LOCAL IMMUNITY AND VACCINATION

The organism is protected against the entry of microorganisms by a barrier constituted by a series of mechanisms. Passive mechanisms include tightness of the epithelia lining the body and carbohydrates (mucus, surface glycoconjugates). Defensins and the inflammatory response represent active, but not specific, protection. The specific mucosal immune system comes into play when these non-specific mechanisms have failed. The mucosal immune response is initiated in lymphoid follicles and their associated epithelium. Rapid transcytosis of antigens is the task of specialized cells in the follicle associated epithelium: the M cells. M cells differ from site to site and from species to species, and could differenciate locally from other epithelial cells. Antigen is brought in contact with the T and B cells present in a pocket formed by the M cells, The stimulated blasts migrate to the underlying follicle and the draining lymph nodes,where they mature, then move on to the bloodstream. The integrin alpha(4) beta(7) allows them to home to the mucosa. Other receptors could be involved in fine tuning the homing site, which is more centered on the induction site than previously thought. B cells differenciate into plasma cells (mainly IgA) in the lamina propria. The IgA transcytosed by the epithelium serve in immune exclusion, intracellular viral neutralisation and export of antigen back to the lumen The IgA response is the major protective response in the mucosal immune system, and is the one that mucosal vaccines attempt to stimulate. T cells home either to the lamina propria (lamina- propria lymphocytes, LPL) or to the epithelium (intraepithelial lymphocytes, IEL). Other IEL come directly from the bone marrow. Gut IEL are mostly CD8(+) and alpha(E) beta(7)(+). Their functional activities include cytoxicity. The mouse-mammary tumor-virus MMTV (which disseminates via the entero-enteric cycle), and Shigella (which takes advantage of the inflammatory response to weaken the epithelial barrier), are examples of pathogens <<highjacking>> the mucosal immune response in their invasive strategies. This interplay of host and pathogen, as well as the compartmentalization of the mucosal immune system, will have to be addressed by vaccinal strategies.