Ecology of Human Disease
What is the name for the ecosystem comprising your body and its synergistically interacting microorganisms?
Holobiont
Saliva, tears, urine, and other bodily fluids contain the enzyme lysozyme. What is the specific biochemical target of lysozyme (not just the molecule, but which microbes have it and what portion is cleaved)?
Peptidoglycan's 1,4 glycosidic bond between NAM and NAG, which is not found in archeal pseudopeptidoglycan or in Mollicutes, which lack cell walls
Which of these is not a part of innate immunity: macrophages, neutrophils, dendritic cells, B cells?
B cells! They are the antibody-producing cells of acquired immunity.
The TLRs that recognize viruses would be found in what part of the host cell?
Cytoplasm
What is the place in your body where Archaea are found, and how do you know that they are there?
In the gut. Gut microbes produce methane. Only Archaea are known to be methanogens.
What organ sytems are exposed to the "outside" and therefore are not sterile?
Digestive tract
Respiratory tract
Urinary tract
Vaginal tract
Name some structures on bacteria that might help a pathogenic E. coli attach firmly enough to the urinary tract to stay there, and avoid being washed away with the flow of urine.
pili or fimbriae
When macrophages phagocytose bacteria, they display molecules on the exterior via:
Major Histocompatibility II complexes, or MHCII
SARS CoV 2 hides its MAMP (which is dsRNA) from TLRs by replicating where?
Inside ER-derived vesicles called replication transcription complexes, or RTCs.
There are two major types of T cells. What are they?
Treg: signal immune system to tolerate bacteria and promote mutualism
Teff: produce cytokines and toxins to kill pathogen-infected cells
Is an opportunistic pathogen autochthonous or allochthonous?
It's autochthonous but out of balance with the rest of the microbiome.
Explain how mucus is both a passive barrier to gut microbes, and a key element in their survival.
Dense mucus closer to the epithelium is impenetrable to bacteria if it's intact. Looser mucus further from the epithelium can harbor bacteria, support biofilm formation, and be used for nutrition. Mucus is also full of toxins like RegIII, an antimicrobial lectin, close to the epithelial border because it's secreted there.
Which of these structures is a MAMP associated only with gram positive bacteria: peptidoglycan, capsule polysaccharides, lipopolysaccharides, or teichoic acid?
teichoic acid
Oxygen can react with NADPH or NADH dehydrogenases to create superoxide. As you already know, superoxide can damage any biological molecule. How does the host produce superoxide to kill bacterial pathogens but not harm itself?
Production of superoxide and other reactive oxygen species occurs inside the phagolysosome.
Which type of cells primes Peyer's patches for breaching of the border, by sampling the local microbes and delivering them to lymphocytes and antigen-presenting cells on the basal side of the gut via transcytosis?
M cells
What ecosystem functions do the microorganisms in your body perform?
Provide vitamins, nutrients, neurotransmitters, hormones.
Detoxify harmful compounds.
Prevent colonization of pathogens.
Entrain immune system.
Gastroferritin in the digestive system and transferrin in the blood both bind iron, keeping it away from microbes. Explain why iron is important for the growth of pathogenic bacteria.
Iron is a cofactor in multiple proteins of the electron transport chain, and needed for keeping the proton gradient intact. Without iron, the cell loses the ability to transfer electrons, and therefore can't perform oxidative phosphorylation.
Which MAMP would be released into the bloodstream only after lysis of a Gram negative bacterial pathogen, and induce fever?
Lipid A
Describe some additional context for the immune system, besides binding of a MAMP to a TLR, that would identify a bacterium as a pathogen rather than a symbiont.
-Wrong place (inside typically sterile tissues)
-Accompanying DAMPs, which mean either the bacterium or other immune cells have damaged the host
This bacterium has an extensive set of Starch Utilization System proteins that bind oligosaccharides for cleavage and uptake. It can also digest host mucus glycans. It also can digest pectins (found in plants). It can change its appearance by varying the molecules in its S layer, its lipopolysaccharide, and its capsule. Who is this bacterium, and how is it important to humans?
Bacterioides thetaiotamicron. Primary successional in gut; performs "niche remodeling" for subsequent community members.
What ecosystem functions does the early successional species Bacteroides thetaiotamicron perform?
Directs synthesis of glycans with a-linked fucose in epithelium. a-linked fucoses are then utilized for nutrition by B. thetaiotamicron!
Induces complex angiogenesis (blood vessel formation) at submucosal epithelium (within 10 days)
Enhances triacylglyceride absorption, import, storage (by repressing ANGPLT4, a repressor of the key lipase)
Stimulates gut innate immune system (directs its own microbial community): immune systems recognize certain pathogens, e.g. Listeria, and ignores symbionts)
Mycoplasma is a genus within the bacterial class Mollicutes, and includes parasites of animals. Could lysozyme stop them from invading? Why/why not?
Mollicutes, which include phytoplasmas and mycoplasmas, lack cell walls. Lysozyme targets peptidoglycan's 1,4 glycosidic bond between NAM and NAG, which is not found in Mollicutes. Lysozyme is useless against these pathogens.
A Toll-like receptor (TLR) expressed in the epithelial cells of the gut would be found where? cytoplasm, cell membrane facing gut lumen, basal cell membrane, or in the tight junctions? Explain your answer.
basal cell membrane, to detect bacteria that have breached the epithelial barrier
Discuss the many roles of IgA in both fostering the microbiome and keeping it at bay.
IgA in breast milk helps establish gut microbiota, and dampens excessive T-cell and B-cell responses to gut microbes (in mice). Conversely, it protects newborn epithelium from opportunistic pathogens. (How does it help some bacteria and inhibit others?)
IgA secreted by B and T cells in Peyer's patches in the gut coats the bacteria in the gut microbiome, helping them adhere to mucus glycoproteins, and inducing bacterial downregulation of surface molecules that activate immune attack
What is the significance of bacterial DNA in the meconium?
It's the infant's first stool; any DNA found here suggests that the uterus is not sterile after all, because this stool was generated while the fetus was still in utero.