Oral tolerance versus oral vaccines

[gatechgirl]

I just finished the 4000 level immunology course at my university. I initially had no particular interest in immunology, but now I can't stop thinking about it!

I have recently received several vaccinations in preparation for an upcoming trip to western Africa (I'll actually be working in an AIDS clinic, yet my question today doesn't have to do with how fascinating AIDS is with respect to immunology). Today, I started my oral typhoid vaccine, US Brand name Vivotif. I began wondering why this immunization was an oral immunization, while most are injections given in the arm. And then I remembered reading and listening to a lecture about mucosal immunity and oral tolerance... I can't help but think that oral vaccinations would elicit the wrong immune response. Wouldn't an antigen (I assume Vivotef is a non-virulent or inactive antigen) delivered orally elicit a weakened immune response upon re-exposure, rather than a heightened one as is being observed in the case of the oral typhoid vaccination? Could someone explain what is happening (or not happening) with oral vaccinations (especially with respect to oral tolerance)???

[John Cuthber]

Typhoid fever is transmitted via food/water. the normal route for infection is oral so oral vaccination should work.

According to the web vivotif is a weakened variety of the bacterium that causes the disease so it should provoke an immune reaction.

[gatechgirl]

I get that... but how does the body discriminate between disease-causing matter you put in your mouth (like typhoid antigen) versus something like food? Why don't antigenically intact macromolecules from food cause an immune reaction (well, they typically don't... food allergy I guess is the short-coming of this), and instead elicits an oral tolerance response, while the body knows for sure that other orally ingested antigens from things that are actually pathogenic and causes an immune response? How does it know the difference, whether to invoke oral tolerance or an immune response against whatever it is presented with?

[CharonY]

Oral tolerance is, to my knowledge, only partly understood.

The common part is that both antigens (food and pathogens) are presented to T-lymphocytes, however the way they are presented changes the antigen-specific responses.It has been found that in absence of inflammatory signals, presentation of antigens to T-cells by dendritic cells favors induction of tolerance rather than activation. The precise molecular reasons are (again, to my limited knowledge as it is not my field) not quite clear but IIRC numerous activities in the spleen, and various lymph nodes as well as the lymphoid mucosa were found to be involved.

Another route is the presentation of food antigens by enterocytes which, in absence of further stimulating molecules causes the T-cells to be unresponsive to further exposure to the antigen (anergy).

I am pretty sure that more up-to-date research should be available, if you look for articles about oral tolerance.