Lecture 21 Flashcards
What body part is considered an immunologically privileged site?
Cornea
Define autografts
Grafts exchanged from one part to another part of the same individual
Define isografts
Grafts exchanged between different individuals of identical genetic constitutions (identical twins)
Define allografts (allogeneic)
Grafts exchanged between nonidentical members of the same species
Define xenografts (xenogeneic)
Graft exchanged between members of different species; these are particularly susceptible to rapid attack by naturally occurring Abs and complement; insertion of human genes into the genomes of the donor animals increases the chances of successful survival
What are the class 1 HLA Ags?
HLA-A/HLA-B; strong barriers to transplantation
What are the class 2 HLA Ags?
HLA-DR, HLA-DP, HLA-DQ; these are the 3 most important for transplantation pairs
What is the difference between direct and indirect allorecognition of grafts?
Direct: T cell recognizes unprocessed allogeneic MHC molecule on graft APCs; primary response against graft
Indirect: T cell recognizes processed peptide of allogeneic MHC molecule bound to self MHC molecule on host MHC; important during direct chronic rejection (when the # of donor professional APCs is low to stimulate a direct immune response)
Describe the different types of rejections (hyperacute, accelerated, acute, chronic)
Hyperacute: takes minutes to hours; preformed antidonor Abs and complement; may be caused by ABO blood group incompatibility
Accelerated: takes days; reactivation of sensitized T cells
Acute: takes days to weeks; primary activation of T cell; both CD4+ and CD8+ T cells can cause rejection
Chronic: takes months to years; both immunologic and nonimmunologic factors; occurs due to the occlusion of blood vessels and subsequent ischemia of the organ
What are the 4 variables that determine the outcome of a transplant?
- Condition of the allograft
- Donor-host antigenic disparity
- Strength of host anti-donor response
- Immunosuppressive regimen
What transplants are ABO blood matching not important?
Corneal transplant, heart valve transplant, bone and tendon grafts
What is needed to prevent hyperactive Ab-dependent rejection of a graft?
Cross matching to test the recipient serum for preformed Abs against donor’s HLAs
What test is performed to test for preformed Abs to donor HLAs?
Microcytotoxicity
What test is used for class 2 HLA typing to determine if the donor cells stimulate proliferation of the recipient’s lymphocytes?
Mixed lymphocyte reaction (MLR)
What are immunosuppressive drugs used for?
Prevention or treatment of rejection after transplantation after transplantation
What are the primary goals of immunosuppression?
1) To effectively control immune responses against graft Ags
2) To minimize drugs’ side effects and toxicities
T/F: Patients on immunosuppressive drugs are more prone to opportunistic infections and have raised incidence of malignancy
True
What is the mechanism of action for steroids?
Anti-inflammatory, inhibition of T cell proliferation, transcriptional inhibition of pro-inflammatory genes, induction of lymphocyte apoptosis; used clinically for transplant rejection
What is the mechanism of action for Cyclosporin A?
Inhibits IL-2 gene transcription, inhibits calcium-dependent pathway of T cell activation; forms a complex in cells (CsA-cyclophilin-calmodulin-calcineurin) that inhibits the translocation of NFATc into the nucleus; inhibits transcription of IL-2,3,4,5, interferon-gamma, TNF-alpha, and GM-CSF; used for induction and maintenance immunoprophylaxis as a basis component of most immunosuppressive protocols in all types of organ transplants
What is the mechanism of action forAnti-CD3 monoclonal antibody (OKT3)?
T cell activation, opsonization, and depletion; blocks the function of the CD3 molecule in the membrane of human T cells; used clinically for induction therapy and treatment of acute or steroid-resistant rejection; effective in prophylaxis and treatment of allograft rejection in all types of solid organ transplants
What is the mechanism of action for Tacrolimus?
Inhibits IL-2 gene transcription, inhibits the calcium-dependent pathway of T cell activation, forms a complex similar to CsA that inhibits the translocation of NFATc to the nucleus, and inhibits transcription of IL-2,3,4,5, IFN-gamma, TNF-alpha, GM-CSF; used in all types of organ transplants for induction and maintenance immunoprophylaxis and treatment of acute rejection
What is the mechanism of action for Anti-CD25 monoclonal antibodies (IL-2R-alpha chain)?
Inhibits IL-2 function
What is the mechanism of action for Sirolimus?
Inhibits cytokine-mediated signal
