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Clinical Pathology > 12 - Immunomodulation & suppression > Flashcards

12 - Immunomodulation & suppression Flashcards

1
Q

Immunomodulation definition

A

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

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2
Q

Immunomodulation definition

A

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

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3
Q

Definition of passive immunisation

A

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

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4
Q

Passive immunisation problems

A

Risk of transmission of viruses

Serum sickness

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5
Q

Passive immunisation types

A

Pooled specific human Ig

Animal sera

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6
Q

Passive immunisation uses

A

Hep B prophylaxis and treatment

Botulism, VZV (pregnancy), diphtheria, snake bites

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7
Q

Active immunisation definition

A

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

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8
Q

Active immunisation immunogenic material

A

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

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9
Q

Active immunisation problems

A

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

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10
Q

What stimulates immunosuppression?

A 
Corticosteroids
Cytotoxic agents
Anti-proliferative agents
DMARD's
Biological DMARD's
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11
Q

Action of corticosteroids

A

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

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12
Q

Corticosteroids - side effects

A

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

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13
Q

Corticosteroid - uses

A

Autoimmune disease
Inflammatory disease
Malignancies (lymphoma)
Allograft rejection

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14
Q

Drug targeting lymphocytes

A

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

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15
Q

Antimetabolites e.g.

A

Azathioprine (used to treat Crohn’s)

Mycophenolate mofetil

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16
Q

Calcineurin inhibitors

A

Ciclosporin A

Tacrolimus

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17
Q

M-TOR inhibitors

A

Sirolimus

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18
Q

IL-2 receptor for mABs

A

Basiliximab

Daclizumab

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19
Q

Calcineurin inhibitors - how do they work

A

Bind to intracellular protein cyclophilin

Prevents activation of NFAT

Stops factors that stimulation cytokines

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

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20
Q

Sirolimus (aka rapamycin) what is it, how work

A

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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21
Q

Calcineurin/mTOR - side effects

A 
Hypertension
Hirsutism
Nephrotoxicity
Hepatotoxicity
Lymphomas
Opportunistic infections
Neurotoxicity
Multiple drug interactions (induce P450)
22
Q

Calcineurin - clinical use

A

Transplantation - allograft rejection

Autoimmune diseases

23
Q

Antimetabolites - what do

A

Inhibit nucleotide (purine) synthesis

24
Q

Antimetabolites - AZA

A

guanine anti-metabolite

25
Q

Antimetabolites - MMF

A

Non-competitive inhibitor of IMPDH

26
Q

Antimetabolites - T and B cell effects

A

Impaired DNA production

Prevents early stages of activated cell proliferation

27
Q

Antimetabolites - MTX

A

Methotrexate

Folate antagonists

28
Q

Antimetabolites - cyclophosphamide

A

Cross-link DNA target

29
Q

Cytotoxic - side effects

A

Bone marrow suppression
Gastric upset
Hepatitis
Susceptibility to infections

Cyclophosphamide - cystatis

MTX - pneumonitis

30
Q

Cytotoxics - clinical use for AZA/MMF

A

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

31
Q

Cytotoxics - clinical use for MTX

A

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

32
Q

Cytotoxics - clinical use for cyclophosamide

A

Vasculitis (Wagner’s, CSS)

SLE

33
Q

Biological DMART’s

A 
Anticytokines
Anti-B cell therapies
Anti-T cell activation
Anti-adhesion molecules
Complement inhibitors
34
Q

Anticytokines - types

A

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

35
Q

Anticytokines - anti-TNF

A

first therapy for RA

Also used in Crohn’s, psoriasis, ankylosing spondylitis

Caution: increased risk of TB

36
Q

Anticytokines - anti-IL-6

A

Tocilizumab

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

May cause problems with control of serum lipids

37
Q

Anticytokines - anti-IL-1

A

Used in AOSD and autoinflammatory syndromes

38
Q

AOSD stands for?

A

Adult’s onset still’s disease

39
Q

Rituximab what is it

A

Chimeric mAb against CD20-B cell surface

40
Q

Rituximab uses

A

Lymphomas, leukaemias
Transplant rejection
Autoimmune disorders

41
Q

Adoptive immunotherapy

A

BMT

SCT

42
Q

BMT stands for

A

bone marrow transplant

43
Q

SCT stands for

A

stem cell transplant

44
Q

Adoptive immunotherapy uses

A

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

45
Q

Immunomodulators - allergy

A

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

46
Q

Allergen specific immunotherapy - indications

A

Allergic rhino-conjunctivitis not controlled on max medical therapy

Anaphylaxis to insect venoms

47
Q

Allergen specific immunotherapy - mechanisms

A

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

48
Q

Allergen specific immunotherapy - routes

A

SC or sublingual for aero-allergens

49
Q

Allergen specific immunotherapy - side-affects

A

Localised and systemic allergic reactions

50
Q

Omalizumab

A

mAb against IgE

Used in Rx of asthma

Also useful in Rx of chronic urticaria and angioedema

may cause severe systemic anaphylaxis

51
Q

Mepolizumab

A

mAb against IL-5

prevents eosinophil recruitment and activation

limited effect on asthma

no clinical efficacy in hypereosinophilic syndrome

Clinical Pathology (65 decks)

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