Immunophysiology and immunopathology

The physiology of the immune system has to encompass the capacity of the cells that constitute it to respond to a wide range of exogenous stimuli, and the capacity to operate under diverse conditions at the periphery as well as in central sites.

An attractive hypothesis is that the difference between immunophysiology and immunopathology should be regarded in evolutionary terms. In this hypothesis, a unicellular organism will respond to an exogenous stimulus (such as cell-cell contact) with a physiological reaction (such as repulsion and phagocytosis). As soon as multicellularity arises, there must be some mechanism to recognize the second cell as self, and hence not a potential target - but this mechanism must make use of the existing recognition pathways to generate such a 'nonresponse'. As soon as this nonresponse to self condition has been achieved, the organism has created for itself a new homeostatic status, which can be maintained and regulated as the molecules concerned turn over and are replaced, but which becomes the physiological immune system for that particular organism.

Subsequently, added on to this very basic recognition mechanism, as the immune system has evolved, we have acquired overlays, so that in mammals there is a complex pattern of genes which have the potential to rearrange and encode for proteins specific for target antigens. If the target is a self product, then these genes may rearrange to encode for the proteins that are involved in positive and negative selection in the thymus, as examples of immunophysiologic reactions. If, on the other hand, the target is extrinsic, then the rearrangement is nor immunophysiologic.

In this context, the major type of immunopathology is clearly breach of tolerance to self. Although this is the most obvious and well-established example, it is not difficult to envisage how other instances might arise. For example, most cytokines have been identified for their role in response to injury and in pathological processes. Presumably, these roles represent immunopathology, and the mediators do have a physiological homeostatic role which has thus far been much more difficult to define.

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