ABSTRACT

The molecular analysis of immunity means just that: the analysis, at the molecular level, of the ability to mount an immune response. It is an analysis of function rather than status. As such, it is critical to understand that although we are able to identify many aspects of the immune system in intricate detail (especially in mice), these aspects may not translate into ‘immunity’. The concept of immunity entails whether an individual can respond to a herpes virus infection, whether immunization against a pathogen will confer protection, whether a broad T cell repertoire returns after a stem cell transplant, and so on. When considering the molecular analysis of immunity in humans, especially in the settings of lymphopenia and immune reconstitution, it is the adaptive arm of the immune system that draws the most attention from immunologists and clinicians. The T and B lymphocytes that make up this arm use their diverse and unique antigen receptors to recognize and respond to intracellular and extracellular pathogens respectively. Not only can adaptive immunity respond to insults, but it can also amplify itself through clonal expansion to generate increased numbers of differentiated memory cells. Lymphocytes use two different but related mechanisms to recognize extracellular and intracellular pathogens. B cells use the immunoglobulin molecules, either on their surface or as a secreted antibody for their activation and defense against pathogens in the extracellular space, respectively. 1 T cells express receptors on their surface that recognize peptide fragments derived from pathogens that are presented on the surface of major histocompatibility (MHC) molecules. 2 The central role of adaptive immunity in fighting infection is nowhere better illustrated than in the morbidity and mortality associated with the immunodeficiency of AIDS or after chemotherapy. 3 , 4 When it comes to cells such as T and B cells, the analysis of immunity can be summarized in three questions:

(1) How many cells are there in the individual?

(2) What do they look like? and

(3) How well do they function?