K.K. Jain, Textbook of Personalized Medicine, DOI 10.1007/978-1-4939-2553-7_17, 551
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Chapter 17
Personalized Approaches to Immune Disorders
Introduction
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 rec-
ognize 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.
It has been shown that NK cells acquire functional competence through ‘licensing’ by
self-MHC molecules (Kim et al. 2005 ). This process results in two types of self-tolerant
NK cells − licensed or unlicensed − and may provide new insights for exploiting NK
cells in immunotherapy. It is possible to engineer entire MHC class I molecules into
mouse cells by inserting only that gene. These studies have revealed that developing
NK cells are 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 indi-
viduals, this virus causes a chronic infection lasting several decades. In other indi-
viduals, 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
treatment do not always have an anti-tumor effect. Although the donor NK cells are
expected to attack leukemic cells as being “non-self,” the outcome is not as expected
in some cases and licensing needs should be considered. Further research is aimed at
developing immunological tests to determine if licensing can be used to predict suc-
cessful eradication of viral infections or anti-leukemia effects.