Flashcards in Transplant Pathology- Nelson Deck (39):
Define autograft, isograft, allograft, and xenograft transplants
Autographt → self to self (like a skin graft)
Isograft → syngeneic (between identical twins)
Allograft → between genetically different individual of the same species
Xenograft → between two species (pig heart valve to human)
Using only one word, state the major barrier to successful transplantation.
State the two groups of antigens that are most important in determining the likelihood of transplant rejection.
Describe the direct pathway of cellular rejection
donor class I and class II MHC antigens on APCs in the graft are recognized by host CD8+ and CD4+ T cells
Describe the indirect pathway of cellular rejection
Host APCs picks up graft antigens and display to CD4 & CD8 cells
What is humoral rejection? What are the types of preformed antibodies?
Humoral rejection = antibodies produced against alloantigens
-Abs to ABO antigens are produced naturally
-Abs to HLA antigens from previous exposure
What are the major types of pretransplant testing?
-ABO compatibility testing
-Detection of preformed Abs
Explain the immunological mechanisms of hyperacute rejection?
With in minutes to hours
**ABO incompatibiity or preformed HLA antibodies
*Doesn't really happen anymore, would most likely be clerical error
Kidney= endothelial damage, thrombi, early neutrophil infiltration, severe ischemic injury in glomerulus
Explain the immunological mechanisms of acute rejection?
-occurs over days to weeks
-T-cell mediated hypersensitivity reactions or from antibody mediated hypersensitivity reactions
Describe the pathological feature of acute rejection in a renal allograft
Tubular damage= **causes endothelitis
Blood vessels with swollen endothelial cells w/ lymphocytic inflammation
Damage primarily in blood vessels → small vessel damage → thrombosis → ischemic injury
Explain the immunological mechanisms of chronic rejection?
-Occurs over months-years
-Cell mediated and antibody-mediated hypersensitivity reactions
-Often secondary to vascular injury
What is the most common cause of renal graft failure?
Describe the pathological feature of chronic rejection in a renal allograft
vascular lumen is replaced by accumulation of smooth muscle cells and connective tissue in the vessel intima
Describe the two major complications of immunosuppressive therapy in the transplant setting
Increases susceptibility for opportunistic infections
Increased risk of malignancies
Define autologous and allogeneic hematopoietic cell transplantation (HCT).
Autologous → uses hematopoietic progenitor cells derived from the individual with the disorder
Allogenic → uses hematopoietic progenitor cells collected from some other than the individual with the disorder
Explain the underlying immunologic mechanisms of graft vs. host disease (GVHD)
GVHD (in allogeneic HCT) → Transplanted immunocompetent T-cells from the donor may recognize the recipient (host) cells as foreign
NOTE*** patients undergoing autologous HCT do not get GVHD!!!
What are the key prerequisites needed for a pt to get GVHD?
-donor graft must contain immunocompetent T-cells
-Recipient must by immunocompromised
-Recipient must have HLA antigens that are foreign to the donor T-cells
Differentiate between acute and chronic GVHD
Acute= 0-100 days post transplant
Chronic= after 100 days post transplant
Describe the principle organ systems involved in acute GVHD
-destruction of small bile duct- jaundice
-ulceration of GI mucosa & blood diarrhea
Describe the principle organ systems involved in chronic GVHD?
-chronic liver disease
-fibrosis of GI tract, decreased absorption, chronic diarrhea
A group of disorders characterized by deposition of amyloid in extracellular space of tissues and organs (resulting in tissue and organ dysfunction)
What is amyloid?
group of pathologic proteins that share similar physical properties
Describe the apperance of amyloid
Cross-beta-pleated sheet configuraiton
What is the typical stain used to stain amyloid?
*on polarization exhibits a green birefringence
Is amyloidosis a single disease entity, or a group of diseases? How does amyloid injure adjacent cells?
-Group of diseases
-Amyloid injures adjacent cells through pressure atrophy
AL (amyloid light chain) amyloid
Made up of either complete immunoglobulin light chains, fragments, or both
AA (amyloid – associated) amyloid
-Proteolysis of a larger precursor protein called SAA (serum amyloid-associated)
-SAA increases in inflammatory conditions, thus this form of amyloidosis is associated with chronic inflammation
Beta-amyloid protein (AB)
-Proteolysis of larger precursor protein called amyloid precursor protein
-Found in cerebral plaques of alzheimer disease
-Normal serum protein that binds and transports thyroxine and retinol
-Mutations can result in amyloid deposition
-Normal serum protein cannot be filtered through dialysis membrane and can accumulate in patients on long term dialysis
-aka Hemodialysis-associated amyloidosis
*predilection for osteoarticular structures
involving several organ systems
Involving a single organ
-when associated with a clonal proliferative plasma cells producing light chain immunoglobulin
- aka AL amyloidosis
**Most common form of amyloidosis in the USA
*usually systemic in deposition
-complication of underlying inflammatory process
-aka reactive systemic amyloidiosis, or AA amyloidosis
**Second most common for of amyloidiosis in the USA
*Common sites- kidney, liver, spleen
group of heterogenous, heritable forms of amyloidosis with several distinctive patterns of organ involvement
How do you diagnose systemic amyloidosis?
-Diagnosis → established by tissue biopsy w/ staining for amyloid
-Immunohistochemistry or liquid chromatography-mass spectrometry can be performed on the tissue biopsy to determine the type of amyloid present.
**NOTE: not all patients with a monoclonal light chain protein detected on protein electrophoresis (serum or urine) have amyloidosis
What are the key clinical symptoms of a patient with systemic amyloidosis?
-Enlarged muscles (tongue, deltoids)
-SS of heart failure, cardiac conduction abnormalities, hepatomegaly, renal dysfunction
What are the major site of clinically important deposition in systemic amyloidosis?