CP5-7 immunotherapeutics and immunomodulation

Question 1

What is immunomodulation?

Answer 1

The act of manipulating the immune system using drugs to achieve a desired immune response

Question 2

What are three therapeutic effects that immunomodulation can lead to?

Answer 2

Immunopotentiation
Immunosuppression
Induction of immunological tolerance

Question 3

What are immunomodulators?

Answer 3

Medicinal products produced using molecular biology techniques including recombinant DNA technology

Question 4

What are different types of immunomodulators?

Answer 4

Substances that are nearly identical to the body’s own key signalling proteins
Monoclonal antibodies
Fusion proteins

Question 5

What are examples of immunomodulator drugs?

Answer 5

Adalimumab
Infliximab
Etanercept
Cetrolizumab

Question 6

How can immunopotentiation be achieved?

Answer 6

Through vaccination (active or passive)
Replacement therapies
Immune stimulants

Question 7

What are risks of passive immunisation?

Answer 7

Transmission of virus
Serum sickness

Question 8

What are 4 types of passive immunisation?

Answer 8

Convalescent plasma
Pooled specific human immunoglobulin
Animal sera (antitoxins and antivenins)
Monoclonal antibodies

Question 9

What are examples of pathologies treated/prevented by passive immunisation?

Answer 9

Covid 19
Hep B
VZV (especially in pregnancy)
Botulism
Diptheria
Snake bites

Question 10

What are examples of immunogenic material used in active immunisation?

Answer 10

Weekend forms of pathogens
Killed/inactivated pathogens
Purified materials e.g. proteins, DNA, RNA
Adjuvants

Question 11

What are disadvantages of active immunisation?

Answer 11

Risk of allergy to vaccine components
Limited usefulness in immunocompromised
Delay in achieving protection

Question 12

When is pooled human immunoglobulin (IV or SC) treatment given?

Answer 12

In patients in antibody deficient states

Question 13

How does G-CSF/GM-CSF therapy work?

Answer 13

Acts on bone marrow to increase production of mature neutrophils

Question 14

What viral infection was alpha interferon mainly used for before new treatments became first line treatment?

Answer 14

Treatment of hep C

Question 15

What is y-interferon used to treat?

Answer 15

Certain intracellular infections like atypical mycobacteria infection
Chronic Granulomatous disease
IL-12 deficiency

Question 16

What are examples of immunosuppression treatments?

Answer 16

Corticosteroids
Cytotoxic agents
Anti-proliferative/anti-activation agents
DMARD’s
Biological-DMARD’s

Question 17

How do corticosteroids work?

Answer 17

Decreases neutrophil margination
Reduces production of inflammatory cytokines
Inhibits phospholipase A2 - reducing arachidonic acid metabolite production.
Cause lymphopenia
Decrease T cell proliferation
Reduces immunoglobulin production

Question 18

What are corticosteroids used to treat?

Answer 18

Autoimmune diseases e.g. CTD, vasculitis and rheumatoid arthritis
Inflammatory diseases e.g. Crohn’s disease, sarcoid, GCA/polymyalgia rheumatica
Malignancies like lymphoma
Allograft rejection

Question 19

What drugs target T cells? What point in the life cycle

Answer 19

Antimetabolites - proliferation
Calcineurin inhibitors - activation
M-TOR inhibitors - activation
IL-2 receptor mABs - activation

Question 20

What are 2 examples of antimetabolites?

Answer 20

Azathioprine (AZA)
Mycophenolate mofetil (MMF)

Question 21

What are 2 examples of calcineruin inhibitors?

Answer 21

Ciclosporin A (CyA)
Tacrolimus (FK506)

Question 22

What is an example of a M-TOR inhibitor?

Answer 22

Sirolimus (rapamycin)

Question 23

What are 2 examples of IL-2 receptor mABs?

Answer 23

Basiliximab
Daclizumab

Question 24

Where in the life-cycle of T cells can T cell targeted immunosuppression act?

Answer 24

activation
proliferation

Question 25

Where in the life-cycle of T cells can T cell targeted immunosuppression act?

Answer 25

activation proliferation

Question 26

How does CyA work?

Answer 26

Binds to intracellular protein cyclophilin to prevent activation of NFAT and stimulate cytokine gene transcription

Question 27

How does tacrolimus work?

Answer 27

Binds to intracellular protein FKBP-12 to prevent activation of NFAT and stimulate cytokine gene transcription

Question 28

How does sirolimus (rapamycin) work?

Answer 28

Binds to FKBP12 to inhibit mammalian target mTOR thus inhibiting response to IL-2 arresting G1-S phase of cell cycle of T-cells i.e. binds to FKBP12 causing disruption to the t-cell cycle at the replication phase

Question 29

What are side effects of calcineurin inhibitors and mTOR inhibitors?

Answer 29

hypertension nephro, neuro and/or hepatotoxicity lymphomas opportunistic infections drug interactions hirsutism (excessive hair growth in women)

Question 30

When are calcineurin and mTOR inhibitors used?

Answer 30

in transplantation for allograft rejection to treat autoimmune diseases

Question 31

How does azathioprine work?

Answer 31

inhibits nucleotide synthesis by acting as a guanine anti-metabolite

Question 32

How does mycophenolate mofetil (MMF) work?

Answer 32

inhibits nucleotide synthesis by preventing production of guanosine triphosphate.

Question 33

What is the mode of action of methotrexate?

Answer 33

Folate antagonist

Question 34

What is the mode of action of cyclophosphamide?

Answer 34

interrupts the cell cycle by cross linking DNA

Question 35

what are the side effects of all cytotoxic drugs?

Answer 35

Bone marrow suppression Gastric upset Heapatitis Susceptibility to infection increases

Question 36

What is a side effect of cyclophosphamide?

Answer 36

Cystitis

Question 37

What is a side effect of methotrexate?

Answer 37

Pneumonitis

Question 38

What is azathioprine and mycophenolate mofetil used for?

Answer 38

autoimmune diseases e.g. SLE and IBD allograft rejection

Question 39

What is methotrexate used to treat?

Answer 39

autoimmune diseases e.g. rheumatoid arthritis and vasculitis rejection in bone marrow transplant

Question 40

What is cyclophosphamide used to treat?

Answer 40

vasculitis e.g. Wagner's SLE

Question 41

What are examples of biologic therapies?

Answer 41

Anti-cytokine Anti-B cell therapies Anti-T cell therapies Anti-adhesion molecules Complement inhibitors Check point inhibitors

Question 42

What are anti-TNF drugs used to treat?

Answer 42

rheumatoid arthritis + other inflammatory conditions including Crohn's disease, psoriasis and ankylosing spondylitis

Question 43

What is an example of an Anti-IL-6 drug?

Answer 43

Tocilizumab

Question 44

How does anti-IL-6 treatment work?

Answer 44

by blocking IL-6 receptors

Question 45

What is anti-IL-6 used to treat?

Answer 45

rheumatoid arthritis and adult onset Still's disease (AOSD) - a rare type of inflammatory arthritis

Question 46

What is anti-IL- 1 used to treat?

Answer 46

AOSD - a rare type of inflammatory arthritis and other autoinflammatory syndromes

Question 47

How does rituximab work?

Answer 47

it's a chimeric monoclonal antibody against CD20 on the B cell surface

Question 48

What is rituximab used to treat?

Answer 48

lymphomas and leukaemia Transplant rejection Autoimmune disorders

Question 49

What are examples of JAK inhibitors?

Answer 49

Baricitinib Upadcitinib Filgotinib Tofacitinib

Question 50

What is an example of a TYK2 inhibitor drug?

Answer 50

BMS-986165

Question 51

What are JAK inhibitors used to treat?

Answer 51

rheumatoid arthritis ankylosing spondylitis psoriatic arthritis ulcerative colitis

Question 52

What are 2 examples of adoptive immunotherapy?

Answer 52

Bone marrow transplant Stem cell transplant

Question 53

What is adoptive immunotherapy used to treat?

Answer 53

Immunodeficiencies like SCID Lymphomas and leukaemia Inherited metabolic disorders like osteropetrosis Autoimmune diseases

Question 54

What immunomodulator therapy is used to treat allergies?

Answer 54

Immune suppressants Allergen specific immunotherapy Anti-IgE monoclonal therapy Anti-IL-5 monoclonal treatment

Question 55

What can be used alongside chemotherapy to help treat tumours?

Answer 55

Checkpoint inhibitors

Question 56

When can allergen specific immunotherapy be used?

Answer 56

In allergic rhinoconjunctivitis (not controlled on maximum medical therapy) Anaphylaxis to insect venom Food allergies

Question 57

What is the mechanism of action of allergen specific immunotherapy?

Answer 57

switches immune response from Th2 (allergic) to Th1 (non-allergic) leads to development of T reg cells and tolerance.