Acute Radiation Disease, MHC 1, MHC 2, autoimmune disease,

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

2. Molecular mechanisms of Acute
Radiation Disease.
 The immune system is the major and most important
mechanism to protect human body ( mammals) from
influence of radiation.
 As a component of defence system immune system
characterized by their ability distinguish modified,
changed molecular structures – distinguish self
antigens from non-self antigen.
 Molecular structures – self antigens, modified after
irradiation, can be “considered” as non-self antigens.

3. Molecular Mechanisms of Acute
Radiation Disease.
 Can we consider Acute Radiation Disease as an
Autoimmune Disease ?
 Can we consider Acute Radiation Disease as a process
similar to hyper acute transplant rejection?
 Can we consider Acute Radiation Disease as a process
similar to an acute transplant rejection ?
 Can we consider Chronic Radiation Disease as a
process similar to a chronic transplant rejection?
 Can we consider Acute Radiation Disease as
hypersensitivity reactions?

4. Molecular Mechanisms of Acute
Radiation Disease.
 Hypersensitivity diseases have been grouped into four
major categories based upon their underlying causes.
These groups are:
 1.) Immediate (type I) hypersensitivity
2.) Antibody-mediated (type II) hypersensitivity
3.) Immune complex-mediated (type III)
hypersensitivity
4.) Cell-mediated (type IV) hypersensitivity.
 Pathology. Clinicopathologic Foundations of
Medicine. Rubin E. et al. Lippincott
Williams&Wilkins.

5. Molecular Mechanisms of Acute
Radiation Disease.
 Antibody mediated autoimmune reactions occurs
hours to days after irradiation (hyper acute reactions),
but may be delayed by several days if sensitization to
damaged by radiation auto antigens has had occure
after relatively small or moderate doses of radiation.
In the worst case of extremely high doses of radiation
scenario of Acute Radiation Disease ( ARS) begins
immediately after irradiation .

6. Molecular Mechanisms Of Acute Radiation
Disease.
 Cellular and protein components of Immune System
mediate distinctions between self and non-self.
 Major Histocompatibility Complex. Major
Histocompatibility Complex class I (MHC I) proteins
protect the host from intracellular
 pathogens and cellular abnormalities through the
binding of peptide fragments
 derived primarily from intracellular proteins.
 http://onlinelibrary.wiley.com/doi/10.1111/j.1399-
0039.2010.01550.x/abstract

7. Molecular Mechanisms of Acute
Radiation Disease.
 T-cell receptors recognize degraded fragments of pathogen
proteins.
 T-cell receptors recognize peptide antigens bound to
human cell-surface molecules.
 MHC Class I and MHC Class II
 Two classes of MHC molecule present peptide antigens
to two types of T cell.
 MHC class I molecules present antigens of intracellular
origin to CD8 T cells.
 MHC class II molecules present antigens of extracellular
origin to CD4 T Cells.
http://course1.winona.edu/kbates/Immunology/chapter1.h
tm

8. Molecular Mechanisms Of Acute Radiation
Disease.
 These peptide-MHC complexes are displayed
 at the cell surface for inspection by cytotoxic T
lymphocytes.
 http://onlinelibrary.wiley.com/doi/10.1111/j.1399-
0039.2010.01550.x/abstract
 The major histocompatibility complex (MHC) contains the
most diverse genes known in vertebrates, the class I and II
loci. These highly polymorphic genes encode cell surface
receptors that play a central role in controlling
immunological self/non- self recognition, and
subsequently tissue rejection, autoimmunity, and immune
responses to infectious diseases.

9. Molecular Mechanisms Of Acute Radiation
Disease.
 The polymorphisms of MHC genes has been maintained by
natural selection over long periods of evolutionary time.
Major Histocompatibility Complex (MHC)
Dustin J Penn, University of Utah, Salt Lake City, Utah,
USA

10. Molecular Mechanisms Of Acute Radiation
Disease.
 Class I antigens located on the surface of all nucleated
cells and comprise two molecules of proteins – a large
44 kDa molecule encoded by class I gene and Beta 2
Microglobulin – small, 12 kDa.

11. Molecular Mechanisms Of Acute Radiation
Disease.
 For the immune system to attack a damaged by
radiation molecular structures, it must be able to
discriminate between the body’s own normal tissue
 (self) and damaged molecular structures recognized as
foreign tissue (non-self).
Immunological self/ non-self recognition is partly
controlled by a set of genes in the ‘Major
Histocompatibility complex’ or ‘MHC’.

12.  Underway.