Dr. Wallace Rowe 
Page 2 
May 15, 1979 
Against this background of microbe-human host parasitism and interaction, it is 
no surprise to learn that E. coli as well as other microorganisms colonizing other areas 
of our body contain antigenic constituents indistinguishable from those found in our own 
native cells, tissues and organs. It is also no surprise to learn that a varying proportion 
of the human population has recognized some of these microbial antigenic stimuli as 
sufficiently non-self or foreign so as to result in production of antibodies which are reactive 
with autologous cells or tissues which coincidentally, share the cross-reactive antigenic 
constituent ( s ) in question. Several cross-reactive microbial-host cell or microbial-host 
tissue systems have been described for E. coli. Str eptococcus pyogenes ( group A 
beta hemolytic streptococci ) and other microorganisms which not uncommonly parasitize 
humans. The titers of auto-antibody resulting from such microbial cross-reactive systems 
are usually of low order in most subjects. Cell-mediated autoreactive immmune 
responses arising from such microbial stimuli appear to be less common and less important 
in terms of risk of autoimmune disease. 
The first point to stress in the context of this discussion is that despite the stage 
seemingly being set for microbe induced host autoimmune responses occurring on a large 
scale, relatively few such autoreactive responses have been characterized in definitive 
fashion. At least one explanation for this is the effective immunosuppressive regulatory 
activity of the mammalian immunological system which is able to prevent such potentially 
self-destructive types of immune responses from being made. The second point to be 
stressed is that in none of the well documented instances of microbe-host cell cross- 
reactivities, have the antibodies in question been clearly shown to be etiologically 
responsible for the diseases with which they have been shown to be associated. More often 
than not, such autoreactive antibodies have been found in variable titers in clinically well 
subjects. In fact, one school of thought holds that such autoreactive immune responses 
may exert beneficial effects with respect to more efficient turnover of our endogenous 
bodily constituents. 
Given the fact that genetic exchange among enteric microorganisms undoubtedly 
occurs spontaneously on a scale far wider than the phenotypic markers of such gene inter- 
action would presently allow us to recognize and given the fact that such spontaneous. 
DNA recombinant events among microorganisms parasitizing mankind have been going 
on since the beginning of time, I am frankly surprised at how few good examples of 
microbe-host cross-reactive immune reactions we can point to at present. I attribute 
this to the extraordinary adaptive capacity of the mammalian immunological system 
to reduce to a minimum those immune responses involving self, including microbial 
cross-reactive responses involving self, which might have undesirable consequences with 
respect to selective and adaptive pressures for the human species on an evolutionary 
time scale. 
[ 266 ] 
