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MICR2221 - Medical Immunology > L16 - immunotherapy > Flashcards

L16 - immunotherapy Flashcards

1
Q

What are conventional immunosuppressive drugs?

A

Corticosteroids
Cytotoxic drugs
Cyclosporin A
Rapmycin

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2
Q

What do corticosteroids do?

A

Inhibit inflammation

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3
Q

What do cytotoxic drugs do?

A

interfere with DNA synthesis - kill immune cells

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4
Q

What does cyclosporin A do?

A

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

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5
Q

What does Rapmycin do?

A

inhibits mTOR pathway - cell proliferation. translation & autophagy

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6
Q

Define immunotherapy?

A

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

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7
Q

Types of immunotherapy?

A

Soluble mediators
Antibody therapy
Cell based
Skewing/suppression

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8
Q

What are the soluble mediators used in immunotherapy?

A

Recombinant cytokines

Cytokine antagonists

Adjuvants

Miscellaneous

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9
Q

What are recombinant cytokines?

A

treat neutropenia in cancer patients & BM donors

PEGylated IFNa

IFNy treated CGD

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10
Q

What are cytokine antagonists?

A

target autoinflammatory disease and Muckle Wells Syndrome

Etanercept - recombinant TNFa receptor-fusion protein

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11
Q

Therapeutic uses of monoclonal antibodies?

A

Rheumatoid arthritis, Crohn’s = Infliximab, Efalizumab

B-cell leukaemia = Rituximab

Breast cancer = Herceptin/Trastuzumab

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12
Q

What are problems with monoclonal antibody therapy?

A

Repeat doses often immunogenic - neutralise anti-antibody antibodies

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13
Q

suffix -Omab?

A

Fully mouse

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14
Q

suffix -Ximab?

A

Chimeric

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15
Q

suffis -Zumab?

A

Humanised

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16
Q

Suffix -Umab?

A

Fully human

17
Q

What do adjuvants do?

A

enhance immune response and the quality of response

physically link antigens to adjuvants

18
Q

How can conjugated adjuvants enhance/skew immune response?

A

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

19
Q

What are IgE mediated allergies?

A

activate mast cell degranulation - inflammation and tissue damage

20
Q

Diff between anti-histamine and immunotherapies for treatment?

A

antihistamine treats symptoms

immunotherpaies change Th2 to Th1/T reg response

21
Q

What is Skewing therapy for suppressing IgE response?

A

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

22
Q

What is tolerance therapy for suppressing IgE response?

A

increase dosage - increase Treg

SLIT/SCIT may be used

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

23
Q

What are Anti-IgE antibodies?

A

Omalizumab

binds to free IgE

decreases expression of high-affinity receptors

Decreases mediator release

Decreases allergic inflammation

24
Q

How can the Th2 response be a good thing?

A

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

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

25
Q

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

A

Helminth

DC-mediated immune skewing

26
Q

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

A

DCs crucial for establishing appropriate response

correct growth factor

27
Q

How can innapropriate response to transplantation be prevented?

A

corticosteroids - long term immunosuppressive

Immune induction therapy - induce T cell unresponsiveness - reset tolerogenic mechanisms

28
Q

How is immunotherapy used in cancer?

A

monoclonal antibodies, soluble mediators

imiquimod - TLR 7/8 agonist

29
Q

Therapeutic strategies to overcome tumour suppression?

A

Activate T cells

Blockade of inhibitory receptor

super T cells

upregulate MHCI IFN-y treatment

30
Q

What is a dendritic cell vaccination?

A

pulse patients DCs with cancer antigen plus adjuvant then re inject

antigen presentation and activation of tumour specific CD8 T cells

31
Q

What are “super” T cells/CAR-T therapy?

A

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

32
Q

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

A

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

33
Q

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

A

Target Mtb in macrophages

fungal - statins, imiquimod

34
Q

When immunotherapy goes wrong?

A

TGN1412 activated T-cells - huge inflammation

MICR2221 - Medical Immunology (16 decks)

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