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Immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

Prognosis of orgna transplantations

A

50% renal lost in 10-12 years
50% lungs at 5 years
Many cases require repeat transplantation - demand>supply

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2
Q

What is immune repsonse in organ transplant against

A

polymorphic HLA gene products incl MHC molecules
AB blood group antigens, minorHC
Antigen specific repsonses directed by lymphocytes
all immune cells play role

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3
Q

What does HLA code for

A

MHC complex
HLa on chromosome 6

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4
Q

What genes code for class 1 MHC molecules

A

HLA-A, B and C
All cells - present atigens to CD8

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5
Q

What genes code for class II MHC molecules

A

HLA-DR, DP, DQ
On APCs present antigen to CD4

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6
Q

Stages of transplant refjection

A

Hyperacute
Acute
Chronic

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7
Q

When does hyperacute rejection occur

A

Minutes to hours after
Pre-exisitng antibody to

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8
Q

Acute rejection types and when

A

Days to weeks
Cellula - T cell mediated or humoral - B cell mediated and T cell

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9
Q

What happens in hyperacute rejection

A

Antibodies rapidly bind to raft antigens targeting blood group and MHC
Activation of complement cascade -> cell lysis MAC and inflammation
Endothelial activation, release of pro-thrombotic substances - platelet aggregation, thrombosis, occlusion of graft microvasculature
Rapid thrombosis and infarction of graft -> death of graft
V rare now due to genetic atching with donor

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10
Q

Key step in acute rejeciton

A

Donor antigens recognition by recipient T cells
Presented on donor ACs or processed and presented by recipient APCs

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11
Q

Direct presentation vs indirect acute rejeciton

A

Direct - Donor APC present anigen to recipient T cells
Indirect - Recipient APCs take up antigens from donor -> recipient cells

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12
Q

Mechanism of acute rejection

A

Donor antigen recognition by recipient T cells
APCs activated expressing co-timulatory molecule eg B7 binds to ligands on T cells ->
effector cells
CD8 - -> tissue damage
CD4 Th 1 cells -> Tissue damage, altered vascular function, ischaemia
CD4 Th2 cells ->B cells activated -> donor specific antibodies -> bind to donor cells, activate complement, endothelial damage and microvasc thrombodiss

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13
Q

Presentation acute transplant rejection

A

Acute deterioration in graft function
Pain in region of graft, graft oedema

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14
Q

Investigations for acute graft rejection

A

Screening for graft function
Differntials of infection, immunosupressant toxicity
Diagnosis w biopsy
Serological tests - Donor specific antibodies

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15
Q

Main featires of crhonic rejection

A

Vascular disease within graft
Fibrosis in graft tissue

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16
Q

Pathology of chronic rejection

A

Chronic inflammation and non immune
Immune is both cellular and humoral
also calcineurin inhibitor toxicity eg ciclosporin, tacrolimus toxicity

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17
Q

What cytokines are relased by CD4 Th1 cells

A

IFN gamma
IL-12

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18
Q

Matching receipient to donor for transplant

A

ABO blood group compatability
Histocompatability - HLA mathcing
Cross matching - test for DSAs in recipient blood.

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19
Q

Which HLAs are more importnat to match

A

esp HL-DR, HLA-A, HLA-B (rest are preferred by not required, vary by organ type)
Complete match is very rare
Renal transplant mathcing v importatn
Liver transplantation may not be required

20
Q

Cross matching testing

A

Physical cross match - recipient serum mixed w separated donor lymphcytes - B and T cells separately
Cytotoxic reaction = present
Virtual cross match -are relevant anti-HLA antibodies been detected prev in recipietns serum - multiplex serological assays for anti-HLA antibodies

21
Q

Immunosupression psot transplant induction treatment

A

Combination
Steroid - IV methylprednisolone
Calcineurin inhibitor - tacrolimus or ciclosporin
Antiproliferative agesnt eg mycophenolate mofetil - MMF
Other anti-T cell therapies -
Basilixumab - anti-IL2 mAb, prevents T cell proliferation

22
Q

What do calcineurin inhbitors do

A

Block T cell activation by TCR path

23
Q

What add if high risk to inuction immunosupression for transplant

A

If high risk also T cell depleting induction (reduce circulating T cells) therapy w ATG - antithymocyte globulin or alemtuzimab - antiCD52 mAB

24
Q

Long term maintenance immunosuppression

A

Corticosteroid (gradually reducing dose over first 3 months)
Clacineurin inhibitor - tacrolimus or ciclosporin
Antiproliferative eg azathioprine, mycophenolate mofetil, sirolimus (rapamycin)

25
Q

Treatment for cellular rejection - T cell mediated

A

Increased immunosupression - high dose IV methylprednisolone 500mg for 3 days
With or without T cell depeleting therapy eg ATG
Usually responds v well

26
Q

Treating antibody mediated acute rejection

A

Potent immunosupression and treatment to remove or supress DSAs
eg methylpred, plasmapharesis to directly remove
High dose IVIG (dmapends immune repsonse)
Anti B cell agents
Other immunospurpression cont as standard
Infection prophylaxis incl co-trimoxazole and valganciclovir

27
Q

Anti B cell agents

A

Bortezomib - proteasome inhibitor - depletes plasma cells
Rituximab - anti CD20 B cell monoclonal antibody

28
Q

Chronic rejection treatent

A

Manage complications
eg HF treat, dialusis
End stage -> indication for re-transplantation

29
Q

What is graft vs host disease

A

T cells in donor organ reconise recipient as oreign -> immune response against host

30
Q

What is GvHD primarily ass w

A

Allogenic haematopoietic stem cell transplantation
Solid organ transplants esp liver and small bowel
Transfusion of irradiated blood products in immunocomp

31
Q

Stages of GvHD

A

Activation of recipient APCs (by cytokines and underlying disease)
Donor T cell activation - recognise recipient antigen on donor and recipient APCs
Cellular and inflammatory effector stage - activated donor CD8 - kill host cells. Inflam cytokines release attract inflam cells -> further tissue damage

32
Q

Types of GvHD and when occur

A

acute - <100 dyas after transplant
Chronic ->100 days

33
Q

Acute GvHD where effected

A

skin, liver, gut

34
Q

Chronic GvHD features

A

Most originate as acute
20% de novo
10% after acute GvHD resolved
Various sites

35
Q

Features of skin GvHD

A

Painful or pruritic erythematous macules
Confluent erythema, erythroderma
Subepidermal bullae, vesicles, desquamation

36
Q

Liver acute GvHD

A

Deranged LFTs
Jaundice

37
Q

Bowel acute GvHD

A

Abdo pain, diarrhoea, GI bleeding, ileus, small bowel obstruction

38
Q

Staging of acute GvHD

A

Grades I-IV
Considers affect on skin, bowel, lvier
IV - life threatening
Depends on function of affected areas

39
Q

Diagnosis of GvHD

A

Clinical evidence of related dysfunction - symtpoms and signs, deranged LFTs
Biopsy of skin, liver or gut - inflammatory infiltrate

40
Q

Features of chronic GvHD

A

Skin - same as acute
Pulmonary - Obsteuctive, dyspnoea, wheeze, cough, non response to bronchdilators
NM - weakness, neuropathic pain, muscle cramps
Ocular - sicca syndrome, haemorrhagic conjunctivitis
Gut - similar to acute
Liver - same as acute GvHD. Rare - portal H[TN, cirrhosis, liver failrue

41
Q

Prevention of GvHD

A

Donor selection
Depeltion of T cells from donor graft
Drugs to supress donor T cells - steroids, ciclosporin, MMF

42
Q

Treating GvHD

A

Depends on severiyy
Mild skin - topical steroids
Systemic steroids and MMF if more severe
V severe = ATG and other T cell targeted therapies - poor outlook
May be beneficial in malignant disease - balance

43
Q

What needs to be tested pre transplantation

A

HLA typing
ABO blood group
Anti-HLA antibodies serology
Hep BsAg,sAb, HIV, hep C Ab, CMV IgG +IgM

44
Q

What physical cross match result is an absolute contraindication to transplant

A

T cell crossmatch - activation of T cells -> cell lysis when recipient and host mixed
B cell not complete contraindiactino

45
Q
A
46
Q
A

Immunology (4 decks)

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