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General Pathology > Transplant Immunopathology > Flashcards

Transplant Immunopathology Flashcards

1
Q

What is the success of organ / tissue transplants dependent on?

A

on the ability to deter or prevent an immune reaction

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2
Q

In organ/tissue transplants, the ability of the body to deter or prevent an immune reaction is accomplished by what? (3)

A
  1. histocompatibility matching between the donor and recipient
  2. immunosuppressive therapy of the recipient (e.g., use of antirejection drugs)
  3. achieving specific unresponsiveness to donor alloantigen(s) (i.e., tolerance).
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3
Q

What is the private, nonprofit organization that manages the organ transplant system in the U.S. under contract with the federal government.

A

United Network for Organ Sharing (UNOS)

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4
Q

For a successful organ, bone marrow or stem cell transplant (graft), what must be matched for the donor and recipient? (2)

A
  • must be matched for ABO blood groups
  • ideally, match as many HLA antigens as possible
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5
Q

Immunosuppression of the recipient (usually using antirejection drugs) is a necessity in all organ, bone marrow, stem cell transplantation, except what? (2)

A
  • in the case of identical twin donor and recipient;
  • autologous bone marrow / stem cell transplants
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6
Q

How can transplant rejection and other adverse immune responses be suppressed in organ transplant

A
  1. Anti-rejection (immunosuppressant) drugs: (cyclosporine, corticosteroids, tacrolimus, sirolimus, azathioprine, mycophenolate mofetil (MMF))
  2. Recipient T-cell depletion
  3. Radiation
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7
Q

The genes that code for _____ are called histocompatibility genes and are localized to a region on the short arm of ______, known as the major _________

A
  • HLA antigens
  • chromosome 6
  • histocompatibility complex (MHC)
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8
Q

What are the three subgroups of the MHC region in Transplant Histocompatibility Matching

A

MHC class I, MHC class II, and MHC class III

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9
Q

What does MHC Class I include?

A

Include the HLA-A, HLA-B, and HLA-C antigens, which are found on almost all human cells

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10
Q

Where are MHC Class II found? What do they include?

A
  • Are chiefly found on immunocompetent cells (macrophages, dendritic cells, Langerhans cells, B-cells, and some T-cells)
  • Include the HLA-DP, HLA-DQ, and HLA-DR antigens
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11
Q

MHC Class III has a very different function than class I and II, but it has a _____ between the other two (on chromosome 6), so they are frequently discussed together

A

locus

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12
Q

Why is it hard for a patient need an organ transplant to find a HLA matched donor?

A

because there are more than 14,000 HLA alleles accounting for more than 10,000 different HLA proteins.

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13
Q

The current standard for HLA matching between transplant recipient and donor is either an ____ or _____ (preferred) (“high resolution”) HLA allelic match to increase transplant survival

A
  • 8 of 8
  • 10 of 10
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14
Q

What is a 10 of 10 HLA allelic match?

A

HLA-A, -B, -C, -DRB1, and -DQB1 matched.

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15
Q

HLA matching of the transplant donor and recipient is most beneficial for what?

A
  • allogenic bone marrow and stem cell transplants
  • (living related donor) kidney transplants
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16
Q

What type of match is considered sufficient in other organ transplants such as heart, lung, liver and pancreatic islet transplantation?

A
  • 6 of 6 HLA match
  • in many cases these transplants will be performed without having a zero HLA mismatch donor organ
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17
Q

What factors can affect the benefit derived from HLA matching

A

donor age, donor type (living vs. dead) and immunosuppression (anti-rejection) protocol

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18
Q

Finding a zero HLA mismatch donor may not be possible for all patients and usually _____ waiting time

A
  • prolongs

(The odds of finding a 6 of 6 HLA match in an unrelated donor is about 1 in 100,000)

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19
Q

What are the 3 categories Bone marrow or hematopoietic stem cell transplants may be

A
  • syngeneic
  • allogeneic
  • autologous
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20
Q

What is a syngeneic transplant?

A

from a genetically identical twin, triplet, etc.
(100% HLA matched)

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21
Q

What is an allogeneic transplant?

A
  • from an HLA-matched related or unrelated donor
  • Usually at least a 7 out of 8 match at HLA-A, -B, -C and -DRB1 (may be lower)
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22
Q

In allogeneic transplants, what does the term “haploidentical” indicates

A

an allogeneic transplant from a half (4 out of 8 HLA) matched related donor with only one mismatch per locus

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23
Q

What is an autologous transplant?

A

a portion of the patient’s own stem cells or bone marrow is removed prior to myeloablative conditioning, screened (to eliminate malignant cells), preserved and reimplanted in the patient after myeloablative conditioning

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24
Q

What are the 3 types of transplant rejections in solid organ transplant?

A
  1. Hyperacute Rejection
  2. Acute Rejection
  3. Chronic Rejection
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25
Q

What are the subcategories of acute transplant rejection?

A
  1. Acute cellular (T-cell mediated) rejection
  2. Acute antibody-mediated (vascular or humoral) rejection
26
Q

Hyperacute Rejection is primarily _____ mediated and occurs in the presence of _____ antibody to donor organs

A
  • antibody
  • pre-existing

(example: natural IgM antibodies specific for ABO blood group antigens)

27
Q

When does hyperacute transplant rejection occur?

A

within minutes of organ transplantation

28
Q

Hyperacute transplant rejection is a combined process in which both cellular and humoral tissue injuries contribute (i.e., a localized Arthus reaction) marked by what?

A

by acute inflammation, fibrinoid necrosis of small vessels, and extensive thrombosis

29
Q

In hyperacute transplant rejection, what happens immediately after the graft is implanted and blood flow is restored

A

antibodies bind to antigens on the graft endothelium and activate the complement and clotting systems → injury, thrombus formation, and ischemic necrosis of the graft

30
Q

_______ is the principal cause of early transplant failure

A

acute transplant rejection

31
Q

When does acute transplant rejection occur?

A
  1. within days of transplantation in the untreated (nonimmunosuppressed) recipient
  2. may appear suddenly months or even years later, after anti-rejection drugs are tapered or discontinued.
32
Q

When is Acute cellular (T-cell mediated) rejection most commonly seen?

A

within the initial months after transplantation

33
Q

Acute cellular (T-cell mediated) rejection is primarily mediated by what?

A

both CD4+ and CD8+ T-lymphocytes directed against the donor tissue / organ graft

34
Q

In Acute cellular (T-cell mediated) rejection, CD4+ T-lymphocytes also secrete ______ and induce ______, which damages the graft

A
  • cytokines
  • inflammation
35
Q

Acute antibody-mediated (vascular or humoral) rejection is primarily mediated by what?

A

anti-donor antibodies that bind to vascular endothelium and activate complement via the classical pathway

36
Q

How is Acute antibody-mediated (vascular or humoral) rejection mainly manifested?

A

by damage to glomeruli and small blood vessels in the transplanted (donor) kidney

37
Q

Chronic Rejection may occur ____ after an otherwise successful transplantation

A

months to years

38
Q

What is chronic transplant rejection primarily caused by?

A

antibody-mediated vascular damage

39
Q

Chronic transplant rejection is dominated by ______, often with intimal thickening and vascular occlusion.

Interstitial fibrosis and tubular atrophy with loss of _____ may occur secondary to the vascular lesions

A
  • vascular changes
  • renal parenchyma
40
Q

When does Graft versus host disease (GVHD) occur?

A

in any situation in which immunologically competent cells or their precursors are transplanted into immunologically incapacitated recipients, and the transferred cells recognize alloantigens in the host

41
Q

Graft versus host disease (GVHD) occurs most commonly in the setting of what?

A

allogeneic bone marrow or stem cell transplantation, but rarely also follow transplantation of solid organs rich in lymphoid cells (e.g., the liver).

42
Q

What is the etiology of Graft versus host disease (GVHD)

A

When such recipients receive normal bone marrow cells from allogeneic donors, the immunocompetent T-cells present in the donor marrow recognize the recipient’s HLA antigens as foreign and react against them

43
Q

________ cells from the donor tissue recognize and attack host tissues in Graft versus host disease (GVHD)

A

CD4+ and CD8+ T

44
Q

When does acute Graft versus host disease (GVHD) occur?

A

within 100 days (median: 2 to 3 weeks) after bone marrow or stem cell transplantation

45
Q

What does clinical manifestation of acute Graft versus host disease (GVHD) result from?

A

from epithelial cell necrosis in 3 principal target organs: liver, skin, and gut.

46
Q

Involvement of skin in acute GVHD usually appears where?

A

first on the neck, ears, and palms of the hands and soles of the feet and then becomes generalized

47
Q

How does generalized acute GVHD present on the skin?

A

as a generalized rash and mucosal ulcerations leading to desquamation in severe cases

48
Q

In acute GVHD, destruction of ______ gives rise to jaundice, and mucosal ____ of the gut results in bloody diarrhea

A
  • small bile ducts
  • ulceration
49
Q

______ is a frequent accompaniment of GVHD.

A

Immunodeficiency

50
Q

GVHD affected individuals are profoundly ______ and are very susceptible to infections, mostly with viruses, such as ____ and _____

A
  • immunosuppressed
  • CMV
  • EBV
51
Q

In acute GVHD, it is believed that in addition to direct cytotoxicity by CD8+ T-cells, considerable damage is inflicted by what?

A

cytokines released by the sensitized donor T-cells

52
Q

Microscopically, graft versus host disease is one of the best examples of a process called _______

A

single cell apoptosis

53
Q

Chronic GVHD occurs when?

A

100 days or more after organ or bone marrow transplantation and may follow the acute syndrome or may occur insidiously

54
Q

Patients of Chronic Graft versus host disease (GVHD) have extensive _____injury, with destruction of skin appendages and fibrosis of the dermis that may resemble _______

A
  • cutaneous
  • systemic sclerosis (scleroderma)
55
Q

In chronic Graft versus host disease (GVHD) chronic liver disease manifested by _____ is also frequent

A

cholestatic jaundice

56
Q

In chronic GVHD, what happens to the immune system?

A
  • The immune system is devastated, with involution of the thymus and depletion of lymphocytes in the lymph nodes.
  • The patients experience recurrent and life-threatening infections
57
Q

_____ symptoms are noted in ~ 80% of patients with extensive chronic GVHD and can cause considerable morbidity.

A

Oral

58
Q

Oral manifestations of chronic GVHD resemble what?

A

those of several autoimmune conditions, including lichen planus, Sjögren’s syndrome, and scleroderma

59
Q

What does the clinical presentation of oral chronic GVHD include? (7)

A
  • mucosal erythema
  • lichen-planus-like changes that can be: reticular; erosive and/or ulcerative
  • hyperkeratosis or leukoplakia
  • mucosal changes associated with decreased salivary gland function and complaints of dry mouth
  • mucoceles
  • sclerotic restriction of mouth opening
  • taste disturbances
60
Q

Patients with chronic GVHD are at an increased risk for developing what? How often should they be evaluated for this?

A

oral cancer and should therefore be evaluated at least twice a year

General Pathology (32 decks)

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