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Chem Path Immunology > L9 Transplantation immunology > Flashcards

L9 Transplantation immunology Flashcards

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1
Q

What are the 3 types of allograft rejection?

A
  1. Hyperacute rejection
  2. Acute rejection
  3. Chronic rejection
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2
Q

_______________(immune cells) is against the graft in hyperacute rejection. Onset within minutes to 1st week.

A

Pre-formed Ab

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3
Q

What are the consequences of hyperacute rejection?

A
  • Blood vessel hemorrhage and occlusion

- organ ischemia and necrosis

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4
Q

Example of hyperacute rejection? How to prevent?

A

Blood transfusion: Cross- matching ABO blood group typing

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5
Q

_________ rejection occurs within 1st 6 months.

A

Acute

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6
Q

_____________(immune cells) is involved in acute rejection.

A
  1. Anti-foreign HLA (human leucocyte antigen) T cells (mainly)
  2. Anti-foreign B cell/ Ab: harder to reverse if involved
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7
Q

Consequence of acute rejection? How to prevent it?

A

Reversible graft destruction;

HLA typing

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8
Q

Prevention of chronic rejection?

A

HLA typing

- best possible graft condition pre- and post- transplantation

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9
Q

The onset for chronic rejection occurs from months to years, and the immune cells involved are?

A

Anti-foreign HLA T cell, B cell, Ab that causes chronic damage

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10
Q

High risk factors for chronic rejection?

A
  1. Frequent acute rejection
  2. High degree HLA mismatch
  3. Poor graft condition
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11
Q

Consequences of chronic rejection? (2)

A
  1. Irreversible graft destruction

2. Fibrosis and scarring of graft

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12
Q

Give examples of organ-specific features of chronic rejection.

A
  1. Kidney: tubular atrophy
  2. Liver: disappeared bile duct
  3. Heart: Vasculopathy (concentric atherosclerosis, deposition of ECM)
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13
Q

What are the 3 factors triggering transplantation rejection?

A
  1. Foreign HLA molecules
  2. Pre-formed antibodies against the graft
  3. MiHA (minor histocompatibility Ag)
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14
Q

What are the sources of foreign HLA molecules in transplantation rejection? (human leucocyte antigen)

A
  • Donor’s HLA class I (A,B,C) : present throughout the graft
  • Donor’s HLA class II (DP, DQ, DR) : Dendritic cells (very potent to trigger T cells), activated endothelial cell (by cytokines in rejection environment)

(A,B, DR have the strongest immunogenicity, ability to provoke immune response)

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15
Q

What is the mechanism of foreign HLA molecules triggering transplantation rejection? (onset?)

A

Acute rejection

  • TCR designed to act towards foreign HLA molecules
  • (recall class I and class II HLA molecules)
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16
Q

How can we prevent foreign HLA molecules transplantation rejection? Desribe briefly.

A

HLA typing: only HLA-A,B,DR required in organ transplant, but all 6 types are required in HSCT

  1. Serological method: subject lymphocytes (donor/recepient) to a panel of Ab specific to different types of HLA > can detect types of HLA on donor/recepient
  2. Molecular method: identify the DNA sequence of HLA genes by PCR, useful in HSCT
17
Q

Pre-formed antibodies against the graft may cause transplantation rejection. Briefly state the sources of them .

A
  1. Anti-foreign HLA Ab formed due to previous exposure to HLAs
    - multuple blood transfusions
    - multuple pregnancies
    - previous allograft rejection
  2. Anti-ABO Antibody (blood group)
18
Q

What is the type of transplantation rejection in Anti-foreign HLA Ab formed due to previous exposure to HLAs?

A

Hyperacute rejection

  • Exceptions: Liver graft: large size, good regeneration ability to withstand Ab-mediated damage
19
Q

How can we prevent Anti-foreign HLA Ab formed due to previous exposure to HLAs?

A

Cross-matching
- subject donor lymphocytes to recepient serum containing Ab > +ve cross-matching means contraindication

  • not routinely done in surgical heart transplant: regular pre-transplant screenings for recipient serum against a panel of HLA types for binding <15 %
20
Q

What is the type of transplantation rejection in Anti-ABO (blood group) Ab? Briefly explain the mechanism.

A

Hyperacute rejection
- Anti-blood group IgM against ABO antigen on graft/ endothelial cell

Exceptions:

  1. Grafts that do not express ABO antigens (cornea, heart valve, HSCT, bone, tendon)
  2. Young infant recepient: very low anti-blood group Ab
21
Q

How can we prevent transplantation rejection in Anti-ABO (blood group) Ab?

A

ABO blood group typing

22
Q

What immune cells are involved in MiHA (minor histocombatibility Ag) type of transplantation rejection?
Immunogenicity c.f. HLA molecules?

A

Non-HLA foreign peptides;

far less immunogenic (can reduce rejection response) than foreign HLA molecules

23
Q

What is the mechanism for MiHA type of transplantation rejection?

A
  • Mild graft rejection
  • degraded peptides from donor with 1 AA difference > recognised by a few T cells > weaker immune response;
    therefore allografts even with perfectly matched HLAs still require immunosuppression.
24
Q

What is the preventive measure for MiHA type of transplantation rejection?
Explain in detail. (4)

A

Immunosuppression
- e.g. Conventional combination for lifelong immunosuppression - Triple immunosuppression treatment

  1. corticosteroid (prednisolone) > generate immune inhibitior
  2. Cytotoxic drug (mycophenolate mofetil) > kills proliferating cells
  3. T-cell inhibitors (cyclosporine/ FK506 = tarcolimus..)

+ used post-treatment for a period of ~1 week, reduce risks of rejection, reverse acute rejection episode
4. Anti-T cell antibody (Atgam: Anti-thymocyte globulin = ATG/ Daclizumab: Anti-IL-2 receptor Ab) > potently kill or block T cell activation

25
Q

Drugs to revert acute rejection episode?

A

IV steroid (methylprenisolone), anti T-cell Ab

26
Q

State some issues of immunoppressant.

A
  1. Increased risk of infections
    - opportunistic bacteria, pneumocystis jirovecii
    - CMV (cytomegalovirus), HHV (human herpes virus)
  2. Increased incidence of malignanct
  3. Side effects
    - Steroids: HT, Weight gain, Bone mineral loss
    - Cyclosporine, tarcolimus: HT, renal dysfunction
27
Q

What do we have to do upon giving immunosuppresants over time?

A

Allografts usually become less immunogenic > scale down immunosuppressant

28
Q

What is the most common cause of motality in allogenic HSCT?

A

Graft-versus-host disease (GVHD)

29
Q

Why patients are subjected to high-dose chemotheraphy before HSCT? (3)

A
  1. Destroy self BM HSC to make room for donor HSC
  2. Destroy recepient’s immune system to prevent rejection
  3. Killing cancer cells
30
Q

What are the 3 differences between Organ transplant and allogenic HSCT?
Explain.

A

Organ transplant vs Allogenic HSCT:

  1. Graft status
    - O: Immune innocuous (harmless) graft
    - A: Immune-agressive graft (with mature T cells)
  2. Recepient (host immune status)
    - O: Immune-competent
    - A: Immunocompromised due to high-dose chemoTx prior
  3. Consequence
    - O: Immune rejection against the graft
    - A: Immune rejection against the recepient
31
Q

Mainly ______________ cells are affected in GVHD, clinical manesfistations include skin rash , heavy diarrhea and jaundice.

A

Epithelial

Skin rash: skin slough off
Heavy diarrhea: GI tract
Jaundice: liver injury

32
Q

Prophalaxis is given to all allogenic HSCT recepients (T-cell inhibitors).

What is the treatment when GVHD actually develops?

A
  • Steroids

- required in 1/3-2/3 patients even with prophylaxis

33
Q

Although depletion of donor T cells from HSC reduces GVHD, but what are the 2 disadvantages to this?

A
  1. Donor T cells can kill residual host immune cell to prevent graft rejection (reverse graft rejection)
  2. Increased risk of cancer relapse: donor T cells could have killed residual cancer cells as foreign cells

Chem Path Immunology (2 decks)

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