20. Depleting and Modifying Immune Cell Function

Question 1

What are integrins?

Answer 1

Cell adhesion molecules

Composed of a/B heterodimers

Question 2

What cells are integrins found in?

Answer 2

Platelets and lymphocytes

Question 3

Name a monoclonal antibody that binds to integrins

Answer 3

Natalizumab

Question 4

What is Natalizumab used for?

Answer 4

Prevents lymphocytes infiltrating into the brain

Used in MS and Crohn’s disease

Question 5

What adverse effect is associated with natalizumab?

Answer 5

PML

Question 6

What is PML?

Answer 6

Progressive Multifocal Leukoencephalopathy

Reactivation of JC virus or HHV 6 in the brain

Question 7

Name a S1P receptor antagonist

Answer 7

Fingolimod

Question 8

What is the ligand for the S1P receptor?

Answer 8

Sphingosine-1-phosphate

Question 9

What is the usual function of sphingosine-1-phosphate?

Answer 9

Release of lymphocytes from lymphoid tissue

Question 10

How does fingolimod work?

Answer 10

Causes S1P receptor to be internalised

Reduces lymphocyte levels in blood and reduces hyperactivity of astrocytes

Question 11

What disease is fingolimod used to treat?

Answer 11

MS

Question 12

What are the adverse effects of fingolimod?

Answer 12

Affects HR and conduction in the heart

Macular oedema

Question 13

Name 2 other a4/B7 antagonists

Answer 13

Vedozilumab

Etrolizumab

Question 14

Name another S1P1 antagonist

Answer 14

Siponimod

Also used for MS and more selective than fingolimod

Question 15

What is rituximab a monoclonal antibody to?

Answer 15

CD20 (specific to B cells)

Question 16

How does rituximab work?

Answer 16

Triggers complement formation and lysis of B cells

Question 17

What diseases is rituximab used to treat?

Answer 17

B cell lymphoma

RA resistant to TNF

Question 18

What adverse effects are associated with rituximab?

Answer 18

SIRS

PML

Question 19

Which drug is a monoclonal antibody to CD52?

Answer 19

Alemtuzumab

Question 20

What cells is CD52 found on?

Answer 20

Mature lymphocytes

Question 21

What diseases is alemtuzumab used for?

Answer 21

MS

T cell leukaemia

Question 22

What is the use of glatiramer in MS?

Answer 22

Induces a Th2 immune response
Production of anti-inflammatory cytokines and neurotrophic factors
Helps remyelinate

Question 23

What is the use of dimethyl fumarate in MS?

Answer 23

Causes apoptosis of lymphocytes
Shifts response from Th1 to Th2
Inhibits pro-inflammatory CKs

Question 24

Name an immune stimulator

Answer 24

Imiquimod

Question 25

What is imiquimod used to treat?

Answer 25

Genital warts

Basal cell carcinoma

Question 26

How does imiquimod work?

Answer 26

Increase CKs, infiltration and apoptosis

Question 27

What is IV IgG used for?

Answer 27

Treat patients with low IgG: can be enriched with certain antibodies against infection
Anti-inflammatory activity

Question 28

Which diseases is IV IgG used to treat?

Answer 28

Immune thrombocytopenia

Kawasaki syndrome

Question 29

What is the target of IV IgG?

Answer 29

FCyRIIa

Question 30

What is the main principle in treatment of RA?

Answer 30

Start with symptomatic treatment, use DMARDs early, starting with monotherapy
Start with cheap drugs first
If mono therapy doesn’t work, move to double and triple

Question 31

What drug is used in mono therapy of RA?

Answer 31

Methotrexate

Question 32

What are the options for double therapy of RA?

Answer 32

Methotrexate and sulfasalazine
Methotrexate and hydroxychlorine
Sulfasalazine and plaquenil

Question 33

Which drugs are used in triple therapy of RA?

Answer 33

Methotrexate, sulfasalazine, hydroxychlorine

Question 34

What treatment should be given in RA if mono, double and triple therapy fail?

Answer 34

Biologic therapy