Immunotherapy for Infectious Diseases

Humoral Immunity 15
Fig. 9. Messenger molecule (cytokine) mediator circuits involved in immunity. Ag, antigen;
IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. (Modified from ref. 56.)
sites of tissue inflammation or infection (Fig. 9). Surprisingly, in HIV infection, specific
chemokine receptors on CD4� target cells are now known to function as coreceptors
required for viral entry.
B-CELLS
Early Development of the Repertoire
The evolutionary selection pressure guiding T-cell and B-cell repertoire development
is the same in each case: to generate a range of specificities that will protect against
various and unpredictable infectious disease challenges while limiting the potential for
reactivity against self. This selection pressure acts on the level of the individual animal,
such that the individual with the most effective repertoire in a particular time and
place is most likely to survive and reproduce. The selection pressure also acts on the
level of the population, such that repertoire diversity maintained within a population
makes it more likely that some individuals will survive to reproduce after an infectious
outbreak.
The downside of clonal deletion as a mechanism for tolerance is that it creates holes
in the repertoire. A pathogen could take advantage of these holes by mimicking self to
evade immune recognition. For T-cells, this problem is dealt with by balanced polymorphism
of MHC within a species. T-cell recognition of peptide in the context of
polymorphic MHC molecules provides each individual with a different T-cell repertoire
complete with different holes (12–14). Thus MHC polymorphism provides protection