Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 109

Orai calcium release-activated calcium channel modulator-1, but not Orai3, is
inhibited by oxidation by reactive oxygen species [ 208 ]. The decreased redox
sensitivity of effector T H cells is correlated with increased amounts of Orai3 and
several cytosolic anti-oxidants.

3.9.4 PIP 3 and IP 4 Signals in Lymphocytes

Membrane lipid phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) regulates mem-
brane receptor functioning, in particular immunoreceptor signaling. Soluble inositol
(1,3,4,5)-tetrakisphosphate (IP 4 ) participates in the development and activity of
leukocytes, such as T and B cells and neutrophils, as it controls phosphoinositide
3-kinases, phosphatase and tensin homolog (PTen), SH2-domain-containing inositol
5-phosphatases SHIP1 and SHIP2 that target PIP 3 in lymphocytes [ 209 ]. Agent IP 4
regulates the membrane recruitment of proteins, as it promotes or impedes their
interactions with PIP 3 Lipid.
In mouse thymocytes, membrane recruitment of inducible T-cell kinase (ITK)
by IP 4 achieves a positive feedback loop on phospholipase-C

1 downstream from
T-cell receptors to produce sufficient amount of the second messenger diacylglyc-
erol to trigger positive selection and generation of a mature T-cell directory [ 209 ].
In humans, inositol (1,4,5)-trisphosphate 3-kinase ITPKc limits T-cell activation
level. Its defect contributes to Kawasaki disease in children. Inositol trisphosphate
3-kinase ITPKb is required for B-cell development and functional competence, as it
restrains store-operated Ca 2 + entry as well as PIP 3 -mediated membrane recruitment
of protein kinase-B in neutrophils [ 209 ].

γ

3.9.5 Immunological Memory

Lymphocytes provide antigen-specific acquired immunity, hence immunological
memory. Immature T- and B-cell activity is restricted mainly to lymphoid tissues.
Activated T cells migrate more efficiently than antigen-unexperienced T cells.
Phenotype and certain features allow to distinguish long-lived memory B and T cells
from short-lived effectors. Antigen-experienced T cells include: (1) central memory
cells that circulate through lymphoid tissues and (2) effector memory cells that do
not move.
Immunological memory confers long-lasting protection. Naive cells of the im-
mune system that have not been previously exposed to a given antigen actually learn
from the first experience of encountering a pathogen to adapt and react quickly
to future invasion. Cells of the adaptive immune system undergo a secondary
expansion and trigger a robust protective response when they re-encounter the same
pathogen. The adaptive immune system is thus characterized by an antigen-specific
memory response.