Bio 220 Final New Material

Some hypotheses about when and how life appeared on Earth

--Prebiotic Soup Model suggests that life began in a pond or ocean as a result of the combination of chemicals from the atmosphere and some form of energy to make amino acids, the building blocks of proteins, which would then evolve into all species. --RNA World Model: proposes that earlier life forms may have used RNA alone for the storage of genetic material.

how the virus knows where it is

-2 component signal transduction. --detect Mg, Fe concentration, pH (both low in host cell vacuole). --low in other places bc we don't want pathogens to access them and use them to grow. -quorum sensing -detects exotoxins made by other cells, and delays toxin synthesis until many bacteria are present.

regulation of calvin cycle

-4 genes involved with carbon fixation into cell -low affinity CO2 transporter, high affinity CO2 transporter (inducible), inducible high affinity HCO3- (uses Na+ as symporter) and inducible high affinity HCO3- (uses ATP). -under regular air, there's not much expression of genes going on because there's CO2 present and it's easy for cell to bring those in. -if CO2 is removed from atmosphere, copies of the inducible high affinity HCO3- go through the roof because there's lacking of CO2, so they stop trying to acquire CO2 to try to acquire HCO3- to fix their CO2.

how antibodies are made

-B cell engulfs microbe, becomes activated and waits until activated by T cell, which has a receptor that binds to B cell and activates it, B cells then turn into plasma cells and secrete antibodies. -dual interaction needed for regulation --if not present, can cause autoimmune diseases if they aren't checked, bc they'll start attacking our cells.

Calvin Cycle Overview

-CO2 molecules are incorporated with ribulose-5-phosphate -for every 3 cycles of the pathway, you will get production of 1 G3P molecule (towards biosynthesis), 6 NADPH, and 9 ATP -18 carbons, so 3 6C molecules, which get broken down into 6 3C molecules. These get converted into 6 G3P molecules, one of which gets used for biosynthesis, which puts us back to 5 G3P molecules or 15C. -6 cycles needed for 1 glucose molecule.

epitope

-IS doesn't recognize entire microbe but small pieces of it. -each small segment of antigen that elicits immune response is called epitope or antigenic determinant. -these will fit perfectly into antibodies.

Hypersensitivity and Autoimmunity

-IS may overreact to foreign antigens or against itself. -allergic hypersensitivity reactions and antigen causing reaction is allergen. autoimmunity is inability to distinguish between self-antigens and foreign antigens. --IS reacts to host cells (autoreactive B cells escape clonal detection; T cells can kill host cells that make self-protein closely resembling foreign pathogen) --i.e. lupus, MS, Type I Diabetes.

antibody structure

-Y shaped structure made up of four polypeptides --two large heavy chains and 2 smaller light chains connected by disulfide bonds. -antibody has constant regions: highly conserved aa (denoted CH and CL for heavy and light chains) and variable regions: highly different aa (denoted VH and VL, form antigen binding site).

functions of antibodies

-agglutination: binds invaders together, which enhances phagocytosis -opsonization: coating antigen with antibody enhances phagocytosis. -neutralization: blocks adhesion of bacteria and viruses to mucosa.

Fever

-also helps immune system - >100.4ºF -molecules that induce fever are called pyrogens. -helps microbes to not grow as well outside of its optimum temperature, which helps to decrease growth rate and allow immune system to catch up.

Biosynthesis

-anabolism -requires essential elements, reduction by reducing agents such as NADPH, and energy by coupling reactions to ATP hydrolysis, NADPH oxidation, or ion flow down transmembrane concentration gradient. -enzymes couple synthetic reactions to reactions releasing energy. -cells regulate enzymes at key steps to control direction of pathway (may be 2 enzymes that only go in one direction for a key step).

containment breaches and disrupted balance

-as long as microbiotia composition is balanced and stays where it belongs, everything is okay. -the accidental penetration of certain organisms beyond a site of colonization can cause infections. (Bacteriodes fragilis = anaerobic gas gangrene). -emotional stress, change in diet, or antibiotic therapy can alter the microbiome balance. -resultant dysbiosis can lead to poor digestion or inflammatory bowel disease.

oral and nasal cavities

-at birth, infant's mouth is colonizes with nonpathogenic Neisseria (G-), streptococcus, lactobacillus (G+). -teeth emerging: Prevotella; Fusobacterium (between gums and teeth) and Streptococcus mutans (enamel). --community shifts because new surfaces arise for colonization. --crevices and spaces are new anaerobic areas between teeth where they can grow. -Nasopharynx and oropharynx are populated by S. aureus and S. epidermis and harmless Streptococci. -can cause disease. --dental procedures will often cause organisms to enter the bloodstream, producing what is caused bacteremia (can lead to subacute bacterial endocarditis).

biofilms and infections

-bacteria can attach to surfaces in bulk, forming a biofilm. -play important role in chronic infections by enabling persistent adherence and resistance to bacterial host defenses and antimicrobial agents.

Roles of T cells

-cell mediated response (pathogen has entered cells, cancer) -T-cells get activated when presented with antigen from APCs (differentiate into helper T cells or effector T cells that release cytokines.)

Respiratory tract

-ciliated mucous lining of trachea, bronchi, and bronchioles makes up the mucociliary escalator (constant beating of cilia that move mucous and bacteria out). -myth: lungs and trachea are usually sterile.

Genomic analysis

-comparing genome sequences, within and between genomes, enables us to track how organisms adapted in the past. -gene duplications provide the opportunity to evolve paralogous genes, or paralogs, with different functions. -degenerative (reductive) evolution occurs when un-needed genes are lost from the genome. ---these organisms save energy by avoiding their replication and expression.

MHC

-consist of membrane proteins with variable regions that can bind antigens. -differ between species and among individuals within species. (help determine whether given antigen is recognized as self or non-self). -Class I MHC: found on all nucleated cells. -Class II MHC: found only on professional antigen presenting cells (dendritic cells, macrophages, B cells). cytotoxic looks for MHC I, helper T cells (in lymph nodes) look for MHC II on phagocytes.

Rubisco

-consists of small and large subunits. --function of small subunit is unknown and some organisms are missing it and can still function. -catalyzes the condensation of CO2 to ribulose 1,5-bisphosphate and the splitting of the unstable 6C intermediate into 2 3C PGA molecules. (In Calvin Cycle) -many organisms contain the rubisco complex within polyhedral structures called carboxysomes. the carboxysome takes up bicarbonate which is then immediately converted to CO2 by carbonic anhydrase. The CO2 is then fixed by rubisco.

molecular regulation of N2 fixation

-costs substantial energy, and therefore the process is highly regulated. -Oxygen and NH4+ availability regulate expression of the nif genes (if both/either are in abundance, there's no need to perform nitrogen fixation), which encode nitrogenase and other nitrogen-fixation proteins. -regulators of nif genes is mediated by several molecular regulators including: nitrogen starvation sigma factor, and NtrB-BtrC two component signal transduction system.

Skin

-difficult to colonize (dry, salty, acidic, protective oils). -10^12 microbes in moist areas (scalp, ears, armpits, genitals) -Mostly Gram + (more resistant to salt and dryness) --good at degrading skin oils, they can tolerate low pH and high salt. --inflames sebaceous glands, causes acne.

what distinguishes adaptive immunity from innate immunity?

-diversity of response (lots of different approaches) -specificity (ability to target single molecule type). -memory (remember pathogens it has encountered previously).

B Cells differentiate into Plasma Cells by Clonal Selection

-each B cell circulating throughout body or in lymphoid organ is programmed to synthesize antibody that reacts with single epitope. -clonal selection: an invading antigen will inadvertently select which B cell clone will proliferate to large numbers. (only this one type of B cell will proliferate). -when B cell contacts its cognate antigen, it is stimulated to proliferate and differentiate into plasma cells (which secrete antibodies) and memory cells.

genetics of antibody production

-each human can synthesize 10^11 antibodies. only 10^8 antigens -each person possess only 1,000 genes involved in antibody formation. -Susumu Tonegawa discovered that antibody genes can move and rearrange themselves within genome of differentiating cell. (also random mutations while replicating, which allows for differences in variable regions of antibodies)

Mechanism of N2 Fixation

-energy-intensive. -N2 + 8H+ + 8e- + 16 ATP --> 2 NH3 + H2 + 16 ADP + 16 Pi. -16 ATP + 12 ATP equivalents = appx 28 ATPs are consumed per N2 fixed. (makes 2 NH3 molecules) (heavily regulated for energy conservation). -nitrogen fixation is catalyzed by the enzyme nitrogenase. -requires four reduction cycles through nitrogenase N2 -> NH=NH -> H2N-NH2 -> 2 NH3 -each step requires ATP and e-.

Strongly selective environments

-environments under intensive selective pressure, i.e.: antibiotic exposure in hospitals reveal rapid evolution. --MRSA -the "fittest" trait depends on environment in which selection occurs. -rapid adaptive evolution may be enhanced by disabling regulation.

toxins subvert to host functions

-exotoxins: proteins produced by various types of bacteria, kill host cells and unlock nutrients. --lysing cells opens up lots of nutrients for uptake. --can damage cellular membrane/matrices, inhibit protein synthesis, and activate second messenger pathways. -endotoxins: part of LPS of G- bacteria, can hyperactivate host IS to harmful levels.

neutrophils

-first responder at site of infection or trauma, represents 50-60% of all leukocytes. phagocytizing cells -releases toxins that kill or inhibit bacteria and fungi and recruits other immune cells to site of infection. -casting NETs (neutrophil extracellular trap): polymeric sticky web that traps them and allows for phagocytosis by other WBCs.

Koch's postulates

-founded chain of infection. ONLY APPLY TO BACTERIA 1. suspected pathogen must be present in all cases of disease and is absent from all healthy animals. 2. suspected pathogen must be grown in pure culture. 3. cells from pure culture of suspected pathogen must cause disease in healthy animal. 4. suspected pathogen must be re-isolated and shown to be same as original. -to prove a particular bacterium caused a specific disease, pure culture of microorganisms were needed. -aren't 100% foolproof (can't be used on unculturable organisms, viruses, variability in host receptor sites where the host may not be infected)

Phylogeny

-full description of branching divergence for a species. -clades are branching groups of related organisms, that share a common ancestor not shared by any organism outside the clade. Each monophyletic group then branches into smaller groups and ultimately species.

Horizontal and vertical gene transfer

-horizontal gene transfer: acquisition of a piece of DNA from another cell. -vertical gene transfer: transmission of an entire genome from parent to offspring. -among prokaryotes, DNA is transferred horizontally by plasmids, transposable elements, and bacteriophages (sometimes takes pieces of host DNA when replicating). ----evidence of transfer is a DNA sequence whose GC/AT ratio differs from rest of genome.

human microbiome

-human bodies carry 10x more microbes than human cells. this makes up the human microbiome. -microbiome helps us as it trains immune system to recognize what is foreign and what belongs. -can also prevent establishment of pathogens on body by using up resources and crowding out pathogens. -also produce compounds we aren't able to synthesize ourselves (B12--comes from microbes in gut). -environmental stresses are different in each location on human body, so microbes associated with those environments must adapt to that environment, which diversifies what is present in each location.

hygiene hypothesis

-human microbiota were shaped by intimate contact with natural environments, but now we are mainly indoors and our use of soaps, antibiotics, and disinfectants has restricted our access to microbes. -microbiota appear less diverse now, which can attribute to inflammatory diseases. -attributes to autoimmune disorders as IS isn't being trained properly. -kids that grow on farms have way fewer allergies than kids that are raised in the city.

reverse TCA cycle

-in some anaerobic bacteria and archaea, the entire TCA cycle functions in "reverse" --this allows the reduction of CO2 to regenerate acetyl-CoA and build sugars. -TCA is in cellular respiration

Infection cycles

-infection cycle is the route an organism takes from one individual to another. -horizontal transmission: from one member of species to another. --fomites: inanimate objects. --vectors: animals -vertical transmission: from parent to child. -accidental transmission: a host who is not part of normal infectious cycle unintentionally encounters that cycle. (i.e. West Nile Virus).

vasoactive factors and cytokines initiate extravasation

-infection releases microbes to tissue. -resident macrophages phagocytize bacteria --release vasoactive factors -> vasodilation -> slowed blood flow -> increase in blood vol -> escape of plasma into tissues -> swelling, redness, heat! -upon binding cytokines, capillary cells express selectins. --cytokines are small proteins that regulate immune response. -additional macrophages extravasate (squeeze between capillary cells and attack bacteria).

Acute Inflammatory Response

-inflammation is critical innate defense -redness, swelling, heat, pain, altered function at affected site. -microbes are introduced, and macrophages gobble up bacteria, and release cytokines. -cytokines help with vasoactive factors, and attract more WBCs, and once infection is cleared, the WBCs and cytokines can work towards healing area.

Immune System

-integrated system of organs, tissues, cells, and cell products. -differentiates self from non-self and neutralizes potentially pathogenic organisms or substances. -it is capable of responding to nearly any foreign molecular structure. -Innate immunity: barriers to infection, nonspecific responses to destroy invading cells, and present at birth. -Adaptive immunity: reaction to specific antigens, will retain memory of those antigens, faster response if exposed a second time.

natural killer cells

-kills tumor cells and virus infected cells -can detect cancer cells through proteins.

commensal microbes benefit the human host.

-make vitamins and digest food -prevent colonization by pathogens -promote host tissue development -we maintain our gut microbiome by secreting complex carbohydrates maintaining environment conducive for our microbiomes to thrive. -microbes also get a place to stay and survive (various niches)

pili and adhesions

-many bacteria typically attach to host cells by pili (fimbriae). (adhesin) -bacteria also carry afimbriate adhesins that mediate binding to host tissues. -after adhesion, can form biofilm.

deploying toxins and effectors

-many protein secretory systems evolved from other cellular structures that serve fundamental cellular functions. -type IV pilus biogenesis -flagellar synthesis -conjugation.

surviving within host

-many virulence factors help microbe escape or resist innate immune mechanisms. -others are dedicated to stealth

virulence

-measure of degree or severity of disease. -measured via the infectious dose and/or lethal dose. -LD50 is number of organisms you must infect the host with in order to kill 1/2 population. --smaller LD50 is more virulent (Agent 1).

pathogen

-microbial agent of disease. -ectoparasite: lives on surface of host. -endoparasite: lives inside host body. -infection occurs when pathogen or parasite enters or begins to grow on host.

oxygen problematic to nitrogen fixation

-needs to occur in a reducing environment (anaerobic). strategies used to deal with this: ---protective proteins. ---temporal separation of photosynthesis. ---specialized cells: heterocysts.

nitrogen assimilation

-nitrogen gas is fixed into ammonium ion only by some species of bacteria and archaea. -aquatic cyanobacteria develop special cells called heterocysts to fix N2. Photosynthesis is turned off to maintain anaerobic conditions. ---don't conduct photosynthesis when doing N2 fixation because O2 kills enzyme.

microbial evasion of adaptive immunity

-numerous viral and bacterial pathogens have developed effective means for avoiding the adaptive immune response. --many viruses produce proteins that down-regulate production of MHC I on infected cell surfaces. (less MHC I means harder for T cell to find it. they can't block them all together because T cells would see that there's no MHC and would think the cell was unhealthy and destroy it as well). -H. pylori expresses proteins that trigger apoptosis of T cells.

obesity and dysbiosis

-obesity involves complex, puzzle-like interactions among genes, diet, and long-term imbalance between energy intake and expenditure. -the studies showing the connections use gnotobiotic animals (germ-free or colonized by a known set of microbes). -Jeffrey Gordon demonstrated that obesity in humans is clearly linked to their microbiomes. (study involved transplantation of microbiomes from monozygotic human twins into germ-free mice). -can influence obesity in two major ways: harvesting of energy from ingested food, and triggering of intestinal inflammation. -metabolic dexterity of intestinal microbes allows them to digest many foods we can't (microbes produce SCFAs that our cells use and ratios of them influence obesity.)

Role of B cells

-originally discovered in Bursa organ in birds -critical to humoral response -sense antigens on the fluid portion of blood (i.e. circulating virus or bacterium not within cells). -differentiates into memory and effector cells. --plasma cells produce antigen targeting antibody

virulence factors

-pathogens must: enter host, avoid normal host defenses, multiply and eventually be transmitted to a new susceptible host, produce disease. -pathogens can be distinguished from their avirulent counterparts by the presence of virulence factors that help accomplish these goals.

Defining a species

-phylogeny (based on DNA relatedness) -ecology (based on shared traits and ecological niche) there is three criteria: ---SSU rRNA > 95% for same genus (16S for prokaryotes, 18S for eukaryotes). --->97% for same species. ---Average nucleotide identity (ANI) of orthologs > 95%.

primary and opportunistic pathogens

-primary: cause disease in healthy hosts. (ex. Shigella flexneri). -opportunistic: cause disease only in immunocompromised patients. -pathogenicity refers to organism's ability to cause disease. (defined in terms of how easily an organism causes disease (infectivity) and how severe that disease is (virulence)).

Divergence through mutation and natural selection

-random mutations: occurs during replication, sometimes horrible, sometimes beneficial. This entirely depends on how critical the protein is and the location on spot of DNA and what it codes for. -natural selection and adaptation: favors organisms that produce more offspring. these are advantages formed from mutation that allows them to have more fitness. -reductive (degenerative) evolution: loss or mutation of DNA encoding unselected traits. this will occur when the environment is very stable to where some genes aren't necessary. this is apparent in parasites as they rely on the host.

microbe acquisition

-recent evidence suggests that microbiome begins to develop before birth. -C-section babies are born sterile and their microbiome looks similar to hospital, natural babies have mother's microbiome. -young babies have microbiomes more diverse than adults, by the time they are 3 diversity assumes adult composition. -mother's breastmilk contains enzymes that can't be broken down by humans but by microbes, which encourages growth of microbiome.

Adaptive evolution

-requires natural selection -evidence for this evolution: genome analysis, strongly selective environments, experimental evolution

Chronic Inflammation

-results from persistent presence of foreign object, which causes permanent tissue damage. -causes: pathogens that resist host defense, nonliving irritant materials. -the body walls off site in granuloma (deposits fibroconnective tissue around lesion). --causes damage to own cells

diverse pathways in carbon fixation

-reverse TCA cycle -acetyl-CoA pathway -3-hydroxylpropionate cycle

Complement

-series of 20 proteins in blood that complement the kill effect in blood. -inserts pores into microbial membrane. -some complement proteins are valuable for opsonization. --flagging cell for destruction. -discovered as the proteins are heat labeled, so when the blood was heated it lost its ability.

T Cells

-serve as link between humoral and cell-mediated immunity. -they develop into thymus and contain surface antigens different from those of B cells. -Helper T cells: display surface antigen CD4 and assist activation of B cells and other T cells -Cytotoxic T cells: display surface antigen CD8, and destroy bacteria and infected host cells.

lymphoid organs

-tissues of IS where great majority of lymphocytes are found are classified as primary or secondary lymphoid organs or tissues, depending on their function. -primary: where lymphocytes mature (hematopoiesis). ---bone marrow or thymus (T cells in thymus, B cells in bone marrow). -secondary: where mature lymphocytes encounter antigens. ---lymph nodes (filter antigens in lymph) ---spleen (filter antigens in blood) ---tonsils and adenoids ---appendix ---peyer's patches

type III secretion

-use a molecular syringe to inject proteins from the bacterial cytoplasm directly into host cell. (similar to flagellum). -allows to invade and become intracellular parasite. -causes inflammation. -genes usually located on pathogenicity island -found in Salmonella, Yersinia, and Shigella

acetyl-CoA pathway

-used by anaerobic soil bacteria, autotrophic sulfate reducers, and methanogens. -two CO2 molecules are condensed through converging pathways to form acetyl-CoA -reducing agent is H2 instead of NADPH.

Stomach

-very high acidity (few microbes survive i.e. helicobacter pylori which survives at pH 1, burrows into protective mucous, and causes gastric ulcers). -decreased stomach acidity: hypochlorydia. --caused by malnourishment (pH isn't as low as a healthy individual). --vibrio cholerae survives stomach passage (establishes infection in less acidic intestine).

pathogenicity islands

-virulence genes can be found on these in the chromosome, on plasmids, or even on phage genomes. -contain clusters of virulence genes with specific functions. -originally inherited through horizontal transmission (have GC content different from rest of genome, often flanked by phage or plasmid genes as they originated from viruses)

What it takes to be successful pathogen

1. colonize (get in) (usually through adhesion) 2. evade IS (don't die too soon) 3. grow, obtain nutrients 4. disseminate within host and to new host. 5. produce disease.

genomes contain two kinds of genomes: 1. informational genes 2. operational genes

1. information genes: encode products essential for transcription and translation. they interact with many cellular components --tend to be transferred vertically. (another reason why 16S is used because it's transferred vertically.) 2. operational genes: encode products that govern metabolism, stress response, and pathogenicity. these function with relative independence. --more likely to be transferred horizontally.

Intestine

10^11-10^13 bacteria/gm of feces (1 mL H2O = 10^6 bacteria). -ratio of 1,000 anaerobes: 1 facultative organism -small amount of O2 diffuses from intestinal wall into lumen is immediately consumed by facultative bacteria like E. coli -infant intestines are initially colonized by large numbers of E. coli that quickly generate a reducing environment, which supports growth of strict anaerobic species. -some 200 bacterial species and few methanogenic archaea comprise intestinal microbiome. -makeup of gut microbiome within single individual is relatively constant but still varies over time. (based on diet and health).

Isotope ratios

Also a biosignature. An isotope ratio provides biosignature with quantitative evidence, if the ratio between certain isotopes of a given element is altered by biological activity. Microbes fix 12CO2 more readily than 13CO2. Thus, limestone depleted of 13C must have come from living cells. -Some enzymes are so specific they differentiate isotopes, for example, photosynthetic enzymes use 12C for CO2 this is called enzyme fractionation. The ratio of 12C/13C can be compared with abiotic sources of same type of rock. --Advantages: Isotope ratios are a highly reproducible physical measurement. Isotope ratios generated by key biochemical reactions can calibrate the time lines of phylogenetic trees. --Limitations: We can't prove absolutely that no abiotic processes could generate a given isotope ratio. Isotope ratios tell us nothing about the shape of early cells or how they evolved.

Which of the following is true of rRNA sequences?

Certain regions of rRNAs are highly conserved among organisms. --Since certain regions of rRNA are highly conserved among organisms, PCR primers can be designed against these regions to amplify rRNAs from different organisms. The sequences in between the primers will differ, allowing rRNA sequences to be used to construct phylogenetic trees.

Which of the following was NOT a prerequisite for the formation of life on Earth?

Diatomic oxygen

Herd-immunity reduces risk for all but which of the following kinds of disease?

Diseases that do not require person to person contact --Herd immunity reduced the risk of transmission from an infected individual to a susceptible one as there are fewer susceptible individuals present, but this only applies if the disease is spread through person to person contact. This can be direct where there must be an exchange of fluids or touch or through indirect means, including accidental transmission. Other diseases caused by means that do not require an infected person to be involved are not protected against by herd immunity.

Requirements for life on Earth

Essential elements were required to compose organic molecules, continual source of energy from the Sun, and temperature needed to be low enough to allow for the formation of liquid water as the early Earth was too hot for water to maintain itself on Earth's surface.

Oxidation states

Evidence for O2 in the biosphere comes from oxidation states of minerals, particular those creating iron. Iron in anaerobic is Fe2+, which is soluble in water. In the presence of diatomic oxygen, it is oxidized to Fe3+. Iron (III) is insoluble in water, which is what makes rust red. Because the transition to a fully aerobic planet was a long transition, there are layers of rock formation where the rock is black as it was anaerobic, and there are layers of rock where the iron is red as it was aerobic and therefore iron (III). These layers are called banded rock formations. A theory by Dianne Newman is that as there was fluctuating levels of O2, the microbes used up all the the oxygen, as Fe2+ is a source of electrons that can be used in metabolism, and therefore she believes the microbes are responsible for precipitating out the red portions of iron oxide. --Advantages: oxidized metals offer evidence of microbial processes even in highly deformed rock. --Limitations: it is hard to rule out abiotic causes of oxidation. Even if the oxidation was biogenic, it doesn't reveal the kind of metabolism.

Biosignatures

Evidence for life in the geological record, which is chemical evidence of biological processes. There have been biosignatures found even earlier than the oldest fossils. Certain organic molecules found in sedimentary rock are known to be formed only by certain microbes. These molecules are used as biosignatures. --Advantages: Biosignatures such as hopanoids are complex molecules specific to bacteria. Hopanoid is a molecule similar to cholesterol that is produced/used by bacteria. It's very stable, so it can survive in environment for a very long time. This process could have been occurring while rock was forming. --Limitations: A biosignature thought specific to one kind of organism may be discovered in others. In the oldest rocks, organic biosignatures are eliminated by metamorphic processes. (Heating in the metamorphic process would destroy hopanoid).

Which of the following is an example of vertical transmission?

Insects pass the yellow fever virus to their offspring in their eggs. --In vertical transmission, progeny are born with the pathogen that they inherited from their parents; the pathogen is passed down (vertically) from one generation to the next. All the other examples listed are horizontal transmission; the pathogen is being transmitted laterally from one organism to another.

Which of the following is NOT a mechanism among the different ones microbes have developed to evade the adaptive immune system?

Isotype switching --Isotype switching occurs in B cells when they receive cytokine signals from helper T cells. Various pathogens down-regulate MHC production in a variety of ways to limit antigen presentation, some can trigger apoptosis of T cells to reduce cytokine production, and some reduce the immune response by inducing production of anti-inflammatory cytokines.

Which of the following is evidence that a pathogenicity island was initially acquired by horizontal transfer?

It has a GC percentage different from the rest of the genome. --A GC content different from the rest of the genome is indicative of horizontal transfer. Passage of genomic islands to daughter bacteria during cell division is an example of vertical transmission. Containing genes for core biological processes does not indicate horizontal transfer.

Virulence is measured by __________, or the dose needed to __________ of hosts.

LD50; kill 50% --LD50 measures how much bacteria or virus is needed to kill 50% of hosts if the microbe can cause death and ID50 measures how much is needed to cause symptoms in 50% of hosts if the microbe does not cause death.

Which of the following is NOT an exotoxin?

LPS -RTX toxin that depolymerizes actin of the cytoskeleton, Hemolytic alpha toxin, and shiga toxin are all exotoxins.

Which cell surface protein is expressed in all nucleated cells?

MHC I --MHC I is present in all nucleated cells, but CD4, CD8, and MHC II are not. CD4 is on helper T cells, CD8 is on cytotoxic T cells, and MHC II is found on certain antigen-presenting cells.

MHC I

MHC I presents intracellular antigens -microbial proteins made in host cytoplasm are degraded -peptides are imported into ER and loaded onto MHC I molecules.

Microfossils

Most convincing evidence for early microbial life, due to the ability to be seen. The earliest microfossils accepted as biogenic are dated 2 billion years ago. Fossils dated 1.2 billion years ago contain larger fossil cells comparable to those of modern eukaryotes. Early microbial cells decayed, and their form was filled in by calcium carbonate or silica. The size and shape of microfossils resemble those of modern cells. --Advantages: Microfossils are visible and measurable under a microscope, offering direct evidence of cellular form. --Limitations: rock formations require subjective interpretation. Some formations may result from abiotic processes.

Rank the following terms from largest size to smallest size—antigen, pathogen, epitope.

Pathogen, antigen, epitope --A pathogen can contain many antigens and each antigen can contain several different epitopes.

Why are vaccines administered to children in multiple doses?

Some diseases are most devastating during childhood and multiple doses will produce long-lasting robust immunity. --Diseases can be more profound in children as their immune system is not fully developed though it is functioning. Some diseases do present more mildly in children but vaccines generally do not cause disease. Compliance is required to enter public schools, though exemptions can be made, but that is not the primary reason to vaccinate children. -number of times is determined on what will create strongest memory of that pathogen.

Which of the following is correct regarding stromatolites?

Stromatolites are the oldest forms of life for which there is clear fossil evidence. --Microbial mats of present-day stromatolites resemble the overall wavy structure of fossil ones. Different types of bacteria associate to form stromatolites using different types of light as their source of energy.

Which of the following is true of the adaptive immune response?

T cells can directly kill infected host cells but B cells cannot directly kill cells. --B cells, which differentiate into antibody-producing plasma cells, mediate humoral immunity. A clonal population of plasma cells will all secrete the same antibody, which will recognize a particular epitope. T cells, which can directly kill infected host cells, mediate cellular immunity.

toll like receptors (TLRs) and nod like receptors (NLRs)

TLR: (WBCs, epithelial cells) which monitor for the presence of extracellular invaders (outside of cell, looking for pieces of invading microbe). NLR: looking for intracellular invaders (MAMPs: microbial associated molecular patterns like LPS or flagella). -when these detect these molecules, it will launch attacks.

Which of the following is true of opportunistic pathogens?

They may arise from normal microbiota --Opportunistic pathogens are normal microbiota that may infect a compromised host. The fact that a pathogen is opportunistic does not imply anything about its antibiotic resistance. Vaccination works primarily on specific pathogens and is not a guarantee of limited infection.

Bacteria can determine they are in a host cell by measuring all of the following EXCEPT

a chemical autoinducer. --Bacteria use a variety of different sensors to detect their environment and signal that they are in a host cell. They use autoinducers to detect their own density.

clade is

a group of organisms that share a common ancestor not shared by other organisms.

Suppose a suspected virulence gene is deleted from a pathogenic organism. If the gene product did indeed decrease virulence, the modified organism will have

a higher LD50 than the unmodified, gene-containing organism. --Virulence cannot be tested in culture, only in a host organism. A higher LD50 means that virulence has decreased, an expected result if a virulence gene is removed. Infectivity is different from virulence and you would not expect a change in species of organisms infected.

What kinds of adverse effects can vaccines cause?

allergic reaction

Extracellular pathogens can attempt to avoid immune detection by

altering their cell-surface proteins. --Inhibiting phagosome-lysosome fusion or growing within a phagolysosome under acidic conditions are methods used by intracellular pathogens. Extracellular pathogens attempt to escape immune detection by altering their cell-surface proteins.

autoimmunity occurs when

antigens that are very similar to self antigens trick the immune system to attack host tissues. --Autoimmunities are immune reactions to self tissues, often stimulated by antigens very similar to self markers being detected. Hypersensitivities occur when foreign antigens stimulate immune responses that are overreactions and do more damage than the antigen would, including antigens that are from benign substances.

Infection vs. Disease

any microbe that launches a successful attack on human or other animal and causes disease must: -breach host's physical and chemical barriers to gain entrance. -survive the innate defense mechanisms and begin to multiply -surmount the last line of defense, which is adaptive immunity.

Cyanobacteria changed the atmosphere on early Earth because they led to increased

atmospheric oxygen levels.

A localized, focal point of infection found within a patient's catheter is most likely employing which virulence mechanism?

biofilm. --Biofilms allow for the microbial colonization of many different types of implanted medical devices and are a serious cause of infection.

Which of the following locations is LEAST likely to harbor commensal microbes?

blood --Blood is usually sterile. The skin, mouth, and vagina interface with the external environment and are colonized by bacteria.

The first cells likely to encounter a pathogen, such as phagocytes, are professional antigen presenting cells (APCs). This means they

can activate cells of the adaptive immune system. --Phagocytes present pieces of the pathogen to cells in the lymph nodes, specifically to T cells that will in turn activate additional adaptive immune system cells.

intracellular pathogens

cell ingests pathogens in phagosome. -some pathogens use hemolysin to break out phagosome fuses with acidic lysosome -some pathogens secrete proteins to prevent fusion. -some pathogens mature in acidic environment. -molecular mimicry where it will mimic proteins of hosts by putting on sialic acid on the outside of their cells. -altering cytokine profiles -stopping programmed host cell death -interfering with autophagy.

Hosts differ in how susceptible they are to certain infections due to differences in

cell surface receptors. --Hosts differ in what cell surface receptors may be available to microbes for attachment. All hosts have the same general cell types and in the case of humans have no cell wall. Bacteria have nonpilus adhesins, not hosts.

extracellular immune avoidance

complement, antibodies bind pathogen -some pathogens secrete thick capsule which will make it hard for WBC to grab onto it, doesn't allow complement or antibodies access to pathogen to bind to it. -some pathogens make proteins to bind to/ confuse antibodies. --will target lower portion, which causes antibody to bind backwards so it can't be flagged for phagocytosis -some pathogens cause cell death. -some will change protein expression so WBCs won't recognize it.

Molecular Koch's Postulates

developed by Stanley Falkow 1. phenotype under study should be associated with pathogenic strains of a species. 2. specific inactivation of the suspected virulence genes should lead to measurable loss in virulence or pathogenicity. The genes should be isolated by molecular methods. 3. reversion or replacement of the mutated gene should restore pathogenicity. -trying to identify genes allowing for virulence within specific type of bacterium, taking it a step further from the original which only is looking at organism.

An individual whose B cells were unable to undergo somatic mutation/hypermutation would probably

fail to produce as large an antibody repertoire as other individuals. --Somatic hypermutation results in increased antibody diversity, so the inability to perform this would lead to less antibody diversity. Isotype class switching is the result of gene splicing, not somatic hypermutation, so it should not be affected.

Which of the following is NOT a factor in dysbiosis?

fecal transplant. --The normal intestinal microbiota can be disturbed by many different factors including stress, antibiotics, and diet. Fecal transplant can be used to treat dysbiosis by introducing new intestinal microflora. --factors are emotional stress, antibiotic therapy, and dietary changes.

microbial attachment

first step towards infection is attachment, also called adhesion. -adhesin is general term for any microbial factor that promotes attachment. -bacteria have variety of strategies to bind to specific host cell receptors.

Carbon Fixation

fixation: covalent incorporation of a small molecule into a larger biochemical material (CO2 and N2 fixation) -autotrophs use CO2 as their sole source or principal carbon source. -requires lots of energy and reduction potential. -4 different CO2 pathways in microbes. -also called Calvin-Benson Cycle or the reductive pentose phosphate pathway. --performed by oxygenic phototrophic bacteria, chloroplasts of algae and plants, facultatively anaerobic purple bacteria, and lithotrophic bacteria.

Although the exact definition of a species for prokaryotes is debated, two individual bacteria can often be considered members of a single species if they

have a high degree of DNA similarity. --DNA similarity can be used to assign organisms to a given species. Many different species can have the same growth requirements or morphologies. Bacteria do not undergo sexual reproduction.

Microbes that colonize the skin need to be resistant to __________ salt and __________ pH.

high; low -skin has pH of 4-6 and relatively high salt concentrations due to epidermal secretions.

A gene coding for __________ proteins is likely to be found in a genomic island of a pathogenic bacterial strain and NOT found in a nonpathogenic strain.

host cell attachment. --A host cell attachment protein is an example of a protein that can contribute to pathogenicity. It is not part of the needed bacterial core machinery like the other choices listed. tRNA amino acyl synthase is part of the core translational machinery, RNA polymerase is part of the core transcriptional machinery, and glucose transporters are part of the core transport machinery.

adaptive immunity

humoral immunity (antibody dependent): -mediated by B cells -produces antibodies that directly target antigens of invaders, and recognizes things floating around in fluid (not yet infiltrated cell). cell-mediated immunity: -involves T cells (look for infected cells) -control antibody production and can directly kill infected host cells, and occurs once invader has infiltrated cell.

Herd Immunity

idea that protection can occur from diseases (human to human) must have certain % of population to be vaccinated against pathogen. -don't have to have everybody -2/3 -if everybody in room is vaccinated except 2 people, the people surrounding are serving as protection for the people who are unvaccinated.

Smallpox was possibly the first disease for which a vaccine was produced. One version of this process used a related disease, cowpox, as a source for the vaccine. The figure below demonstrates immunological specificity between the two viruses, which means

if two pathogens share key antigenic determinants, they can produce cross-protection, but generally immune responses to one antigen do not transfer to a different antigen. --The best antigens are specific and do not protect from different pathogens with different antigens. Some small antigens cannot provoke a response by themselves but can if bound to another larger component, but this is not related to immunological specificity. The variola and vaccinia viruses share similar enough epitopes that they allow cross-protection.

The primary antibody response differs from the secondary antibody response in that

in the primary response, plasma cells differentiate from naive B cells, whereas in the secondary response plasma cells may differentiate from memory B cells. --Both antibody responses are triggered by exposure to an antigen. In the primary response, plasma cells differentiate from naive B cells, whereas in the secondary response plasma cells may differentiate from memory B cells, leading to a more rapid appearance of circulating antibodies. During the secondary response mechanisms increase the antibody affinity for an antigen.

Extravasation of immune cells depends on

increased permeability of endothelial cell junctions. --Extravasation of immune cells depends on increased permeability of endothelial cell junctions and increased vasodilation. Antibodies are not necessary for extravasation. Selectin expression is increased prior to extravasation.

hygiene hypothesis states

increased use of hygiene products and a mostly indoor lifestyle leaves us with untrained immune systems. --The hygiene hypothesis states that the shift from humans living in microbe rich environments to microbe poor ones has left our immune systems less tolerant and controlled due to limited exposure to microbes as children. This leads to increases in inflammatory and autoimmune disorders due to immune system dysfunction.

The figure below shows the mechanisms pathogens use to misdirect the immune system. Which of the following is a mechanism to stop the last resort of the host cell to clear the infection?

inhibit apoptosis. --Intracellular pathogens can employ many mechanisms to persist within host cells, but the host cell may trigger apoptosis as a last resort to be rid of the infection. Some microbes including Mycobacterium tuberculosis can inhibit this by stopping some critical signals in the process.

Which of the following is true of the normal intestinal microbiota?

it can help aid digestion and absoprtion of nutrients. --Some intestinal microbes secrete enzymes that break down complex carbohydrates into forms humans can absorb. Hundreds of different species, including yeasts and protists, can be present. The microbes can be a problem, causing possible infection in the host, if they colonize a different tissue.

Stromatolites

layers of phototrophic microbial communities grew and died, and their form was filled in by calcium carbonate silica. These are rock formations with many interior layers (like stroma). It's due to cyanobacteria growing on surface, with sediment and dust settling on top of the cyanobacteria and over hundreds or thousands of years these layers form, showing the fossilized cyanobacteria. These are still present in remote areas on Earth (but a lack of predators are required). --Advantages: Fossil stromatolites appear in the oldest rock of the Archaean eon. Their distinctive shapes resemble those of modern living stromatolites. --Limitations: Some layered formations attributed to stromatolites have been shown to be formed by abiotic processes.

Reductive evolution is the

loss or mutation of DNA encoding unselected traits. --Reductive evolution is the loss or mutation of DNA that encodes unselected traits. If a trait is not selected for, mutations can accumulate. There is no such thing as oxidative evolution.

immunological specificity

means that antibody made to one epitope will not bind to other epitopes. -cross binding to similar epitopes can happen. -i.e. antibody similar to cowpox virus will bind to similar epitope on smallpox virus (used in vaccination). -cross protection will work only if 2 proteins critical to the pathogenesis of the two different microorganisms share key antigenic determinants -won't work if they differ significantly (infection with one strain of rhinovirus will not immunize the victim against second strain).

immunogenicity

measures effectiveness by which an antigen elicits immune response. -proteins are most effective antigens (form more diverse chemical forms and maintain 3º structures). -nucleic acids and lipids are less immunogenic. antigen presenting cells: degrade pathogen proteins, attach antigens to MHC for presentation. -two types: professional antigen presenting cells MHCII (suck up things from blood stream and display them to elicit immune response) other type are the non-professional which are all other nucleated cells MHC I. (all cells but not red blood cells) -MHC I presents health status of cell (virus, bacteria, cancer). -MHC II presents it to elicit immune response.

Experimental evolution in a lab

microbes are popular due to short generation times. -experiment on evolution in lab was conducted by Richard Lenski at Michigan State University. -1988 began the Long-Term Evolution Experiment when he founded 12 populations of E. coli from a single clone. Every 24 hours 1% of population was transformed to new medium then grew for 6.7 generations per day. Every 500 generations samples of each population were frozen for later study (archive). -many changes have been observed, such as the evolution of bacteria that can grow faster than the ancestor and form larger cells. One thing that occurred around 33,000 where the E. coli could grow aerobically on citrate (discovered as the optical density was was higher (higher growth)).

Moderate fever can actually be beneficial because it

moves the temperature outside the pathogens' optimal range. --If a pathogen grows more slowly there is more time for the immune system to respond and control the pathogen to reduce the infection. Increasing temperature outside the optimal and reducing iron availability can slow growth. Enzymatic denaturation might occur in the host as well as the pathogen and likely is not possible with moderate fever. Inflammation is not directly related to fever.

A major mechanism of microbial evolution is genome duplication and divergence as discussed in Chapter 9. This allows for existing genes to acquire mutations as there is a "backup" copy of the gene that will continue to function. Genes that have diverged through mutation to have different function are called

paralogs. --Paralogs are identified through sequence alignment to show both their similarity and subsequent divergence.

Microbial species of the microbiota may interfere with colonization of pathogens by all EXCEPT which of the following mechanisms?

phagocytosis. --Commensal species may limit pathogen colonization via competition for resources (space and food) or by synthesizing antimicrobial compounds. Phagocytosis occurs as part of the host immune response.

Innate Immunity

physical barriers, chemical barriers, white blood cells. -physical barriers include: tight junctions, stomach (acidic), skin (keratin, oil, acidic, sloughing off), eyes (tearing), and mucous membranes (trap, destroys pathogens). -chemical barriers are: defensins (small antimicrobial cationic peptides which destroy invader's cell membrane effectively stopping PMF and killing them (effective against G+ and G-, fungi, and viruses). -WBC work together to destroy foreign invaders --different types are formed by differentiation of stem cells produced in bone marrow

MHC II

presents extracellular antigens -microbial proteins made outside of cell are endocytosed in endosome. -they are then degraded and placed on MHC II molecules.

primary and secondary antibody responses

primary: via disease or vaccination, antibodies appear in serum after several days -B cells that bind antigens make antibodies -some B cells become memory cells. secondary: via a second exposure to pathogen or booster dose. -antibodies appear within blood in hours, lot higher in concentration. -different memory cells retain memory for different period of time, that's why vaccine booster times vary.

Complement protein factor C3b is an opsonin, which means it can

promote phagocytosis. --Some complement factors are anaphylatoxins and trigger degranulation and stimulate chemotaxis. If C3b binds to LPS, it will trigger the complement cascade and many additional factors form a MAC, but by itself it will promote phagocytosis.

Koch's postulates have been modified to identify pathogenicity genes. These postulates include that the gene's phenotype should be associated with pathogenic strains, the gene should be isolated by molecular methods, and the gene

reduces pathogenicity if inactivated and restores it if recovered. --The molecular Koch's postulates demonstrate that a specific gene is a virulence gene, and so a loss and regain of function shows this. While pathogenicity islands are often flanked by homologous genes to phages or plasmids, indicating horizontal transfer, these are not required. Many virulence factors do allow mimicry of the host or immune system avoidance, but these are specific functions not a demonstration that the gene is a virulence factor.

genomic and energetic costs of biosynthesis lead microbes to evolve several strategies to control these costs

regulation: molecules within cell regulate concentrations of reactants/products to control direction of metabolism. genome loss/cooperation: easier to pick something up from environment than to manufacture it yourself. competition and predation (secondary pdts): actinomycetes (where we get antibiotics from) they are known for producing secondary metabolites that are antibiotics. --when nutrient conc is good, they don't produce them. --when nutrient conc is bad, the genes for antibiotics are turned on, and these kill off other organisms in surrounding environment that are in competition with bacterium. once organisms die, the nutrients that were inside them now become substrates for the actinomycetes to use themselves.

One reason why RNA molecules are the leading candidate as the first informational molecule is that

some RNA molecules can function as enzymes. --RNAs are proposed as an early informational molecule because they can serve as both information carriers and catalysts. Even in present time, there are some ribozymes, that is, enzymes whose catalytic activity depends on RNA and not on amino acids.

The current research shows the link between obesity and the microbiome is likely based on the

specific species composition of the microbiota.

molecular clock

temporal information contained in macromolecular sequence. with a particular gene, mutations will only occur at a certain rate. -when comparing organisms based on the number of mutation differences, you can determine the time at which they converged. standard assumptions when using 16S rRNA: -minimum number of changes have occurred. -functional sequences change more slowly, as mutations don't occur in that area. -third base codon positions show more random change (Wobble hypothesis) (any mutations are silent).

Foodborne pathogens likely use __________ as a portal of entry.

the mouth --Portals of entry are how pathogens get into hosts and pathogens often specialize to use particular ones. The fecal oral route is very common for foodborne pathogens.

From Salmonella enterica's standpoint, an advantage of a type III secretion system for toxin delivery is that

the toxin is not diluted in the environment. --Type III secretion systems use special delivery proteins to inject toxin directly into the host cell cytoplasm thereby avoiding the problem of dilution in the environment. Exotoxins can be just as virulent as toxins injected directly into the cytoplasm.

The E. coli O104:H4 outbreak of 2011 was caused by a strain that had Shiga toxin and antibiotic resistance traits not present in its closest relative. This most likely indicates

there was a horizontal gene transfer event. --While multiple mutations and genome duplication and divergence are possible, they are much less likely than a horizontal gene transfer event. It is also extremely unlikely that Shigella would change enough to look like a different species.

may substrates for biosynthesis arise from glycolysis and TCA cycle

these are reversible, and can go both ways.

Which of the following parameters increases the immunogenicity of proteins?

tighter binding to MHC proteins. --To elicit immunogenicity, an antigen must be placed on a membrane protein called the major histocompatibility complex (MHC). The more tightly an antigen binds to these MHC surface proteins, the more immunogenic it is because it is easier for T cells to recognize the complex. Larger proteins tend to be more immunogenic because they have more epitopes. A similarity to self-proteins will tend to decrease immunogenicity. Paradoxically, intermediate exposures are often more immunogenic than either high or low doses.

Which of the following is a physical barrier to microbial infection in innate immunity?

tightly linked epithelial cells. --Tightly linked epithelial cells are a physical barrier. Acidic pH, superoxide radicals, and antimicrobial peptides are all chemical barriers.

autophagy

used as universal innate defense mechanism to fight intracellular pathogens. --intracellular pathogens have evolved mechanisms that prevent autophagy and prolong their survival.

3-hydroxypropionate cycle

used by thermophiles, like bacterium Chloroflexus and the archaean Sulfolobus. -in all, three molecules of CO2 are fixed into one molecule of pyruvate, which serves as substrate for biosynthesis.

Chronic inflammation can be caused by all the following EXCEPT

vaccination. --microbes that resist host defenses, the continued presence of a nonliving irritating particle, autoimmune reactions all can cause chromic inflammation.

Organisms acquire DNA

via horizontal transmission from cells of any domain, and also from vertical transmission. --Horizontal transmission can cross domain barriers (e.g., mitochondria, genes from thermophilic archaea transferred to thermophilic bacteria).

If a patient presents with an elevated lymphocyte count compared to other white blood cells, they likely have a(n)

viral infection. -Neutrophil elevation indicates a bacterial infection as they are phagocytes, eosinophil elevation indicates a parasite infection and basophil elevation indicates an allergy, and lymphocyte elevation a viral infection. These occur due to the different function of each cell type.