11b – Immunity at Mucosal Surfaces

Question 1

How do cells migrate at mucosal surface?

Answer 1

-trafficking of immune cells

Question 2

‘common mucosal immune system’ concept:

Answer 2

-says that after an immune response is induced at one site, cells migrate to ALL other mucosal sites
-believed it for many years, but now we know trafficking is more SPECIFIC

Question 3

Trafficking is highly specific:

Answer 3

-large and small intestine have different ‘adressins’ and cells us different homing molecules
*mucosal surfaces are connected, but compartmentalized

Question 4

CCR9 knockout in mice:

Answer 4

-IgA plasma cells no longer find their way to the intestine
*have an impaired immune response

Question 5

Trafficking and administration of vaccines:

Answer 5

-very important
-if want a response at a specific site, think about where you inject the vaccine
*compartmentalization

Question 6

Oral route: effective response in

Answer 6

-small intestine (proximal)
-ascending colon
-mammary and salivary glands

Question 7

Oral route: non-effective response in

Answer 7

-distal large intestine
-genital mucosa
-tonsils

Question 8

Rectal route: effective response in

Answer 8

-rectum
Ex. HIV

Question 9

Rectal route: non-effective response in

Answer 9

-small intestine
-proximal colon

Question 10

Nasal or tonsillar route: effective response in

Answer 10

-upper airway
-regional secretions
-genital mucosa

Question 11

Nasal or tonsillar route: non-effective response in

Answer 11

-gut

Question 12

Vaginal route: effective response in

Answer 12

-genital mucosa

Question 13

Vaginal route: non-effective response in

Answer 13

-intestine

Question 14

Skin route: effective-response in

Answer 14

-gut?

Question 15

Skin route: non-effective response in:

Answer 15

-most mucosal sites

Question 16

Regulation of immune responses at mucosal surfaces:

Answer 16

1. Immune exclusion
2. Oral tolerance

Question 17

Immune exclusion:

Answer 17

-immune responses are being induced and secretory antibodies are produced to keep antigens away
>when material is trapped in M cells or taken up by dendritic cells and danger signal is present

Question 18

Oral tolerance:

Answer 18

-non-adherent food antigens are not recognized as danger signal by epithelial cells
*use Treg cells to suppress the response

Question 19

How to maintain oral tolerance?

Answer 19

-if danger signals present=mount a response
-if danger signals absent (ex. food)=use Treg to suppress the response
>IL-10 and TGF-beta

Question 20

Shift from homeostasis to inflammation when things go wrong:

Answer 20

1. Normal permeability: mucosal tolerance by Treg
2. Minor defect: food allergy
3. Increased permeability: food allergy
4. Massive influx of Ags and MAMPs
   *vicious cycle leading to inflammation (chronic IBD, tissue damage)

Question 21

How do we distinguish between commensal and pathogenic bacteria?

Answer 21

-LOCATION
>if bacteria (good or bad) are sitting on top=we don’t recognize the danger signals and all is good
-distance
-low amounts of antigens

Question 22

‘pathobionts’:

Answer 22

-mucus is still intact and some bacteria are allowed to come in contact with our cells
>immune system is on ALERT

Question 23

Mucous barrier no longer intact:

Answer 23

-our epithelial cells recognize the danger signals and start inflammation
>switch from homeostasis to full blown immune response

Question 24

Intact mucus layer:

Answer 24

*very important!
-anything that disturbs it can have bad consequences

Question 25

Things that can disturb the mucus layer:

Answer 25

-stress
-antibiotics
-drugs
-infections
-etc.