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Year 5 path SW > Immuno 10: Immuno Modulating Therapies 2 > Flashcards

Immuno 10: Immuno Modulating Therapies 2 Flashcards

1
Q

How do Corticosteroids inhibit Prostaglandins and hence have an anti-inflammatory effect ?

A

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

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2
Q

Give 2 examples of Eicosanoids ?

A

Prostaglandins

Leukotrienes

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3
Q

Give 3 examples of immune modulating functions of corticosteroids ?

A 
Inhibit Prostaglandin synthesis 
Inhibit Phagocyte entry into inflamed tissues
Causes lymphopenia (Lymphocytes sequester in lymphoid tissues)
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4
Q

Give 3 examples of Anti-proliferative agents ?

A

Cyclophosphamide
Mycophenolate
Azathioprine
Methotrexate

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5
Q

What is the mechanism by which cyclophosphamide inhibits lymphocyte proliferation?

A

Cyclophosphamide alkylates guanine bases on DNA
Prevents cell replication particularly in rapidly dividing cells (cancer, lymphocytes)
Affects B>T cells

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6
Q

Give 3 examples of diseases in which Cyclophosphamide is indicated ?

A

SLE
GPA (granulomatosis with polyangitis) (wegner’s granulomatosis)
Cancers- Hodgkin’s lymphoma

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7
Q

Suggest 3 side effects of cyclophosphamide ?

A 
Hair loss 
Sterility 
Haemorrhagic cystitis
toxic metabolite is excreted in the urine 
bladder cancer 
haem malignancies
non-melanoma skin cancer 
infection eg P. jirovecii
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8
Q

Describe the mechanism by which azathioprine inhibits DNA replication ?

A

Metabolised to 6-mercaptopurine which blocks synthesis of adenine and guanine
prevents DNA replication
preferentially inhibits T cell activation and proliferation

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9
Q

Give 3 indications for azathioprine ?

A

Transplantation
auto-immune diseases
Crohn’s and UC

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10
Q

Which genetic polymorphism contraindicates the use of azathioprine because of risk of bone marrow suppression ?

A

Thiopurine methyl transferase (TPMT)

check for TPMT activity or gene variants before treatment is started

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11
Q

What is an alternative to azathioprine used in transplantation ?

A

Mycophenolate Mofetil

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12
Q

Which virus can cause Multifocal leukoencephalopathy infection in the immunocompromised patient ?

A

JC virus

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13
Q

How does plasmapheresis work ?

A

Patients blood is separated and the plasma is treated to remove immunoglobulins and is then re-infused

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14
Q

When is Plasmaphoresis indicated ?

A

Severe transplant rejection (antibodies against donor HLA)
Severe acute myasthenia gravis
Goodpasture’s syndrome

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15
Q

What is the role of IL2 in the T cell response ?

A

IL2 causes T cell proliferation

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16
Q

How does cyclosporin inhibit T cell proliferation ?

A

Cyclosporin is a calcineurin inhibitor.
It blocks IL2 production
Thereby inhibiting T cell proliferation

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17
Q

How do Anti-thymocyte globulins cause T cell depletion ?

A

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

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18
Q

Which cells are affected by Rituximab ?

A

B cells

Rituximab targets CD20 a B cell marker

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19
Q

Name a drug that inhibits leukocyte binding to VCAM1 and is used to treat relapsing-remitting Multiple sclerosis ?

A

Natalizumab

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20
Q

Which disease is characterised by a IL6 producing tumour

A

Castleman’s disease

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21
Q

List 4 diseases in which anti-TNF alpha antibodies (infliximab) is indicated ?

A

Rheumatoid arthritis
Ankylosing spondylitis
Psoriasis/psoriatic arthritis
IBD

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22
Q

Explain what effect RANK L binding to RANK receptors has on bone ?

A

RANKL produced by Osteoblasts binds to RANK receptor on osteoclast precursors causing them to differentiate into Osteoclasts.
This causes increased bone resorption

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23
Q

What is Osteoprotegrin (OPG) and what role does it have in controlling bone resorption ?

A

OPG is secreted by Osteoblasts and is a decoy receptor for RANKL to reduce activation and differentiation of Osteoclasts.
Hence inhibiting bone resorption

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24
Q

What is the mechanism by which Denosumab works in Osteoporosis treatment ?

A

Monoclonal antibody to RANKL so that it cant bind to RANK receptor on osteoclast precursors.
This reduces Osteoclast resorption of bone

25
Q

What is a complication of osteoporosis treatment with denosumab ?

A

Avascular necrosis of the jaw

26
Q

Name a drug that prevents DNA replication especially of T cells

A

Mycofenylate mofetil

27
Q

Which immuno modulating drug causes a transient increase in neutrophil count ?

A

Prednisolone

28
Q

Which immuno modulating drug can cause gingival hypertrophy as a side effect?

A

Ciclopsporin

29
Q

List 3 side effects of methotrexate ?

A

Pneumonitis
pulmonary fibrosis
cirrhosis

30
Q

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

A

D) Plasmapherisis

can remove the Ach receptor antibodies in the blood so is useful initially. Later needs acetylcholinesterase inhibitors.

31
Q

Name a monoclonal antibody drug that targets IL-2 to prevent T cell proliferation. This drug is used prophylactically in allograft transplant.

A

Basiliximab

Targets CD25 on the alpha chain of IL-2 which stops T-cell proliferation if they are presented with donor HLA.

32
Q

Name a drug that is a CTLA4- IgG fusion protein and is used in the treatment of rheumatoid arthritis resistant to DMARDs ?

A

Abatacept

A fusion protein between CTLA4 and Immunoglobulin IgG.
Binds to APCs to prevent them from stimulating T cells.

33
Q

Name 2 drugs used to treat malignant melanoma ?

A

Ipilimumab

Pembrolizumab

34
Q

Which drug works by inhibiting phospholipase A2 ?

A

Prednisolone

35
Q

Which mutation if present can cause severe neutropenia with azathioprine treatment ?

A

TPMT

can’t metabolise azathioprine

36
Q

Which 2 drugs can be used in transplant rejection ?

A
  • OKT3 Muromonab (CD3 inhibitor mouse monoclonal antibody)
  • ATG (anti thymocyte globulin)

(can also do plasmapheresis if antibody mediated rejection or IVIG)

37
Q

List 2 drugs that can be given before transplant

A
  • Basiliximab

- Alemtuzumab (anti CD52)

38
Q

What is Ustekinumab used for ?

A

Psoriasis

-Targets IL12 and IL23

39
Q

List 4 drugs given as maintenance therapy post transplantation ?

A
  • Cyclosporin
  • Mycofenolate mofetil
  • Azathioprene
  • Prednisolone
40
Q

what are the effects of steroids on phagocytes

A

decreased traffic of phagocytes into inflamed tissue
reduce the expression of adhesion molecules on the endothelium
–> transient increase in neutrophil count
decreased phagocytosis
decreased release of proteolytic enzymes

41
Q

what are the effects of steroids on lymphocyte function

A

lymphopaenia - sequestration of lymphocytes into lymphoid tissue
blocks cytokine gene expression
decreased antibody production
promotes apoptosis

42
Q

mechanisms of mycophenolate mofetil

A

blocks de novo nucleotide synthesis
prevents replication of DNA
prevents B > T cell proliferation

43
Q

indications for mycophenolate mofetil use

A

transplantation

AI diseases and vasculitis

44
Q

side effects of mycophenolate mofetil

A

BM suppression
teratogenic
infection - HSV reactivation, progresisve multifocal leukoencephalotahy (JC virus)

45
Q

what is plasmapheresis

A

patient blood passed through a separator
cellular contents reinfused
plasma treated to remove antibodies and reinfused
can get rebound antibody production

46
Q

indications for plasmaphoresis

A

severe antibody-mediated disease eg:
goodpastires syndrome
severe acute myasthenia gravis
severe transplant rejection

47
Q

what is the role of calcineurin inhibitors

A

eg ciclosporin and tacrolimus
prevent T cell signalling
IL2 acts on T cells and prevents T cell activation and proliferation
side effects = nephrotoxicity, hypertension, neurotoxicity, diabetogenic, dysmorphic features

48
Q

what is the role of JAK inhibitors

A 
eg tofacitinib (JAK1+ JAK 3 inhibitor)
interferes with JAK-STAT signalling 
influences gene transcription 
inhibits the production of inflammatory molecules 
effective in rheumatoid arthritis
49
Q

what is the role of PDE4 inhibitors

A

eg apremilast
PDE4 important for the metabolism of cAMP
leads to increase in cAMP
cAMP activates PKA which prevents activation of TF
leads to decrease in cytokine production
used in psoriasis and psoriatic arthritis

50
Q

what is the role of anti-thymocyte globulin

A

thymocytes from humans injected into rabbits
take antibodies they make against the thymocytes
serum taken an injected into patient
causes T cell depletion
useful in allograft rejection
S/E - infusion reactions, leukopenia, infection, malignancy

51
Q

what is the role of basiliximab

A

antibody directed against CD25
prophylaxis of allograft rejection
targets IL2 receptor
inhibits T cell proliferation

52
Q

what is the role of abartacept

A

receptor made form a fusion of CTLA4 + IgG Fc component

binds CD80 and CD86 - reduced T cell activation

53
Q

what is rituximab

A

anti-CD20 antibodies
expressed on mature B cells but not plasma cells
depletion of mature B cells
used in lymphoma, rheumatoid arthritis, SLE
2 IV doses every 6-12 months

54
Q

what is natalizumab

A

antibody against alpha 4 integrin
inhibits leukocyte migration
used in MS

55
Q

what is tocilizumab

A

antibody against IL6 receptor
reduced activation of macrophages, T cells, B cells and neutrophils
rheumatoid arthritis

56
Q

which agents target TNF alpha

A

infliximab, adalimumab, certolizumab, golimumab
used in: rheumatid arthritis, ankylosing spondylitis, psoriasis, IBD
etanercpt - TNF alpha antagonist

57
Q

list other agesnts that target cytokines

A

ustekinumab - antibody to p40 subunit of IL12 and IL23
secukinumab - antibody to IL17A
denosumab - antbody against RANKL (osteoporosis)

58
Q

which vaccines should not be given to immunosuppressed people

A

polio
measles
BCG
yellow fever

Year 5 path SW (106 decks)

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