 the central nervous , immune , and endocrine systems communicate through multiple common messengers . over evolutionary time , what may be termed integrated defense system(s ) ( ids ) have developed to coordinate these communications for specific contexts ; these include the stress response , acute - phase response , nonspecific immune response , immune response to antigen , kindling , tolerance , time - dependent sensitization , neurogenic switching , and traumatic dissociation ( td ) . 
 these idss are described and their overlap is examined . 
 three models of disease production are generated : damage , in which idss function incorrectly ; inadequate / inappropriate , in which ids response is outstripped by a changing context ; and evolving / learning , in which the ids learned response to a context is deemed pathologic 
 . mechanisms of multiple chemical sensitivity ( mcs ) are developed from several ids disease models . 
 model 1a is pesticide damage to the central nervous system , overlapping with body chemical burdens , td , and chronic zinc deficiency ; model 1b is benzene disruption of interleukin-1 , overlapping with childhood developmental windows and hapten - antigenic spreading ; and model 1c is autoimmunity to immunoglobulin - g ( igg ) , overlapping with spreading to other igg - inducers , sudden spreading of inciters , and food - contaminating chemicals . 
 model 2a is chemical and stress overload , including comparison with the susceptibility / sensitization / triggering / spreading model ; model 2b is genetic mercury allergy , overlapping with : heavy metals / zinc displacement and childhood / gestational mercury exposures ; and model 3 is mcs as evolution and learning . 
 remarks are offered on current mcs research . 
 problems with clinical measurement are suggested on the basis of ids models . 
 large - sample patient self - report epidemiology is described as an alternative or addition to clinical biomarker and animal testing.imagesfigure 1figure 2figure 3figure 1figure 2figure 3figure 4figure 5 
Images