Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

386 Glossary
press the proper receptor/counter-receptor pairs. These signals control the induction
of T lymphocyte-mediated immune responses as well as the maturation of B lymphocytes.
The `two-signal hypothesis` was an earlier concept of the co-stimulation concept,
initially seeing interleukin-2 as the second and co-stimulating signal. Later, B7
with its receptor CD28 were recognized as a major co-stimulatory molecule combination.
CpG motif
Immune-stimulating, unmethylated CG dinucleotides in various sequence contexts
found in bacterial DNA. Vertebrate DNA contains 20 times fewer CG sequences
that, usually, are methylated and in sequence contexts that are not immune stimulatory.
The receptor for CpG is the Toll-like receptor 9 (TLR-9) which is expressed by B
lymphocytes and plasmacytoid dendritic cells.
Cross-priming
Induction of a T cellular immune response that is restricted by the MHC of the immunized
individual rather than the MHC of the cells used for immunization. Crosspriming
was originally reported for immunizations of F1 mice against cells of one of
the parental mouse strains. These immunizations resulted partly in the induction of
CD8 + cytotoxic T lymphocyte responses that were specific for minor histocompatibility
antigens of one of the parent strains, but restricted by the MHC of the other parent.
The term cross-priming is most often used to describe the ability of antigen-presenting
cells to take up and present MHC class I-restricted antigens derived from other cells.
Cytokine
Small soluble proteins and transfer signals from one cell to another. Cytokines include
a number of different protein families such as interferons, interleukins or chemokines
with various different functions in the immune system. They are important immune
regulating molecules and serve as growth and differentiation factors or as suppressors
of immune responses.
Cytotoxic T lymphocyte (CTL)
Effector T lymphocyte that, upon specific, MHC-restricted antigen recognition, lyse
other cells. Most of the CTLs express the CD8 accessory receptor and are MHC class
I restricted. However, there are also CD4 + MHC class II-restricted CTLs. Cytolysis
may be achieved by (1) a mechanism depending on the pore-forming perforin and
granzyme, and (2) a Fas/Fas ligand-dependent mechanism. The differential actions
of these two mechanisms are not yet completely understood. In both cases, the attacked
cell dies by apoptosis. Perforin by itself forms only pores and leads to necrosis.
In conjunction with granzymes, the components of intracellular death pathways are
accessible and induced. Of the eight described granzymes, only granzyme B was unequivocally
linked to the induction of apoptosis. CTLs themselves are relatively resistant
to their own cytolytic machineries ± factors at the cell membrane that resemble
the decay accelerating factor as well as cytosolic serine esterase inhibitors (Serpins)
are involved in this protection.