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FMS > FMS Week 10: Transplantation > Flashcards

FMS Week 10: Transplantation Flashcards

1
Q

Transplantation Definition

A

Transplantation is the process of taking cells, tissues, or organs, called a graft, from one individual (donor) and placing them into an individual (Recipient)

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2
Q

Autograft Definition

A

from one part of the body to another e.g. trunk to arm

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3
Q

Isograft Definition

A

between genetically identical individuals (e.g. monozygotic twins, or within an inbred strain)

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4
Q

Allograft Definition

A

between different members of the same species (e.g. Mr. Smith to Mr. Jones)

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5
Q

Xenograft Definition

A

between members of different species (e.g. monkey to man)

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6
Q

HLA Mismatches AKA

A

Alloantigens

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7
Q

HLA Mismatches can lead to …

A

Transplant Rejection

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8
Q

Types of transplant rejection

2 listed

A
  • Transplant Rejection
  • Host-versus-Graft Disease
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9
Q

HLA Class I is expressed on what cells

A

HLA Class I is expressed on all nucleated cells

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10
Q

HLA Class II is expressed on which cells?

A

HLA Class II is expressed on Professional Antigen Presenting Cells (APCs) such as

  • Dendritic Cells (DCs)
  • Macrophages (Monocytes)
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11
Q

HLA Class II is upregulated on?

A

Endothelial cells

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12
Q

Type of HLA expression

A

Co-dominant expression

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13
Q

Co-dominant expression definition

A

Maternal and Paternal alleles are fully expressed

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14
Q

MHC alleles are on which chromosome?

A

Chromosome 6

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15
Q

MHC Class II Haplotypes

3 listed

A
  • HLA-DP
  • HLA-DQ
  • HLA-DRB1
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16
Q

MHC Class I Haplotypes

3 Listed

A
  • HLA-B
  • HLA-C
  • HLA-A
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17
Q

Main ways to be exposed to HLA proteins

3 listed

A
  • Transfusion
  • Pregnancy
  • Transplant
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18
Q

3 Pathways of allorecognition

A
  • Direct
  • Semi-Direct
  • Indirect
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19
Q

Direct Allorecognition Mechanism

A

Recipient T cell recognizes self or non-self peptide represented on non-self MHC from a donor APC

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20
Q

Semidirect Allorecognition Mechanism

2 listed

A
  • Recipient T cell recognizes non-self peptides on self MHC on Recipient APC
  • Recipient T Cell Recognizes self peptide on non-self MHC on Recipient APC
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21
Q

Indirect Allorecognition Mechanism

A

Recipient T cell recognizes non-self peptide on self MHC on recipient APC

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22
Q

Direct Allorecognition accounts for what % of Allorecognition?

A

1-10%

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23
Q

Indirect Allorecognition accounts for what % of Allorecognition?

A

< 0.1 %

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24
Q

Semidirect Allorecognition accounts for what % of Allorecognition?

A

~90%

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25
Q

Direct Allorecognition Donor or Recipient APC?

A

Donor APC

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26
Q

Semidirect Allorecognition Donor or Recipient APC?

A

Recipient APC

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27
Q

Indirect Allorecognition Donor or Recipient APC?

A

Recipient APC

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28
Q

Mixed Lymphocyte Reaction Steps

4 listed

A
  • Mix blood mononuclear cells from two donors in tissue culture
  • Responder T cell recognition of allogeneic MHC Class I & II molecules
  • Clonal expansion and functional differentiation of responder T cells
  • Effector functions of both CD8 and CD4 T cells
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29
Q

Mixed Lymphocyte Reaction: MHC Class I Interactions and Result

4 Listed

A
  • Recipient CD8 T Lymphocyte (Responder cell) recognizes MHC Class I presented on allogeneic Donor APC
  • Recipient allogeneic CD8 CTLs are activated
  • Allogeneic CTLs kill and lyse target cell expressing allogeneic MHC
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30
Q

Mixed Lymphocyte Reaction: MHC Class II Interactions and Result

4 Listed

A
  • Recipient CD4 T Lymphocyte (Responder cell) recognizes MHC Class II presented on allogeneic Donor APC
  • Recipient allogeneic CD4 Helper T cells are activated
  • Allogeneic Helper T Cells secrete cytokines when contacting Allogeneic Donor MHC Class II
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31
Q

Immunological Components of Rejection

SEE LATER

A
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32
Q

Types of Rejection Reactions of Solid Organ Transplants

4 Listed

A
  • Hyperacute
  • Accelerated
  • Acute
  • Chronic
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33
Q

Hyperacute rejection timeline

A

minutes-hours

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34
Q

Hyperacute Rejection Cause

A

Preexisting anti-donor antibodies in the recipient and complement

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35
Q

Accelerated Rejection Timeline

A

Days

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36
Q

Accelerated Rejection Cause

A

Reactivation of sensitized lymphocytes against donor antigens (memory response)

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37
Q

Acute Rejection Timeline

A

Days-weeks/months

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38
Q

Acute Rejection Cause

A

Primary activation of lymphocytes against donor antigens (de novo)

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39
Q

Chronic Rejection Timeline

A

months-years

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40
Q

Chronic Rejection Causes

5 listed

A
  • HMI
  • CMI
  • Cytokines
  • Immune Complexes
  • Fibrosis
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41
Q

HMI AKA

A

Humoral Immunity

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42
Q

CMI AKA

A

Cell-Mediated Immunity

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43
Q

Hyperacute Graft Rejection

4 Steps

44
Q

Acute Cell-mediated Rejection Allorecognition Type

A

Direct Recognition

45
Q

How are organ’s dendritic cells activated in Acute Rejection?

A

The inflamed state of the organ activates the donor dendritic cells

46
Q

Acute Cell-mediated Rejection

4 Steps

47
Q

Acute Cell-mediated Rejection can result in?

3 Listed

A
  • Parenchymal cell damage
  • interstitial inflammation
  • Endotheliatitis
48
Q

Acute Cell-mediated Graft Rejection: Tubulointerstitial Pattern Description

A

Inflammatory cells in the interstitium and between epithelial cells of the tubules (tubulitis)

49
Q

Acute Cell-mediated Graft Rejection: Vascular Pattern Description

A

Rejection vasculitis, with inflammatory cells attacking and undermining the endothelium (endotheliitis)

50
Q

Most Common pattern of Cell-mediated Acute Rejection

A

Tubulointersitial Pattern

51
Q

Acute Rejection is __________ Mediated.

A

Antibody &/or T Cell

52
Q

Acute Rejection can involve?

A

Antibodies and T cells

53
Q

Acute Humoral Rejection of kidney graft can result in?

3 listed

A
  • Rapid decline in urine output,
  • Rise in serum Creatinine,
  • Tenderness and edema of graft
54
Q

Acute Humoral Rejection associated pathologies

2 listed

A
  • Inflammation in peritubular capillaries (capillaritis)
  • Immunoperoxidase stain - C4d deposition in peritubular capillaries and a glomerulus
55
Q

Chronic Rejection Allorecognition Type

A

Indirect Allorecognition

56
Q

Chronic Rejection occurs after how much time post-transplant?

A

Months or years

57
Q

Chronic Rejection Vascular Effects

3 listed

A
  • Proliferative inflammatory lesions of the small arteries, thickening of the glomerular basement, and interstitial fibrosis lead to vasculature changes and loss of function
  • Vascular changes often due to T cell-mediated damage and antibody against HLA alloantigen(s)
  • Vascular occlusion & Interstitial fibrosis
58
Q

Chronic Rejection histopathologic effects

4 listed

59
Q

Immunosuppressive Drugs Basic Categories

3 Listed

A
  • Anti-inflammatory
  • Inhibition of signaling pathways of T cell activation
  • Cytotoxic; interfere with DNA replication
61
Q

solid organ transplant

62
Q

Cyclosporine and Tacrolimus Mechanism of Action

A

Blocks T cell cytokine production by inhibiting the phosphatase calcineurin and thus blocking activation of the NFAT transcription factor

63
Q

Mycophenolate Mofetil Mechanism of Action

A

Blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis in lymphocytes

64
Q

Rapamycin (Sirolimus) Mechanism of Action

A

Blocks lymphocyte proliferation by inhibiting mTOR and IL-2 signaling

65
Q

Corticosteroids Mechanism of Action

A

Reduce inflammation by effects on multiple cell types

66
Q

Antithymocyte Globulin Mechanism of Action

A

Binds to and depletes T cells by promoting phagocytosis or complement-mediated lysis (used to treat acute rejection)

67
Q

Anti-IL-2 Receptor (CD25) Antibody Mechanism of Action

2 listed

A
  • Inhibits T cell proliferation by blocking IL-2 binding
  • may also opsonize and help eliminate activated IL-2R-expressing T cells
68
Q

CTLA4-Ig Mechanism of Action

A

Inhibits T cell activation by blocking B7 costimulator binding to T cell CD28

69
Q

Anti-CD52 (alemtuzumab) Mechanism of Action

A

Depletes lymphocytes by complement-mediated lysis

70
Q

HLA Testing for Solid Organ Transplant

5 listed

A
  1. Tissue Typing - Recipient
  2. HLA Antibody Testing - Recipient
  3. Tissue Typing Donor
  4. Flow-Based Crossmatch
  5. Post-Transplant Monitoring
71
Q

Tissue Typing - Recipient Purpose

A

Determine HLA molecules the recipient expresses

72
Q

HLA Antibody Testing - Recipient Purpose

2 Listed

A
  • Does the recipient have HLA antibody (Screen)
  • What is the specificity of each HLA antibody? (Identification)
73
Q

Tissue Typing - Donor Purpose

3 Listed

A
  • Determine HLA molecules the donor expresses
  • Determine HLA mismatch antigens with recipient
  • Does the recipient have donor-specific antibody (DSA)?
74
Q

Flow-Based Crossmatch Purpose

2 Listed

A
  • Donor cells + recipient serum
  • Does DSA cause reactivity?
75
Q

DSA AKA

A

Donor-specific Antibody

76
Q

Post-Transplant Monitoring Purpose

A

Does the recipient have DSA?

77
Q

Hematopoietic Stem Cell Transplantation are performed on who?

A

transplants are performed to treat patients with life-threatening malignant and non-malignant disease

78
Q

Hematopoietic Stem Cell Transplantation Treatment Reasons

5 listed

A
  • Rescue of marrow after irradiation/chemotherapy
  • Immunotherapy against a neoplasm
  • Treating a bone marrow failure
  • Treating an immune system disorder
  • Treating an inherited metabolic disorder
79
Q

Goals of Hematopoietic Stem Cell Transplantation

2 listed

A
  1. Rid recipient of disease
  2. reconstitute immune response
80
Q

Hematopoietic Stem Cell Transplantation Process 3 steps

81
Q

Hematopoietic Stem Cell Transplantation: Relative time of recovery for Neutrophils, macrophages, eosinophils, and basophils?

A

1-2 months

82
Q

Hematopoietic Stem Cell Transplantation: Relative time of recovery fro Natural Killer Cells

A

3-4 Months

83
Q

Hematopoietic Stem Cell Transplantation: Relative time to recovery T cells

A

6-12 months

84
Q

Hematopoietic Stem Cell Transplantation: Relative time to recovery B cells

A

12-24 months

85
Q

Clinical Outcomes of Bone Marrow Transplant Correlates with?

86
Q

MiHA

A

Minor Histocompatibility Antigens

87
Q

Patients recieving HLA identical Bone Marrow can still get?

88
Q

Minor Histocompatibility Antigens role in GVHD

A
  • Polymorphic self-proteins (non-HLA) that differ in amino acid sequence between individuals can lead to GVHD
  • Processed and presented by APC and recognized by T cells as non-self since T cells were never selected to be tolerant for them
89
Q

GVHD Steps

3 Listed

90
Q

Pathophysiology of GVHD

3 listed

91
Q

Acute GVHD after HSCT

92
Q

Chronic GVHD after HSCT

93
Q

HSCT AKA

A

Hematopoietic Stem Cell Transplantation

95
Q

HSC grafts depleted of T cells reduce?

But

May also compromise what?

2 listed

96
Q

NK cells AKA

A

Natural Killer Cells

97
Q

How do NK cells contribute to GVL effects?

3 things listed

98
Q

Alloreactive NK cells can reduce the incidence of?

A

Leukemic Relapse

99
Q

HLA Testing for solid organ transplant example

100
Q

Direct Allorecognition summary

A

is unique to transplantation and refers to the recognition by recipient T cells of intact donor HLA/peptide complexes expressed on the surface of graft-derived antigen presenting cells (APC)

101
Q

Indirect Allorecognition summary

A

refers to the recognition by recipient T cells of processed donor HLA molecule presented by recipient HLA molecules

102
Q

Semi-direct Allorecognition summary

A

Involves the acquisition by recipient APCs of donor exosomes (and likely other extracellular vesicles) released by passenger leukocytes or the graft

103
Q

During the development of aGVHD

A

activation of various immune cells, especially donor T cells, leads to damage of target organs including skin, liver, lungs and gut

104
Q

aGVHD AKA

A

Acute Graft Versus Host Disease

105
Q

cGVHD AKA

A

Chronic Graft Versus Host Disease

106
Q

cGVHD Pathology

2 listed

A
  • Thymic destruction, wither from pretransplant conditioning or aGVHD, and chronic stimulation of donor T cells contribute to cGVHD
  • widespread tissue fibrosis
107
Q

GVL effect

A

when alloreactive T/NK cells in the graft help to rid the patient of residual leukemia cells

FMS (34 decks)

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