Historical links between toxinology and immunology.

Research on bacterial toxins is closely linked to the birth of immunology. Our understanding of the interaction of bacterial protein toxins with immune cells has helped to decipher immunopathology, develop preventive and curative treatments for infections, and propose anti-cancer immunotherapies. The link started when Behring and Kitasato demonstrated that serotherapy was effective against 'the strangling angel', namely diphtheria, and its dreadful toxin discovered by Roux and Yersin. The antitoxin treatment helped to save thousands of children. Glenny demonstrated the efficacy of the secondary immune response compared to the primary one. Ramon described anatoxins that allowed the elaboration of effective vaccines and discovered the use of adjuvant to boost the antibody response. Similar approaches were later made for the tetanus toxin. Studying antitoxin antibodies Ehrlich demonstrated, for the first time, the transfer of immunity from mother to newborns. In 1989 Marrack and Kappler coined the concept of 'superantigens' to characterize protein toxins that induce T-lymphocyte proliferation, and cytokine release by both T-lymphocytes and antigen presenting cells. More recently, immunotoxins have been designed to kill cancer cells targeted by either specific antibodies or cytokines. Finally, the action of IgE antibodies against toxins may explain their persistence through evolution despite their side effect in allergy.

Selective immunotoxic lesions of basal forebrain cholinergic neurons: twenty years of research and new directions.

The advent of the selective cholinergic toxin, 192 IgG-saporin, dramatically shaped subsequent research on the role of the basal forebrain in learning and memory. In particular, several articles (including the authors' 1995 Behavioral Neuroscience paper; M. G. Baxter, D. J. Bucci, L. K., Gorman, R. G. Wiley, & M. Gallagher, 1995) revealed that selective removal of basal forebrain cholinergic neurons had surprisingly little effect on spatial learning and memory. Here, as part of the series commemorating the 30th anniversary of Behavioral Neuroscience, we describe how our earlier findings prompted a reconsideration of the cholinergic contribution to cognitive function and also led to several new research directions, including renewed interest in basal forebrain GABA-ergic neurons and cholinergic contributions to neurocognitive development. The authors also describe how the successful use of 192 IgG-saporin led to the development and popularity of a wide range of selective new neurotoxic agents. Finally, they consider the utility of the permanent lesion approach in the wake of new transgenic and optogenetic methods.

Selective immunotoxic lesions of basal forebrain cholinergic cells: effects on learning and memory in rats.

Male Long-Evans rats were given injections of either 192 IgG-saporin, an apparently selective toxin for basal forebrain cholinergic neurons (LES), or vehicle (CON) into either the medial septum and vertical limb of the diagonal band (MS/VDB) or bilaterally into the nucleus basalis magnocellularis and substantia innominata (nBM/SI). Place discrimination in the Morris water maze assessed spatial learning, and a trial-unique matching-to-place task in the water maze assessed memory for place information over varying delays. MS/VDB-LES and nBM/SI-LES rats were not impaired relative to CON rats in acquisition of the place discrimination, but were mildly impaired relative to CON rats in performance of the memory task even at the shortest delay, suggesting a nonmnemonic deficit. These results contrast with effects of less selective lesions, which have been taken to support a role for basal forebrain cholinergic neurons in learning and memory.