Melvin Cohn and Rodney E. Langman

The Salk Institute, P.O. Box 85800, San Diego, California, 92186-5800

Received 8/15/96; Accepted 9/9/96; On-line 10/1/96

3. THE DECISION PATHWAYS OF AN IMMUNE RESPONSE

Decision 1, is the antigen self or nonself? If it is self, an immune response must be inactivated; if it is nonself, an immune response must be activated and further control passed on to Decision 2, in order to determine which effector class would be optimal in ridding the pathogen? This latter decision is needed to cope with multiple, often contradictory effector reactions. For any given pathogen, there are ineffective and effective effector functions. In many cases the ineffective effector functions can block the efficacy of the effective effector functions because both compete for the recognition of antigen. The S-NS discrimination, determines the specificity with which the effector response rids the inducing pathogen without self-destructing. The specificity of the effector response is composed of several elements, one of which is the specificity of the antigen-receptor on responsive cells itself.

Decision 2, the choice of class of effector function is related to the location and the nature of the pathogen, because these factors determine the ability of a particular effector function to destroy and rid the pathogen. Cell-bound pathogens such as viruses, intracellular bacteria, rickettsia, and certain protozoan parasites require a response in the cell-mediated effector class. In general, the cell-mediated mode is a delaying tactic. The infection is slowed down but not ridded. A virally infected cell that is lysed by a cytotoxic lymphocyte can liberate free virus capable of infecting other cells albeit at a much lower yield. To rid this virus, a humoral response is eventually required. In many cases of viral infection, the effector response is initially cell-mediated with a subsequent switching over to the humoral response. In a few cases, generally involving non-viral intracellular pathogens, the cell-mediated mode is sufficient to keep the infection in check.

Free pathogens, such as bacteria, initially require a humoral antibody response. In this case there are a handful of effector functions available to the immune system; including, complement lysis, antibody dependent cellular cytotoxicity, opsonization, chemical warfare (e.g., histamine and serotonin release), neutralization of toxicity, and blockage of invasiveness. These effector functions are associated with different Ig isotypes, albeit with some overlap. A choice must be made between these isotypes that relates them to the effectiveness of ridding the pathogen.

There are three key questions to consider: What are the factors governing a learned S-NS discrimination? What does evolution look at when selecting upon the humoral response? What are the requirements for a regulation of class?