Kunkel Lecture: Fundamental immunodeficiency and its correction

Abstract

"Fundamental immunodeficiency" is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is "adopted immunity," not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity.

Figure 1.

Function of the human immune system. The immune system is the set of cellular and soluble factors by which the germline genome interacts with the somatic, mitochondrial, fetal, and microbiotal genomes to protect the individual’s ability to propagate the species. Arrows between genomes signify epigenetic, transcriptional, and posttranscriptional influences on expression of genes in one genome of an individual by the alleles present in the individual’s other genomes.

Figure 2.

Encoded and adopted immunity together comprise the contemporary human immune system. The alleles in an individual’s metagenome (see Fig. 1) determine his or her encoded immune response. The genes in the societal groups to which an individual belongs influence the groups’ potential for cooperative endeavors. Society can adopt behaviors that help the encoded immune system compensate for fundamental immunodeficiency, such as provision of nutrition (including vitamins), sanitation (including shelter, potable water, hygiene, and disposal of waste), vaccines, and antimicrobial agents. Such forms of immunity were only recently adopted and are not automatically maintained. Some sectors of society have withdrawn from vaccines. Globally, society has unintentionally been on course to abandon antimicrobial agents.