Chapter 5 Flashcards

1
Q

What continues to pose a major challenge to the long-term success of organ transplants?

A

Alloimmune response

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2
Q

How can allograft rejections be categorized?

A

Hyperacute (mins to hrs)
Acute (days to wks)
Chronic (mos to yrs)

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3
Q

What is the purpose of the innate immune system?

A

Detect and eliminate foreign pathogens on the basis of a broad range of molecular/cellular markers

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4
Q

What are examples of agents of innate immunity?

A

NK cells
Toll-like receptors (TLRs)
The complement cascade

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5
Q

What is the adaptive immune system?

A

Has the capacity to generate highly specific immune responses

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6
Q

What are the four axes of the adaptive immune system?

A

Specificity
Inducibility
Memory
Tolerance to self

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7
Q

What is the function of MHC class I?

A

Expressed by all nucleated cells
Presenting antigens from within the cells
Humans express HLA-A, B, and C

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8
Q

What is the function of MHC class II?

A

Typically presents antigens present in the extracellular space
Humans express HLA-DP, DQ, and DR
Comprises an alpha and a beta chain

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9
Q

What are members of antigen-presenting cells?

A

Dendritic cells (DCs)
Tissue macrophages
B cells

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10
Q

What is currently the mainstay of antirejection immunotherapy at the time of transplantation?

A

T-cell-directed immunosuppression

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11
Q

What genes compose the MHC?

A

Six genes mapped to a region of chromosome 6

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12
Q

How are alloantibodies detected?

A

Via crossmatch assays in clinical HLA laboratories at transplant centers

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13
Q

What organ is more resistant to antibody-mediated damage?

A

Liver

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14
Q

Where is the MHC class II expressed?

A

On the thymic epithelium and APCs

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15
Q

Describe hyperacute rejection

A

Occurs within minutes of graft revascularization and is the result of preformed antibodies directed against donor alloantigens

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16
Q

How can a hyperacute rejection be prevented?

A

Panel reactive antibody assay

Crossmatching

17
Q

What is the most frequent form of rejection seen clinically? What is it the result of?

A

Acute rejection

Result of alloreactive T-cell activation via the direct and indirect pathways of antigen presentation

18
Q

Over what time period does acute rejection occur?

A

Within a few weeks of transplantation

19
Q

What is the major cause of late graft failure?

A

Chronic rejection

20
Q

Over what time period does chronic rejection occur?

A

Mos to yrs after transplantation

21
Q

How are organs preserved?

A

Hypothermia is induced by flushing the organs with 4 degrees C preservation solution and storing them on ice

22
Q

Which kidney is the graft of choice in renal transplantation and why?

A

Left kidney because of a longer renal vein and easier access to the renal artery

23
Q

When is there high acute mortality in a liver transplant?

A

If a liver transplant occurs for acute liver failure as opposed to chronic liver dz

24
Q

When do the worst outcomes occur in a liver transplant?

A

With Hep C and advanced malignancy

25
Q

What must occur with donors and recipients of heart transplants?

A

They must be ABO and size (within 20% total body weight) compatible

26
Q

What is the most frequent symptom of rejection of a heart transplant?

A

Fatigue

27
Q

What is the gold standard of dx of acute cardiac allograft rejection?

A

Endomyocardial biopsy

28
Q

What is the MOA of steroids?

A

Suppress the immune system via inhibition of DNA and RNA synthesis

29
Q

What is long-term administration of corticosteroids associated with?

A
HTN
Hyperlipidemia
Hyperglycemia
Catarct formation
Osteoporosis
Psychosis
Pancreatitis
GI tract bleeding, ulceration and perforation
Poor wound healing
Growth retardation
30
Q

Which calcineurin inhibitors can cause nephrotoxicity?

A

Cyclosporine

Tacrolimus

31
Q

Which cell cycle inhibitor causes less nephrotoxicity than calcineurin inhibitors? What else could it cause?

A

Sirolimus
However, it causes more HTN, hepatic artery thrombosis
Also can cause hyperlipidemia, pneumonitis, acne, and rashes and can interfere with wound healing

32
Q

What are some characteristics of mycophenolate mofetil?

A

Antimetabolite
No renal toxicity but causes bone marrow suppression
Contraindicated in pregnancy

33
Q

When is azathioprine used?

A

In pts intolerant to MMF (mycophenolate mofetil)

34
Q

Which antimetabolite is rarely used?

A

Methotrexate

35
Q

What is the exception to methotrexate being rarely used?

A

Pediatric heart transplant

36
Q

What are examples of anti-t lymphocyte antibodies?

A

Thymoglobulin
Basiliximab (Simulect)
Alemtuzumab (Campath)
Belatacept (Nulojix)

37
Q

What is rituximab (Rituxan) used for?

A

Anti-b lymphocyte antibody

Hodgkin B-cell lymphoma