Immuno 10: Immuno Modulating Therapies 2 Flashcards
How do Corticosteroids inhibit Prostaglandins and hence have an anti-inflammatory effect ?
Corticosteroids INHIBIT Phospholipase A2
(Normaly)
Phospholipase A2 converts phospholipids into Arachidonic acid
Arachidonic acid is converted to Prostaglandins or leukotrienes by COX enzymes.
Prostaglandins cause Inflammation
Give 2 examples of Eicosanoids ?
Prostaglandins
Leukotrienes
Give 3 examples of immune modulating functions of corticosteroids ?
Inhibit Prostaglandin synthesis Inhibit Phagocyte entry into inflamed tissues Causes lymphopenia (Lymphocytes sequester in lymphoid tissues)
Give 3 examples of Anti-proliferative agents ?
Cyclophosphamide
Azathioprine
Methotrexate
What is the mechanism by which cyclophosphamide inhibits lymphocyte proliferation?
Cyclophosphamide alkylate guanine bases on DNA
Prevents cell replication particularly in rapidly dividing cells (cancer, lymphocytes)
Give 3 examples of diseases in which Cyclophosphamide is indicated ?
SLE
GPA (granulomatosis with polyangitis) (wegner’s granulomatosis)
Cancers- Hodgkin’s lymphoma
Suggest 3 side effects of cyclophosphamide ?
Hair loss
Sterility
Haemorrhagic cystitis
Describe the mechanism by which azathioprine inhibits DNA replication ?
Metabolised to 6-mercaptopurine which blocks synthesis of adenine and guanine
Give 3 indications for azathioprine ?
Transplantation
auto-immune diseases
Crohn’s and UC
Which genetic polymorphism contraindicates the use of azathioprine because of risk of bone marrow suppression ?
Thiopurine methyl transferase (TPMT)
What is an alternative to azathioprine used in transplantation ?
Mycophenolate Mofetil
Which virus can cause Multifocal leukoencephalopathy infection in the immunocompromised patient ?
JC virus
How does plasmapheresis work ?
Patients blood is separated and the plasma is treated to remove immunoglobulins and is then re-infused
When is Plasmaphoresis indicated ?
Severe transplant rejection
Severe acute myasthenia gravis
Goodpasture’s syndrome
What is the role of IL2 in the T cell response ?
IL2 causes T cell proliferation
How does cyclosporin inhibit T cell proliferation ?
Cyclosporin is a calcineurin inhibitor.
It blocks IL2 production
Thereby inhibiting T cell proliferation
How do Anti-thymocyte globulins cause T cell depletion ?
Thymocytes (lymphocytes from human thymus) were injected into rabbits
Rabbits produced antibodies to the thymocytes
The antibodies are retrieved and injected into humans to cause a non-specific immune response against T cells
Which cells are affected by Rituximab ?
B cells
Rituximab targets CD20 a B cell marker
Name a drug that inhibits leukocyte binding to VCAM1 and is used to treat relapsing-remitting Multiple sclerosis ?
Natalizumab
Which disease is characterised by a IL6 producing tumour
Castleman’s disease
List 4 diseases in which anti-TNF alpha antibodies (infliximab) is indicated ?
Rheumatoid arthritis
Ankylosing spondylitis
Psoriasis/psoriatic arthritis
IBD
Explain what effect RANK L binding to RANK receptors has on bone ?
RANKL produced by Osteoblasts binds to RANK receptor on osteoclast precursors causing them to differentiate into Osteoclasts.
This causes increased bone resorption
What is Osteoprotegrin (OPG) and what role does it have in controlling bone resorption ?
OPG is secreted by Osteoblasts and is a decoy receptor for RANKL to reduce activation and differentiation of Osteoclasts.
Hence inhibiting bone resorption
What is the mechanism by which Denosumab works in Osteoporosis treatment ?
Monoclonal antibody to RANKL so that it cant bind to RANK receptor on osteoclast precursors.
This reduces Osteoclast resorption of bone
What is a complication of osteoporosis treatment with denosumab ?
Avascular necrosis of the jaw
Name a drug that prevents DNA replication especially of T cells
Mycofenylate mofetil
Which immuno modulating drug causes a transient increase in neutrophil count ?
Prednisolone
Which immuno modulating drug can cause gingival hypertrophy as a side effect?
Ciclopsporin
List 3 side effects of methotrexate ?
Pneumonitis
pulmonary fibrosis
cirrhosis
A patient with signs of severe myasthenia gravis requires ventilation. Which one of the following would be the most suitable treatment ?
A) Corticosteroids
B) Ciclosporin
C) Tacrolimus
D) Plasmapheresis
D) Plasmapherisis
can remove the Ach receptor antibodies in the blood so is useful initially. Later needs acetylcholinesterase inhibitors.
Name a monoclonal antibody drug that targets IL-2 to prevent T cell proliferation. This drug is used prophylactically in allograft transplant.
Basiliximab
Targets CD25 on the alpha chain of IL-2 which stops T-cell proliferation if they are presented with donor HLA.
Name a drug that is a CTLA4- IgG fusion protein and is used in the treatment of rheumatoid arthritis resistant to DMARDs ?
Abatacept
A fusion protein between CTLA4 and Immunoglobulin IgG.
Binds to APCs to prevent them from stimulating T cells.
Name 2 drugs used to treat malignant melanoma ?
Ipilimumab
Pembrolizumab
Which drug works by inhibiting phospholipase A2 ?
Prednisolone
Which mutation if present can cause severe neutropenia with azathioprine treatment ?
TPMT
can’t metabolise azathioprine
Which 2 drugs can be used in transplant rejection ?
- OKT3 Muromonab (CD3 inhibitor mouse monoclonal antibody)
- ATG (anti thymocyte globulin)
(can also do plasmapheresis if antibody mediated rejection or IVIG)
List 2 drugs that can be given before transplant
- Basiliximab
- Alemtuzumab (anti CD52)
What is Ustekinumab used for ?
Psoriasis
-Targets IL12 and IL23
List 4 drugs given as maintenance therapy post transplantation ?
- Cyclosporin
- Mycofenolate mofetil
- Azathioprene
- Prednisolone
