfere with the process of NETosis?

A

capsule - forms a slimy layer for the bacteria to “slip” through

128
Q

Why do monocytes differentiate into macrophages

A
  • monocytes circulate the bloodstream
  • as they are attracted to sites by cytokines they differentiate into macrophages while travelling though blood vessels
  • macrophages will secrete more cytokines to attract other phagocytes
  • they must differentiate because secreting cytokines while traveling through the blood is dangerous
129
Q

what are monocytes

A

large structures that can ingest many microbes at one time
- usually found circulating but some organs contain patrolling resident macrophagese

130
Q

examples of patrolling resident macrophages

A
  1. Kuppfer cells in liver
  2. Langerhans cells in the skin
  3. microglia in the brain
  4. alveolar macrophages in the lungs
131
Q

dendrocytes possess…

A

long protrusions that can squeeze through tight spaced to sample microbes

132
Q

what is the “language of our immune system”

A
  • cytokines, chemokines and interferons
  • close-range actin “hormone” system that allow cells of the body to communicate
  • effective in signalling danger and anti-inflammatory signals after danger has passed
133
Q

cardinal signs acute inflammation

A

heat, swelling (edema), redness, pain, altered function

134
Q

basic inflammatory response

A
  1. infection occurs
  2. resident macrophages engulf pathogens
  3. vasoactive factors and cytokines help deliver additional phagocytes
  4. healing proceeds as pathogens are destroyed
135
Q

Fever…

A

can be part of an inflammatory response, and heightens activity of components of the innate immune system (complement works better when the body is warmer)

136
Q

macrophages and dendrocytes are…

A

antigen-presenting cells

137
Q

what are antigen-presenting cells

A
  • cells (macrophages and dendrocytes) that process antigens and display them on their surfaces for T cells
  • form a link between the innate and adaptive immune system
138
Q

role of antigen presenting cells

A
  • phagocytosis of antigens
  • fusion of lysosome and phagosome
  • enzymes start to degrade enemy cell
  • enemy cell broken into small fragments
  • fragments of antigen presented on APC surface
  • leftover fragments released by exocytosis
139
Q

what are Peyer’s patches

A
  • specialist sites within the small intestine that take up antigens in the gut for presentation to macrophages
  • rich in M cells (what takes up the bacteria)
  • helps the body differentiate between self and non-self when faced with a complex microbiome
140
Q

what component of the cell allows some pathogens to evade the innate immune system

A

capsule

141
Q

how do receptors of the immune system recognize pathogens

A
  • Pattern recognition receptors (PRRs) recognize invariant and essential microbial factors unique to the microbiome
  • they do this by recognizing MAMPs (microbe-associated molecular patterns)
142
Q

what are the 2 types of pattern recognition receptors (PRRs)

A
  1. Toll-like receptors (TLR) - outside the cell
  2. NOD-like receptors (NLR) - onside the cell
143
Q

Toll-like receptor (TLR) and their mode of action

A
  • transmembrane receptors that recognize pathogen products
  • on binding to ligand they stimulate cytokines to signal inflammatory response
  • induce macrophages to produce antimicrobial proteins and peptides
144
Q

NOD-like receptor (NLR) and their mode of action

A
  • internal (cytoplasmic) NOD like receptors bind MAMPs inside host cells
  • they activate cytokine production and form an inflammasome that activates the adaptive immune response and triggers apoptosis (GOOD)
145
Q

what is an inflammasome

A

a protein complex that allows rapid secretion of certain cytokines

146
Q

what are natural killer cells

A
  • lymphocytic cells distinct from T and B cells
  • NON-phagocytic
  • large and granular
  • don’t attack the pathogens themselves, instead attack host cells that have become overwhelmed by pathogens
  • have pseudopod extensions
147
Q

NK cells mechanism of action

A
  1. NK cell alerted by interferons or macrophage-generated cytokines
  2. infected host cell signals an “altered self” response (through changes on MHC class I molecules)
  3. NK cell binds to infected cell, perforin punches holes in the cell membrane
  4. “granzyme” moves through the pores and induces infected cell to undergo apoptosis
148
Q

what is efferocytosis

A
  • a process where neutrophils consume apoptotic bodies
  • neutrophils dispose of apoptotic cell bodies along with the intruder microbes
  • inflammation is kept to a minimum
149
Q

what is the adaptive immune response

A
  • branch of the immune system that has memory, develops as the need arises
  • ## includes cell-mediated and humoral-mediated immunity (intertwined)
150
Q

cell-mediated vs humoral immunity

A

Cell-mediated = teams of T-cells work together to recognize antigens displayed on infected cells - target infections in the body CELLS
Humoral = antibodies (from B cells) directly target microbial invaders - target infections if the body’s HUMORS (fluid’s)

151
Q

how does adaptive immunity develop

A
  • immune system recognizes small pieces of a given antigen - EPITOPES
  • over a 3-4 day period following exposure to the invader the immune response develops
152
Q

how do epitopes develop

A
  1. phagocytosis of the bacteria/pathogen
  2. antigen is broken up into many epitopes (can have one or more epitopes)
  3. epitopes released from a cells as immunogenicity or haptens
  4. immunogenicity can generate an immune response
153
Q

what are haptens

A

small molecules that are too small to elect an immune response on its own, but when bound to a larger molecule can act as an antigen

154
Q

what is immunogenicity

A
  • the effectiveness by which an antigen elects an immune response
  • increasing immunogenicity = lipids, carbs, proteins
  • proteins are more 3D
155
Q

T cell development

A
  • education begins before birth
  • T cells are born from hematopoietic stem cells found in bone marrow
  • as they mature each will develop a unique T cell receptor which reacts to a different random epitope
  • the thymus gland is where T cells develop
156
Q

T cell education

A

T cells mature in the thymus gland before they can be released into the body, they are tested on…
- ability identify self-MHC peptides (positive selection)
- reactivity against self antigens in the thymus (negative selection)
If they fail these tests they are instantly killed so they don’t attack healthy cells in the body

157
Q

how do T cells of older adults get education?

A
  • most T cell education occurs just before or at the time of birth
  • reserves of educated T cells are maintained by the body and reproduce at a balanced rate
158
Q

2 types of “effector” T cells

A
  1. Cytotoxic T cells (CD8+)
    - seek and destroy cells presenting antigens
  2. Helper T cells (CD4+)
    - memorize databanks of antigens an alert B-cells if circulating antigen is detected
159
Q

memory and regulatory T cells

A
  1. memory TH cells
    - retain antigen affinity of the originally activated T cell
    - act as later effector cells during reinfection
    - overtime memory can get hazy, but can pass traits onto next generation
  2. T-reg cells
    - do not promote an immune response but help restore homeostasis after infection
    - lack of these is associated with chronic inflammation
160
Q

what are MHC proteins

A
  • proteins onto which infected cells or APCs place antigens for display to the immune system
    2 types…
    MHCI: display antigens on the surface of an infected cell, cytotoxic T cells come to kill the CELL
    MHCII: display antigens on the surface of APCs, helper T cells take further steps to neutralize infection. want ANTIGEN killed, not the cell
161
Q

initiation of cell-mediated (T cell) response to an antigen

A
  • APCs that have phagocytosed a pathogen travel to lymph nodes (secondary lymphoid organ) to display their captured antigens to T cells
  • the binding of antigen-loaded MHCI or MHCII to TCRs activated T cells and the response begins
  • T cells directly kill the infected host and may also produce cytokines that initiate macrophages to migrate
162
Q

how do helper T cells activate humoral immunity

A
  • helper T cells are the conduit between APCs and B cells
  • free floating antigens from the microbe bind to B cell receptors specific for an epitope
  • 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- then differentiated into a plasma cell to make antibodies
163
Q

B-cells can differentiate into…

A
  1. Plasma cells: make antibodies, short-lived
  2. memory B cells: speed up a subsequent immune response to the same invader, survive a decade or more
164
Q

RECAP: stages of the immune response

A
  • APCs engulf a pathogen and travel to the nearest lymph node - as they move they digest the pathogen and display its antigens on their surface
  • At the lymph node garrison the APCs activate T cells and free antigens activate 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
  • plasma cells and memory cells travel to the bone marrow
165
Q

how does antigen dose effect T and B cells

A
  • if the antigen 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 (anergy)
166
Q

“anatomy” of antibodies

A
  • has 4 polypeptide chains: 2 large heavy chains and 2 smaller light chains
  • small and large chain are bound by disulfide bonds
  • constant region (body) and variable region (head)
  • Fc region of the body reacts with complement or binds the surface of cells`
167
Q

what is the Fc region of an antibody

A
  • bottom of the antibody
  • reacts with complement OR binds to the surface of cells
168
Q

constant and variable regions of antibodies

A
  • constant regions are conserved aa sequences - 5 heavy chain and 2 light chain types
  • heavy chain defines the class: IgA, IgM, IgG, IgD, IgE
  • each class is common to a species (isotope)
169
Q

isotype vs allotype vs idiotype

A

isotype: defines the various heavy chains of a SPECIES
allotype: differences in the constant region shared by some but not all members of a species
idiotype: differences in the hypervariable region within an individual

170
Q

IgG antibody

A
  • simplest, smallest, most abundant antibody
  • monomer with 4 classes (IgG1-4)
  • binds and opsonizes microbes
  • binds and neutralizes viruses
  • activates the classical complement pathway
171
Q

IgA antibody

A
  • major secreted antibody of mucosal surfaces (sIgA found in tears, breast milk and on mucosal surfaces)
  • found as a dimer, linked by disulfide bonds to the J-chain protein
  • secretory piece is wrapped around both molecules during secretion
  • can bind 4 antigens
172
Q

IgM antibody

A
  • can be found as monomers on the surface of B cells (part of receptor)
  • most commonly found asthma pentamer held together by J-proteins - one IgM can bind 10 antigens
  • first antibody isotype detected during the course of infection
173
Q

IgD antibody

A
  • trace amounts in the blood
  • exists in monomeric form of the surface of B cells
  • does NOT bind complement
  • plays role in B cell activation but function not well understood
  • possible enhances mucosal homeostasis and immune surveillance by basophils and mast cells
174
Q

IgE antibody

A
  • trace amounts in blood
  • mostly found on the surfaces od mast cells and basophils which are loaded with inflammatory mediators
  • when 2 molecules of IgE on mast cells or basophils are cross-linked by antigen, cells degranulate and act quickly to amplify the immune response
  • primary role = amplify the body’s response to invaders
175
Q

what is an allergy

A
  • antigens which are harmless to most people are threats to some
  • anti-allergen IgE triggers release to chemicals such as histamine form mast cells, or leukotrienes from eosinophils
176
Q

the allergy response

A
  1. allergy-prone person first encounters the allergen (e.g. ragweed)
  2. large amounts of ragweed IgE is made
  3. anti-ragweed IgE attaches to mast cells
  4. on second encounter cross-linking of IgEof mast cells triggers a signal cascade causing release of chemicals such as histamine
  5. person suffers from sneezing, runny nose, watery eyes and itching
177
Q

what is anaphylaxis

A
  • very severe form of an allergy
  • excess histamine triggers smooth muscle contraction (e.g. contraction of lung smooth muscles interferes with breathing)
178
Q

excess histamine in allergies

A
  • weakens junctions between cells lining blood vessels
  • fluid is forced from the circulation into the tissues
  • the fluid contains histamine and the reaction spreads rapidly
179
Q

why does an epipen help neutralize allergies

A
  • epipen releases epinephrine to increase cAMP from cells
  • cAMP decreases degranulation of cells and strops histamine production immediately
180
Q

which antibody classes bind complement

A

IgG and IgM

181
Q

which antibody class is transmitted across the placenta

A

IgG

182
Q

the classical complement pathway and adaptive immunity

A
  • antibodies made as part of the adaptive immune response activate the classical pathway
  • C3 is the major player
183
Q

the lectin-mediated complement pathway

A
  • lectins are made in the liver and bind sugars in bacterial cells
  • allow complement proteins to bind and trigger the formation of C3 convertase, then the pathway is the same as the classical pathway
184
Q

why do we need 3 different complement pathways

A

3 pathways = 3 ways to recognize pathogens = minimized virulence of pathogen phase variation

185
Q

what are “shapeshifting” pathogens

A
  • virulence strategy is to change their antigens regularly to elude the immune system
  • new antigens are not recognized by antibodies and are thus invisible to cytotoxic T cells
186
Q

how does the gut microbiota fend off invaders while hosting a vast and complex ecosystem like the gut microbiota

A
  1. epithelial barriers are studded with T cells that have encountered antigens (inter epithelial lymphocytes are sensitive of pathogens)
  2. dendritic cells reach between epithelial cells to sample antigens from the microbiota
  3. M cells in peyer’s patches also sample antigens
187
Q

sIgA and the lumen of the gut

A
  • sIgA coats microbiota components in the gut that are considered to be threats
  • prevents bound microbes from penetrating the barrier
  • may promote colonization of certain important beneficial microbes allowing them to stick around and colonize
188
Q

positioning of TLRs and their responses

A
  • TLRs on epithelial side facing the gut lumen see many antigens
  • TLRs on the basal side of the layer see fewer antigens only from invasive pathogens
  • TLRs on basal side are much more reactive
  • many beneficial microbes have evolved to dampen TLR signalling
189
Q

what is immunologic specificity

A
  • the degree to which an antibody recognizes an antigen
  • can distinguish between similar-looking antigens
190
Q

earliest clues about immunospecificity came from…

A

small pox
- survivors of the disease did not get it again

191
Q

cross-protection: small pox example

A
  • inoculation of cowpox worked to protect against smallpox
192
Q

why is prevention of disease better than curing the disease

A
  • suffering an infection with a pathogen results in an immune response with innate driven protection
  • for nasty pathogens this comes with risk of high morbidity and sometimes mortality
  • also comes with risk of infecting others nearby
  • disease prevention comes without the risk of pathogen-mediated disease
193
Q

what is immunization

A
  • tricking the body into seeing a pathogen and raising an immune response without the risk of pathogen-mediated disease
  • vaccination is a type of immunization that works because of our adaptive immune response
194
Q

what are the 4 types of vaccination

A
  1. killed whole organisms
  2. live attenuated organisms
  3. subunit vaccines
  4. nucleic acid vaccines
195
Q

killed whole organisms - basic vaccination type

A
  • benefits: easy to produce, many antigens presented for robust response
  • drawbacks: complete inactivation is difficult
  • e.g. Salk vaccine for polio, HepA
  • the Cutter incident: some batches of the Salk vaccine were incorrectly tested and passed which contained live virus - caused many cases of paralysis
196
Q

live attenuated organisms - basic vaccination type

A
  • organisms are weakened before administration to give the immune system the upper hand
  • benefits: pathogen infection process is appropriate, many antigens presented to immune system
  • drawbacks: difficult to produce, contraindicated for those immunosuppresed
  • examples: BCG, sabin vaccine for polio
197
Q

subunit vaccines - basic vaccination type

A
  • selected, purified antigenic components of pathogens
  • benefits: easy to produce, no chance of infection
  • drawbacks: hard to find a protective antigen
  • come subunit vaccines contain subunits of antigens from multiple pathogens on the same backbone for efficiency
  • e.g. S. pneumonia capsular antigen, viral capsids from papilloma virus, toxoid vaccines
198
Q

nucleic acid vaccines - basic vaccination type

A
  • include mRNA vaccines and viral vector vaccines
  • mRNA vaccine contains mRNA that codes for specific antigen that is wrapped in a lipid layer and injected - briefly makes the target antigen to stimulate an immune response
  • benefits: easy to make, quick to get to market, no chance of infection
    drawbacks: cold chain distribution, poor public understanding
  • e.g. spikevax and cmirnaty (Covid)
199
Q

which vaccine type is good for variants

A

nucleic acid vaccines because can be developed fast

200
Q

why do we vaccinate early in childhood

A
  • passive immunity from mother protects child for first couple months after birth
  • after this period the child needs antibodies it can’t make yet so they are vaccinated
  • HepB is given right at birth because mother can easily pass it to child
  • most other vaccines are given just past 2 months
201
Q

why might we need repeated doses of a vaccine?

A
  1. boost response
  2. overcome antigenic changes (mutations)
  3. waning memory
202
Q

need for repeated vaccine dose - boost response

A
  • the first dose of a vaccine leads to early synthesis of IgM (bigger Ab) followed by IgG (more specific Ab)
  • the second “booster” dose results in a rapid response because memory B cells were formed during the response
  • the boost ensures sufficient antibodies with reactivity toward the antigen are circulating the body, protecting against reinfection
203
Q

need for repeated vaccine dose - overcoming antigenic changes

A
  • some pathogens change their antigens rapidly (variants)
  • a vaccine primes the body against an antigen that may be lost or changed
  • e.g. for covid and influenza we need s slightly different vaccine as soon as the virus mutates
204
Q

need for repeated vaccine dose - waning memory

A

memory T cells and memory B cells are not indefinite
- as they replicate over time they lose specificity and eventually become unprotective
- e.g. need a tetanus shot every 10 years

205
Q

which type of vaccination is usually superior to the others

A

live attenuated vaccine
- elects the proper response for the most protection

206
Q

Salk (dead) vs Sabin (live attenuated) polio vaccines

A
  • Salk vaccine elects an antibody response that is protective against paralysis but it does not elect the mucosal response
  • later a person can get mild form of disease through the fecal-oral route and pass on the infection to unvaccinated people
  • Sabin vaccine is more protective
207
Q

how is the covid 19 mRNA vaccine only partially protective

A
  • the vaccine is injected and the antibody response is protective against severe disease, but does not elect the typical mucosal response
  • a person can get a mild form of disease through natural infection and pass it on to others
208
Q

what is herd immunity

A

vaccinating a large part of the community effectively interrupts the transmission of the disease
- it protects immunocompromised people who cannot get vaccinated as they rely on others

209
Q

why does the concept of herd immunity not work for tetanus

A

tetanus is not spread from person to person

210
Q

contributions to the discovery of antibiotics

A

Ernst Duchesne: originally discovered penicillium molds
Alexander flemming: rediscovered penicillin and is credited for it
Howard Florey and Enrst Chain: credited with purification of penecillin

211
Q

Gerhard Domagk’s contribution to antibiotics

A
  • after infection by a pinprick, he injected his daughter with a dye called Prontosil
  • prontosil is not active on plates because it needs to be metabolized to sulfanilamide by the body
  • too much prontosil is toxic
212
Q

Prontosil and the development of sulfa drugs

A
  • prontosil is metabolized to sulfanilamide by the body
  • sulfa looks similar to PABA which is the pre-cursor for folic acid
  • humans cannot synthesize folic acid, but bacteria can
  • sulfanilamide replaces PABA to inhibit the enzyme that makes folic acid
  • this interrupts bacterial metabolism
213
Q

Selman Waksman’s contribution to antibiotics

A
  • screened 10000 strains of soil bacteria for antimicrobial activity
  • lead to his discovery of streptomycin
214
Q

selective toxicity of antibiotics

A
  • possible because let elements of microbial physiology are unique from eukaryotic cells
  • e.g. can target peptidoglycan in bacterial cell walls and the different units in their ribosomes
215
Q

bactericidal vs bacteriostatic antibiotics

A

bactericidal: kill the bacterium itself
bacteriostatic: prevents growth of the bacterium but does not kill it

216
Q

why are bacteriostatic antibiotics effective if they don’t kill the pathogen

A
  • they buy time for the immune system to gain the upper hand
217
Q

the term antibiotic is reversed for compounds that…

A

affect bacteria

218
Q

what does antibiotic effectiveness depend on

A
  • the organism being treated
  • the attainable tissue levels of the srug
  • the route of administration
219
Q

in vitro we can measure the _____ of an antibiotic against its target

A

minimum inhibitory concentration (MIC)

220
Q

what are common antibiotic targets in bacterial cells

A
  • cell wall synthesis
  • cell membrane integrity
  • DNA synthesis
  • RNA synthesis
  • Protein synthesis
  • metaboloism
221
Q

which antibiotics are cell wall inhibitors

A
  • penicillins
  • cephalosporins
  • vancomycin
  • bacitracin
  • monobactams
222
Q

which antibiotics are cell membrane inhibitors

A
  • polymyxins
  • daptomycin
  • gramicidin
223
Q

what is the specific component targeted by cell wall antibiotics

A

peptidoglycan

224
Q

how does Bacitracin work as a cell wall antibiotic

A
  • prevents bactoprenol from accepting new units of UDP-NAM
  • can’t get NAM from the cytosol to the cell wall
225
Q

how does Cycloserine work as a cell wall antibiotic

A
  • inhibits the 2 enzymes that form the precursor peptide of the NAM side-chain
  • can’t make the dipeptide
  • useful for treating tuberculosis
226
Q

which cell wall antibiotics inhibit peptide cross-linking

A

vancomycin, penicillin and cephalosporins

227
Q

how does vancomycin work as a cell wall antibiotic

A
  • binds to the D-Ala-D-Ala terminal end of the disaccharide and prevents binding of transglycosylases and transpeptidases
  • inhibits crosslinking of NAM molecules
228
Q

what are beta-lactam antibiotics (target cell wall)

A
  • derived from fungi
  • consist of a beta-lactam ring structure to which R groups can be added to
  • if a lactam ring is added to the cell wall, enzymes start to add R groups which do not work with the cell structure
  • cell wall loses rigidity and the cell will swell and die
229
Q

what are penicillin binding proteins

A

transpeptidase and transglycosylase - enzymes involved in cell wall building

230
Q

bacteria’s mechanism to beta-lactam antibiotic resistance

A
  1. inheritance of a gene that codes for a beta lactamase gene
  2. inheritance of a gene that codes for an altered penicillin-binding protein that does not bind the antibiotic (not as good as first mechanism)
231
Q

cephalosporin cell wall antibiotics - used in worst case scenarios

A
  • beta-lactam antibiotic which has been synthetically altered to combat the development of resistance
  • microbes adapt quick
  • only used to slow down the development of reisstance
232
Q

gramicidin - cell membrane antibiotic

A

a cyclic peptidase that inserts into the bacterial genome

233
Q

polymyxin - cell membrane antibiotic

A
  • binds to both the outer and inner membranes of G-bacteria
  • disrupts the inner membrane like a detergent
234
Q

which cell membrane antibiotics can only be used topically

A

gramicidin and polymyxin - because they have activity towards mammalian cell membranes

235
Q

daptomycin - cell membrane antibiotic

A
  • aggregates in G+ bacterial membranes to form channels
  • effective against MRSA
236
Q

examples of drugs that affect DNA synthesis

A
  1. sulfa drugs
  2. quinolones
  3. metronidazole
237
Q

Sulfa drugs - DNA synthesis antibiotics

A
  • interfere with nucleic acid synthesis by preventing synthesis of THF
  • selectively toxic to Bactria because they make their own folic acid and we do not
238
Q

quinolones - DNA synthesis antibiotics

A
  • target microbial topoisomerase which catalyzes changes in DNA topology to allow replication and transcription
  • not often used because they are toxic to mitochondria (because they used to be bacteria)
239
Q

metronidazole - DNA synthesis antibiotics

A
  • example of a pro-drug (needs to be converted to active form)
  • activated on reduction by microbial flavodoxin or ferrodoxin, found in ANAEROBIC bacteria
  • nicks DNA at random once activated
  • not effective against aerobic bacteria
240
Q

examples of RNA synthesis antibiotics

A
  1. rifampicin
  2. actinomycin D
    - only rifampicin is used clinically
241
Q

rifampicin - RNA synthesis antibiotic

A
  • binds to exit tunnel of bacterial RNA polymerase, blocking RNA from exiting
  • halts transcription
  • turns bodily secretions bright orange
242
Q

protein synthesis antibiotics overview

A
  • bind and interfere with the function of bacterial rRNA
  • bacterial ribosomes have unique properties
  • can target either the 30S or 50S subunit of the ribosome
243
Q

30S subunit antibiotics examples

A
  1. Aminoglycosides
  2. Tetracyclines
244
Q

aminoglycosides - 30S ribosome antibiotic

A

binds 16S ribosomal RNA (part of 30S ribosome) and cause translation misreading of mRNA
- results in peptides being jumbled or truncated

245
Q

tetracyclines - 30S ribosome antibiotic

A
  • bind to and distort the ribosomal A site
  • can interfere with bone development in fetuses and young children
246
Q

examples of 50S ribosome antibiotics

A
  1. Macrolides and lincosamides
  2. chloramphenicol
  3. Oxazolidinones
  4. Streptogramins
247
Q

Macrolides and lincosamides - 50S ribosome antibiotics

A

inhibit translocation of the growing peptide chain

248
Q

chloramphenicol - 50S ribosome antibiotics

A

inhibits peptidyltransferase activity
- can depress production of blood cells in the bone marrow in some people
- not used for a long time

249
Q

oxazolidinone - 50S ribosome antibiotics

A

binds to 23S rRNA component and prevents formation of the protein synthesis 70S initiation complex

250
Q

streptogramins - 50S ribosome antibiotics

A

types A and B that are used together, both bind to the peptidyltransferase site

251
Q

mupirocin - targeting aminoacyl tRNA synthetases

A
  • binds to bacterial enzymes that attach amino acids to the end of tRNA molecules, halting protein synthesis
  • used topically in creams to treat infections by G+ bacteria
  • cannot be used internally because it is rapidly degraded in the bloodstream
252
Q

when does antibiotic resistance become a problem

A
  • when we use high concentrations of antibiotics for long periods of time
  • this exerts selective pressure on bacteria to evolve
253
Q

what are the strategies bacteria uses for antibiotic resistance

A
  1. keep antibiotics out of the cell
  2. prevent antibiotics from binding their target
  3. dislodge an antibiotic bound to its target
254
Q

ABR strategy 1: keep antibiotics out of the cell

A
  • destroy the antibiotic before they can enter the cell (e.g. using beta-lactamases)
  • decrease membrane permeability by expressing narrower pores (e.g. fluoroquinolone resistance)
  • pump the antibiotic out of the cell using specific transporters (e.g. tetracycline resistance)
255
Q

ABR strategy 2: prevent antibiotics from binding their target

A
  • bacteria modify the target so that it no longer binds the antibiotic (e.g. shape of PBP or ribosomal proteins)
  • add modifying groups to the antibiotic so that the antibiotic is inactivated (e.g. amino glycoside resistance through production of enzymes that change antibiotic structure)
256
Q

ABR strategy 3: dislodge an antibiotic bound to its target

A
  • ribosome protection or rescue - some G+ organisms make proteins that bind to ribosomes and dislodge or prevent the binding of antibiotics that bind near the peptidyltransferase site
257
Q

resistance may be acquired…

A
  1. intrinsically: natural resistance (e.g. G-bacteria and vancomycin)
  2. through genetic mutations: gene encoding the antibiotic target acquired a mutation making it drug resistant
  3. through receipt of an antibiotic resistance gene: a resistant gene is carried on a mobile genetic element such as a plasmid, transposon or integron
258
Q

ways that we have adopted taking antibiotics inappropriately

A
  • used in enormous quantities
  • prescribed inappropriately
  • not taken appropriatly
259
Q

antibiotic stewardship

A
  • should never be used to that viral infections
  • do not use if the patients microbiome includes strains that are already resistant
  • know which resistant strains are prevalent
  • consider how long they need to be taken for
  • use narrow-spectrum
260
Q

what is SARS-CoV-2

A
  • severe acute respiratory syndrome Coronavirus-2
  • an enveloped, positive strand RNA virus in the family coronaviridae (Group IV)
  • the 7th corona virus found to infect humans
261
Q

important proteins on SARS-CoV-2

A

envelope protein: interacts with M protein to form the viral envelope
nucleocapsid protein: binds to RNA genome to make helical ribonucleoprotein
membrane protein: determines shape of viral envelope
spike protein: binds to host cell receptors to facilitate viral entry

262
Q

How does SARS-CoV-2 replicate itself in the cells of those infected

A
  1. spike protein on the virion binds to ACE2, TMPRSS2 helps the vision enter
  2. the virion releases its RNA
  3. some RNA is translated in to proteins by the cell’s machinery
  4. some of these proteins form a replication complex to make more RNA
  5. proteins and RNA are assembled into a new virion in the golgi and released
263
Q

what are spike proteins

A
  • proteins found on viruses that initiate infection by binding to ACE2 on the host membrane
264
Q

what are harmful effects of angiotensin II

A
  • modulates blood pressure through contraction of vascular smooth muscle
  • influences sodium resorption in the kidney
  • involved in inflammation, blood clotting, mitochondrial function
265
Q

what happens when Spike protein of SARS-CoV-2 binds ACE2

A
  • it disrupts the equilibrium between ACE2 and ANGII which causes increased damage to cells
  • ACE2 cannot break ANGII so it exerts harmful effects such as out of control BP and causing organ damage
266
Q

ACE2 levels are higher in cells of those that…

A

have hypertension, cardio vascular disease, diabetes and are older
- renders then high risk of sever Covid-19

267
Q

a key factor in determining severity of damage in COVID-19 patients is…

A

the amount of angiotensin they are producing

268
Q

the INNATE immune response to SARS-CoV-2

A
  • virus outside host is recognized by TLRs: TLR2 recognizes envelope protein, other TLRs activated by components of the virus
  • internalized viruses are recognized by internal PRRs
  • interferons are quickly released to warn cells
  • antigens are displayed on MHCI for targeting g by cellular immune response
  • more cytokines released in the process
269
Q

the ADAPTIVE immune response to SARS-CoV-2

A
  • helper and cytotoxic T cells are the first APCs to get to the lymph node
  • B cells get activated and IgM, IgA and IgG specific to viral epitopes are made after a lag period
  • after covid infection B cells are activated but the selection process is not complete properly and protection does not last long
  • after vaccination B cell activation is more robust and complete to antigen used in immunization
  • after disease is cleared memory T cells are sent ot the lung
270
Q

disease outcomes depend on many factors…

A
  1. immunosenescence
  2. co-morbidities
  3. viral exposure
  4. extent of cytokine storm and collateral damage
  5. presence of neutralizing antibodies specific to the infection strain
271
Q

serious disease and death from covid result when…

A

lungs become damaged by actions of the immune response and are unable to absorb oxygen

272
Q

antiviral treatment of covid-19

A
  • Paxlovid is oral delivered, acts as a protease inhibitor
  • Veklury is injected into the bloodstream and inhibits viral RNA polymerase
  • both medications cause severe side effects
  • must be administrated within a few days of symptoms
273
Q

why was ivermectin thought to have possible protection against covid

A
  • it is an anti-parasitic drug known to inhale interferon expression and inhibit viral replication
274
Q

what is enterohemorrhagic E. coli (EHEC)

A
  • causes serious diarrheic infection that can lead to kidney destruction (hemolytic ureic syndrome - HUS)
  • E.coli O157 [NM], NM = non-motor (no flagella)
275
Q

EHEC is a zoonotic disease…

A
  • associated with cattle and other ruminants
  • lives as a commensal in the ruminant gut
  • transmitted via contaminated meat or vegetables
276
Q

symptoms of EHEC

A

bloody diarrhea, weakness, HUS

277
Q

how does EHEC infect plants and animals - mechanism

A
  • possess a type 3 secretion system, acts as an injectisome
  • allows bacteria to directly inject its proteins into cells
  • injects a number of effector proteins into host
  • first protein = Tir - inserts itself into the host cell membrane and becomes the receptor for the bacterial adhesin
  • bacteria can make tight conditions with host
  • Tir recruits actin monomers to its cytosolic side, which form onto polymers and forces up the cell membrane
  • bacteria sits on a “pedestal”
278
Q

EHEC and Shiga toxin

A
  • shiga toxin is an exotoxin secreted by EHEC
  • shiga toxin binds to 28S rRNA of 50S subunit
  • this blocks protein production, initiates apoptosis and signals inflammation through cytokines
  • toxin has tropism for endothelial cells of vascular system and kidneys
  • causes small blood vessels to become damages, worst effects seen in kidneys
279
Q

treatment for EHEC and HUS

A
  • supportive treatment includes hospitalization, dialysis and hydration
  • antitoxins are in development
  • kidney damage can be permanent
  • antibiotics should not be used because it would kill E. coli and release shiga toxin into the environment (BAD)
280
Q

prevention of EHEC

A
  • very acid tolerant but poorly heat tolerant
  • et fully cooked meat and wash vegetables
281
Q
A

MICR 2420 (3 decks)

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