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Flashcards in Immunotherapeutics Deck (54):
1

define immunomodulation

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

2

what mechanisms can be used for immunomodulation

• Immunization
• Replacement therapy
• Immune stimulants
• Immune suppressants
• Anti-inflammatory agents
• Allergen immunotherapy (desentization)
• Adoptive immunotherapy

3

define immunomodulators.

medicinal products produced using molecular biology techniques including recombinant DNA technology, in order to modular the immune system,

4

What are the main classes of immunomodulators.

Monoclonal antibodies- made using specific technology and they target specific cell types.
fusion proteins- 2 proteins with different biological function.
Substances that are identical to body's own signalling problems.

5

Give a example of an immunomodulator

TNF

6

define immunopotentiation

to encourage a immune response by administration of another product.

7

how is immunopotentiation carried out

immunisation
replacement therapies
immune stimulanats

8

define passive immunity

transfer of specific, high-titre antibody from donor to recipient. Provides immediate but transient protection

9

problems with passive immunity

Risk of transmission of viruses- as it is a blood product
Serum sickness- increased immunoglobulin, forms complex and activates complement.

10

uses of passive immunisation

Hep B prophylaxis and treatment
Botulism, VZV (pregnancy), diphtheria, snake bites

11

define active immunity

To stimulate the development of a protective immune response and immunological memory

12

what kinds of immune material are used in an active immunisation

weakened forms of the pathogen
killed inactivated pathogens
purified materials
components vaccines- e.g. bacterial cell wall.
adjuvants (substance added to vaccine to increase body's immune response to it)

13

problems with active immunity

allergy to vaccine component
delay in protection
limited usefulness in the immunocompromised.

14

how is replacement therapy carried out

• Pooled human immunoglobulin (IV or SC)- plasma form lots of donors and therefore has lots of antibodies

15

how does immune stimulation take place (examples)

• G-CSF/GM-CSF – colony stimulating factor (specific to certain cells). Act on bone marrow to increase production of mature neutrophils.
• IL-2 (Stimulates T cell activation- rarely used).
• α-interferon (Main use in treatment of Hep C)
• β-interferon (Used in therapy of MS)

16

Names of drugs or molecules used in immunosuppression

• Cortocosteroids- majority
• Cytotoxic/ agents
• Anti-proliferative/activation agents
• DMARD’s
• Biologic DMARD’s

17

How do corticosteroids work

• Decreased neutrophil margination- so they don’t enter the tissue.
• Reduced production of inflammatory cytokines
• Inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
• Lymphopenia
• Decreased T cells proliferation- increased doses toxic to T cells
• Reduced immunoglobulins production – make T cells less likely to respond to proliferation.

18

main side effects of corticosteroids.

• Carbohydrate and lipid metabolism
– Diabetes
– Hyperlipidaemia
• Reduced protein synthesis
– Poor wound healing
• Osteoporosis
• Glaucoma and cataracts
• Psychiatric complications

19

Uses of corticosteorids.

• Autoimmune diseases
– CTD, vasculitis, RA
– Used as induction agent- short term and long term in a cocktail of drugs.
• Inflammatory diseases
– Crohn’s, sarcoid, GCA/polymyalgia rheumatica
• Malignancies
– Lymphoma- corticosteroid toxic to T or B cell so can treat B/T cell lymphoma.
• Allograft rejection – transplantation

20

Name the drugs used in T cel targeted immunosuppression

Anti-IL-2 receptor mAbs, CyA, Tacrolimus, Sirolimus, Azathioprine MMF.

21

What types of drugs target lymphocytes

Antimetabolites- Azathioprine, MMF
Calcineurin inhibitors (Ciclosporin A, tACROLIMUS
M-TOR inhibitors- sirolimus
IL2 receptor mABs- Basilximab
Daclizumab

22

What is the function of calcineurin inhibitors

prevent T cell activation
interfere with initial signals after T cell receptor activation

23

mode of action of CyA and effect on T cell

– Binds to intracellular protein cyclophilin.
– Prevents activation of NFAT
– Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription.
– Reversible inhibition of T-cell activation, proliferation and clonal expansion

24

mode of action tacrolimus and effect on T cell

– Binds to intracellular protein FKBP-12.
Prevents activation of NFAT
– Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription.
– Reversible inhibition of T-cell activation, proliferation and clonal expansion

25

mode os action sirolimus (rapamycin) and effect on T cell

• Mode of action
– Inhibits response to IL-2
• T cell effects
– Cell cycle arrest at G1-S phase

26

side effects of calcineurin and mTOR

• Hypertension
• Hirsutism
• Nephrotoxicity
• Hepatotoxicity
• Lymphomas
• Opportunistic infections
• Neurotoxicity
• Multiple drug interactions (induce P450)

27

clinical use of alcineurin and mTOR

transplantation- allograft rejection
autoimmune diseases.

28

How do antimetabolities- against T and B cells work

Inhibit nucleotide (purine) synthesis- needed in DNA synthesis.
prevents T and B cell proliferation.

29

which base metabolite is AZA

guanine

30

MMF prevents the production of what

guanosine triphosphate.

31

Name a folate antagonist

methotrexate

32

Name a drug which cross links DNA

Cyclophosphamide

33

Side effects of antimetabolities.

– Bone marrow suppression
– Gastric upset
– Hepatitis
– Susceptibility to infections

34

Cytotoxic clinical use
AZA/MMF

– Autoimmune diseases (SLE, vasulitis, IBD)
– Allograft rejection

35

clinical use MTX

– RA, PsA, Polymyositis, vasculitis
– GvHD in BMT

36

clinical use of Cyclophosphamide

– Vasculitis (Wagner’s, CSS)
– SLE

37

Biologic DMARD’s use what types of immune manipulations

• Anti-cytokines (TNF, IL-6 and IL-1)
• Anti-B cell therapies
• Anti-T cell activation
• Anti-adhesion molecules
• Complement inhibitors

38

what drug was used to treat RA initially

Anti TNF

39

what conditions is Anti TNF used to treat

RA, Crohns, ankolysing spondylitis.

40

what conditions is Anti IL6 used to treat

RA, AOSD (adult onset stills disease)

41

what conditions is Anti IL1 used to treat

AOSD (adult onset stills disease)

42

Ritiximab is a monoclonal antibody against

CD20- B cell surface

43

what conditions is Ritiximab used to treat

lymphoma, leukaemia, transplant rejection

44

adoptive immunotherapy includes

• Bone marrow transplant (BMT)
• Stem cell transplant (SCT)

45

uses of adoptive immunotherapy.

– Immunodeficiencies (SCID)
– Lymphomas and leukemias
– Inherited metabolic disorders (osteopetrosis)
– Autoimmune diseases

46

immunotherapy can be provided for what specifically.

allergen

47

how does immunotherapy work

• Give allergen subcutaneous or sublingually over time and increase the dose slowly every time- over time tolerance will be induced via a specific

48

2 types of monoclonal antibodies

Omalizumab
Mepolizumab

49

what is omalizumab used for

• mAb against IgE- remove Ig E from mast and basophils.

50

what condition is omalizumab used for

asthma, chronic urticaria and angioedema

51

major side effect of omalizumab

systemic anaphylaxis

52

what is mepolizumab used for

• mAb against IL-5
• Prevents eosinophil recruitment and activation

53

how does immunmodulation work biochemically.

– Switching of immune response from Th2 (allergic) to Th1 (non-allergic)
– Development of T reg cells and tolerance

54

Name 4 immunomodulators which are used in allergies

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