This essay is a selected aspect of the history of contemporary immunology seen from a "what can we learn" point of view. It is limited to the ideas and experiments from which we might draw a take-home message. The emphasis is on the convoluted pathway that was actually used by immunologists to arrive at understanding compared to the direct pathway that could have been used given the knowledge at that time. It takes the reader through the instructionist era of the 1940s to the present by stressing the elements of thinking most conducive to the arrival at a default understanding of the intact immune system. It is a personalized account because the author participated directly in the debates that led eventually to agreed-upon or default conceptualizations. Given this, a peek at the future is attempted as a test of the validity of a Cartesian or reductionist approach to arriving at simplification of complexity and at the maximizing of generalization. A reasoned guess (i.e., a theory) is the only way we have to understand the world around us.
Keywords: BCR; Concepts; Dendritic cells; Self-nonself discrimination; TCR.