L16 - immunotherapy

Question 1

What are conventional immunosuppressive drugs?

Answer 1

Corticosteroids
Cytotoxic drugs
Cyclosporin A
Rapmycin

Question 2

What do corticosteroids do?

Answer 2

Inhibit inflammation

Question 3

What do cytotoxic drugs do?

Answer 3

interfere with DNA synthesis - kill immune cells

Question 4

What does cyclosporin A do?

Answer 4

suppresses IL-2 and T-cell proliferation - inhibit NFAT

Question 5

What does Rapmycin do?

Answer 5

inhibits mTOR pathway - cell proliferation. translation & autophagy

Question 6

Define immunotherapy?

Answer 6

Treating disease via immune modulation (activation, suppression, skewing)

Question 7

Types of immunotherapy?

Answer 7

Soluble mediators
Antibody therapy
Cell based
Skewing/suppression

Question 8

What are the soluble mediators used in immunotherapy?

Answer 8

Recombinant cytokines

Cytokine antagonists

Adjuvants

Miscellaneous

Question 9

What are recombinant cytokines?

Answer 9

treat neutropenia in cancer patients & BM donors

PEGylated IFNa

IFNy treated CGD

Question 10

What are cytokine antagonists?

Answer 10

target autoinflammatory disease and Muckle Wells Syndrome

Etanercept - recombinant TNFa receptor-fusion protein

Question 11

Therapeutic uses of monoclonal antibodies?

Answer 11

Rheumatoid arthritis, Crohn’s = Infliximab, Efalizumab

B-cell leukaemia = Rituximab

Breast cancer = Herceptin/Trastuzumab

Question 12

What are problems with monoclonal antibody therapy?

Answer 12

Repeat doses often immunogenic - neutralise anti-antibody antibodies

Question 13

suffix -Omab?

Answer 13

Fully mouse

Question 14

suffix -Ximab?

Answer 14

Chimeric

Question 15

suffis -Zumab?

Answer 15

Humanised

Question 16

Suffix -Umab?

Answer 16

Fully human

Question 17

What do adjuvants do?

Answer 17

enhance immune response and the quality of response

physically link antigens to adjuvants

Question 18

How can conjugated adjuvants enhance/skew immune response?

Answer 18

antigen linked to PAMP - will engage signalling via PRR

mature in phagosome presenting peptides on surface to T helper cells

allergen without adjuvant = Th2 (bad for allergens)

allergen with adjuvant = Th1

Question 19

What are IgE mediated allergies?

Answer 19

activate mast cell degranulation - inflammation and tissue damage

Question 20

Diff between anti-histamine and immunotherapies for treatment?

Answer 20

antihistamine treats symptoms

immunotherpaies change Th2 to Th1/T reg response

Question 21

What is Skewing therapy for suppressing IgE response?

Answer 21

CpG, TLR4 agonists + allergen = Th1 (IgG) response

Question 22

What is tolerance therapy for suppressing IgE response?

Answer 22

increase dosage - increase Treg

SLIT/SCIT may be used

mutate allergens so presented by DCs in different way = tolerogenic response

Question 23

What are Anti-IgE antibodies?

Answer 23

Omalizumab

binds to free IgE

decreases expression of high-affinity receptors

Decreases mediator release

Decreases allergic inflammation

Question 24

How can the Th2 response be a good thing?

Answer 24

many autoimmune/ auto-inflammatory are caused by Th1/Th17

e.g. IBS, Type 1 diabetes, MS, Rheumatoid arthritis

Question 25

What can skew the immune system away from a Th1 response?

Answer 25

Helminth DC-mediated immune skewing

Question 26

How can the immune system be suppressed by tolerogenic DC therapy?

Answer 26

DCs crucial for establishing appropriate response correct growth factor

Question 27

How can innapropriate response to transplantation be prevented?

Answer 27

corticosteroids - long term immunosuppressive Immune induction therapy - induce T cell unresponsiveness - reset tolerogenic mechanisms

Question 28

How is immunotherapy used in cancer?

Answer 28

monoclonal antibodies, soluble mediators imiquimod - TLR 7/8 agonist

Question 29

Therapeutic strategies to overcome tumour suppression?

Answer 29

Activate T cells Blockade of inhibitory receptor super T cells upregulate MHCI IFN-y treatment

Question 30

What is a dendritic cell vaccination?

Answer 30

pulse patients DCs with cancer antigen plus adjuvant then re inject antigen presentation and activation of tumour specific CD8 T cells

Question 31

What are "super" T cells/CAR-T therapy?

Answer 31

change extracellular domain to have antibody on outside intracellular domain has multiple activating domains boost T cel response T cells can recognise lipids and carbs - not normally recognise

Question 32

What is host-directed therapy for infectious disease (viral)?

Answer 32

Target host response rather than pathogen e.g. IFN therapies against viral infection target host-dependent life cycle HIV - alter conformation of CCR5 = no entry microRNA-122 host factor - increases HCV

Question 33

What is host-directed therapy for infectious disease (bacterial)?

Answer 33

Target Mtb in macrophages fungal - statins, imiquimod

Question 34

When immunotherapy goes wrong?

Answer 34

TGN1412 activated T-cells - huge inflammation