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group_1_presentation_1_-_kidney_transplant_rejection [2016/01/29 23:58] prabahd |
group_1_presentation_1_-_kidney_transplant_rejection [2018/01/25 15:18] (current) |
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| ==== Minimizing Risks of Rejection ==== | ==== Minimizing Risks of Rejection ==== | ||
| Human Leukocyte Antigen (HLA) is the human version of the commonly studied Major Histocompatibility Complex (HMC), highly involved in immunological reactions. This HLA molecule is expressed on the surface of all cells in the human body, presenting randomly generated peptides from the interior[20]. This allows for the immune system to monitor whether cells are healthy or infected, as well as whether an immune response needs to be mounted. To prevent the immune system from recognizing the newly transplanted graft as foreign, the donor and recipient both have their HLA genes checked using high-resolution DNA typing techniques[20]. The HLA system has loci across chromosome 6, expressing 3 classes of HLA[20]. When matching HLA between the donor and recipient, HLA –A, –B, and –DR are checked for similarities[20]. There are a vast number of alleles for these genes (>800 type –A and –B, >400 type –DR), adding to the complexity of matching donors and recipients appropriately to minimize risk of rejection[20]. | Human Leukocyte Antigen (HLA) is the human version of the commonly studied Major Histocompatibility Complex (HMC), highly involved in immunological reactions. This HLA molecule is expressed on the surface of all cells in the human body, presenting randomly generated peptides from the interior[20]. This allows for the immune system to monitor whether cells are healthy or infected, as well as whether an immune response needs to be mounted. To prevent the immune system from recognizing the newly transplanted graft as foreign, the donor and recipient both have their HLA genes checked using high-resolution DNA typing techniques[20]. The HLA system has loci across chromosome 6, expressing 3 classes of HLA[20]. When matching HLA between the donor and recipient, HLA –A, –B, and –DR are checked for similarities[20]. There are a vast number of alleles for these genes (>800 type –A and –B, >400 type –DR), adding to the complexity of matching donors and recipients appropriately to minimize risk of rejection[20]. | ||
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| + | <style float-right> | ||
| + | {{:chromosome_6.jpg|}} | ||
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| + | ''Figure 6: Chromsome 6 Expresses 3 Classes of HLA'' | ||
| + | </style> | ||
| Internationally, HLA matching between donors and recipients differ by the acceptability of mismatches[20]. Countries with organ transplant systems regulate the amount of HLA mismatch they deem is acceptable in order for the transplant to be viable[20]. In the United States, because the majority of organ donors belong to Caucasian ancestry, the HLA alleles are skewed towards certain populations[20]. This puts recipients of differing ancestral backgrounds at a disadvantage when an organ transplant is vital for their health, such as in the case of end-stage renal diseases[20]. | Internationally, HLA matching between donors and recipients differ by the acceptability of mismatches[20]. Countries with organ transplant systems regulate the amount of HLA mismatch they deem is acceptable in order for the transplant to be viable[20]. In the United States, because the majority of organ donors belong to Caucasian ancestry, the HLA alleles are skewed towards certain populations[20]. This puts recipients of differing ancestral backgrounds at a disadvantage when an organ transplant is vital for their health, such as in the case of end-stage renal diseases[20]. | ||
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| - Semi-direct allorecognition occurs when recipient antigen-presenting cells “capture” donor MHC complexes with an antigen from the graft and presenting it to T-cells of the recipient’s immune system. The function of semi-direct allorecognition has not yet been elucidated [3]. | - Semi-direct allorecognition occurs when recipient antigen-presenting cells “capture” donor MHC complexes with an antigen from the graft and presenting it to T-cells of the recipient’s immune system. The function of semi-direct allorecognition has not yet been elucidated [3]. | ||
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| + | <style float-left> | ||
| + | {{:allorecognition.jpg?300x200}} | ||
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| + | ''Figure 7: Allorecognition in Renal Transplants'' | ||
| + | </style> | ||
| ==== Types of Rejection ==== | ==== Types of Rejection ==== | ||
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| Overall, allorecognition leads to the priming of T-cells, activating them to respond to the presenting antigen. In most cases, dendritic cells or other antigen-presenting cells are exposed to these peptides first, resulting in their activation and migration to the thymus. In the thymus, the antigen is presenting via MHC to T-cells, allowing for their maturation and ability to launch an immune response [20]. Recently, it has been elucidated that T-cells do not necessarily need to become activated at the Thymus, but can also be activated directly at the graft via interactions with the endothelial cell lining of the transplant [20]. The microenvironment where T-cells become activated leads to the differentiation of T-cells, varying in their cytokine signatures and functionalities (CD8+ T-cells versus CD4+ T-cells). This differentiation depends on the expression of a master transcription factor, determining the final subset of cytotoxic T-cells (CD8+) and T-helper cells (CD4+). During renal transplants, there are many factors that can affect the microenvironment post-transplant [20]: | Overall, allorecognition leads to the priming of T-cells, activating them to respond to the presenting antigen. In most cases, dendritic cells or other antigen-presenting cells are exposed to these peptides first, resulting in their activation and migration to the thymus. In the thymus, the antigen is presenting via MHC to T-cells, allowing for their maturation and ability to launch an immune response [20]. Recently, it has been elucidated that T-cells do not necessarily need to become activated at the Thymus, but can also be activated directly at the graft via interactions with the endothelial cell lining of the transplant [20]. The microenvironment where T-cells become activated leads to the differentiation of T-cells, varying in their cytokine signatures and functionalities (CD8+ T-cells versus CD4+ T-cells). This differentiation depends on the expression of a master transcription factor, determining the final subset of cytotoxic T-cells (CD8+) and T-helper cells (CD4+). During renal transplants, there are many factors that can affect the microenvironment post-transplant [20]: | ||
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| + | <style float-right> | ||
| + | {{:rejection_mech.png?300x200}} | ||
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| + | ''Figure 8: Mechanisms of Rejection'' | ||
| + | </style> | ||
| * Immune status of the recipient at the time of transplant | * Immune status of the recipient at the time of transplant | ||
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| <style float-right> | <style float-right> | ||
| - | {{:fungi.png|}} | + | {{:fungi.png?200x220}} |
| - | ''Figure 6: Cyclosporine from a Fungal Origin'' | + | ''Figure 9: Cyclosporine from a Fungal Origin'' |
| </style> | </style> | ||
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| <style float-left> | <style float-left> | ||
| - | {{:3d2.png|}} | + | {{:3d2.png?371x265}} |
| - | ''Figure 7: 3D Print Technology for Customizing Organs'' | + | ''Figure 10: 3D Print Technology for Customizing Organs'' |
| </style> | </style> | ||
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| 3D-Prints is a relatively new application that is being used to print many organs such as the heart, kidneys and other crucial organs <sup>[18]</sup>. | 3D-Prints is a relatively new application that is being used to print many organs such as the heart, kidneys and other crucial organs <sup>[18]</sup>. | ||
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| ====== References ====== | ====== References ====== | ||
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| [20] Wood, K. J., & Goto, R. (2012). Mechanisms of rejection: current perspectives. Transplantation, 93(1), 1-10. | [20] Wood, K. J., & Goto, R. (2012). Mechanisms of rejection: current perspectives. Transplantation, 93(1), 1-10. | ||
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