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Clinical Pathology > Immunotherapeutics > Flashcards

Immunotherapeutics Flashcards

1
Q

define immunomodulation

A

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

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2
Q

what mechanisms can be used for immunomodulation

A
  • Immunization
  • Replacement therapy
  • Immune stimulants
  • Immune suppressants
  • Anti-inflammatory agents
  • Allergen immunotherapy (desentization)
  • Adoptive immunotherapy
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3
Q

define immunomodulators.

A

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

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4
Q

What are the main classes of immunomodulators.

A

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.

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5
Q

Give a example of an immunomodulator

A

TNF

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6
Q

define immunopotentiation

A

to encourage a immune response by administration of another product.

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7
Q

how is immunopotentiation carried out

A

immunisation
replacement therapies
immune stimulanats

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8
Q

define passive immunity

A

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

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9
Q

problems with passive immunity

A

Risk of transmission of viruses- as it is a blood product

Serum sickness- increased immunoglobulin, forms complex and activates complement.

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10
Q

uses of passive immunisation

A

Hep B prophylaxis and treatment

Botulism, VZV (pregnancy), diphtheria, snake bites

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11
Q

define active immunity

A

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

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12
Q

what kinds of immune material are used in an active immunisation

A

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)

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13
Q

problems with active immunity

A

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

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14
Q

how is replacement therapy carried out

A

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

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15
Q

how does immune stimulation take place (examples)

A
  • 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)
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16
Q

Names of drugs or molecules used in immunosuppression

A
  • Cortocosteroids- majority
  • Cytotoxic/ agents
  • Anti-proliferative/activation agents
  • DMARD’s
  • Biologic DMARD’s
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17
Q

How do corticosteroids work

A
  • 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.
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18
Q

main side effects of corticosteroids.

A 
•	Carbohydrate and lipid metabolism
–	Diabetes
–	Hyperlipidaemia
•	Reduced protein synthesis
–	Poor wound healing
•	Osteoporosis
•	Glaucoma and cataracts
•	Psychiatric complications
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19
Q

Uses of corticosteorids.

A

• 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

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20
Q

Name the drugs used in T cel targeted immunosuppression

A

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

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21
Q

What types of drugs target lymphocytes

A 
Antimetabolites- Azathioprine, MMF
Calcineurin inhibitors (Ciclosporin A, tACROLIMUS
M-TOR inhibitors- sirolimus
IL2 receptor mABs- Basilximab
Daclizumab
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22
Q

What is the function of calcineurin inhibitors

A

prevent T cell activation

interfere with initial signals after T cell receptor activation

23
Q

mode of action of CyA and effect on T cell

A

– 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
Q

mode of action tacrolimus and effect on T cell

A

– 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
Q

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

A

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

26
Q

side effects of calcineurin and mTOR

A
  • Hypertension
  • Hirsutism
  • Nephrotoxicity
  • Hepatotoxicity
  • Lymphomas
  • Opportunistic infections
  • Neurotoxicity
  • Multiple drug interactions (induce P450)
27
Q

clinical use of alcineurin and mTOR

A

transplantation- allograft rejection

autoimmune diseases.

28
Q

How do antimetabolities- against T and B cells work

A 
Inhibit nucleotide (purine) synthesis- needed in DNA synthesis.
prevents T and B cell proliferation.
29
Q

which base metabolite is AZA

A

guanine

30
Q

MMF prevents the production of what

A

guanosine triphosphate.

31
Q

Name a folate antagonist

A

methotrexate

32
Q

Name a drug which cross links DNA

A

Cyclophosphamide

33
Q

Side effects of antimetabolities.

A

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

34
Q

Cytotoxic clinical use

AZA/MMF

A

– Autoimmune diseases (SLE, vasulitis, IBD)

– Allograft rejection

35
Q

clinical use MTX

A

– RA, PsA, Polymyositis, vasculitis

– GvHD in BMT

36
Q

clinical use of Cyclophosphamide

A

– Vasculitis (Wagner’s, CSS)

– SLE

37
Q

Biologic DMARD’s use what types of immune manipulations

A
  • Anti-cytokines (TNF, IL-6 and IL-1)
  • Anti-B cell therapies
  • Anti-T cell activation
  • Anti-adhesion molecules
  • Complement inhibitors
38
Q

what drug was used to treat RA initially

A

Anti TNF

39
Q

what conditions is Anti TNF used to treat

A

RA, Crohns, ankolysing spondylitis.

40
Q

what conditions is Anti IL6 used to treat

A

RA, AOSD (adult onset stills disease)

41
Q

what conditions is Anti IL1 used to treat

A

AOSD (adult onset stills disease)

42
Q

Ritiximab is a monoclonal antibody against

A

CD20- B cell surface

43
Q

what conditions is Ritiximab used to treat

A

lymphoma, leukaemia, transplant rejection

44
Q

adoptive immunotherapy includes

A
  • Bone marrow transplant (BMT)

* Stem cell transplant (SCT)

45
Q

uses of adoptive immunotherapy.

A

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

46
Q

immunotherapy can be provided for what specifically.

A

allergen

47
Q

how does immunotherapy work

A

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

48
Q

2 types of monoclonal antibodies

A

Omalizumab

Mepolizumab

49
Q

what is omalizumab used for

A

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

50
Q

what condition is omalizumab used for

A

asthma, chronic urticaria and angioedema

51
Q

major side effect of omalizumab

A

systemic anaphylaxis

52
Q

what is mepolizumab used for

A
  • mAb against IL-5

* Prevents eosinophil recruitment and activation

53
Q

how does immunmodulation work biochemically.

A

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

54
Q

Name 4 immunomodulators which are used in allergies

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

Clinical Pathology (45 decks)

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