Microbiota and the Immune Response Flashcards
What are some good results of commensal bacteria?
we need bacteria do generate secondary lymphoid tissue
mucosal immunity
keep pathogenic agents out
What are some diseases that have been associated with a deficient or improper microbiota?
immune encephalitis, IBD, obesity, arthritis,
What is unique about the commensal composition at various mucosal areas?
composition of bacteria varies
How does commensal gut bacteria contribute to good health?
provide energy by metabolizing dietary polysaccharides
provide vitamins
required for development of the immune system
protect from pathogenic bacteria
How do commensals protect from intestinal inflammation?
balance pro and anti inflammatory immune reactions
What is the relationship between Th1, Treg cells, and commensal bacteria?
Th17 is needed for protection from pathogenic bacteria, but overproduction of IL17 can lead to intestinal inflammation
Th17 cells are regulated by Tregs - a healthy balance is generated by a healthy intestinal microbiota
What are some examples of organisms inducing specific responses?
Segemented filamentous bacteria (SFB) induces Th17
B. fragilis regulates Treg cells
S. typhimunum regulates Th1 cells
What can dysbiosis result in?
favoring pro-inflammatory (Th17, Th1) over antiinflammatory (Treg) state
What can cause dysbiosis?
antibiotics
diet
toxins
defects in intestinal barrier
What is a precipitating factor of IBD?
changes in development or composition of intestinal microbiota results in a T cell mediated inflammatory response
What happens if you take a mouse engineered to develop IBD and do a fecal transplant to a wt mouse?
the wt mouse will develop IBD
How can IBD be treated?
with Bacteroides fragilis, which induces an anti-inflammatory response
What are some situations in which the incidence of allergy is decreased
Children growing up on farms
Children attending day care during first 6 months of life
east german children compared to west german
what is a situation in which the incidence of allergy is increased?
Children given antibiotics within the first year of life
What does a rise in immune disorders coincide with?
a decline in infectious disease
What is allergy due to?
Th2 IgE response
What down regulates Th2 responses?
Th1 responses
What elicits a Th1 response, and what are the factors involved?
bacteria and viruses
IL-2, IFN-gamma
What would decreased bacterial and viral infections result in?
insufficient Th1 response, which would increase Th2 response (IgE)
What regulates the Th1 and Th2 responses?
Commensals
What is EAE, and how are commensals implicated in its management?
autoimmune disease where Ab are directed against the myelin sheath - if you give a mouse with EAE intestinal bacteria that induce Tregs, you can prevent EAE
What do TLR5 knockout mice develop?
increased food intake, insulin resistance, diabetes, obesity
altered gut microbiota
What does antibiotic treatment do to the TLR5 knockout mice?
reverses obesity
What happens if you do a fecal transplant form a TLR5 knockout to a wildtype mouse?
the wt will develop obesity, indicating that gut microbiota can cause metabolic syndrome
What happens if you transplant the microbiota from a lean and obese twin to two different mice?
the obese microbiota will induce the wt mouse to become obese
the lean microbiota will induce the wt mouse to become lean
What happens when a lean and obese mouse were cohabitated?
obese mouse developed the microbiota of the lean mouse and obesity did not develop
If given low-fat diet, lean-associated microbiota can
prevent obesity in mice with obese-associated microbiota.
With high-fat diet, lean microbiota did not prevent obesity.
What does a high fat diet do?
induces changes in the microbiota that can promote obesity
affects innate lymphoid cells to secrete IL-22 which induces expression of anti-microbial peptides which will alter the microbiota
What disease are gut microbial dysbiosis associated with?
IBD, type 2 diabetes, necrotizing enterocolitis
What are some causes of microbial dysbiosis?
host genetics: mutations in NOD2, IL23R, ATG16L, IGRM
lifestyle: diet and stress
early colonization: birth in hospital, altered exposure to microbes
medical practices: vaccination, antibiotic use, hygiene
disease: increased Th1, Th2, Th17 cells
health: increased Tregs
How does the composition of a babies microbial composition differ based on the method of delivery?
vaginal: microbiota more resembles vagina of mother
cesarian: microbiota more resembles skin of mother
What does an increase in C-sections correlate with?
an increase in food allergy
What does antibiotic therapy have on the effectiveness of cancer treatment?
Antibiotic Treatment Impairs Cancer Therapy
What do commensals do?
suppress inflammatory responses and protect from disease in the intestines and other organs
How do commensals mediate protection?
balance Th(Th1 and Th17, pro-inflammatory) and Treg (anti-inflammatory) cells as well as Th1 and Th2 cells
What does dysbiosis of gut commensals contribute to?
chronic inflammatory diseases (eg IBD)
autoimmunity, allergy, and obesity
What can cause dysbiosis?
diet, antibiotics, stress, and possibly by early childhood exposure to commensals
What can antibiotics that kill commensals result in?
alter cancer drug effectiveness
