excitations in DNA
Electrons in Photosynthetic Reaction Centers
of anti-tumor immunity
V. Osipov, O.
It is well established that likewise foreign agents
(viruses, bacteria, distinct protein molecules) tumor cells can
stimulate immune response directed to destroy them. There are two
types of reactions to the presence of foreign agent - antigen. The
first is non-specific immune reactions. Elements of non-specific
anti-virus and anti-tumor defense are both NK (natural killer) cells
and LAK-cells populations. They can kill tumor cells without preliminary
recognizing certain antigen. The mechanism of non-specific immune
response is described more detail in .
As non-specific immune reaction usually is not sufficient
to destroy the tumor cells population, clone of lymphocytes specific
to tumor antigen is formed. This is specific immune reaction.
The are two forms of specific immune response - humoral
and cellular. The first is concluded with production of specific
protein molecules - antibodies by mature B cells, plasma cells.
Antibodies bind to foreign antigens forming complex that is eliminated
from an organism .
This immune reaction is effective to fight infection disease caused
by viruses and bacteria. Antibodies produced in response to tumor
cells formation can bind to tumor antigens. As tumor cell can lose
its surface antigens, complex antigen-antibody leaves tumor cell
before process of antibody dependent lysis develops. Anti-tumor
antibodies block antigens of tumor cells and T cell receptors, preventing
tumor cells from cytolytic impact .
Thus these immune complexes worse development of disease.
The cellular form of specific immune response is used by an organism
mainly against foreign cells (cells of transplanted tissues and
organs, in tumor transformation). In process of cellular immune
response clone of T lymphocytes (CD8+ T cells) specific to foreign
antigen is formed. By means of T cell receptors CD8+ T cells bind
to antigen determinants presented on the surface of tumor cell and
Differentiation of both B lymphocytes and T lymphocytes specific
to tumor antigen into plasma cells and cytotoxic T lymphocytes respectively
is consists of some similar stages [1,3,17].
Let us briefly describe the process T lymphocyte differentiation.
Three stages can be singled out: presentation of both tumor antigen
with MHC-II and antigen with MHC-I molecules by antigen-presenting
cells to helper T cell and T lymphocyte precursor respectively;
production of interleukine-2 by helper T cells in response to antigen
presentation and activation T lymphocyte precursor proliferation;
proliferation and differentiation into cytotoxic T lymphocytes under
influence of interleukine-2. Cytotoxic T lymphocytes recognize tumor
antigens with MHC-I molecule on the surface of tumor cells bind
to tumor cells and kill them [1,3,17].
During process of differentiation
all intercellular interactions are mediated by system of interleukins.
There are more then 20 interleukins. All of them carry out different
functions in forming of anti-tumor defense .
However tumor growth results in a disbalance between the production
and regulation of cytokins as well as in a reduction of corresponding
receptors. For example, amounts of interleukine-2 (Il-2) and interleukine-12
(Il-12) decrease markedly during the malignant growth. As a result,
the activity of killer cells and, accordingly, the strength of the
anti-tumor immune response become weaker .
The methods for enhancement of both the anti-tumor
resistance and the general condition of the immune system in tumor-bearing
organisms are of current interest. In particular, one of the modern
methods in the immunotherapy refers to the use of cytokins [5,6].
Interleukine-2 is considered as the main cytokine responsible for
the proliferation of cells containing Il-2 receptors and their following
Il-2 is mainly produced by activated CD4+ T cells. Many investigations
give evidence that Il-2 plays an important role in specific immunological
reactions to foreign agents including tumor cells. Besides, this
cytokine provides enhancement of natural killer (NK) cell cytotoxic
Clinical trials show that there are positive treatment effects at
low doses of Il-2 [6,8,9].
At the same time, at high doses of Il-2 treatment may cause serious
hematological violations revealed by anemia, granulocytopenia, thrombocytopenia,
Recently, a recovery of IL-2 production after the
exposure of tumor-bearing mice to low-intensity centimeter waves
was experimentally observed .
This indicates that exposure to centimeter electromagnetic waves
can be used for an enhancement of the anti-tumor immune response.
This finding stimulates our interest to study the influence of exposure
on tumor-immune dynamics.
A theoretical investigation of cancer growth under
immunological activity has a long history .
Most of the known models consider dynamics of two main populations:
effector cells and tumor cells. The behavior of cancer growth under
the effect of immunity as well as the effect of therapy was the
central point of these investigations. The effect of cytokines on
the disease dynamics has been considered only in few models [12,13]
In the framework of our research we have formulated
the dynamical model for the anti-tumor immune response based on
a scheme of intercellular cytokine-mediated interactions 
with the interleukine-2 taken into account .
The production of Il-2 is considered to depend on the antigen presentation.
Our study shows that the production rate of Il-2 has a distinct
influence on the tumor dynamics. At low production of Il-2 a progressive
tumor growth to a highest possible value occurs. At high production
rate of Il-2 there is a regression of tumor to a small value when
the dynamical equilibrium between the tumor and the immune system
is achieved. In the case of the medium production of Il-2 both these
regimes can be realized depending on the initial tumor size and
the condition of the immune system. The influence of low-intensity
electromagnetic microwaves is considered as a parametric perturbation
of the dynamical system. The pronounced immunomodulating effect
is found with the suppression of tumor growth and the normalization
of Il-2 concentration in good agreement with the recent experimental
results on immunocorrective effects of centimeter electromagnetic
waves in tumor bearing mice.
Nowadays in the framework of proposed model we consider
strategies for combining chemotherapy and immunotherapy of tumors.
Different methods of chemotherapy alone certainly provide increase
of progression free survival time as well as complete remission
of tumor in few percent of cases. Enhancement of the chemotherapeutic
effect by increase of drug dose is not possible. As chemotherapeutic
drugs usually kill cells in the process of division, beside tumor
cells dividing much more rapidly than most normal cells, fast-growing
cells are also killed by chemotherapy. Normal cells susceptible
to drugs are marrow cells, hair, stomach lining, and immune cells
Therefore it is necessary to find out method of combining destructive
chemotherapy and immunotherapy. Clinical trials show that of all
the currently employed treatment modalities, cisplatin-based (chemical
drug) regimens combined with biologic agents such as interferon-a
and interleukine-2, have attained the highest clinical response
The mechanism of biochemotherapy's enhanced activity against cancer
is not known, but a large amount of preclinical data points to some
biological interactions that may be involved. One of hypotheses
for the mechanism of this therapeutic action is enhancement of the
chemotherapeutic effect by induction of local NO (nitric oxide)
production, which would inhibit the repair of chemotherapy-induced
DNA damage .
NO production is induced by interferon-g [1,15].
Beside this it might be suggested that TNF-a
(tumor necrosis factor a) production
induced by interleukine-2 is increased by immunotherapeutic interleukine-2
As TNF-a induce apoptosis (programming
cell destruction), increase of its production can enhance the chemotherapeutic
effect. Following this facts and taking into account that in the
process of division cells are more susceptible to drugs 
we add our system with corresponding terms and equation describing
chemotherapeutic drug dynamics. Preliminary results of calculations
show that the use of sequential a biochemotherapy strategy concluded
in chemotherapy followed immediately by biotherapy allows to enhance
the time, for which tumor size riches dangerous value, by approximately
20-25 days. Received results are in qualitative agreement with clinical
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of Electrons in Photosynthetic Reaction Centers
In plants and bacteria the energy of light is stored
in the energy of the electric potential later used to form chemical
bonds. The reaction center complex from the anoxygenic purple photosynthetic
bacteria are the best understood of all photosynthetic organisms,
from both a structural and a functional point of view. Photosynthesis
begins when light is absorbed by an antenna pigment. The photons
from the antenna pigment procced to the reaction centers (RC). The
photosynthetic reaction centers is a special pigment-protein complex,
that functions as a photochemical trap. The precise details of the
charge separations reactions and subsequent dark electron transport
(ET) form the central question of the conversion of solar energy
into the usable chemical energy of photosynthetic organism. The
function of the reaction center is to convert solar energy into
biochemical amenable energy.
Despite the striking symmetry of the cofactors into
2 branches of RC, there arisses very big asymmetry in ET. The electron
transfer proceeds only along the one branch from two possible at
least with 10:1 ratio. Our understanding of the primary processes
in photosynthesis is not complete without explanation of the strong
asymmetry in ET. This is the first step to a better understanding
of the process of electron transfer and thus the transport of energy
in photosynthetic organisms. Consequently, it could open a way for
using the solar energy more efectively. We present some models to
elucidate the unidirectionality of the primary charge-separation
process in the bacterial reaction centers.
See more about the photosynthesis in bacteria at the gallery section
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