Immunological Features of the Alimentary Tract

Question 1

As a recap, list some differences between the innate and adaptive immune system.

Answer 1

INNATE:

• prevents infection and avoids disease
• non-specific
• no memory
• mediated by macrophages, epithelial barriers, secretions, etc.

ADAPTIVE:

• responds to infection and prevents disease
• highly specific response to targeted microbes
• has memory
• mediated by lymphocytes, antibodies, etc.

Question 2

Where would we find systemic and mucosal immunity?

Answer 2

SYSTEMIC: bone marrow, spleen, thymus, lymph system, blood circulation

MUCOSAL: mucous membranes - eyes, nose, mouth, lungs, gut, genitourinary tract

Question 3

Describe the surfaces of the mucosal immune system.

Answer 3

It covers all the mucosal surfaces (e.g., oral, nasal, lacrimal surfaces, GI tract, bronchial tract, genito-urinary tract and mammary glands).

All of these sites are normally colonised by microbes. This is the main route of entry for infectious microorganisms.

Question 4

The mucosal immune system has innate and adaptive mechanisms.
Expand.

Answer 4

Innate mechanisms of protection include:
mucin, peristalsis, antimicrobial peptides and proteins (e.g., lysozymes, lactoferrin, phagocytes).

Adaptive mechanisms are also present: the mucosal/secretory immune system.

Question 5

There are different ways in which pathogens can get across gut surfaces.
List 3 of them.

Answer 5

1) If there is a breach in the epithelium, the pathogen can get into the sublamina (connective tissues under the epithelium).
2) Langerhans cells have extensions to ‘sample’ what’s in the lumen of the gut. The pathogen can adhere to it, and be brought in when the cell moves off.
3) The main way that pathogens get in is via the Peyer’s Patches. The patches are actively sampling the gut via M-cells, which go to do the sampling. lymphocyte underneath.

Question 6

How do M-cells work?

Answer 6

The M-cell sits on top of the epithelial layer and samples the gut fluid lumen, then sends it down to the lymphocytes underneath.

Question 7

Tests were done showing the antibody response of Peyer’s patches.
What do the tests tell us?

Answer 7

1) In order to generate an immune response, the immunogen has to be taken up by the Peyer’s patch.
2) The antibodies produced are not limited to just that one site.

Question 8

List some M-cell targets for uptake.

Answer 8

• particles and macromolecules
• viruses
• parasites
• bacteria

Question 9

Describe the migration of immune cells from Peyer’s patches.

Answer 9

Once a pathogen gets through to the lymphocytes, an immune response is triggered. A B-lymphocyte will start to mature into a B-cell.
As they do this, they migrate from the patch to the local lymph node, then enter back into the blood circulation.

Question 10

Describe the idea of common mucosal immunity.

Answer 10

A significant aspect of the mucosal immune system is that, instead of going to the blood circulation and producing antibodies, the mucosal lymphocytes home back to the mucosal immune system, back to the gut they originally came from (and the surrounding gut). They also home to other mucosal surfaces.

This response of encountering an antigen at one mucosal site leading to immunity across al mucosal sites is called the common mucosal immune system. In this response, the lymphocytes have to home to a secretory gland before they can start producing antibodies.

Question 11

Describe mucosal antibodies.

Answer 11

• predominantly SIgA
• found in all secretions and breast milk
• provide passive immune protection in new-born infants

Question 12

Describe the two additional components in SIgA antibodies.

Answer 12

The SIgA is dimerised by a joining protein, so it can now bind to 4 antigens, making it ‘better’.

It also has a secretory component which protects it from being degraded by proteolytic enzymes (that we or bacteria produce).

Question 13

Describe the mechanism of action of the antibodies.

Answer 13

With other antibodies:

• they bind to key functional sites on microbes and toxins
• agglutinate
• induce inflammation
• recruit immune cells

However, with SIgA, it doesn’t cause the last two points as we don’t want to inflame the gut.

Question 14

List some approaches to oral immunisation.

Answer 14

• attenuated virus (e.g. polio)
• attenuated recombinant bacterial mutants (e.g. salmonella typhi)
• mucosal adjuvants [make the vaccine work better] (e.g. cholera toxin)
• liposome, microspheres
• capsules
• transgenic edible plants

Question 15

How would you test the concept of oral vaccine production in plants?

Answer 15

1) Grow plants which express hepatitis vaccine to maturity and harvest the edible tissue.
2) Feed uncooked tubers to animals or humans and analyse the immune response.

Question 16

Describe oral vaccine delivery using GM plants.

Answer 16

1) The Hep B surface antigen is transferred from yeast into a plant cell (potato used as a prototype).
2) Potato plants are regenerated from transformed cells.
3) The hepatitis vaccine is correctly expressed by potato plants.
4) GM potatoes are harvested that contain the hepatitis vaccine.

Question 17

What is an obstacle with mucosal immunity (oral tolerance)?

Answer 17

If an antigen is first encountered through the mucosal immune system, the systemic immune system may become unresponsive (tolerised) to that antigen.

Question 18

How is oral tolerance helpful?

Answer 18

• we need to have tolerance to food, otherwise, we will have a food allergy