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Minggu, 10 Juni 2018

Frontiers | An Updated View of the Intracellular Mechanisms ...
src: www.frontiersin.org

Cross-presentation is the ability of certain antigen-presenting cells to extract, process and present extracellular antigens with class I MHC molecules to CD8 T cells (cytotoxic T cells). Cross-priming, the result of this process, describes CD8 cytotoxic T8 cell stimulation to activated Cytotoxic CD8 cells T. This process is necessary for immunity against most tumors and viruses that do not easily infects antigen-presenting cells, but intracellular tumors and viruses that infect peripheral tissue cells. Cross-presentation is also required for the induction of cytotoxic immunity by vaccination with protein antigens, for example, tumor vaccination.

Cross-presentation is important, as it allows the presentation of exogenous antigens, usually presented by MHC II on dendritic cell surfaces, also presented via MHC I pathways. MHC I pathways are commonly used to present endogenous antigens that have infected certain cells. However, cross-presentation cells can utilize MHC I pathways to remain uninfected, while still triggering an adaptive immune response of activated cytotoxic T8 cells to infected peripheral tissue cells.


Video Cross-presentation



History

The first evidence of cross presentation was reported in 1976 by Michael J. Bevan after grafted cell injection carries a minor minor histocompatibility (MHC) molecule. This results in a CD8 T-cell response induced by antigen-receiving cells to foreign MHC cells. Therefore, Bevan implies that these antigen presenting cells must have swallowed and crossed presented these foreign MHC cells to host CD8 cytotoxic cells, thus triggering an adaptive immune response against the grafted tissue. This observation is called "cross-priming".

Then, there is much controversy about cross presentation, which is now believed to be due to the peculiarities and limitations of some of the experimental systems used.

Maps Cross-presentation



Cross Presenting Cells

Although the main and most efficient cells are dendritic cells, macrophages, B lymphocytes and sinusoidal endothelial cells have also been observed to traverse present antigens in vivo and in vitro. However, in vivo dendritic cells have been found to be the most efficient and common antigen presenting cells to traverse the antigens present in MHC I molecules. There are two subtypes of dendritic cells; plasmacytoid (pDC) and myeloid (mDC) dendritic cells. pDCs are found in the blood and are able to traverse present direct antigens or from neighboring apoptotic cells, but the major physiological significance of pDCs is IFN type I secretion in response to bacterial infections. mDC categorizes DC migration, DC residents, Langerhans cells, and inflammatory dendritic cells. All mDCs have special functions and secretory factors, but they are all still able to bypass existing antigens to activate cytotoxic CD8 T cells.

There are many factors that determine cross-presentation functions such as antigen absorption and processing mechanisms, as well as environmental signals and cross-dendritic cell activation. Cross activation presents dendritic cells depending on stimulation by CD4 T helper cells. The CD40/CD40L co-stimulatory molecule together with the presence of hazards of exogenous antigens is the catalyst for dendritic cell administration, and thus cross-presentation and naïve CD4 cytotoxic T cell activation.

Frontiers | Application of Antigen Cross-Presentation Research ...
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Volar and Cytosolic Redirects

In addition to the solid structure retrieval, dendritic cell phagocytosis simultaneously modifies the kinetics of endosomal trade and maturation. As a result, the external soluble antigen is targeted to the cross-presentation MHC class I cross-path rather than the Class II MHC pathway. [18] However, there is still uncertainty in terms of the cross-presentation mechanistic pathways in cells presenting antigens. Currently, there are two main lines proposed, cytosolic and vacuolar.

The vacuolar pathway begins through endocytosis of extracellular antigens by dendritic cells. Endocytosis results in the formation of phagocytic vesicles, where an increasingly acidic environment along with enzyme activation such as lysosomal protease triggers the degradation of antigens into peptides. The peptide can then be loaded into the groove of MHC I in the phagosome. It is unclear whether the MHC I molecule is being exported from the endoplasmic reticulum prior to loading the peptide, or being recycled from the cell membrane prior to loading the peptide. Once the exogenous antigen peptide is loaded onto the class I MHC molecule, the complex is exported to the cell surface for presentation of a cross antigen presentation.

There is also evidence to suggest that cross-presentation requires a separate path in the proportion of cross-linking CD8 () dendritic cells. <20> This line is called the cytool transfer path.. Similarly, with the vacuolar pathway, the antigen is brought into the cell through endocytosis. An antigen protein is transported out of this compartment into the cytoplasm by an unknown mechanism. In the cytoplasm, exogenous antigens are processed by proteasome and degraded into peptides. This processed peptide can be transported by the TAP transporter into the endoplasmic reticulum, [14] [16] or return to the same endosome to load onto the class I MHC complex, [17] . It is believed that the loading of MHC I occurs in both the ER and the phagocytic vesicles such as the endosome in the cytosolic pathway. For the MHC I class contained in the Endoplasma Reticulum, exogenous antigen peptides are loaded onto class I MHC molecules with the help of peptide loading proteins and counter proteins such as beta-2 microglobulin, ERAP, tapapsin, and calreticulin. After loading the antigen peptide, the MHC molecule is transported out of the ER, through the Golgi complex, and then to the surface of the cell for cross presentation.

It appears that both pathways may occur in antigen presenting cells, and may be influenced by environmental factors such as proteasome and phagocytic inhibitors.

Oxidized Lipids Block Antigen Cross-Presentation by Dendritic ...
src: www.jimmunol.org


Relevance for immunity

Cross-presentation has been shown to play a role in the defense of immunity against many viruses (herpesvirus, influenzavirus, CMV, EBV, SIV, papillomavirus, etc.), bacteria (listeria, salmonella, E. coli , < i> M. tuberculosis , and others) and tumors (brain, pancreas, melanoma, leukemia, etc.). Although many viruses can inhibit and degrade the activity of dendritic cells, cross-linked dendritic cells that are not affected by the virus can absorb infected peripheral cells and still show exogenous antigens to cytotoxic T cells. Cross priming action can increase immunity to antigens targeting intracellular peripheral tissues that can not be mediated by antibodies produced by B cells. Also, cross-priming avoids viral immune-avoidance strategies, such as antigen-suppression suppression. As a result, immune responses to a virus that is capable of doing so, such as the herpes virus, rely heavily on cross presentation for successful immune responses. Overall, cross-presentation help in facilitating adaptive immune responses to intracellular virus and tumor cells.

Cross-presentations dependent dendritic cells also have implications for cancer immunotherapy vaccines. Injection of specific anti-tumor vaccines can be targeted to a subset of certain dendritic cells in peripheral skin tissue, such as migratory dendritic cells and langerin cells. After vaccine-induced activation, dendritic cells may migrate to lymph nodes and activate CD4 T helper cells as well as prime CD8 T cytotoxic cells. This mass generation of specially activated CD8 cell T cells enhances anti-tumor immunity, and is also able to overcome many of the effects of immune suppression of tumor cells.

Antigen Processing And Presentation Pathways | giftsforsubs
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Relevance for immune tolerance

Cross presenting dendritic cells has a significant impact on the promotion of central and peripheral immune tolerance. In central tolerance, dendritic cells are present in the thymus, or site of T cell development and maturation. Thymus dendritic cells can absorb dead epiphytic thymus epithelial cells, and bypass the current "self" peptide in class I MHC as a negative selection test on T cells cytotoxicity that has a high affinity for self peptides. The presentation of tissue-specific antigen is initiated by medullary thymic epithelial cells (mTEC), but reinforced by thymic dendritic cells after AIRE expression and swallowing mTECs. Although the function of dendritic cells in central tolerance is still relatively unknown, it appears that thymic dendritic cells act as a complement of mTEC during negative selection cells.

In terms of peripheral tolerance, peripheral tissue that rests dendritic cells is capable of promoting self-tolerance to cytotoxic T cells that have an affinity for self peptides. They can present tissue specific antigens in the lymph nodes to regulate cytotoxic T cells from initiating adaptive immune responses, as well as regulating high affinity cytotoxic T cells for self-independent tissues but still escaping from central tolerance. Cross Presenting DCs are able to induce anergy, apoptosis, or regulatory status of T for high affinity cytotoxic T cells. It has major implications for defense against automatic immune disorders and specific cytotoxic T cell regulation itself.

Oxidized Lipids Block Antigen Cross-Presentation by Dendritic ...
src: www.jimmunol.org


References


Oxidized Lipids Block Antigen Cross-Presentation by Dendritic ...
src: www.jimmunol.org


External links

  • Cross Presentation at US National Library of Medicine Subject Medical Headings (MeSH)

Source of the article : Wikipedia

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