Transplantation immunology
Gabriel Virella in Medical Immunology, 2019
Acute rejection usually occurs within the first few days to months after transplantation and is generally due to inadequate immunosuppression due to noncompliance or early immunosuppression underdosing. Currently, less than 10% of transplanted kidneys experience clinically significant acute cellular rejection episodes leading to graft loss at 1 year. When taking place in the first few days after grafting, it may correspond to a secondary (second set) immune response, implying that the recipient has been previously carried a sensitization to the HLA antigens present in the donated organ as a consequence of a previous antigen exposure, such as transplant, pregnancy, or blood transfusions. This particular phenomenon is known as an accelerated acute rejection. When acute rejection occurs beyond the first week after grafting, it usually corresponds to a first set, or primary, response.
The Major Histocompatibility Complex
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Early acute rejection occurs within 10 days after transplantation. This reaction may be mediated by antibodies (acute humoral rejection), or by cells (acute cellular rejection). In the former, there is a vasculitis with little cellular infiltrate of the vessel wall. In the latter, a dense cellular proliferation is evident in vessels. Acute cellular rejection is mediated by a combination of DTH, and direct cytotoxicity by CTLs and NK cells. Late acute rejection occurs 11 or more days after transplantation. This reaction is mainly the result of the attack on the graft by IgG alloantibodies. These may be demonstrated with immunofluorescence. Chronic rejection is an indolent process of gradual tissue destruction with exuberant fibrosis and effacement of normal tissue architecture. Deposits of IgG and C3 are also prominent in this form of rejection.
The Host Response to Grafts and Transplantation Immunology
Julius P. Kreier in 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
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].
Donor-specific antibodies following liver and intestinal transplantation: Clinical significance, pathogenesis and recommendations
Published in International Reviews of Immunology, 2019
Laura J. Wozniak, Robert S. Venick
Despite the recent introduction of criteria for liver AMR and increased recognition of liver AMR as a cause of graft dysfunction, the diagnosis remains challenging. Most previously published studies of acute liver AMR have used the criteria for diagnosis of AMR in kidney and heart transplantation, which are as follows: (a) clinical signs of acute rejection and graft dysfunction; (b) histological changes indicative of acute injury; (c) deposition of C4d (a cleavage product of complement); (d) the presence of donor-specific HLA antibodies (DSA) [63]. Past reports of the findings of liver AMR include portal expansion by edema and ductular reaction with neutrophilic inflammation (similar to features seen with bile duct obstruction), cholestasis, hepatocellular necrosis, and ischemic injury, as well as portal vein endothelial cell hypertrophy, portal eosinophilia, and eosinophilic central venulitis [64–68]. Diffuse C4d deposition in the portal veins and capillaries, demonstrated by immunohistochemistry (IHC) and/or immunofluorescence, has also been described [57,66,67].
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.
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