Transplants and Amyloidosis Flashcards
self to self (Skin graft)
Autograft:
syngeneic, between identical twins
Isograft:
between genetically different individuals of the same species
Allograft:
between 2 species (pig heart valve to human)
Xenograft:
Using only one word, state the major barrier to successful transplantation.
REJECTION – recipient’s immune system recognizes the graft as being foreign and attacks it.
State the two groups of antigens that are most important in determining the likelihood of transplant rejection.
ABO and HLA compatible grafts have a better chance of avoiding rejection.
ABO antigens expressed on endothelial cells and many epithelial cells
HLA-A, B, C antigens expressed on all nucleated cells and platelets, including lymphocytes, hematopoietic cells, epithelial cells, and endothelial cells
HLA-DR antigens are expressed on APCs
Occurs as a result of ABO incompatibility or preformed anti-HLA antibodies in the recipient:
Hyperacute rejection
can result from T cell-mediated hypersensitivity reactions:
Acute rejection
occurs over months and years
often secondary to vascular injury
result of both cell-mediated and antibody-mediated hypersensitivity reactions.
Chronic rejection
No nice round capillary loops
kidney allograft showing endothelial damage, platelet and
thrombin thrombi
early neutrophil infiltration
severe ischemic injury in a glomerulus
Fibrinoid necrosis
Hyperacute pathological findings
a kidney allograft with inflammatory cells (CD4+ and CD8+ T lymphocytes) in the interstitium and between epithelial cells of the tubules (tubulitis).
CD8+ T lymphocytes may also injure vascular endothelial cells, causing *endotheliitis
characterized by blood vessels exhibiting swollen endothelial cells with lymphocytic inflammation.
Acute cell mediated pathological findings
kidney allograft with inflammatory cells in peritubular capillaries.
development of anti-donor antibodies, and thus the damage is primarily within the blood vessels.
thrombosis
ischemic injury
deposition of the complement breakdown factor C4d
immunohistochemical stain (brown staining)
Acute humoral mediated rejection pathological findings
Changes manifest in the vessels.
Graft arteriosclerosis
vascular lumen is replaced by smooth muscle cells and connective tissue in the vessel intima.
Ischemic atrophy and fibrosis.
Chronic pathological findings
Which type of rejection is the most common cause of renal graft failure?
CHRONIC REJECTION
Describe the two major complications of immunosuppressive therapy in the transplant setting.
Increased susceptibility for opportunistic infections
-(CMV, pneumocysitis) as well as increased susceptibility for common community acquired infectious diseases
Increased risk of malignancies
- EBV associated post transplant lymphoproliferative disorders (PTLD)
- squamous cell carcinoma of skin
- Kaposi sarcoma.
***Patients undergoing autologous HCT do not get?
GVHD
immunologically competent donor T cells recognize the recipient’s HLA antigens as foreign and react against them is called?
GVHD
Time cutoff for differentiating acute vs chronic GVHD?
100 days
Key prerequisites for GVHD are:
Donor graft must contain immunocompetent T-cells.
Recipient must be immunocompromised.
Recipient must have HLA antigens that are foreign to the donor T-cells.
Most common long term toxicities of ALLOGENEIC HCT:
o Chronic GVHD**
o Infections
o Treatment related myelodyspiasia/secondary leukemia
o Secondary solid tumors
o Cardiac disease
o Pulmonary toxicity
o Most common long term toxicities of AUTOlogous HCT:
o Treatment related myelodyspiasia/secondary leukemia
o Secondary solid tumors
o Cardiac disease
o Pulmonary toxicity
o Infection
Define amyloidosis:
a group of disorders characterized by the deposition of amyloid (a protein) in the extracellular space of tissues and organs, resulting in tissue and organ dysfunction.
What special stain is typically used to stain amyloid?
Congo Red Stain: appears red. On polarization, the red stained amyloid exhibits a green birefringence
Made up of:
- complete Ig light chains
- amino terminal fragments of light chains
- or both chains are usually made of lambda light chain protein
AL (amyloid light chain) amyloidosis
