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pathology (guide) > Immunology - Transplantation > Flashcards

Immunology - Transplantation Flashcards

1
Q

What is an isograft?

A

A transplant from a twin

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2
Q

What is an allograft?

A

A transplant from the same species

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3
Q

What is a zenograft?

A

A transplant from a different species

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4
Q

What is a split graft?

A

A transplant shared by two recipients (e.g. liver)

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5
Q

What can a living donor donate?

A
  • Bone marrow
  • Kidney
  • Liver
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6
Q

What can a deceased donor donate?

A

Solid organs:
- Kidney (most commonly transplanted organ)
- Heart
- Pancreas
- Lungs
- Liver

Other:
- Small bowel
- Free cells (BM, pancreas islets)
- Temporary (blood, skin, burns)
- Cornea
- Framework (bone, cartilage, tendons, nerves)
- Composiet (hand, face)

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7
Q

What is a transplant rejection + its three stages?

A

The immune system mounting a response to “foreign” (Non-self) antigens)

Stages:
- Recognition
- Activation
- Effector function

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8
Q

What cells are involved in immune recognition?

A
  • T cells: recognise antigen presented via MHC (I/II) on APCs
  • B cells: recognise just antigen
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9
Q

What are the different HLA classes and where are they expressed?

A

HLA Class I
- A, B, C
- Expressed on all cells

HLA Class II
- DP, DQ, DR
- Expressed on APCs
- Can be upregulated on other cells under stress

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10
Q

What factors are recognised during transplantation + their features?

A

Human Leukocyte Antigens (HLA):
- Most important: DR > B > A
- Coded by MHC complex on Chr 6
- Cell surface proteins
- Present foreign antigens to T cells leading to activation

Minor HLA
- Other polymorphic self peptides

ABO Blood Antigens

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11
Q

How can foreign antigens be recognised during transplantation?

A

Direct:
- Donor APC presents foreign antigen +/or MHC to recipient T cells
- Seen in ACUTE REJECTION

Indirect:
- Recipient APC presents donor antigen to recipient T cells
- e.g. Immune system working normally, as it would for an infection
- Seen in CHRONIC REJECTION

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12
Q

What components are involved in transplant rejection

A
  • T cell mediated
  • Antibody mediated
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13
Q

What are the events of T cell activation?

A
  • Proliferate
  • Produce cytokines
  • Provide help to activate CD8+ cells
  • Help antibody production
  • Recruit phagocytic cells
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14
Q

What are the three phases of T cell mediated response in regards to transplant rejection?

A
  1. Recognition of foreign antigens
  2. Activation of antigen-specific T lymphocytes
  3. Effector phase of graft rejection
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15
Q

What happens during the effector phase of T-cell mediated response in regards to transplant rejection?

A
  1. Graft infiltration by allreactive CD4+ cells
  2. Cytotoxic T cells: release toxins (granzyme B), punch holes in target cells (perforin), apoptotic cell death (Fas ligand)
  3. Macrophages: phagocytosis, release of proteolytic enzymes, production of cytokines, production of oxygen + nitrogen radicals
  4. Abs bind to graft endothelium

Organ damage = Cytotoxic T cells + Macrophages

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16
Q

What are the three phases of antibody-mediated response in regards to transplant rejection?

A
  1. Recognition of foreign antigens
  2. Proliferation + maturation of B cells with Ab production
  3. Abs bind graft endothelium leading to intra-vascular disease (+organ damage)
17
Q

What are some features of the proliferation + maturation phase of the antibody-mediated response in regards to transplant rejection?

A
  • Anti-HLA Ab not naturally occurring - preformed due to transplant, pregnancy, transfusion OR post-formed (arise after transplant)
  • Anti-A/B Abs naturally occur as per blood group
18
Q

What is the mechanism of a hyperacute transplant rejection, its time onset, pathology + treatment?

A

Mechanism:
- Preformed Ab which activates complement

Time:
- Mins - Hrs

Pathology:
- Thrombosis + Necrosis

Tx: (Prevention)
- Crossmatch (ABO groups)
- HLA-matching

19
Q

What is the mechanism of an acute (cellular) transplant rejection, its time onset, pathology + treatment?

A

Mechanism:
- CD4 activating a Type IV reaction

Time:
- <6mths

Pathology:
- Cellular infiltrate

Tx:
- T-cell
- Immunosuppression

20
Q

What is the mechanism of an acute (Ab-mediated) transplant rejection, its time onset, pathology + treatment?

A

Mechanism:
- B cell activation: Ab attacks vessels

Time:
- <6mths

Pathology:
- Vasculitis
- C4d

Tx:
- Ab removal
- B cell immunosuppression

21
Q

What is the mechanism of a chronic transplant rejection, its time onset, pathology + treatment?

A

Mechanism:
- Immune + non-immune mechanism
- RFs: multiple acute rejections, HTN, hyperlipidaemia

Time:
- >6mths

Pathology:
- Fibrosis
- Glomerulopathy
- Vasculopathy (ischaemia)
- Bronchiolitis obliterans (lungs)

Tx:
- Minimise organ damage

22
Q

What is the mechanism of a GVHD transplant rejection, its time onset, pathology + treatment?

A

Mechanism:
- Donor cells attacking host

Time:
- Days-wks

Pathology:
- Skin (rash)
- Gut (D+V, bloody stool)
- Liver (jaundice) involvement

Tx:
- Prevention/immunosuppression-corticosteroids

23
Q

What is an acute vascular rejection?

A
  • After xenograft
  • Similar to hyperacute, but 4-6 days after transplant
24
Q

What are the possible number of HLA mismatches + what are the likelihodds in different circumstances?

A
  • 6
  • Parent-child = 3/6
  • Sibling-sibling = 25% 0/6, 50% 3/6, 25% 6/6
  • Stranger = 1 in 100,000
25
Q

What processes are considered pre-transplant in terms of matching?

A
  • Determine donor + recipient blood group + HLA: tissue typing (PCR analysis of DNA)
  • Check recipient’s pre-formed Ab against ABO + HLA: 3 assay types
  • Cross-match: via CDC + FACS (tests if serum from recipient is able to bind/kill donor lymphocytes - +ve crossmatch is CI for transplantation)
  • Screening is done twice pre-transplant, once before + once after specific organ assigned
26
Q

What processes are considered post-transplant in terms of matching?

A
  • Repeat assays to check for new Abs against graft
  • Weekly - monthly checks for rejection
27
Q

What is a cytotoxicity assay and what does it look for?

A
  • Complement dependent cytotoxicity
  • Does recipient serum kill donor lymphocytes?
28
Q

What is a FACS test and what does it look for?

A
  • Flow cytometry
  • Does recipient serum bind donor lymphocytes?
29
Q

What does a solid phase/Luminex test look for?

A
  • Does recipient serum contain Abs to individual HLA molecules?
30
Q

What are some immunosuppressive regimes?

A
  • Induction (pre-transplant): Suppress T cell response (e.g. anti-CD52 Alemtuzumab or anti-CD25 Basiliximab or OKT3/ATG)
  • Baseline immunosuppression (e.g. SNI + MMF/Azathioprine +/- steroids)
  • Tx for acute rejection as needed
31
Q

What is the treatment for acute rejection?

A

Cellular:
- Steroids (3X methylprednisolone pulses + oral taper)
- OKT3/ATG

Ab-mediated:
- IVIG
- Plasma exchange
- Anti-C5
- Anti-CD20

32
Q

What is the process of a haematopoeitic stem cell transplant?

A
  • Elimiate hosts immune system (total body irradiation, cyclophosphamide, other drugs)
  • Replace with own (autologous) or HLA-matched donor (allogenic) bone marrow
33
Q

What are some indications for a haematopoeitic stem cell transplant?

A
  • Life threatending primary immunodeficiency (SCID, leucocyte adhesion defect)
  • Haematological cancer
34
Q

What is graft versus host disease and its symptoms?

A
  • Occurs in allogenic HSCT
  • Donor lymphocytes recognise + attack host HLA
  • Related to degree of HLA-incompatibility

Sx:
- Skin desquamation
- Rash
- GI disturbance (nausea, vomiting, abdominal pain, diarrhoea, bloody stool)
- Liver failure (jaundice)
- BM failure

35
Q

What is the prophylaxis and treatment for graft versus host disease?

A

Prophylaxis:
- Methotrexate/cyclosporine
- Irradiate blood components for immunosuppressed pts

Tx:
- Corticosteroids

36
Q

What are some post-transplant complications?

A

Infection:
- Increased risk of conventional infections: bacterial, viral, fungal
- Opportunistic infections: CMV, BK virus, pneumocystis carinii

Malignancy:
- Viral associated (X100): Kaposi’s sarcoma (HHV8), lymphoproliferative disease (EBV)
- Skin cancers (X20)
- Other cancers (e.g. lung, colon) (X2-3)

Atherosclerosis:
- HTN
- Hyperlipidaemia
- X20 increased risk in death from MI compared to age-matched general population

pathology (guide) (84 decks)

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