Biology Reference
In-Depth Information
1.3.2 Hierarchy of Cellular Receptors
Hierarchy may also be observed amongst cellular receptors: for example, cell surface
receptors operate through long signal-transmission pathways. In contrast, steroid-
thyroid hormone and vitamin D receptors are nuclear regulatory proteins. Nuclear
receptors are very powerful and are capable of overruling membrane receptors.
This is the reason for the tremendous regulatory influence of the HPA axis. Some
peptide hormones were proposed to release nuclear regulatory peptides (e.g., PRL)
during intracellular processing, but the existence of this phenomenon remains
controversial.
At the cellular level, adhesion molecules that deliver cell-to-cell signals are domi-
nant for delivering signals that are specific for the position of a single cell in the
body. Such positional signaling consists of adhesion and CTK signals that decide the
function of a given cell in the tissues
[66]
. Each cell is bombarded by a myriad of
signals at any time. Activated cells cap the occupied receptors to one pole of the cell
where receptor interaction will take place. Positive signals to the cell are transmit-
ted by phosphorylation of receptors by protein kinases, whereas negative signaling
involves rapid dephosphorylation of the activated (phosphorylated) sites by phos-
phatases (Ship). The balance of positive and negative signals decides if the cell will
be activated or remain inactive
[67]
.
1.4 Immunological Memory
We observed that the secondary antibody response was partially independent of
the pituitary. In Hypox rats we obtained a secondary antibody response that was
of similar titer to the primary response
[38]
. This observation shows that memory
cells of the ADIM system do not require pituitary hormones for survival and func-
tion; they are autonomous. However, their ability to recruit naïve lymphocytes to
expand the secondary response was impaired. This observation also showed that
memory cells survived the severe adaptive immunodeficiency present in Hypox ani-
mals. Others also observed that in immunodeficient (lymphopenic) hosts, memory
T cells not only survive, but also undergo antigen and MHC-independent homeostatic
proliferation (HP), the biological significance of which is to preserve and regenerate
the immunocompetence of the host after severe, debilitating diseases.
1.4.1 HP of Lymphocytes
In lymphopenic/immunodeficient hosts,
naïve and memory CD4
and CD8
T cells,
naïve B cells, and natural killer
(
NK
)
cells undergo HP
. This proliferation is MHC
and antigen independent, and B cells share many of the inductive and regulatory
characteristics established for naïve and memory T cells and NK cells
[68-70]
.
Naïve T cells can be induced to undergo HP of variable speed with a few members
of the common gamma-chain (gamma c) (CD132) family of CTKs. The speed of pro-
liferation depends on the levels of the particular CTK involved
[71]
.
