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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Acute rejection is the first phase of rejection which occurs within a few weeks or months of graft implantation. This form of rejection occurs in graft recipients that possess mature, graft-reactive T lymphocytes and is characterized by infiltration of the graft tissue with these lymphocytes. The first change is accumulation of small lymphocytes on the capillary and venule walls. The lymphocytes pass through the vascular endothelium and infiltrate the grafted tissue. With the passage of time the infiltration becomes intense and diffuse. This response is self-sustaining and has been called a vicious cycle caused by the local release of cytokines, which up-regulate expression of MHC molecules, which activate more cytokine release, and so on. The infiltrating cells cause the progressive disruption of the capillaries and venules. Fluids accumulate in the tissues, and eventually the blood flow to the grafted tissue is interrupted. With the failure of the blood supply, the graft dies. A renal allograft undergoing acute cellular rejection is shown in Figure 11.1D
Hypersensitivity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
There are four types of HVGR: Hyperacute rejection occurs within minutes of transplantation by interaction of preformed cytotoxic antibodies in the host's circulation with HLA class I antigens expressed on the endothelium of the graft. The result is complement activation, coagulation, microvascular thrombosis and graft infarction.Accelerated rejection occurs within 4 days of transplantation by cellular and humoral mechanisms in recipients who have been sensitized previously against the donor's antigens.Acute rejection is a T-lymphocyte-mediated reaction, which occurs during the first month after transplantation.Chronic rejection is characterized by the slow loss of tissue function over a period of months or years. It may be a cellular immune response, an antibody response or a combination of the two. It is associated with chronic immune-mediated destruction and arteriolar narrowing with ischaemia of the graft.
Renal disease
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
The features of acute rejection include: Deteriorating renal functionFeverOliguriaGraft swelling and tendernessAltered echogenicity of renal parenchyma and blurring of corticomedullary junction on US
Lessons from transmissible cancers for immunotherapy and transplant
Published in Immunological Medicine, 2022
Rafael Cardoso Maciel Costa Silva, Carolina Panis, Bruno Ricardo Barreto Pires
Transplant rejection is mediated mostly by the adaptive immune system [3]. There are three main mechanisms by which adaptive immunity is triggered to mediate allogeneic tissue rejection: direct, indirect, and semi-direct [4]. The direct pathway is based on the ability of dendritic cells (DCs) from the donor tissue (or transmissible cancer) to present allopeptides and activate host T cells through a non-self MHC. Around 1–10% of T cells can recognize the complex non-self MHC-peptide and mount a specific immune response [5]. The direct pathway is believed to be the dominant immune response during acute rejection. The ability of non-self MHC to present more than one allopeptide, referred as the multiple binary complex model, seems to contribute to the amplification of immune responses and graft rejection [6,7]. The indirect pathway is related to the presentation, by host DCs, of peptides from polymorphic antigens (or neoantigens, in the case of tumors) of the donor [2]. This pathway is associated with late chronic rejection of the transplanted tissues, and it is believed that the T cells clones reactive to this polymorphic alloantigens are distinct from those activated by the direct pathway [2]. The semi-direct pathway is related to the shedding by exosomes, from donor cells, of peptide-loaded MHC into the membrane of recipient DCs, which will present donor MHC-allopeptides to T cells. Several murine studies demonstrated the acquisition of intact alloantigens to recipient DCs after vascularized allograft challenge [8–10]. The semi-direct anddirect pathway would lead to activation of the same T cell clones [2].
Immunosuppressive effect of PLGA-FK506-NPs in treatment of acute cardiac rejection via topical subcutaneous injection
Published in Drug Delivery, 2021
Cheng Deng, Qiaofeng Jin, Ya Wu, Huiling Li, Luyang Yi, Yihan Chen, Tang Gao, Wenyuan Wang, Jing Wang, Qing Lv, Yali Yang, Jia Xu, Wenpei Fu, Li Zhang, Mingxing Xie
Heart transplantation (HT) is a standard treatment for patients with irreversible end-stage heart failure, and acute rejection is one of the major causes of morbidity and mortality after HT (Olymbios et al., 2018; Stehlik et al., 2018). Patients have to take immunosuppressants for the rest of their life to prevent and treat the occurrence of acute rejection. Currently, tacrolimus (FK506), which inhibits calcineurin by binding with FK506-binding protein to suppress various cytokines production and T cell proliferation and activation, has been widely used to treat solid organ transplantation rejection and many other immunological disorders (Schreiber & Crabtree, 1992). However, long-term use of FK506 brings huge economic costs and inevitably causes many side effects, including nephrotoxicity, opportunistic infections, and malignancies. Many studies have developed FK506 delivery systems to prolong survival time and reduce side effects, and some of the new strategies have been widely studied in skin, liver, corneal, and islet transplantation (Xu et al., 2014; Shahzad et al., 2018; Tung Thanh et al., 2018; Wu et al., 2019; Xie et al., 2020).
Covid-19 in kidney transplant recipients: a systematic review of the case series available three months into the pandemic
Published in Infectious Diseases, 2020
Mihai Oltean, John Mackay Søfteland, Jasmine Bagge, Jan Ekelund, Marie Felldin, Andreas Schult, Jesper Magnusson, Vanda Friman, Kristjan Karason
Although the prevalence of renal dysfunction was high, and the patients were on low or no immunosuppression, no graft biopsies were performed. Whereas only one acute rejection episode was reported, one has to take into account the short follow-up time in all studies as acute rejection may take some time to develop. Performing a biopsy in a patient infected with COVID-19 is associated with a potential SARS-CoV-2 exposure in the health care facility and the risk-benefit ratio must be considered under these circumstances [29]. Several patients developed supratherapeutic tacrolimus levels contributing to nephrotoxicity due to pharmacologic interactions and required continuous renal replacement therapy. While this may be due to other factors as well, it is difficult to rule out that some patients may have developed an acute rejection. Rejection should be kept in mind as a cause of renal dysfunction together with infection-related kidney involvement seen in about one-third of the hospitalized, non-transplanted COVID-19 patients [30,31]. As SARS-CoV-2 binds to ACE2 protein which is abundantly expressed on the proximal tubule and in podocytes, it is conceivable that the virus, apart from systemic inflammation, may directly affect the kidneys.