Immune System IV - Solid Organ Transplantation

Question 1

Describe the three ways in which rejection can occur?

Answer 1

Hyperacute = mins (pre-formed Abs)
Acute = days/weeks - T-cell and Ab mediated
Chronic = months/years - Ab and complement mediated

Question 2

Describe hyperacute rejection?

Answer 2

Recipient already carries alloantibodies against blood group Ag or non-self MHC (HLA-Ab)
These react and complement and coagulation cascade is initiated leading to organ vessels becoming blocked and organ death

Question 3

Describe acute rejection?

Answer 3

T-cell mediated - causes organ infiltration and dysfunction
Takes a few days/weeks
Can be humorally (Ab) mediated

Question 4

How does chronic rejection occur?

Answer 4

Secondary to endothelial damage caused by
1. alloantibodies
2. immune complex deposition
3. complement activation
Allo-reative T-cells secrete CCL5 - attracting macrophages leading to fibrosis = chronic inflammation and damage

Question 5

Describe chronic rejection?

Answer 5

Concenteric arteriosclerosis of graft blood vessels with infiltrative fibrosis. Associated with ischaemia re-perfusion injury (restoration of blood flow = increased oxidative stress)

Question 6

Describe the two ways in which alloAg may be presented?

Answer 6

Direct = DONOR APC activates cognate T-cell (recognises DONOR MHC molecule (obtains 2nd signal) and Ag) = activated T-cell migrates to graft and attacks - due to NON-self Ag = polyclonal response
Indirect = RECIPIANT APC processes the peptide from the graft and activates it's own cognate T-cell with it's own SELF-MHC molecule = oligoclonal

Question 7

Name 6 ways to manage the prevention of rejection?

Answer 7

1. ABo match
2. HLA match
3. Immunosuppress
4. Calcinerurin inhibitors
5. mTOR inhibitors
6. Anti-proliferatives

Question 8

Give two examples of calcinerurin inhibitors?

Answer 8

Ciclosporin

Tacrolimus

Question 9

Give an example of an mTOR inhibitor?

Answer 9

Sirolimus

Question 10

Give two examples of anti-proliferatives?

Answer 10

Azathioprim

Mycophenolate

Question 11

Give 5 ways in which the immune system can be modulated?

Answer 11

Anti-thymocyte globulin (destroys T-cells)
Prednisalone
Rutiximab - Anti-B-cell
Bortezomib - attacks plasma cells
Plasmaphoraesis

Question 12

Describe graft vs host disease?

Answer 12

Rejection of HOST against graft following bone marrow transplant. Graft = immunologically competent cells - host appears foreign
Risk factors = neonates//immunosuppressed

Question 13

Describe the features of ACUTE GvHD? (dermo/liver/GI)

Answer 13

Dermo = painful macules
Liver = asymptomatic: increased bilirubin + ALT + AST + ALK Phos (similar picture to cholestatic jaundice 
GI = abdominal pain + diffuse diarrhoea + GI bleed + dyspepsia

Question 14

Describe the features of CHRONIC GvHD? (dermo/ocular/pulmonary)

Answer 14

Dermo = atrophy and erythema of oral mucosa + lichenoid lesions of skin and buccal and labia mucosa + sclerodermatous skin thickening
Ocular = sjogrens 
Pulmonary = obstructive lung diseases non-responsive to bronchodilators

Question 15

What is the primary treatment for GvHD?

Answer 15

Tacrolimus and Methylprednisalone
2nd line = Sirolimus
3rd line = Methotrexate