12 - Immunomodulation & suppression Flashcards Preview

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Flashcards in 12 - Immunomodulation & suppression Deck (51):
1

Immunomodulation definition

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

2

Immunomodulation definition

Medicinal products produced using molecular biology techniques including recombinant DNA technology
e.g. monoclonal antibodies + fusion bodies

3

Definition of passive immunisation

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

4

Passive immunisation problems

Risk of transmission of viruses
Serum sickness

5

Passive immunisation types

Pooled specific human Ig
Animal sera

6

Passive immunisation uses

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

7

Active immunisation definition

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

8

Active immunisation immunogenic material

Weakened form of pathogen
Killed inactivated pathogens
Purified materials (proteins, DNA)
Adjuvants

9

Active immunisation problems

Allergy to any vaccine component
Limited usefulness in immunocompromised
Delay in achieving protection

10

What stimulates immunosuppression?

Corticosteroids
Cytotoxic agents
Anti-proliferative agents
DMARD's
Biological DMARD's

11

Action of corticosteroids

Decreased neutrophil margination
Reduced production of inflammatory cytokines
Inhibition of phospholipase A2 (less arachidonic acid metabolite production)
Lymphopenia
Decreased T cells proliferation
Reduced immunoglobulins production

12

Corticosteroids - side effects

CHO and lipid metabolism - diabetes and hyperlipidaemia
Reduced protein synthesis - poor wound healing
Osteoporosis
Glaucoma and cataracts
Psychiatric complications

13

Corticosteroid - uses

Autoimmune disease
Inflammatory disease
Malignancies (lymphoma)
Allograft rejection

14

Drug targeting lymphocytes

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

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Antimetabolites e.g.

Azathioprine (used to treat Crohn's)
Mycophenolate mofetil

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Calcineurin inhibitors

Ciclosporin A
Tacrolimus

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M-TOR inhibitors

Sirolimus

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IL-2 receptor for mABs

Basiliximab
Daclizumab

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Calcineurin inhibitors - how do they work

Bind to intracellular protein cyclophilin

Prevents activation of NFAT

Stops factors that stimulation cytokines

Reversible inhibition of T-cell activation, proliferation and clonal expansion

20

Sirolimus (aka rapamycin) what is it, how work

Macrolide antibiotic
Binds to FKBP12 but different effects
Inhibits mammalian target of rapamycin (mTOR)

Inhibits response to IL-2

Cell cycle arrest of T cells at G1-S phase

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Calcineurin/mTOR - side effects

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

22

Calcineurin - clinical use

Transplantation - allograft rejection
Autoimmune diseases

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Antimetabolites - what do

Inhibit nucleotide (purine) synthesis

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Antimetabolites - AZA

guanine anti-metabolite

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Antimetabolites - MMF

Non-competitive inhibitor of IMPDH

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Antimetabolites - T and B cell effects

Impaired DNA production

Prevents early stages of activated cell proliferation

27

Antimetabolites - MTX

Methotrexate
Folate antagonists

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Antimetabolites - cyclophosphamide

Cross-link DNA target

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Cytotoxic - side effects

Bone marrow suppression
Gastric upset
Hepatitis
Susceptibility to infections

Cyclophosphamide - cystatis

MTX - pneumonitis

30

Cytotoxics - clinical use for AZA/MMF

AZA/MMF - autoimmune diseases (SLE, vasculitis, IBD), allograft rejection

31

Cytotoxics - clinical use for MTX

MTX - RA, PsA, polymyositis, vasculitis, GvHD in BMT

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Cytotoxics - clinical use for cyclophosamide

Vasculitis (Wagner's, CSS)
SLE

33

Biological DMART's

Anticytokines
Anti-B cell therapies
Anti-T cell activation
Anti-adhesion molecules
Complement inhibitors

34

Anticytokines - types

Anti-TNF
Anti-IL-6
Anti-IL-1

35

Anticytokines - anti-TNF

first therapy for RA

Also used in Crohn's, psoriasis, ankylosing spondylitis

Caution: increased risk of TB

36

Anticytokines - anti-IL-6

Tocilizumab

Blocks IL-6 receptor
Used in therapy of RA and AOSD

May cause problems with control of serum lipids

37

Anticytokines - anti-IL-1

Used in AOSD and autoinflammatory syndromes

38

AOSD stands for?

Adult's onset still's disease

39

Rituximab what is it

Chimeric mAb against CD20-B cell surface

40

Rituximab uses

Lymphomas, leukaemias
Transplant rejection
Autoimmune disorders

41

Adoptive immunotherapy

BMT
SCT

42

BMT stands for

bone marrow transplant

43

SCT stands for

stem cell transplant

44

Adoptive immunotherapy uses

Immunodeficiencies (SCID)
Lymphomas & leukaemias
Inherited metabolic disorders (osteopetrosis)
Autoimmune disease

45

Immunomodulators - allergy

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

46

Allergen specific immunotherapy - indications

Allergic rhino-conjunctivitis not controlled on max medical therapy

Anaphylaxis to insect venoms

47

Allergen specific immunotherapy - mechanisms

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

48

Allergen specific immunotherapy - routes

SC or sublingual for aero-allergens

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Allergen specific immunotherapy - side-affects

Localised and systemic allergic reactions

50

Omalizumab

mAb against IgE

Used in Rx of asthma

Also useful in Rx of chronic urticaria and angioedema

may cause severe systemic anaphylaxis

51

Mepolizumab

mAb against IL-5

prevents eosinophil recruitment and activation

limited effect on asthma

no clinical efficacy in hypereosinophilic syndrome

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