radiation protection: antigen presenting cells
TRANSCRIPT
Radiation Protection: Antigen Presenting
Cells.Dmitri Popov MD (Russia), PhD (Russia, Canada)
Advanced Medical Technology and Systems Inc. [email protected]
Anti Radiation, Anti-Autoimmune, Anticancer Vaccine.Next presentation.• RESEARCH PROPOSAL:
Anti Radiation, Anti-Autoimmune, Anticancer Vaccine. Pre-clinical evaluation.
• [more]• Dmitri Popov• Full-text · Research Proposal · Nov 2015• ADD RESOURCES• File name: RadiationProtectionAntigenPresentingcells..pptx
DOI: 10.13140/RG.2.1.3185.6400
Anti-Radiation Vaccine and Antigen Presenting cells.• An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen
complexed with major histocompatibility complexes (MHCs) on their surfaces; this process is known as antigen presentation. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process antigens and present them to T-cells.
• Almost all cell types can serve as some form of APC, and APCs are found in a large variety of tissue types. Professional antigen-presenting cells, including macrophages, B cells, and dendritic cells, specialize in presenting foreign antigen to T helper cells, while other cell types can present antigen originating inside the cell to cytotoxic T cells. In addition to the MHC family of proteins, Antigen presentation relies on other specialized signaling molecules on the surfaces of both APCs and T cells.
• https://en.wikipedia.org/wiki/Antigen-presenting_cell
Anti-Radiation Vaccine and Antigen Presenting cells.• Antigen-presenting cells are vital for an effective
adaptive immune response, as the functioning of both cytotoxic and helper T cells is dependent on APCs. Antigen presentation allows for the extreme specificity of adaptive immunity and can contribute to immune responses against both intracellular and extracellular pathogens. It is also involved in defense against tumors. Some new therapies against cancer involve the creation of artificial APCs to prime the adaptive immune system to target malignant cells.
• https://en.wikipedia.org/wiki/Antigen-presenting_cell
Anti-Radiation Vaccine and Antigen Presenting cells.• Antigen-presenting cells fall into two categories: professional and non-professional.• T cells cannot recognize, and therefore cannot respond to, 'free' or soluble antigen. T
cells can only recognize and respond to antigen that has been processed and presented by cells via carrier molecules like MHC and CD1 molecules. Most cells in the body can present antigen to CD8+ T cells via MHC class I molecules and, thus, act as "APCs"; however, the term is often limited to specialized cells that can prime T cells (i.e., activate a T cell that has not been exposed to antigen, termed a naive T cell). These cells, in general, express MHC class II as well as MHC class I molecules, and can stimulate CD4+ ("helper") T cells as well as CD8+ ("cytotoxic") T cells, respectively. T cells must be activated by interacting with an APC, usually a dendritic cell, before they can divide and perform their function.
• To help distinguish between the two types of APCs, those that express MHC class II molecules are often called professional antigen-presenting cells.
• https://en.wikipedia.org/wiki/Antigen-presenting_cell
Anti-Radiation Vaccine and Antigen Presenting cells.• Professional APCs specialize in presenting antigen to T cells.[3] They are
very efficient at internalizing antigens, either by phagocytosis or by receptor-mediated endocytosis, processing the antigen into peptide fragments, and then displaying those peptides, bound to a class II MHC molecule, on their membrane. The T cell recognizes and interacts with the antigen-class II MHC molecule complex on the membrane of the antigen-presenting cell. An additional co-stimulatory signal is then produced by the antigen-presenting cell, leading to activation of the T cell. The expression of co-stimulatory molecules and MHC class II are defining features of professional APCs. All professional APCs also express MHC class I molecules as well. https://en.wikipedia.org/wiki/Antigen-presenting_cell
Anti-Radiation Vaccine and Antigen Presenting cells.• The main types of professional antigen-presenting cells are dendritic
cells, macrophages, and B cells. However, it has been observed that antigen presentation to CD4+ cells via MHC class II is not restricted to the classically professional APCs. Other leukocytes, including granulocytes such as mast cells and neutrophils, can be induced to do so, as can endothelial and epithelial cells under certain circumstances. However, there is little evidence that these atypical APCs are able to activate naive CD4+ T cells.
• https://en.wikipedia.org/wiki/Antigen-presenting_cell
Anti-Radiation Vaccine and Antigen Presenting cells.• Dendritic cells (DCs) are antigen-presenting cells (also known
as accessory cells) of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.
Anti-Radiation Vaccine and Antigen Presenting cells.• The blood DCs are typically identified and enumerated in flow
cytometry. Three types of DCs have been defined in human blood: the CD1c+ myeloid DCs, the CD141+ myeloid DCs and the CD303+ plasmacytoid DCs. This represents the nomenclature proposed by the nomenclature committee of the International Union of Immunological Societies.[10]Dendritic cells that circulate in blood do not have all the typical features of their counterparts in tissue, i.e. they are less mature and have no dendrites. Still, they can perform complex functions including chemokine-production (in CD1c+ myeloid DCs), cross-presentation (in CD141+ myeloid DCs), and IFNalpha production (in CD303+ plasmacytoid DCs).
Anti-Radiation Vaccine and Antigen Presenting cells.• Dendritic cells are derived from hematopoietic bone marrow
progenitor cells. These progenitor cells initially transform into immature dendritic cells. These cells are characterized by high endocytic activity and low T-cell activation potential. Immature dendritic cells constantly sample the surrounding environment for pathogens such as viruses and bacteria. This is done through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs).
Anti-Radiation Vaccine and Antigen Presenting cells.• Every helper T-cell is specific to one particular antigen. Only professional
antigen-presenting cells (macrophages, B lymphocytes, and dendritic cells) are able to activate a resting helper T-cell when the matching antigen is presented. However, macrophages and B cells can only activate memory T cells whereas dendritic cells can activate both memory and naive T cells, and are the most potent of all the antigen-presenting cells. Whereas mature dendritic cells are able to activate antigen-specific naive CD8+ T cells, the formation of CD8+ memory T cells requires the interaction of dendritic cells with CD4+ helper T cells. This help from CD4+ T cells additionally activates the matured dendritic cells and licenses them to efficiently induce CD8+ memory T cells, which are also able to be expanded a second time. For this activation of dendritic cells, concurrent interaction of all three cell types, namely CD4+ T helper cells, CD8+ T cells and dendritic cells, seems to be required. https://en.wikipedia.org/wiki/Dendritic_cell
Anti-Radiation Vaccine and Antigen Presenting cells.Altered function of dendritic cells is also known to play a major or even key role in allergy and autoimmune diseases like lupus erythematosus and inflammatory bowel diseases (Crohn's disease and ulcerative colitis).
S6-Dendritic_Cells_with_Conidia_in_Collagen.ogg.360p.webm
Anti-Radiation Vaccine and Antigen Presenting cells.• Images come from :• https://www.google.ca/search?
q=radiation+and+antigen+presenting+cells&start=10&sa=N&espv=2&biw=1366&bih=623&tbm=isch&imgil=c0XL75ucYAlCPM%253A%253BH9f-ImZMUuvUUM%253Bhttp%25253A%25252F%25252Fwww.cancernetwork.com%25252Foncology-journal%25252Fsynergizing-radiation-therapy-and-immunotherapy-curing-incurable-cancers&source=iu&pf=m&fir=c0XL75ucYAlCPM%253A%252CH9f-ImZMUuvUUM%252C_&usg=__OwZ6GqvZz6O_ve2XQRuJgiKuC0Y%3D&ved=0ahUKEwih_96nnI_LAhXGaRQKHbGCCRU4ChDKNwgy&ei=pgPNVqGUMMbTUbGFpqgB#imgrc=P3_F2Oyyecpu3M%3A
Anti-Radiation Vaccine and Antigen Presenting cells.
Anti-Radiation Vaccine and Antigen Presenting cells.
Anti-Radiation Vaccine and Antigen Presenting cells.
Anti-Radiation Vaccine and Antigen Presenting cells.
Anti-Radiation Vaccine and Antigen Presenting cells.
Anti-Radiation Vaccine and Antigen Presenting cells.• Dendritic cells are antigen-presenting cells (APCs) which play a crucial
role not only in inducing adaptive immune response to foreign antigens (Ags), but also in maintaining T cell tolerance to self-Ags, thus minimizing autoimmune reactions (Banchereau and Steinman, 1998).
• T lymphocytes are main player in the cell-mediated adaptive immune response. After migration of progenitor T cells from the bone marrow to the thymus T cells differentiate, resulting in the expressionof thetypicalco-receptorsCD4,CD8andtheassembly of functional T cell Ag receptors (TCRs).
Anti-Radiation Vaccine and Antigen Presenting cells.• Whereas the majority of CD4+ T cells are helper T (Th) cells
selectivelybindingtoMHCclassIIproteins,themajorityofCD8+ T cells are cytotoxic T cells (CTLs) restricted to binding to MHC class I proteins (Banchereau and Steinman, 1998).
Anti-Radiation Vaccine and Antigen Presenting cells.• The main function of Ag-specific CD8+ T cells (CTLs) is to eradicate
infected or tumor cells through the release of cytolytic molecules and CD95 ligation, eventually leading to the programed cell death (apoptosis) of the target cell. Besides antigenic stimulation (signal 1) and co-stimulation by APCs (signal 2), inflammatorycytokinessuchasIL-12andtypeIinterferons(IFNs) are important for driving effector T cell expansion and function (Arens and Schoenberger,2010).
Anti-Radiation Vaccine and Antigen Presenting cells.• Higher radiation doses (>2 Gy)
resultinamassivekillingofbloodcellssuchaslymphocytes(Donnelly etal., 2010) and even in a halting of the proliferation of hematopoietic progenitors, thereby causing hematological crisis (Goans and Waselenko, 2005).
• Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells.
• Katrin Manda1 et al.
• Front. Oncol., 24 August 2012 | http://dx.doi.org/10.3389/fonc.2012.00102
Anti-Radiation Vaccine and Antigen Presenting cells.• Pecautetal.(2001)published animal data which correlates with the
situation in humans; they showed that HD-IR led to a loss of spleen and thymus mass. They observed decreasing leukocyte and lymphocyte (CD4+ as well as CD8+ subpopulations) numbers in the blood and spleen of mice treated with WBI,applying doses up to 3 Gy.
• Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells.
• Katrin Manda1 et al.
• Front. Oncol., 24 August 2012 | http://dx.doi.org/10.3389/fonc.2012.00102
Anti-Radiation Vaccine and Antigen Presenting cells.• High-dose ionizing radiation is applied in approximately 50% of all
cancer patients and represents a major component of standard cancer therapy (Baskar etal., 2012). Recent investigations have demonstrated that the success in cancer treatment is contingent upon synergy of radiotherapy with the host’s immune response.
• Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells.
• Katrin Manda1 et al.
• Front. Oncol., 24 August 2012 | http://dx.doi.org/10.3389/fonc.2012.00102
Anti-Radiation Vaccine and Antigen Presenting cells.• Ionizing radiation and autoimmunity. Induction of autoimmune disease in mice by high
dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells.
• J Immunol. 1994 Mar 1;152(5):2586-95.• Sakaguchi N1, Miyai K, Sakaguchi S.• Ionizing radiation can functionally alter the immune system and break self-tolerance.
High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it
Anti-Radiation Vaccine and Antigen Presenting cells.• In contrast, irradiation of both the thymus and the peripheral
lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development.
• http://www.ncbi.nlm.nih.gov/pubmed/8133066
Anti-Radiation Vaccine and Antigen Presenting cells.• Depletion of T cells from the inocula abrogated the preventive activity.
CD4+ T cells mediated the autoimmune prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells.
• http://www.ncbi.nlm.nih.gov/pubmed/8133066
Anti-Radiation Vaccine and Antigen Presenting cells.• Autoantibodies and immunoglobulins among atomic bomb
survivors.• Radiat Res. 1994 Jan;137(1):89-95.• Fujiwara S1, Carter RL, Akiyama M, Akahoshi M, Kodama K, Shimaoka
K, Yamakido M.
Anti-Radiation Vaccine and Antigen Presenting cells.• The purpose of this study was to determine if exposure to atomic bomb radiation
affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.
Anti-Radiation Vaccine and Antigen Presenting cells.• The important role of autosensitization in the development of radiation sickness has been
shown by several investigations . Autoantibodies were first detected in the blood of irradiated animals by the complement fixation reaction 3-4 weeks , and by Wannier's method on the third day after irradiation. However, during the experimental development of methods of combined treatment of radiation sickness, too little use has been made of desensitizing preparations. No investigation has been made of the possible desensitizing effect of preparations and, in particular, antibiotics used for the treatment of radiation sickness. Meanwhile, reports have recently appeared suggesting that the therapeutic effect of antibiotics in radiation sickness may be due to some extent to their action of metabolic processes and on the reactivity of the host ctmte independently of their antibacterial properties . There are some reports that antibiotics are able to suppress the phenomena of anaphylaxis.
• http://www.ncf net.org/radiation/TemirgalievAutoimmuneProcessRadiationSicknessAntibiotics.pdf
Anti-Radiation Vaccine and Antigen Presenting cells.• Autoantibodies to the liver, spleen, kidney, lymphatic glands, aorta,
heart, large and small intestine were determined. It has been found that in rabbits, on the second day after their exposure to ionizing radiation, there form autoantibodies, whose titer increases with the progression of radiation sickness.
• http://www.ncf-net.org/radiation/TemirgalievAutoimmuneProcessRadiationSicknessAntibiotics.pdf
Anti-Radiation Vaccine and Antigen Presenting cells.• Anti Radiation, Anti-Autoimmune, Anticancer Vaccine.• Next presentation.
Anti-Radiation Vaccine and Antigen Presenting cells.• http://www.slideshare.net/dlpopov/radiation-and-self-tol
erance-mechanism• http://www.slideshare.net/dlpopov/radiation-protectionp
rotease-inhibition• http://www.slideshare.net/dlpopov/radiation-cytotoxicity• http://www.slideshare.net/dlpopov/leukocyte-and-lymph
ocyte-cytotoxicity• http://www.slideshare.net/dlpopov/prophylaxis-and-treat
ment-of-acute-toxic-radiation-cerebrovascular-syndrome-associated-with-longterm-space-flight-to-mars
Anti-Radiation Vaccine and Antigen Presenting cells.• http://www.slideshare.net/dlpopov/preclinical-evaluation-and-
clinical-application-of-novel-crossmodal-multidisciplinary-biotechnology-with-antiradiation-prophylaxis-antiradiation-vaccine-and-therapy-regimens-antiradiation-antidote-and-anticancer-postradiation-prophylaxis
• http://www.slideshare.net/dlpopov/anti-radiation-antidote-inhibition-and-neutralization-of-radiation-toxicity-with-therapeutic-monoclonal-antibodies
Anti-Radiation Vaccine and Antigen Presenting cells.• http://www.slideshare.net/dlpopov/acuteradiation-disease-acute-radi
ation-vasculitis• http://www.slideshare.net/dlpopov/neutron-radiation-radiation-prot
ection• http://www.slideshare.net/dlpopov/radiation-protection-49178938• http://www.slideshare.net/dlpopov/handrons-radiation-protection• http://www.slideshare.net/dlpopov/radiation-toxicity-tolllike-receptor
s
Anti-Radiation Vaccine and Antigen Presenting cells.• http://www.slideshare.net/dlpopov/radiation-toxity-complement-syst
em-activation• http://www.slideshare.net/dlpopov/radiation-toxicity-tolllike-receptor
s• http://www.slideshare.net/dlpopov/radiation-toxicity-necrosis-apopt
osis• http://www.slideshare.net/dlpopov/antiradiation-vaccine-40518777• http://www.slideshare.net/dlpopov/233240482-antiradiationuvvaccin
e
Anti-Radiation Vaccine and Antigen Presenting cells.• http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20070021485.p
df• http://www.ncbi.nlm.nih.gov/pubmed/17867496• http://www.radioprotection.org/articles/radiopro/pdf/2008/05/0000
10.pdf• http://www.intechopen.com/books/statistics/current-topics-in-ionizin
g-radiation-research/radiation-toxins-molecular-mechanisms-of-toxicity-and-radiomimetic-properties-
Anti-Radiation Vaccine and Antigen Presenting cells.• RADIOPROTECTION - VOL. 43 - N◦ 5 (2008) 253 Article published by
EDP Sciences and available at • http://www.radioprotection.org • or http://dx.doi.org/10.1051/radiopro:2008514