Transplant Pathology- Nelson Flashcards Preview

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Flashcards in Transplant Pathology- Nelson Deck (39):
1

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)

2

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

REJECTION

3

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

ABO antigens
HLA antigen

4

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

5

Describe the indirect pathway of cellular rejection

Host APCs picks up graft antigens and display to CD4 & CD8 cells

6

What is humoral rejection? What are the types of preformed antibodies?

Humoral rejection = antibodies produced against alloantigens

Preformed antibodies=
-Abs to ABO antigens are produced naturally
-Abs to HLA antigens from previous exposure

7

What are the major types of pretransplant testing?

-ABO compatibility testing
-HLA typing
-Detection of preformed Abs
-Lymphocyte crossmatch

8

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

9

Explain the immunological mechanisms of acute rejection?

-occurs over days to weeks
-T-cell mediated hypersensitivity reactions or from antibody mediated hypersensitivity reactions

10

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

11

Explain the immunological mechanisms of chronic rejection?

-Occurs over months-years

-Cell mediated and antibody-mediated hypersensitivity reactions

-Often secondary to vascular injury

12

What is the most common cause of renal graft failure?

Chronic rejection

13

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

14

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

Increases susceptibility for opportunistic infections

Increased risk of malignancies

15

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

16

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!!!

17

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

18

Differentiate between acute and chronic GVHD

Acute= 0-100 days post transplant

Chronic= after 100 days post transplant

19

Describe the principle organ systems involved in acute GVHD

-dermatitis
-destruction of small bile duct- jaundice
-ulceration of GI mucosa & blood diarrhea

20

Describe the principle organ systems involved in chronic GVHD?

-dermal fibrosis
-chronic liver disease
-fibrosis of GI tract, decreased absorption, chronic diarrhea

21

Define amyloidosis

A group of disorders characterized by deposition of amyloid in extracellular space of tissues and organs (resulting in tissue and organ dysfunction)

22

What is amyloid?

group of pathologic proteins that share similar physical properties

23

Describe the apperance of amyloid

linear
Non-branching fibrils
Cross-beta-pleated sheet configuraiton

Appears amorphous
Eosinophilic
Hyaline
Extracellular substance

24

What is the typical stain used to stain amyloid?

CONGO RED
*on polarization exhibits a green birefringence

25

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

26

AL (amyloid light chain) amyloid

Made up of either complete immunoglobulin light chains, fragments, or both

27

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

28

Beta-amyloid protein (AB)

-Proteolysis of larger precursor protein called amyloid precursor protein

-Found in cerebral plaques of alzheimer disease

29

Transthyretin (TTR)

-Normal serum protein that binds and transports thyroxine and retinol

-Mutations can result in amyloid deposition

30

B2-microglobulin

-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

31

Systemic amyloidosis

involving several organ systems

32

Localized amyloidosis

Involving a single organ

33

Primary amyloidosis

-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

34

Secondary amyloidosis

-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

35

Hereditary amyloidosis

group of heterogenous, heritable forms of amyloidosis with several distinctive patterns of organ involvement

36

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

37

What are the key clinical symptoms of a patient with systemic amyloidosis?

-Waxy skin
-Easy bruising
-Enlarged muscles (tongue, deltoids)
-SS of heart failure, cardiac conduction abnormalities, hepatomegaly, renal dysfunction
-Neuropathy
-Impaired coagulation

38

What are the major site of clinically important deposition in systemic amyloidosis?

Kidneys
Heart
Liver

39

Age-related systemic amyloidosis

due to amyloid deposition associated with normal TRR protein

*occurs in pts w/ advanced age

*typically heart is invovled (cardiomyopathy and arrhythmias)