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Classic and Current Opinions in Human Organ and Tissue Transplantation - PubMed

  • ️Sat Jan 01 2022

Review

. 2022 Nov 1;14(11):e30982.

doi: 10.7759/cureus.30982. eCollection 2022 Nov.

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Review

Classic and Current Opinions in Human Organ and Tissue Transplantation

Angus N Oli et al. Cureus. 2022.

Abstract

Graft tolerance is a pathophysiological condition heavily reliant on the dynamic interaction of the innate and adaptive immune systems. Genetic polymorphism determines immune responses to tissue/organ transplantation, and intricate humoral and cell-mediated mechanisms control these responses. In transplantation, the clinician's goal is to achieve a delicate equilibrium between the allogeneic immune response, undesired effects of the immunosuppressive drugs, and the existing morbidities that are potentially life-threatening. Transplant immunopathology involves sensitization, effector, and apoptosis phases which recruit and engages immunological cells like natural killer cells, lymphocytes, neutrophils, and monocytes. Similarly, these cells are involved in the transfer of normal or genetically engineered T cells. Advances in tissue transplantation would involve a profound knowledge of the molecular mechanisms that underpin the respective immunopathology involved and the design of precision medicines that are safe and effective.

Keywords: allo-transplant; brief history; graft tolerance; grafting; kidney transplantation; regenerative medicine; tissue engineering; tissue transplantation; types of transplantation; xeno-transplant.

Copyright © 2022, Oli et al.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Timeline of landmark achievements in kidney transplantation. This figure has been developed using Biorender [https://biorender.com/] license number: YP24IH1241. Image Credit: Susmita Sinha.
Figure 2
Figure 2. Clinical Stages of Graft Rejection. Notes: APC=Antigen Presenting Cell, CD=Clusters of Differentiation. This figure has been developed using Biorender [https://biorender.com/] License Number: DA24ILUA8K. Image Credit: Susmita Sinha.
Figure 3
Figure 3. Clinical Stages of Graft Rejection. Notes: APC=Antigen Presenting Cell, MHC=Major Histocompatibity Complex, CD=Clusters of Diffrentiation, T Cell= A Subclass of Lymphocytes. This figure has been developed using Biorender [https://biorender.com/] License Number: DA24ILUA8K. Image Credit: Susmita Sinha.
Figure 4
Figure 4. Role of Natural Immunity in Graft Rejection. Notes: APC=Antigen Presenting Cell, DAG=Diacyl Glycerol, LAT=Linker for Activation of T-Cell, MAPK=Mitogen-Activated Protein Kinase, RAS=Rat Sarcoma, PKC=Protein Kinase C, SAPK=Stress Activated Protein Kinasse, JNK=c-Jun N-terminal Kinase, CD=Clusters of Differentiation, PIP=Phosphatidyl Inositol Phosphate, PKB=Protein Kinase B, NFκβ= Nuclear Factor kappa beta, Th=T hepler cells, IL=Interleukin. This figure has been developed using Biorender [https://biorender.com/] license number: VY24J04THQ. Image Credit: Susmita Sinha.
Figure 5
Figure 5. Illustrating the regulatory effect of T regulatory cells on the immune system. Treg cells release anti-inflammatory cytokines like IL10 and TGFβ and also convert ATP to AMP, which together inhibits the proliferation of effector T lymphocytes. Treg cells release perforin that attacks effector T cells and causes their apoptosis. CD25 expression from Treg cells causes sequestration of IL 2 and decreases the proliferation of Natural Killer cells (NK cells). Treg cells also directly inhibit the proliferation of B lymphocytes and reduce the expression of CD 80 and CD 86. Treg also promotes the differentiation of monocyte to M2 macrophages and suppresses the conversion of monocyte to M1 macrophages, which is pro-inflammatory. Treg also causes neutrophils to reduce the secretion of IL 6 and CXCL. Notes: Treg cell: T regulatory cell. NK cell: Natural killer cell. IL: Interleukin. TGF: Transforming Growth Factor. CXCL: CXC chemokine Ligand., ATP: Adenosine Triphosphate, AMP: Adenosine Monophosphate, CD: Clusters of differentiation, T Cell: Subclass of Lymphocytes, IL: Interleukin. This figure has been developed using BioRender [https://biorender.com/] License Number: PL24IU7VJY. Image Credit: Rahnuma Ahmad
Figure 6
Figure 6. Showing the mechanism of different immunosuppressive drugs on T and B lymphocytes. Drugs inhibit specific pathways, cell cycle, and DNA synthesis by inhibiting mTOR, NFkB, NAFT, and JAK, which decreases lymphocyte activation and proliferation and promotes graft tolerance. mTOR: mammalian target of rapamycin. NFkB: Nuclear Factor kB. NAFT: Nuclear factor of activated T cells. JAK: Janus Kinase. This figure has been developed using Biorender [https://biorender.com/] license number: RC24IZS47Z. Image Credit: Rahnuma Ahmad

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