Questions
2–3 questions in university professional exams
Difficulty
Medium
Importance
High yield for medical and life sciences board exams
Overview
HLA typing and transplant immunology revolve around the Major Histocompatibility Complex (MHC), which acts as the body's internal 'ID card' system. Mastering this topic is essential for understanding how the immune system distinguishes 'self' from 'non-self', a fundamental concept for both clinical diagnostics and organ transplantation.
MHC Class I and II Molecules
MHC molecules are cell surface glycoproteins responsible for presenting peptide antigens to T-cells. Class I molecules are found on all nucleated cells, while Class II are restricted to antigen-presenting cells (APCs) like macrophages and dendritic cells.
- MHC Class I presents endogenous antigens to CD8+ T-cells
- MHC Class II presents exogenous antigens to CD4+ T-cells
- HLA genes are located on chromosome 6p21
- HLA-A, B, C encode Class I; HLA-DR, DQ, DP encode Class II
- High polymorphism in the peptide-binding groove
HLA Typing Techniques
HLA typing is the process of identifying an individual's HLA alleles to ensure histocompatibility before organ or bone marrow transplantation. Modern laboratory diagnostics rely on both serological and molecular genetic approaches.
- Serological typing using complement-dependent cytotoxicity (CDC)
- Molecular typing via PCR-SSP (Sequence Specific Primers)
- PCR-SSO (Sequence Specific Oligonucleotide) probing
- Next-Generation Sequencing (NGS) for high-resolution matching
- Importance of identifying HLA-A, B, and DR alleles
Cross-Matching and Transplant Immunology
Cross-matching is a vital pre-transplant test that determines if a recipient has pre-formed antibodies against the donor's HLA antigens. A positive cross-match indicates high risk of hyperacute rejection and is a contraindication for transplant.
- Hyperacute rejection: Occurs within minutes due to pre-existing antibodies
- Acute rejection: Mediated by T-cells, occurring over days to weeks
- Chronic rejection: Fibrosis and vascular damage over months or years
- Graft-versus-Host Disease (GVHD): Donor T-cells attack host tissues
- CDC cross-match assay is the gold standard for donor-recipient screening
Exam Tip
Always remember the Rule of 8: MHC Class I interacts with CD8 (1 x 8 = 8), and MHC Class II interacts with CD4 (2 x 4 = 8).
Common Mistakes
- Confusing the roles of MHC Class I and II regarding which T-cell sub-type they activate
- Failing to distinguish between hyperacute, acute, and chronic rejection timelines
- Incorrectly stating that HLA typing is only used for transplants, ignoring its role in disease susceptibility research
More Revision Notes
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