Podcast
Questions and Answers
If a patient who has undergone a bone marrow transplant presents with a new, intensely pruritic rash on their palms and soles, accompanied by persistent nausea and elevated liver enzymes, which of the following is the MOST likely underlying cause?
If a patient who has undergone a bone marrow transplant presents with a new, intensely pruritic rash on their palms and soles, accompanied by persistent nausea and elevated liver enzymes, which of the following is the MOST likely underlying cause?
- A delayed hypersensitivity reaction to a newly prescribed antibiotic, unrelated to the transplant.
- Acute graft-versus-host disease (GVHD), with donor T-cells attacking skin, GI tract, and liver. (correct)
- Drug toxicity from immunosuppressive medications, directly damaging the liver and causing a secondary skin reaction.
- An opportunistic fungal infection secondary to immunosuppression, manifesting cutaneously and hepatically.
A researcher is investigating novel therapeutic targets for graft-versus-host disease (GVHD). Targeting which of the following interactions would MOST directly disrupt the initiation of the GVHD cascade?
A researcher is investigating novel therapeutic targets for graft-versus-host disease (GVHD). Targeting which of the following interactions would MOST directly disrupt the initiation of the GVHD cascade?
- The release of pro-inflammatory cytokines, such as TNF-alpha and IL-6, by activated macrophages.
- The presentation of host antigens by dendritic cells to donor T helper cells via MHC class II molecules. (correct)
- The Fas-FasL interaction between cytotoxic T cells and host cells.
- The interaction between cytotoxic T-cells and target cells via perforin and granzymes.
Which of the following scenarios presents the HIGHEST risk for developing graft-versus-host disease (GVHD) following a hematopoietic stem cell transplant?
Which of the following scenarios presents the HIGHEST risk for developing graft-versus-host disease (GVHD) following a hematopoietic stem cell transplant?
- Transplant from a fully HLA-matched sibling after T-cell depletion of the graft.
- Transplant from an HLA-matched sibling with no minor histocompatibility antigen matching performed.
- Transplant from an HLA-matched unrelated donor with minimal T-cell depletion into a patient with myeloablative conditioning. (correct)
- Transplant from an HLA-mismatched unrelated donor into a patient with complete immune reconstitution post-transplant.
A patient undergoing evaluation for graft-versus-host disease (GVHD) following a liver transplant presents with jaundice, elevated alkaline phosphatase, and ascites. A liver biopsy is performed. Which of the following histological findings would be MOST indicative of GVHD?
A patient undergoing evaluation for graft-versus-host disease (GVHD) following a liver transplant presents with jaundice, elevated alkaline phosphatase, and ascites. A liver biopsy is performed. Which of the following histological findings would be MOST indicative of GVHD?
A researcher is investigating the role of specific cytokines in the pathogenesis of acute graft-versus-host disease (GVHD). Blocking which of the following cytokines would MOST likely reduce the amplification of the immune response and subsequent tissue damage in GVHD?
A researcher is investigating the role of specific cytokines in the pathogenesis of acute graft-versus-host disease (GVHD). Blocking which of the following cytokines would MOST likely reduce the amplification of the immune response and subsequent tissue damage in GVHD?
A patient who underwent allogeneic hematopoietic stem cell transplantation develops severe, refractory acute graft-versus-host disease (GVHD) affecting the gastrointestinal tract. Besides standard immunosuppressive therapy, which of the following interventions would be MOST appropriate to consider NEXT?
A patient who underwent allogeneic hematopoietic stem cell transplantation develops severe, refractory acute graft-versus-host disease (GVHD) affecting the gastrointestinal tract. Besides standard immunosuppressive therapy, which of the following interventions would be MOST appropriate to consider NEXT?
Why is HLA matching between donor and recipient critical in hematopoietic stem cell transplantation to mitigate the risk of graft-versus-host disease (GVHD)?
Why is HLA matching between donor and recipient critical in hematopoietic stem cell transplantation to mitigate the risk of graft-versus-host disease (GVHD)?
Which characteristic regarding graft-versus-host disease (GVHD) is CORRECT?
Which characteristic regarding graft-versus-host disease (GVHD) is CORRECT?
A research team aims to develop a novel therapy that selectively inhibits the activation of donor T helper cells in graft-versus-host disease (GVHD) without causing broad immunosuppression. Which of the following targets would be the MOST specific to achieve this goal?
A research team aims to develop a novel therapy that selectively inhibits the activation of donor T helper cells in graft-versus-host disease (GVHD) without causing broad immunosuppression. Which of the following targets would be the MOST specific to achieve this goal?
A physician is explaining to a patient the importance of receiving irradiated blood products prior to a hematopoietic stem cell transplant. What is the PRIMARY rationale for using irradiated blood products in this setting?
A physician is explaining to a patient the importance of receiving irradiated blood products prior to a hematopoietic stem cell transplant. What is the PRIMARY rationale for using irradiated blood products in this setting?
Flashcards
Graft Versus Host Disease (GVHD)
Graft Versus Host Disease (GVHD)
A systemic disorder where grafted immune cells recognize the host as foreign and attack recipient's cells.
Common GVHD Settings
Common GVHD Settings
Bone marrow, lymphoid-rich solid organs (e.g., liver), and unirradiated blood transfusions.
Organs Affected by GVHD
Organs Affected by GVHD
Skin, gastrointestinal tract, and liver are the most commonly affected organs.
Pathogenesis of Acute GVHD
Pathogenesis of Acute GVHD
Signup and view all the flashcards
Graft
Graft
Signup and view all the flashcards
Host
Host
Signup and view all the flashcards
Major Histocompatibility Complex (MHC)
Major Histocompatibility Complex (MHC)
Signup and view all the flashcards
Dendritic Cells Role in GVHD
Dendritic Cells Role in GVHD
Signup and view all the flashcards
Key Cytokines in GVHD
Key Cytokines in GVHD
Signup and view all the flashcards
Cytotoxic T Cell Action
Cytotoxic T Cell Action
Signup and view all the flashcards
Study Notes
- Graft Versus Host Disease (GVHD) is a systemic disorder where the graft's immune cells attack the recipient's body cells.
- GVHD occurs when immunologically competent donor cells are transplanted into an immunodeficient recipient.
Settings for GVHD Occurrence
- Following bone marrow transplantation/stem cell transplants, this is the most common scenario.
- After solid organ transplants rich in lymphoid cells like the liver.
- Following a transfusion of unirradiated blood, especially in immunocompromised individuals.
Epidemiology of GVHD
- Acute GVHD can occur in up to 50% of patients receiving stem cell transplants from an HLA-matched sibling.
- GVHD complications lead to death in more than 10% of stem cell transplant recipients.
- GVHD risk significantly increases when the donor and recipient are not well HLA-matched.
Organs Affected by GVHD
- Skin is involved in 70-74% of cases due to rapid cell division, the most common manifestation is a pruritic or painful maculopapular rash often on the palms, soles, and nape of the neck.
- The gastrointestinal (GI) tract is involved in 44% of cases because the gut has a high epithelial cell turnover rate, symptoms include diarrhea, nausea, and vomiting.
- Liver involvement occurs because the liver contains antigen-presenting cells (APCs) that interact with donor T cells, abnormalities include elevated bilirubin and alkaline phosphatase levels.
Pathogenesis of GVHD
- Donor T cells recognize the recipient’s cells as foreign and attack epithelial cells in the skin, liver, and gut, leading to acute GVHD.
- Graft refers to transplanted or donated tissue such as bone marrow, peripheral blood, and liver.
- Host refers to the person receiving the transplant.
- The immune system identifies and attacks foreign invaders using major histocompatibility complex (MHC) proteins, also known as human leukocyte antigens (HLA), to distinguish self from non-self.
MHC and GVHD Risk
- MHC Class I molecules are found on all nucleated cells, and MHC Class II molecules are found on antigen-presenting cells (APCs).
- Each person has unique MHC genes, making HLA matching between donors and recipients challenging.
- Even in HLA-identical individuals, minor histocompatibility antigens can still trigger an immune response, leading to GVHD.
Key Elements for GVHD
- The graft must contain immune cells, mainly T cells, which occurs in hematopoietic stem cell transplants.
- The host’s immune system is suppressed (immunosuppressed), allowing donor cells time to proliferate.
- The host is immunologically different from the donor, the recipient’s HLA antigens must appear foreign to the grafted immune cells.
GVHD Mechanism
- Host dendritic cells travel to lymph nodes and present host antigens to donor helper T cells via MHC Class II molecules, and donor helper T cells recognize these antigens as foreign and activate.
- Activated TH1 cells release cytokines, including Interleukin-2 (IL-2) which stimulates T cell proliferation, Interferon-gamma (IFN-γ) enhances antigen presentation and macrophage activation and Tumor Necrosis Factor-alpha (TNF-α), IL-1, and IL-6, promoting inflammation and tissue destruction.
- Cytotoxic T cells recognize host antigens on MHC Class I molecules and become activated.
- They release perforin and granzymes, perforin creates pores in target cells, granzymes enter through the pores and trigger apoptosis (programmed cell death) and Fas-FasL signaling also triggers apoptosis.
- The final outcome is extensive tissue damage in affected organs (skin, liver, and gut) with severe inflammation and immune-mediated destruction of host cells.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
