Biology Reference
In-Depth Information
7.3 Sensing Adaptive Immune Reactions by the CNS
In the adaptive immune system, an antigen is recognized first by phagocytic cells,
such as a macrophage, dendritic cell, or the like. The specific effector cells of
ADIM are T and B lymphocytes, which bear immunoglobulin antigen receptors on
their surfaces. These receptors have exquisite specificity for the antigenic determi-
nants (epitopes) they recognize. Lymphocytes mediate the highly specific adaptive
immune response. After phagocytosis of exogenous antigens by antigen-presenting
cells (APCs), the antigen is digested (“processed”) and short peptides are presented
sequentially by surface major histocompatibility (MHC) molecules to CD4 T cells.
T helper type 2 (Th2) cells develop via stimulation by epitopes presented in the con-
text of surface MHC-II. B lymphocytes also recognize macromolecular antigens
via surface immunoglobulin receptors (conformational recognition), pinocytose the
antigens, and process the antigens and present epitopes via their MHC-II to Th2
helper cells. Once activated, the helper cells secrete cytokines (IL-4, -6, -8, etc.) and
stimulate the presenting B lymphocytes for antibody formation. In turn, Th1 cells
induce cell-mediated immunity by recognizing
endogenous antigens
, which may be
presented by any nucleated cell after processing and presentation of the epitopes via
their surface MHC-I molecules. IL-2 and IFN are major cytokines of this reaction.
Effector CD4 cells, which deliver delayed-type hypersensitivity reactions, and
CD8 killer T cells are induced. CD4 cells induce an inflammatory response at
sites of antigen depots, whereas killer T cells recognize cells with abnormal MHC-I
(e.g., virus-infected or cancer cells). Such abnormal cells trigger killer T cells for
cytotoxicity. The adaptive immune system is clonal and the specific clones prolif-
erate only when stimulated by antigen, a process that takes approximately 1 week
in the primary response and in which most of the antibodies produced are immuno-
globulin (Ig)M. After repeated immunization, secondary responses develop, which
are boosted by memory cells and hence develop faster (within 3-4 days) and produce
predominantly IgG antibodies
[2]
.
7.3.1 Cytokine Feedback Signals to the Hypothalamus
After injection of rats with various antigens (e.g., lipopolysaccharide, bovine serum
albumin, tetanus anatoxin), C-fos gene and protein expression were induced in neu-
rons of the paraventricular nucleus (PVN) in the hypothalamus. These experiments
indicate that after ordinary immunization, there is activation of neurons in the PVN,
which is the center of neural immunoregulation. This result proves that the CNS
receives signals as soon as an immune reaction is initiated. This was true for both
T-cell-dependent and T-independent antigens
[39]
.
By now there is voluminous evidence for the existence of feedback pathways
between the immune system and the brain. The idea of immune-derived feedback
by cytokines was pioneered by Besedovsky and co-workers, and it has subsequently
been proven by many laboratories
[40]
.
The following cytokines were found to serve as feedback signals from the
immune system to the brain: IL-1, TNF, different types of interferons, IL-2, IL-6,
