IMMUNITY IV
Transplantation: The transplantation of organs to replace these that are terminally diseased has become common place. Invariably (unless between monozygotic twins) the HLA type of the graft and recipient are mismatched termed ((Allograft)), which induces a vigorous immune response estimated at up to 5% of the T - cell receptors , with both HLA class I & II molecules acting as targets. Compatibility of HLA loci improves graft survival, immunosuppression, with drugs is nevertheless still required.Otherwise , an allograft , though initially accepted, will be rejected during the next two weeks (first set rejection ). If tissue from the same donor is re-grafted into the recipient, rejection is accelerated and occurs within 2 - 3 days(second set rejection). Rejection is mediated by both CD4+ & CD8+ T - cells. In some instances, hyper-acute graft rejection may occur (within few hours) and is mediated by pre - existing antibodies which bind to vascular endothelial cells and activate complement.
T - cell responses to xenograft (use of animal organ ) may be less vigorous than allografts . The presence of antibodies that react with endothelial cells on the graft result in the activation of the complement system and hyperactive graft rejection ensues.
Modulation of Immune response: Immunosupression by drugs or antibodies: In diseases generated by an excessive or abnormal immune response , immunosuppressive drugs provide the basis of current treatment regimen . However, drugs like cyclophosphamide , methotrexate ,& corticosteroids have broad spectrum activities, therefore, disrupt the function of many cell types, so prolonged treatment may increase the incidence of B - cell Lymphoma.
Characteristics of effective vaccine: Safety: no disease must be caused by the vaccine itself. Protection: must be at the population level & prevent disease when the infectious agent is encountered. Long lasting effects: protection must be long lasting , i.e. induce T& B - cell memory. Cost: inexpensive to be produced and delivered. Administration: easy to deliver with no side effects.
Approaches to vaccine design: Intact pathogen: * Heat killed or chemically denaturized. ** Attenuated by growth condition or genetic manipulation. Subunit vaccine : * Recombinant proteins. ** synthetic peptides.