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YEAR 5: Immunopathology > Immuno: Immune modulating therapies Pt.5 > Flashcards

Immuno: Immune modulating therapies Pt.5 Flashcards

1
Q

Describe the mechanism of action of vedolizumab.

A
  • Antibody that blocks alpha4beta7 integrin
  • Inhibits leukocyte migration to site of inflammation
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2
Q

What is vedolizumab used for?

A

Inflammatory bowel disease

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3
Q

What are some adverse-effects of vedolizumab?

A
  • Infusion reaction
  • Hepatotoxic
  • Infection (PML)
  • Risk of malignancy
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4
Q
A
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5
Q

Describe the mechanism of action of tocilizumab.

A
  • Antibody against IL-6 receptor
  • Results in reduced activation of macrophages, neutrophils, T cells, and B cells
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6
Q

What are the main indications of tocilizumab?

A
  • Castleman’s disease (IL-6-producing tumour)
  • Rheumatoid arthritis
  • Giant cell arteritis
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7
Q

List three types of anti-TNFα antibodies.

A
  • Infliximab
  • Adalimumab
  • Certolizumab
  • Golimumab

Given SC
Infliximab can also be IV

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8
Q

What is TNF-alpha?

A

It is a critical molecule in the cytokine cascade responsible for the inflammatory response in inflammatory conditions

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9
Q

List some uses of anti-TNFα antibodies.

A
  • IBD (UC and Crohns)
  • Ankylosing spondylitis
  • Rheumatoid arthritis
  • Psoriasis and psoriatic arthritis
  • Familian Mediterranean fever
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10
Q

List some side-effects of anti-TNFα antibodies.

A
  • Infusion reactions
  • Infection (TB reactivation, HBV, HCV)
  • Lupus-like conditions
  • Demyelination
  • Malignancy

Screen for latent TB before starting

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11
Q

Describe the mechanism of action of etanercept. What are some indications for its use?

A
  • It is a decoy receptor that mops up TNFα thereby inhibiting its action
  • Used in psoriasis and psoriatic and rheumatoid arthritis, and ankylosing spondylitis

NOTE: it is given as a SC injection

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12
Q

Describe the inflammasome pathway

A
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13
Q

What conditions is the IL-23 and IL-17 pathway important for?

A

Ankylosing spondylitis, psoriasis and psoriatic arthritis, IBD (not IL-17)

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14
Q

Which antibodies inhibit IL-17 and IL-23?

A

Secukinumab - IL-17
Guselkumab - IL-23

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15
Q

Which interleukins integral to the pathophysiology of asthma and eczema?

A

IL-4, IL-5, IL-13 are key cytokines in Th2 and eosinophil responses

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16
Q

Which antibodies can be used in the treatment of asthma and eczema?

A

Dupilumab - IL-4
Mepolizumab - IL-5
Tralokinumab - IL-13

17
Q

Describe the mechanism of action of denosumab.

A
  • RANKL is produced by osteoblasts and it acts on RANK receptors on osteoclasts
  • It promotes osteoclast differentiation and function, thereby leading to increased bone resorption
  • Osteoprotegrin is a natural decoy receptor for RANKL which regulates the system
  • Denosumab binds to RANKL and reduces osteoclast differentiation and function

It is used for osteoporosis

18
Q

What adverse reactions are common across immunosuppressive agents?

A
  • Infusion and injection site reactions (biologics)
  • Increased risk of acute infection
  • Increased risk of chronic infection reactivation
  • Increased of malignancy
  • Increased risk of auto-immunity
19
Q

List some types of infusion reaction.

A

IgE mediated (T1 hypersensitivity)

  • Urticaria
  • Hypotension
  • Tachycardia
  • Wheeze

Non-T1 hypersensitivity

  • Headache
  • Fever
  • Myalgia
20
Q

Describe injection site reactions

A
  • Peak at 48 hours
  • Reslts in cutaneous necrosis
  • May also occur at previous injection sites (recall reactions)
  • Mixed cellular infiltrate (CD8 cells)
  • Not generally IgE or immune complexes
21
Q

Describe the infection risk possed by immunosuppressive therapy and its management

A
  • Risk of infection often >2x background risk
  • Prevent with hygiene precautions and vaccination (avoid live vaccines)
  • Temporarily stop immunosuppression in case of infection
  • Consider atypical organisms and use appropriate antibiotics
22
Q

Which diseases should you screen for before starting immunosuppression

A
  • TB - Quantiferon
  • HBV, HCV - serology
  • HIV - serology
23
Q

What is JC virus and why is it dangerous in immunosuppression?

A
  • John Cunningham Virus
  • Common polyomavirus - majority of population has been exposed to it
  • Usually kept well under control by immune system
  • In the case of severe immunosuppression, the virus can reactivate and destory oligodendrocytes, leading to PML
24
Q

What malignancies are associated with immunosuppression?

A
  • Lymphoma (EBV)
  • Non-melanoma skin cancer (HPV)
  • Melanoma

Risks appear lower with targeted forms of immunosuppression than with regimes used in transplantation

YEAR 5: Immunopathology (25 decks)

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