Radiation Toxicity, Radiation Toxins, Immune Reactions, Antiradiation Vaccine.

1. Dmitri Popov. PhD, Radiobiology.
MD (Russia)
Advanced Medical Technology and Systems
Inc. Canada.

2.  Toll-like receptors (TLRs) are a class
of proteins that play a key role in the innate
immune system.
 They are single, membrane-spanning, non-
catalytic receptors usually expressed
in sentinel cells such
as macrophages and dendritic cells, that
recognize structurally conserved molecules
derived from microbes.

3.  . Once these microbes have breached physical
barriers such as the skin or intestinal
tract mucosa, they are recognized by TLRs,
which activate immune cell responses. The
TLRs
include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6,
TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and
TLR13.

4.  A group of transmembrane proteins, Toll-like
 receptors (TLRs), play critical roles as
pattern-recognition receptors.

5.  TLR has common effects, such as
inflammatory cytokine induction or
upregulation of costimulatory molecule
expression, but also has its specific function,
exemplified by type I IFN-inducing ability.

6.  Immunoadjuvant effects are not only critical in
antimicrobial immunity but are also involved in
manifestations of autoimmunity.
 TLR agonists are now promising therapeutic tools
for various immune disorders, including allergy
and Acute and Chronic Radiation Disorders.
 Tsuneyasu Kaisho, MD, PhD,a and Shizuo Akira,
MD, PhDb,c Kanagawa and Osaka, Japan.
 http://www.intechopen.com/books/current-
topics-in-ionizing-radiation-research/radiation-
toxins-molecular-mechanisms-of-toxicity-and-
radiomimetic-properties-

7.  Therefore understanding molecular
mechanisms on TLRs should be quite useful
in the development of therapeutic strategy
against allergy and autoimmune
 Diseases include Acute and Chronic Radiation
Diiseases . (J Allergy Clin Immunol
2006;117:979-87.)

8.  Host defense in mammals copes with pathogens
through 2 types of immunity: innate and adaptive
immunity.
 Innate immunity functions as a pathogen sensor and
pattern recognition sensor and contributes to the
eradication of pathogens or autoimmune reactions
and the establishment of adaptive immunity. These
functions heavily depend on pattern-recognition
receptors (PRRs).
 Tsuneyasu Kaisho, MD, PhD,a and Shizuo Akira, MD,
PhDb,c Kanagawa and Osaka, Japan.
 http://www.intechopen.com/books/current-topics-
in-ionizing-radiation-research/radiation-toxins-
molecular-mechanisms-of-toxicity-and-
radiomimetic-properties-

9.  Toll like receptors (TLRs), are featured by
their potent ability to activate antigen-
presenting cells (APCs).
 Innate immune cells carry the molecules that
can not only recognize the microorganisms or
not self- patterns but can also trigger the
signaling pathways, leading to production of
inflammatory cytokines or type I IFNs.

10.  TLRs can recognize common molecular
structures detected in certain groups of
microorganisms as non-self. These were
originally called pathogen-associated
molecular
 patterns, but here we call them
microorganism-associated molecular
patterns (MAMPs)

11.  TLRs can also recognize proteins. TLR5
recognizes a protein, flagellin, which is a
component of the bacterial flagella. Some
scientists in USSR ( from 1970) and later in
USA reported that flagellin derivates could be
effective radioprotective medical substance.


12.  Autoantibodies that are commonly associated
with systemic auto immune diseases — such
as systemic lupus erythematosus (SLE),
 scleroderma and Sjögren’s syndrome (BOX 1)
— bind DNA, RNA or macromolecular
complexes that contain DNA or RNA.

13.  Intracellular autoantigens become ‘visible’ to
the immune system when they accumulate on
the plasma membrane during apoptotic cell
death, necroptotic cell death, necrosis and
subsequent uptake and processing by
activated antigen-presenting cells (APCs)
then leads to a loss of tolerance.

14.  Radiation induced apoptosis or necroptosis or
necrosis results in the cleavage of these
molecules (by granzyme B, other proteases or
nucleases2), thereby creating neo-epitopes that
can be recognized as foreign by cells of the
adaptive immune system.
 Toll-like receptors in systemic autoimmune
disease. Ann Marshak-Rothstein.
 http://www.intechopen.com/books/current-
topics-in-ionizing-radiation-research/radiation-
toxins-molecular-mechanisms-of-toxicity-and-
radiomimetic-properties-

15.  Neo-epitopes could also be generated
 by other forms of post-translational modification or by structural
modifications induced by environmental factors such as ionized
radiation or UV radiation or High Frequency Radiation.
 However, data continue to accumulate in support
 of the idea that auto-antigens are auto-antigens because they
are auto-adjuvants: that is, they have the capacity to activate the
innate immune system directly and therefore promote self-
directed immune responses. Utz, P. J., Gensler, T. J. & Anderson,
P. Death, autoantigen modifications, and tolerance. Arthritis Res.
 2, 101–114 (2000).
 4. Plotz, P. H. The autoantibody repertoire: searching
 for order. Nature Rev. Immunol. 3, 73–78 (2003).
 Toll-like receptors in systemic autoimmune disease. Ann
Marshak-Rothstein.

16.  Acute Radiation Syndromes is a complex of acute
autoimmune, inflammatory disease that arises after
different doses and different types of radiation and affect
the hematopoietic system, central and peripheral nervous
system, gastro-intestinal system, liver, skin, kidneys,
lungs, vasculature, serous membranes and multiple
organs. The effector mechanisms of inflammation depend
on lymphocytes, neutrophils, monocytes, platelets and
mast cells and involve the complement, kinin and
coagulation cascades.
 Toll-like receptors in systemic autoimmune disease. Ann
Marshak-Rothstein.
 http://www.intechopen.com/books/current-topics-in-
ionizing-radiation-research/radiation-toxins-molecular-
mechanisms-of-toxicity-and-radiomimetic-properties-

20.  Self –molecular ligands potentially contribute
to autoantibody production with formation
of immune complexes. Self -molecular
ligands could play role of autoantigens.
 Many of the common autoantigens are
released from dead and dying cells, and
might become available to the immune
system as a result of excessive cell damage
by radiation and an inability to appropriately
clear apoptotic-cell debris.