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Immunological tests have an important place in the future of personalized medi-
cine. The role of immune system in personalization of treatment in infections and
cancer has already been discussed in earlier sections.
Personalized Approaches in Immunology
The innate immune system is the fi rst line of host defense against infectious agents.
There are many variations of response in individuals. Immunology has already been
playing an important role in personalization of therapy, e.g. blood grouping and
cross-matching for blood transfusion.
Comprising the third largest lymphocyte population, natural killer (NK) cells
recognize and kill cellular targets and produce pro-infl ammatory cytokines. These
potentially self-destructive effector functions can be controlled by inhibitory recep-
tors for the polymorphic major histocompatibility complex (MHC) class I molecules
that are expressed on target cells. However, the genes for the MHC proteins and the
NK cell receptors are inherited independently from one another, and can vary widely.
NK cells acquire functional competence through ‘licensing’ by self- MHC molecules
that results in two types of self-tolerant NK cells − licensed or unlicensed − and may
provide opportunities for exploiting NK cells in immunotherapy. NK cells can be
induced to become functional by Ly49, an inhibitory receptor on their surface, which
plays an activating, or licensing, role in enabling immature NK cells to develop into
functioning, self-tolerant cells. The licensing concept might explain differences in
response among human patients with HCV infections. In many individuals, this
virus causes a chronic infection lasting several decades. In other individuals, the
virus seems to be controlled and eradicated as they have “better licensed” NK cells
that mount a better response to the virus. Licensing might also explain why donor
NK cells given to leukemia patients during bone marrow transplantation as treat-
ment do not always have an anticancer effect. Although the donor NK cells are
expected to attack leukemic cells as being “non-self,” the outcome in some cases is
not as expected and licensing needs should be considered. Further research is aimed
at developing immunological tests to determine if licensing can be used to predict
successful eradication of viral infections or anti-leukemia effects.
Immunological tests have an important place in the future of personalized medi-
cine. The role of immune system in personalization of treatment in infections and
cancer has already been discussed in other chapters.
Pharmacogenetics and Pharmacogenomics
of Immunosuppression
Immunosuppressive therapy has markedly improved over the past years with the
advent of highly potent and rationally targeted immunosuppressive agents. Since
these drugs are characterized by a narrow therapeutic index, major efforts have
17 Personalized Approaches to Immune Disorders