Immune therapies Flashcards
Contains preformed IgG against full range of organisms
Used for immune deficiencies and passive vaccination
A. Human Normal Immunoglobulin
Containes Ig specific to Rabies, VZV, HBV etc.
A. Specific immunoglobulin post-exposure prophylaxis
Used to boost immune response to HBV, HCV, Kaposi’s, Hairy cell leukaemia, CML and MM
A. INF-a
Used to boost immune response in relapsing-remitting MS
A. INF-B
Used to boost immune response in Chronic Granulomatous Disease
A. INF-y
Anti-CTLA4 antibody
Blocks immune checkpoint allowing T cell activation
Used in advanced melanoma
A. Ipilimumab
Anti-PD1
Blocks immune checkpoint allowing T cell activation
Used in advanced melanoma
A. Pembrolizumab/Nivolumab
This type of drug inhibits phospholipase A2, reducing prostaglandin synthesis
- Used in autoimmune and inflammatory disease as well as prevention and treatment of transplant rejection
A. Corticosteroids e.g. prednisolone
SE - Cushing’s syndrome, osteoporosis, peptic ulceration
This group of drugs are cytotoxic agents. Acting by inhibiting DNA synthesis, they target cells with rapid turnover. Can you name 4 examples and give their specific function?
A. Antiproliferative agents
- Cyclophosphamide - alkylating agent
- Mycophenolate mofetil - prevents guanine synthesis
- Azathioprine - metabolised to 6-MP which blocks de novo purine synthesis
- Methotrexate - inhibits DHFR
Give three side effects of anti-proliferative agents
A. Bone marrow suppression, teratogeny, infection
What must you be aware of when prescribing azathioprine?
A. TMPT polymorphism prevents metabolism in some people
When is plasmapheresis indicated?
A. Severe antibody mediated disease e.g. Goodpasture’s, myasthenia gravis, vascular rejection and antibody mediated rejection
What is the mechanism of tacrolimus and cyclosporin?
A. Calcineurin inhibitor –> prevents transcription of IL-2 –> reduces T cell proliferation
(Group: inhibitors of cell signalling)
Which inhibitor of cell signalling is less nephrotoxic?
A. Sirolimus
Can you name 5 inhibitors of cell signalling and give their specific mechanisms?
Hint: CASTT
A. Cyclosporin - calcineurin inhibitor Apremilast - PED4 inhibitor Sirolimus - blocks clonal proliferation of T cells Tofacitinib - JAK inhibitor Tacrolimus - calcineurin inhibitor
What are the side effects of tacrolimus and cyclosporin?
A. Both nephro- and neurotoxic, HTN
Tacro: diabetogenic
Cyclo: gum hypertrophy, dysmorphism
Anti-CD25 (IL2 receptor alpha chain) used in allograft rejection?
A. Basiliximab
Anti-CTLA4 Ig used in rheumatoid arthritis?
A. Abatacept
Anti-CD20 used in lymphoma, RA and SLE?
A. Rituximab
Anti-alpha4 integrin used in MS and Crohn’s?
A. Natalizumab
Anti-IL6R used in Castleman’s disease and RA?
A. Tocilizumab
What is the mechanism of Muromonab-CD3 (OKT3) and when is it used?
A. Blocks CD3 on T cells (mouse monoclonal antibody)
Used in active allograft transplant rejection
Can you name 6 agents directed at cell surface antigens?
Hint: barnTM
A. Basiliximab - anti-CD25 Abatacept - anti-CTLA4 Ig Rituximab - anti-CD20 Natalizumab - anti-alpha4 integrin Tocilizumab - anti-IL6R Muromonab-CD3 - blocks CD3
Which biologics are indicated in rheumatoid arthritis? Name 4.
A. infliximab adalimumab certolizumab golimumab (all anti-TNFa) tofacitinib (JAKi), abatacept (CTLA4), tocilizumab (IL-6R), rituximab (CD20), etanercept (TNFa/BR p75-IgG fusion protein)
Which agent directed at cell surface antigens can result in CMV infection?
A. Alemtuzumab (used in CLL)
Which two agents target CD25 and are used in transplant rejection?
A. Basiliximab and Daclizumab
What is the mechanism and class of efalizumab?
A. Anti-CDIIa (cell surface antigen)
Which agent causes lymphocyte depletion and modulation of T cell activation and migration?
A. Anti-thymocyte globulin (ATG)
Give four examples of anti-TNFa antibodies used in rheumatoid arthritis, psoriasis, ankylosing spondilitis and IBD.
A. Infliximab
Adalimumab
Certolizumab
Golimumab
What is the mechanims of infliximab and adalimumab?
A. anti-TNFa
Which cytokine-directed agent is used in osteoporosis when bisphosphonates are contraindicated?
A. Denosumab - anti-RANKL
Also used in MM and bony mets
Anti-IL-12 and IL-23, used in psoriasis and psoriatic arthritis?
A. Ustekinumab
Mechanism of secukinumab?
A. Anti-IL-17
Used in psoriasis, psoriatic arthritis and ankylosing spondilitis
Which agents make patients more susceptible to infection with TB?
A. Agents directed against cytokines e.g. infliximab, etanercept, ustikinumab etc.
Mechanism of golimumab?
A. Anti-TNFa
Which agent alkylates guanine base of DNA?
A. Cyclophosphamide
Give two examples of pre-transplant induction agents?
A. Alemtuzumab (anti-CD52)
Basiliximab (anti-CD25)
or OKT3/Murmonab-CD3
Which agents could you use post-transplant to reduce rejection?
A. Calcineurin inhibitor e.g. tacrolimus/cyclosporin MMF/AZA (cytotoxic) Steroids OKT3/Muromonab-CD3 ATG
A 45 year old man with myasthenia gravis presents to A&E with difficulty in breathing. Assisted ventilation is administered. Which of the following is the best initial management of his condition?
- Ciclosporin
- Tacrolimus
- Rapamycin
- Corticosteroids
- Plasmapheresis
A. 5 Plasmapheresis
Severe myasthenia gravis (myasthenic crisis) is typified by paralysis of the respiratory muscles requiring ventilator assistance. The best management is plasmapheresis because it rapidly removes anti-AchR abs from circulation.
Long term treatment involves Ach-esterase inhibitors and immunosuppressive agents e.g. corticosteroids.