Transplants and Amyloidosis

Question 1

self to self (Skin graft)

Answer 1

 Autograft:

Question 2

syngeneic, between identical twins

Answer 2

 Isograft:

Question 3

between genetically different individuals of the same species

Answer 3

 Allograft:

Question 4

between 2 species (pig heart valve to human)

Answer 4

 Xenograft:

Question 5

Using only one word, state the major barrier to successful transplantation.

Answer 5

 REJECTION – recipient’s immune system recognizes the graft as being foreign and attacks it.

Question 6

State the two groups of antigens that are most important in determining the likelihood of transplant rejection.

Answer 6

 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

Question 7

Occurs as a result of ABO incompatibility or preformed anti-HLA antibodies in the recipient:

Answer 7

Hyperacute rejection

Question 8

can result from T cell-mediated hypersensitivity reactions:

Answer 8

Acute rejection

Question 9

occurs over months and years

often secondary to vascular injury

result of both cell-mediated and antibody-mediated hypersensitivity reactions.

Answer 9

Chronic rejection

Question 10

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

Answer 10

Hyperacute pathological findings

Question 11

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.

Answer 11

Acute cell mediated pathological findings

Question 12

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)

Answer 12

Acute humoral mediated rejection pathological findings

Question 13

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.

Answer 13

Chronic pathological findings

Question 14

Which type of rejection is the most common cause of renal graft failure?

Answer 14

 CHRONIC REJECTION

Question 15

Describe the two major complications of immunosuppressive therapy in the transplant setting.

Answer 15

 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.

Question 16

***Patients undergoing autologous HCT do not get?

Answer 16

GVHD

Question 17

immunologically competent donor T cells recognize the recipient’s HLA antigens as foreign and react against them is called?

Answer 17

GVHD

Question 18

Time cutoff for differentiating acute vs chronic GVHD?

Answer 18

100 days

Question 19

 Key prerequisites for GVHD are:

Answer 19

 Donor graft must contain immunocompetent T-cells.

 Recipient must be immunocompromised.

 Recipient must have HLA antigens that are foreign to the donor T-cells.

Question 20

Most common long term toxicities of ALLOGENEIC HCT:

Answer 20

o Chronic GVHD**

o Infections

o Treatment related myelodyspiasia/secondary leukemia

o Secondary solid tumors

o Cardiac disease

o Pulmonary toxicity

Question 21

o Most common long term toxicities of AUTOlogous HCT:

Answer 21

o Treatment related myelodyspiasia/secondary leukemia

o Secondary solid tumors

o Cardiac disease

o Pulmonary toxicity

o Infection

Question 22

Define amyloidosis:

Answer 22

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.

Question 23

What special stain is typically used to stain amyloid?

Answer 23

 Congo Red Stain: appears red. On polarization, the red stained amyloid exhibits a green birefringence

Question 24

Made up of:

• complete Ig light chains
• amino terminal fragments of light chains
• or both chains are usually made of lambda light chain protein

Answer 24

AL (amyloid light chain) amyloidosis

Question 25

Proteolysis of SAA

SAA is increased in inflammatory conditions as part of the acute phase response

associated with chronic inflammation.

SAA (serum amyloid associated protein

• synthesized in the liver and circulates in the serum associated with high density lipoprotein.

Answer 25

AA (amyloid associated) amyloidosis

Question 26

• amyloid precursor protein –>
• Proteolysis of larger precursor protein
• found in cerebral plaques of

Alzheimer disease

Answer 26

Beta-amyloid protein

Question 27

a normal serum protein that binds and transports thyroxine and retinol.

heritable–> neuropathic/cardiomyopathic amyloidosis

Answer 27

Transthyretin (TTR)

Question 28

normal serum protein cannot be filtered through dialysis membranes

can accumulate in patients on long term dialysis (>20 years)

the condition is known as hemodialysis-associated amyloiodosis.

Answer 28

Beta2-microglobulin

Question 29

Most common amyloidosis

AL type, usually systemic deposition

heart, kidney, peripheral nerve, gastrointestinal tract, respiratory tract, but nearly any other organ

monoclonal proliferation of plasma cells.

Answer 29

Primary amyloidosis

Question 30

Amyloid protein is of the AA type, systemic distribution.

 Secondary to a chronic inflammatory condition

Can also be seen associated with renal cell carcinoma and Hodgkin lymphoma.

 Sites commonly affected include kidney, liver, and spleen.

Answer 30

Reactive systemic amyloidosis

Question 31

deposition of amyloid derived from beta-2 microglobulin,

end-stage renal disease

**joint disease!

Answer 31

Hemodialysis associated amyloidosis

Question 32

Dx of amyloidosis?

Answer 32

Tissue biopsy with staining

**fat pad/rectal if thought systemic