Aani Immuno: Transplant & Immune therapies Flashcards
Which cell features are recognised in transplant/grafts?
HLA (A/B/DR)
Minor HLA
ABO Blood Antigens
What are the types of recognition in transplants?
Direct - the donor’s APCs present the antigens
Indirect - the recipients APCs present the antigens
Which kind of antigen presentation is involved in Chronic rejection?
Indirect
Which kind of antigen presentation is involved in Acute rejection?
Direct
What can you give before transplantation to reduce rejection?
Suppress T cell responses.
Anti-CD52 Alemtuzumab or Anti-CD25 Basiliximab
How can you prevent rejection from start to finish?
- Determine donor and recipient HLA (Using PCR).
- Check recipient’s preformed Abs against donor HLA and ABO
- CROSS-MATCH
- Check for new Abs after transplantation
- Give immunosuppressive therapy e.g. AntiCD25/D52
How to treat episodes of acute rejection?
- Cellular - give steroids
2. Ab-mediated - plasma exchange or IVIG or Anti C5
Apart from rejection, name some post-transplant complications
- Infection
- Atherosclerosis
- Malignancy
Mnemonic for remembering the anti-proliferative immune therapies?
Aaniya Can't Make More Azathioprine Cyclophosphamide Methotrexate Mycophenolate Sodium/Mofetil
What is methotrexate used for?
RA
Psoriasis
Crohn’s
Side effect of methotrexate?
Reduces folate –> Megaloblastic anaemia
What is Mycophenolate Sodium/Mofetil used for?
Transplantation and vasculitis
Side effect of mycophenolate mofetil?
Herpes virus reactivation
What is azathioprine used for?
Transplantation, autoimmune/inflamm diseases
Contraindications to azathioprine?
Allopurinol use
TPMT Polymorphism
Cyclophosphamide indication?
Anti cancer agent
Vasculitis
Connective Tissue disease
S/E of cyclophosphamide
Infertility & hair loss
Mnemonic for T-Cell Signalling Inhibitors
ST CAT Sirolimus Tacrolimus Cyclosporin Apremilast Tofacitinib
Sirolimus indications? And mechanism?
Rejection prophylaxis
Blocks T Cell proliferation
Tacrolimus indications? And mechanism?
Rejection prophylaxis
Inhibits calcineurin which reduces IL2 so it reduces T cell function
Cyclosporin indications? And mechanism?
Rejection prophylaxis
Inhibits calcineurin which reduces IL2 so it reduces T cell function
Which is the least nephrotixic of the T cell signalling inhibitor drugs?
Sirolimus
S/E of Tacrolimus?
Nephrotoxicity
S/E of Cyclosporin?
Nephrotoxicity
Gym Hypertrophy
Apremilast indication and mechanism?
Psoriasis & psoriatic arthritis
Inhibits PDE4
Tofacitinib mechanism? Indication?
JAK inhibitor
Rheumatoid arthritis
Cell surface antigen drugs used in transplant rejection prophylaxis?
Basiliximab
Daclizumab
MuromonabCD3
Anti-Thymocyte Globulin (ATG)
What does Basiliximab do?
Inhibits CD25 via IL2 receptor
Indications and S/Es of Basiliximab?
Used in rejection prophylaxis
Can cause injection or infusion reaction
Daclizumab mechanism? Indication ?
Anti- CD25 via IL2 receptor
Good for organ transplantation
Anit Thymocyte Globulin (ATG) indications? Mechanism?
Allograft rejection
Inhibits migration of T Cells
What does Natalizumab do? Indications?
Anti-alpha-4 integrin via VCAM1 and MadCAM1 so inhibits T Cell migration. Used in Relapsing MS and Crohns
S/E of Natalizumab?
Hepatotoxic
Hyperlipidaemia
What does Abatacept do?
Anti- CTRL4 Ig so inhibits T Cell migration
What is abatacept used for?
Rheumatoid arthirits
Abatacept S/E?
Cough
Tocilizumab indications?
Castleman syndrome & RA
Tocilizumab mechanism?
Anti IL6 causing low T cells, low B cells, low macrophages and low neutrophils
Alemtuzumab indications?
Graft rejection
CLL
MS
Rituximab indications?
Lymphoma
RA
SLE
Alemtuzumab mechanism?
Anti CD52
S/E of alemtuzumab?
CMV infection
Treatment of CLL?
Chlorambucil
Fudarabine
Alemtuzumab
Rituximab mechanism?
Anti CD20. Depletes mature B Cells
MuromonabCD3 mechanism? Indication?
Anti CD3 on t cells.
Allograph rejection
(mouse Ab)
Efalizumab mechanism?
Anti CD2a
Reduces T Cell migration
Mnemonic for TNF alpha inhibitors?
I'm A Cool Girl. Alpha mums, like Ada and Goli, certainly inflict pain Infliximab Adalimumab Certolizumab Golimumab
Infliximab mechanism?
TNF alpha inhibitor
Indications for TNF alpha inhibitors?
RA Psoriasis Psoriatic arthritis IBS Ankylosing Spondylitis
Ustekinumab mechanism? Indications?
IL12 & IL23 inhibitor
Used in psoriasis & psoriatic arthritis
Secukinumab mechanism? Indications?
IL17A inhibitor
Used in psoriasis & psoriatic arthritis
Etanercept mechanism? Indications?
TNF alpha Br p75IgG
Used in psoriasis & psoriatic arthritis
Denosumab mechanism? Indications?
Anti-Rank
Osteoporosis
MM
Bony Mets
S/E of denosumab
Avascular necrosis of the jaw
Which drug should be prescribed in osteoporosis?
Denosumab
TNFa inhibitor used in ankylosing spondylitis. It may cause lupus-like syndromes and demyelination as a side effect.
Etarnacept
A 63 year old man received a renal transplant 5 years ago. He has now started to develop herpes infections and on recent investigations bone marrow suppression is seen. Which drug is responsible?
Mycophenolate Mofetil
Which treatment is the most appropriate for x-linked agammaglobulinaemia?
Antibody replacement therapy
A 2 month old child presents with recurrent infections, failure to thrive, persistent diarrhoea and reticular dysgenesis (low neutrophil, lymphocytes, macrophage, platelets). What is the treatment of choice?
Bone Marrow Transplant
Anti-TNF alpha antibody used to treat inflammatory bowel disease?
Infliximab/Adalimumab/Certolizumab/Golimumab