Inflammation and immunology
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Immunosuppression may result from specific therapy or may occur as a complication of therapy. To maintain the survival of transplanted organs, drugs and other therapies are administered to suppress the immune response. The main immunosuppressive drugs are designed to suppress specifically the afferent arm of the immune response, blocking the activation of immune cells reactive to the allogeneic (foreign) MHC and other antigens present on the cells of the transplanted organ. Such drugs include tacrolimus, mycophenolate mofetil, and azathioprine. However, if this suppression is overcome and the patient experiences an episode of transplant rejection, the strategy shifts to one targeted at suppressing the effector arm of the response. In these clinical circumstances high-dose corticosteroids are used and, if these are not wholly effective, humanized monoclonal antibody may be used to deplete immunocompetent cells.
Uterus transplantation
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
Since immunological tolerance, precluding the need for maintenance immunosuppression, has proven to be elusive, immunosuppressive drugs are still used to evade graft rejection in transplanted organs. Induction therapy (i.e., perioperative prophylactic immunosuppression) is commonly used to prevent acute rejection in the first months after transplantation. The maintenance therapy is normally given as a combination of drugs with diverse pharmacokinetics to minimize adverse effects. Optimizing the level of immunosuppression requires a balance between preventing episodes of rejection and the adverse effects of the immunosuppressive drugs. The need for immunosuppressive medications is not at a constant level, and the high blood levels of immunosuppression necessary initially can, shortly after the transplantation procedure, be reduced to a lower maintenance level. During pregnancy, physiologic and hemodynamic changes occur, inducing changes in the plasma concentrations of drugs, hence these need to be monitored thoroughly (38).
Challenges in Delivering Gene Therapy
Yashwant Pathak in Gene Delivery, 2022
With the body’s immune response affecting the delivery for gene therapy, there must be strategies to circumvent this immune response. One way of regulating an immune response has been the use of immunosuppressive agents like cyclosporine, tacrolimus, and cyclophosphamide [42]. These immunosuppressive drugs block various pathways that result from antigen presentation all the way to the activation of B and T cells. By using these drugs in conjunction with gene therapy, the immunosuppressive drugs inhibit the synthesis and release of cytokines, while preventing the differentiation of CD4 cells, hence blocking an immune response [43]. This method could hold promising results, such that the suppression of the immune response will allow the vector to unpack the DNA and allow it to integrate the host cell.
Engineering drug delivery systems to overcome mucosal barriers for immunotherapy and vaccination
Published in Tissue Barriers, 2020
Jacob C. McCright, Katharina Maisel
Therapeutic treatments targeting the immune system are becoming more and more prevalent. They range from classic vaccines and allergen immunotherapy to the cancer immunotherapies that have raised hopes of defeating this devastating disease. New immunotherapy treatments are constantly being developed, and many are applied to treat diseases of mucosal surfaces. These include the above-mentioned allergies and cancer, along with other diseases like inflammatory bowel disease and pulmonary fibrosis. In diseases where the immune response must be controlled and reduced, such as allergies, transplantation, and inflammatory bowel disease, immunosuppressive therapies are generally employed. Immunosuppressive drugs include antibodies that, e.g. block pro-inflammatory cytokines or prevent lymphocyte interaction with antigen-presenting cells, molecules that block cell division of B and T cells (cytostatics), and corticosteroids that prevent transcription of genes of pro-inflammatory cytokines.72 In contrast, pro-inflammatory immunotherapies are used to turn on immune responses that have either been suppressed, like in cancer, or to induce responses to specific antigens such as during vaccination. These immunotherapies include antibodies that activate lymphocytes by, e.g. targeting checkpoint inhibitors that serve to turn off the immune response, pro-inflammatory cytokines that activate immunity, and molecules that activate antigen-presenting cells, e.g. toll-like receptor agonists, and thus cause a down-stream immune cascade.72,73
Immunosuppressive activity of daphnetin on the humoral immune responses in ovalbumin-sensitized BALB/c mice
Published in Immunopharmacology and Immunotoxicology, 2021
Bo-Cui Song, Meng-Meng Jiang, Shuang Zhang, Hui Ma, Min Liu, Zhong-Ren Fu, Rui Wu, Chun-Yu Tong
Immunosuppressive drugs are very effective and widely used for the treatment of autoimmune diseases, allergic diseases, and transplant rejection [1–3]. Although the disease can usually be successfully controlled by immunosuppressive drugs such as cyclosporin A (CsA), Rituximab, Methotrexate, tacrolimus (FK506), and Azathioprine, the toxicity is the major obstacle for the potent drugs already known in the wider use of these immunosuppressive drugs [4–7]. In recent years, the regulation of either humoral response or cell-mediated immune response, by using external agents such as natural products has been generating a lot of interest in the Immunosuppressive drug research field [8,9]. Natural products have been attracting more and more attention for their ascertained effectiveness with few or no traditional side-effects.
Can we safely use systemic treatment in atopic dermatitis during the COVID-19 pandemic? Overview of selected conventional and biologic systemic therapies
Published in Expert Review of Clinical Immunology, 2021
Monika Marko, Rafał Pawliczak
Management of allergies and diseases related to atopy has also become a serious challenge, because the immune response after SARS-CoV-2 infection is so far only poorly understood. Many patients are under therapy with biologic drugs that suppress the type 2 immune response through various mechanisms and may alter it favorably or unfavorably [38]. So far, the role of type 2 cytokines in the pathogenesis and severity of COVID-19 is not well understood; therefore, patient guidelines for biologics targeting allergic response pathways during this pandemic are scarce [43]. Currently, there is insufficient evidence to demonstrate the possible immune interactions and the potential dangers of these biological substances in the event of SARS-CoV-2 infection. We also do not know whether allergy patients are at increased risk of severe COVID-19 [38]. Many questions arise when considering the use of biologics to treat allergic diseases during the COVID-19 pandemic. The main ones focus on the degree of increased risk of infection or development of severe disease as a result of SARS-CoV-2 infection in patients allergic to biologics targeting type 2 inflammation. The degree of side effects that result from potential immunosuppressive drugs and the benefits of combating diseases such as severe asthma and atopic dermatitis are also considered [43].
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