Clinical Foundations and Transplant Immunology
Core concepts
Candidates must master HLA genetics and nomenclature (class I A/B/C, class II DR/DQ/DP), the structure of antibody-mediated versus T-cell-mediated responses, and the effector pathways that drive graft injury. Know complement biology (classical pathway activation by donor-specific antibody, C4d as a footprint), co-stimulation, and the distinction between direct, indirect, and semi-direct allorecognition. Understand crossmatch methods (complement-dependent cytotoxicity, flow cytometry, virtual crossmatch from single-antigen beads) and what a positive crossmatch predicts. Learn ischemia-reperfusion injury, innate immune activation, and the molecular mechanisms of the immunosuppressants you will manage.
Traps
Questions love to blur class I versus class II expression patterns (class I on all nucleated cells; class II on antigen-presenting cells, with inducible expression on endothelium). Another trap is conflating a positive T-cell crossmatch (prior sensitization, high risk of cellular rejection) with a positive B-cell crossmatch (may reflect antibody or non-HLA factors). Remember that hyperacute rejection is preformed antibody and complement driven, whereas acute cellular rejection is T-cell driven. Do not confuse donor-specific antibody mean fluorescence intensity with a functional assay.
Worked example
A patient with a calculated panel-reactive antibody of 95% has donor-specific antibodies against a prospective donor's HLA-DQ7 with high mean fluorescence intensity. Rule of thumb: high-intensity donor-specific antibody plus a positive flow crossmatch means the pair is unacceptable unless a desensitization protocol is planned; a negative virtual crossmatch with no donor-specific antibody generally permits transplantation even with a high panel-reactive antibody.
Study strategy
Build a table linking each immunosuppressant to its molecular target, and practice interpreting crossmatch scenarios as clinical decisions rather than lab trivia.