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Questions and Answers
Which virus is associated with lymphoma?
What is a major concern regarding organ transplantation?
Which of the following is a consequence of immunosuppression?
What is the main purpose of immune checkpoint inhibitors?
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Why is non-altruistic organ donation illegal in most countries?
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Which immune checkpoint is targeted by the drug pembrolizumab?
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What can lead to the evasion of immune responses by cancer cells?
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What type of cancers have shown benefit from immune checkpoint inhibitors?
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What is chronic allograft failure primarily associated with?
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What does HLA typing help with in the context of transplantation?
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What does a positive cross-match indicate?
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What is the role of C4d staining in post-transplant biopsy?
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What is a major long-term complication of immunosuppressive treatment?
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Which medication is specifically used for cytomegalovirus prophylaxis?
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Which of the following types of vaccines is appropriate for transplant recipients?
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What factor does NOT contribute to chronic allograft failure?
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Study Notes
Chronic Allograft Failure
- Chronic rejection leads to graft loss, characterized by vascular smooth muscle proliferation, interstitial fibrosis, and scarring.
- Pathogenesis remains poorly understood; factors include immunological damage, hypertension, hyperlipidaemia, and chronic drug toxicity.
Pre-Transplantation Testing
- HLA Typing: Identifies individual HLA polymorphisms for donor-recipient matching.
- Recipients screened for anti-HLA antibodies; presence can exclude from transplantation.
- Donor-Recipient Cross-Matching: Functional assay that tests recipient serum against donor lymphocytes; a positive result indicates a contraindication for transplantation due to hyperacute rejection risk.
Post-Transplant Biopsy: C4d Staining
- C4d is a complement protein fragment; its deposition in graft capillaries indicates classical complement pathway activation.
- Useful for early diagnosis of vascular rejection.
Complications of Transplant Immunosuppression
- Long-term immunosuppression requires a combination of two or more drugs to minimize adverse effects.
- Major complications are infection and malignancy; prophylactic medications like ganciclovir and trimethoprim-sulfamethoxazole reduce some infection risks.
- Immunization is critical; killed vaccines are appropriate, while live vaccines are avoided due to immune suppression.
- T-cell suppression increases malignancy risks, particularly for virus-associated tumors linked to Epstein-Barr virus, human herpesvirus 8, and human papillomavirus.
Organ Donation
- Shortage of organ donors is a significant challenge; cadaveric donors often come from healthy individuals who suffered brainstem death.
- Living donation is common in renal transplants, typically from altruistic relatives, but carries risk for donors and is tightly regulated.
- Non-altruistic organ donation, including sale, is illegal in most countries.
Tumour Immunology
- The immune system plays a critical role in monitoring and eliminating damaged or mutated cells.
- Cancer immunogenicity and specificity affect the immune system's effectiveness in targeting cancer cells.
- Tumor antigens may be poorly expressed or mutate, evading immune responses.
- Cancer cells can exploit inhibitory pathways meant to maintain self-tolerance, aiding evasion of immune destruction.
- Immune checkpoint inhibitors (e.g., targeting CTLA-4, PD1, PD-L1) enhance anti-tumor immunity; examples include ipilimumab, nivolumab, and pembrolizumab.
- These therapies have shown efficacy in several cancers but may cause serious inflammatory side effects.
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Description
This quiz explores the complex interplay between tumour immunology and chronic allograft failure, a significant cause of graft loss. It delves into the mechanisms of chronic rejection, associated factors, and the importance of pre-transplantation testing. Test your knowledge on HLA typing and its role in immunological compatibility.
