Microbiota And Immune System (innate)

Question 1

Where in the gut are the most microbiota

Answer 1

Colon followed by ileum

Question 2

What can dysbiosis be caused by

Answer 2

Diet, stress, genetics, antibiotics, hygriene

Question 3

What is the genetic link to Crohn’s disease which is inappropriate response to microbiota

Answer 3

Mutation in the nod 2 receptors (intracellular)

Question 4

What do nod 2 have as their pamps

Answer 4

Muramyl dipeptide (in peptidoglycan cell wall)

Question 5

Which types of cells in gut (epithelial) produce defensins and what are defensins a and b

Answer 5

Paneth cells

Defensins are antimicrobial peptides which are cationic (+ve) and produce pores in bacteria

Question 6

Normally , what would happen at gut epithelial to kill bacteria

Answer 6

Muramyl dipeptide will be recognised by nod 2 and this causes release of defensins to kill bacteria

Question 7

What are defensins attracted to

Answer 7

-ve cell membranes

Question 8

Which types of things can allow for over proliferation of microbiota in gut

Answer 8

Diet/ nutrients

Question 9

What would happens when a lot of microbiota are in gut

Answer 9

Muramyl dipeptide will break through the cells via endocytosis

Pamp detected via nod 2 and many defensins released which attract macrophages etc

Question 10

Why would mutation to nod 2 end up in crohns inflammation

Answer 10

Defensins can’t be released bc no signalling from nod 2

This means macrophages will form a cytokine storm to try to eradicate it

This causes inflammation

Question 11

How would steroid treatment help crohns

Answer 11

Anti inflammatory via stopping prostaglandin and leukotrienes

Also blocks th1 macrophages

Question 12

What is rheumatoid arthritis

Answer 12

Complex autoimmune genetic disease

Deposits at joints cause inflammation and edema swelling

Question 13

Which bacteria were found to increase RA likeliness

Answer 13

Segmented filamentous bacteria (dysbiosis if increased)

Question 14

How do segmented filamentous cause RA and it’s symptoms

Answer 14

Bind to receptors and form signalling cascade

This stimulates th 17 proliferation and therefore more IL 17 release

IL 17 cytokines cause inflammation via attraction of cells and Edema

IL 17 also activate auto reactive B cells which then produce auto antibodies (auto immunity)

Question 15

What produces deposits in RA

Answer 15

The auto antibodies produced via auto reactive B cells

Question 16

How does lactobacillus prevent uti usually

Answer 16

Lower ph via glucose metabolism production of lactic acid

Question 17

Which bacteria causes uti

Answer 17

UPEC E. coli

Question 18

How can e coli upec move from urethra opening up the UT eg to bladder or kidney

Answer 18

Via flagella

Question 19

Which 3 things protect the UT

Answer 19

Urine (flush bacteria)
Epithelial barrier
Defensins

Question 20

Which receptor when not mutated can identify UPEC

Answer 20

Toll like 5

Question 21

What does toll like 5 identify on UPEC

Answer 21

Their flagellins

Question 22

What do the bladder epithelium then release when roll like 5 bind to flagellin from UPEC

Answer 22

Defensins

Question 23

Which type of mutation is common to toll like 5 causing uti

Answer 23

SNP from C to T

Question 24

How does cystitis (bladder uti) occur due to C to T mutation in toll 5

Answer 24

Lack of signalling to release defensins

Inflammatory markers released instead eg macrophages and neutrophils

Causes inflammation and bleeding in bladder = cystitis

Question 25

Do toll 5 still recognise flagellum when they have the C to T mutation

Answer 25

Yes