Microbiota and the Immune Response

Question 1

What are some good results of commensal bacteria?

Answer 1

we need bacteria do generate secondary lymphoid tissue

mucosal immunity

keep pathogenic agents out

Question 2

What are some diseases that have been associated with a deficient or improper microbiota?

Answer 2

immune encephalitis, IBD, obesity, arthritis,

Question 3

What is unique about the commensal composition at various mucosal areas?

Answer 3

composition of bacteria varies

Question 4

How does commensal gut bacteria contribute to good health?

Answer 4

provide energy by metabolizing dietary polysaccharides

provide vitamins

required for development of the immune system

protect from pathogenic bacteria

Question 5

How do commensals protect from intestinal inflammation?

Answer 5

balance pro and anti inflammatory immune reactions

Question 6

What is the relationship between Th1, Treg cells, and commensal bacteria?

Answer 6

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

Question 7

What are some examples of organisms inducing specific responses?

Answer 7

Segemented filamentous bacteria (SFB) induces Th17

B. fragilis regulates Treg cells

S. typhimunum regulates Th1 cells

Question 8

What can dysbiosis result in?

Answer 8

favoring pro-inflammatory (Th17, Th1) over antiinflammatory (Treg) state

Question 9

What can cause dysbiosis?

Answer 9

antibiotics
diet
toxins
defects in intestinal barrier

Question 10

What is a precipitating factor of IBD?

Answer 10

changes in development or composition of intestinal microbiota results in a T cell mediated inflammatory response

Question 11

What happens if you take a mouse engineered to develop IBD and do a fecal transplant to a wt mouse?

Answer 11

the wt mouse will develop IBD

Question 12

How can IBD be treated?

Answer 12

with Bacteroides fragilis, which induces an anti-inflammatory response

Question 13

What are some situations in which the incidence of allergy is decreased

Answer 13

Children growing up on farms

Children attending day care during first 6 months of life

east german children compared to west german

Question 14

what is a situation in which the incidence of allergy is increased?

Answer 14

Children given antibiotics within the first year of life

Question 15

What does a rise in immune disorders coincide with?

Answer 15

a decline in infectious disease

Question 16

What is allergy due to?

Answer 16

Th2 IgE response

Question 17

What down regulates Th2 responses?

Answer 17

Th1 responses

Question 18

What elicits a Th1 response, and what are the factors involved?

Answer 18

bacteria and viruses

IL-2, IFN-gamma

Question 19

What would decreased bacterial and viral infections result in?

Answer 19

insufficient Th1 response, which would increase Th2 response (IgE)

Question 20

What regulates the Th1 and Th2 responses?

Answer 20

Commensals

Question 21

What is EAE, and how are commensals implicated in its management?

Answer 21

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

Question 22

What do TLR5 knockout mice develop?

Answer 22

increased food intake, insulin resistance, diabetes, obesity

altered gut microbiota

Question 23

What does antibiotic treatment do to the TLR5 knockout mice?

Answer 23

reverses obesity

Question 24

What happens if you do a fecal transplant form a TLR5 knockout to a wildtype mouse?

Answer 24

the wt will develop obesity, indicating that gut microbiota can cause metabolic syndrome

Question 25

What happens if you transplant the microbiota from a lean and obese twin to two different mice?

Answer 25

the obese microbiota will induce the wt mouse to become obese the lean microbiota will induce the wt mouse to become lean

Question 26

What happens when a lean and obese mouse were cohabitated?

Answer 26

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.

Question 27

What does a high fat diet do?

Answer 27

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

Question 28

What disease are gut microbial dysbiosis associated with?

Answer 28

IBD, type 2 diabetes, necrotizing enterocolitis

Question 29

What are some causes of microbial dysbiosis?

Answer 29

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

Question 30

How does the composition of a babies microbial composition differ based on the method of delivery?

Answer 30

vaginal: microbiota more resembles vagina of mother cesarian: microbiota more resembles skin of mother

Question 31

What does an increase in C-sections correlate with?

Answer 31

an increase in food allergy

Question 32

What does antibiotic therapy have on the effectiveness of cancer treatment?

Answer 32

Antibiotic Treatment Impairs Cancer Therapy

Question 33

What do commensals do?

Answer 33

suppress inflammatory responses and protect from disease in the intestines and other organs

Question 34

How do commensals mediate protection?

Answer 34

balance Th(Th1 and Th17, pro-inflammatory) and Treg (anti-inflammatory) cells as well as Th1 and Th2 cells

Question 35

What does dysbiosis of gut commensals contribute to?

Answer 35

chronic inflammatory diseases (eg IBD) autoimmunity, allergy, and obesity

Question 36

What can cause dysbiosis?

Answer 36

diet, antibiotics, stress, and possibly by early childhood exposure to commensals

Question 37

What can antibiotics that kill commensals result in?

Answer 37

alter cancer drug effectiveness