Ver, these research did not evaluate repeat antigen exposure, because it
Ver, these research did not evaluate repeat antigen exposure, since it has been shown that subsequent HEL antigen exposures do not lead to immunologic boosting [96] for reasons that remain beneath investigation. Ongoing experiments working with KEL transgenic RBCs, that are capable of generating memory and boostable responses in C57BL6 animals [97], are investigating the impact of RBC exposure as neonates and subsequent responses when these same animals are retransfused as adults. Characteristics from the transfused RBC antigens themselves also play essential roles in figuring out recipient responsiveness versus nonresponsiveness. One example is, nonresponsivenessFactors Influencing RBC Alloimmunization: Lessons Discovered from Murine PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/18041834 ModelsTransfus Med Hemother 204;4:406tolerance for the hGPA antigen occurs when the initial antigen exposure takes place in the absence of an adjuvant [96]. This nonresponsiveness is antigenspecific, with nonresponders towards the hGPA antigen being totally capable of responding to other distinct RBC antigens. RBC antigen copy number might contribute to whether a specific antigen is capable of inducing an immune response following transfusion, as suggested by studies that have shown antigen density to become a key determinant of immunologic responsiveness to nonRBC antigens [92]. Even though hGPA copy quantity has not been formally evaluated, flowcytometric MedChemExpress BH 3I1 crossmatching of those RBCs with monoclonal antihGPA results inside a three log shift and in vitro agglutination, suggesting that the copy number is quite high. Ongoing research are comparing recipient immune responses to transfused RBCs expressing higher, mid, and low levels in the human KEL2 antigen. Studies in animals suggest that soluble antigen (outside in the context of RBC immunology) could be capable of inducing nonresponsiveness, and potentially even tolerance, based on the route of exposure [22, 23]. In addition, animal research have shown that principal antigen exposure by means of the nasal mucosa decreases secondary responses to subsequently 
transfused RBC antigens [73, 24]. Such studies have been completed working with immunodominant Rh(D) peptides too as immunodominant KEL peptides. One particular study has suggested that there may be antigenspecific mechanisms for lowering Tcell responsiveness with immunodominant peptides: following a key i.v. transfusion of RBCs with a secondary intranasal peptide exposure to an immunodominant peptide of an antigen expressed around the RBC surface, the authors have been capable to lower the Tcell response [73]. Other murine studies have lately explored the use of RBCs as automobiles to induce tolerance to nonRBC antigens, with antigenspecific tolerance towards the OVA antigen observed following immunization with OVAentrapped RBCs [2]. RBC Exposure via Transfusion or Pregnancy Although this evaluation has focused on components that may influence immune responses to transfused RBCs, exposure to paternally derived foreign RBC antigens may also happen in the course of pregnancy. Within the KEL2 murine model, antiKEL glycoprotein alloantibodies develop not simply following transfusion of KEL2 RBCs into C57BL6 mice [97] but also just after pregnancy in C57BL6 female mice bred with KEL2 transgenic males [7]. The titers of antiKEL glycoprotein immunoglobulins enhance with repeat antigen exposure, whether or not the exposure is as a result of many RBC transfusions or because of several pregnanciesdeliveries [7, 97]. All IgG subtypes are generated in response to KEL2 RBC exposure by each pregnancy and transfusion, with these antibodies bein.