oral tolerance vs immunity

Gregory R. Harriman gregoryh at bcm.tmc.edu
Sat Jul 8 14:17:02 EST 1995

In article <preston-070795165938 at>,
preston at warren.med.harvard.edu (Mike Preston) wrote:
> Just an additional question and comment.  What is the immune response that
> you are looking for?  Is an antibody response going to be effective for
> what you want your vaccine to do, or does a TH1 type inflammatory T cell
> response constitute "protective immunity?" 
>         Oral tolerance most often refers to T cell tolerance (TH1).  The
> mechanisms of suppression, anergy vs active supression, depend on the
> antigen and dose (high doses can also induce oral tolerance) and other
> factors. You can still induce strong serum and mucosal antibody responses
> following oral administration of antigen even when tolerance in the TH1
> type T cell compartment is induced. 
>         Thus, if an antibody mediated effect is what you are looking
for, you are
> more likely to be succesful with oral immunizations . 

     Sorry, but this is not entirely correct.  Previous studies on oral
tolerance have shown that one can induce systemic tolerance to both
cell-mediated and humoral immune responses.  In fact, some of the earliest
studies in animals addressed tolerance to immediate hypersensitivity
reactions which are antibody-mediated (ie. IgE).  Most studies which have
successfully induced systemic (or mucosal) antibody responses by oral
feeding have utilized some type of mucosal adjuvant in addition to antigen
(eg. cholera toxin).  As has previously been stated, the rules which
govern induction of an immune response versus tolerance after oral feeding
are poorly understood currently.  Consequently, one must take somewhat of
an empirical approach in ascertaining how best to induce an immune
response with a given antigen.  For those interested in learning more
about mucosal immunology, one book which I find useful is the "Handbook of
Mucosal Immunology", P.L. Ogra, M.E. Lamm, J.R. McGhee, J. Mestecky, W.
Strober and J. Bienenstock, editors.  Academic Press, 1994.

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