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YEAR 5: Immunopathology > Immuno: Transplantation Pt.1 > Flashcards

Immuno: Transplantation Pt.1 Flashcards

1
Q

Which organ is most commonly transplanted?

A
  • Kidneys
  • Followed by Liver
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2
Q

What is the average half-life of a transplanted kidney?

A
  • 12 years
  • Deceased donors slightly lower ~ 10 years
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3
Q

What are the three phases of an immune response to a graft?

A
  • Phase 1: recognition of foreign antigens
  • Phase 2: activation of antigen-specific lymphocytes
  • Phase 3: effector phase of graft rejection
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4
Q

What are the most relevant cellular proteins that can determine compatibility?

A
  1. ABO blood group
  2. HLA
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5
Q

Which chromosome is HLA encoded on?

A

Chromosome 6

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6
Q

What are the two major types of rejection?

A
  • T cell-mediated rejection
  • Antibody-mediated rejection
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7
Q

What are the alleles of HLA class I and class II?

A
  • Class I - A, B, C
  • Class II - DR, DQ, DP
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8
Q

Describe the basic structure of HLA Class I and Class II.

A

Class I

  • 3 alpha domains
  • 1 beta-2 microglobulin domain
  • 1 transmembrane domain

Class II

  • 2 alpha domains
  • 2 beta domains
  • 2 transmembrane domains
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9
Q

Where are HLA class I and class II expressed?

A
  • Class I: all cells
  • Class II: antigen-presenting cells (can be upregulated at times of stress)
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10
Q

Which HLA alleles are most immunogenic?

A

A, B and DR

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11
Q

What is 1:1:0 in terms of mismatches

A

For A, B and DR

Others e.g. DQ are still antigenic

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12
Q

Where do the antigen-presenting cells that interact with host T cells come from?

A

From the recipient and the donor (the donor organ will contain many APCs)

NOTE: a lot of these interactions will happen in lymph nodes

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13
Q

Which test is used to give a definitive diagnosis of graft rejection?

A

Biopsy

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14
Q

Describe the phases of T-cell mediated rejection.

A
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15
Q

Describe the effector phase of T-cell mediated graft rejection.

A

Activated CD8+ T-cells

  • Release toxins to kill target cells - granzyme B
  • Punch holes in target cells - perforin
  • Induce apoptosis - Fas ligand

CD4+ T-cells recruit and activate macrophages which:

  • Phagocytose cells
  • Release proteolytic enzymes
  • Produce inflammatory cytokines
  • Release oxygen and nitrogen free radicals
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16
Q

What are the typical histological features of T-cell mediated rejection?

A
  • Lymphocytic interstitial infiltration
  • Tubulitis - WBCs within the tubular epithelium
  • Arteritis - WBCs within vascular wall
17
Q

What are the 3 signals of T-cell activation?

A
  1. Antigen/MHC interaction with TCR
  2. Co-stimulatory molecular expression - CD80/86 interaction with CD28
  3. IL-2
18
Q

What other explanation might there be for graft failure other than rejection?

A

Immunosuppressive drugs may be nephrotoxic

19
Q

Where are AB antigens expressed?

A

On erythrocytes AND endothelial cells

20
Q

What are the three phases of antibody-mediated rejection?

A
  • Phase 1: B-cells recognise to foreign HLA
  • Phase 2: proliferation and maturation of B cells with anti-HLA antibody production
  • Phase 3: effector phase - antibodies bind to graft endothelium = intravascular disease
21
Q

What is a key difference between the production of anti-AB and anti-HLA antibodies?

A
  • Anti-AB antibodies are naturally occuring (pre-formed)
  • Anti-HLA antibodies are not naturally occuring but can be pre-formed due to previous exposure to epitopes (e.g. previous transplant, pregnancy) or post-formed (after transplantation)
22
Q

Outline the pathophysiology of antibody-mediated transplant rejection.

A
  • Antibodies bind to HLA on the endothelium of blood vessels within the transplanted organ
  • The antibodies fix complement which leads to formation of MAC and endothelial cell lysis
  • Binding of complement also recruits inflammatory cells
  • This leads to inflammation of the microcirculation (capillaritis)
  • This leads to procoagulant tendencies and occlusion of the microcirculation leading to graft fibrosis and necrosis
23
Q

What are the main histological features of antibody-mediated transplant rejection?

A
  • Presence of inflammatory cells within the capillaries of the graft (HALLMARK)
  • Immunohistochemistry can show fixation of complement fragments on the endothelial cell surface
24
Q

What are the three main approaches to preventing graft rejection?

A
  • AB/HLA typing
  • Screening for antibodies
  • Overcoming organ mismatch issues

YEAR 5: Immunopathology (25 decks)

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