Flashcards in Immunomodulation and Immunosuppression Deck (28):
1
Immunomodulation
Manipulating the immune system using immunomodulatory drugs to achieve a desired immune response.
2
Biologics- Immunomodulators
Products using molecular biologic techniques including recombinant DNA technology e.g. monoclonal antibodies, fusion proteins etc.
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An example of a biologic immunomodulator
anti-TNF (pro-inflammatory cytokine) e.g. infliximab, etanercept
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Passive immunisation is used for what infectious agents?
Hep B, botulism, VZV, antivenom
5
Give 2 examples of immunostimulation
Pooled human immunoglobulin for antibody deficiencies
G-CSF/GM-CSF (colony stimulating factor) act on bone marrow to increase production of mature neutrophils e.g. neutropenic patients post chemo
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Give 6 effects of corticosteroid actions
Decrease neutrophil margination
Decrease production of pro-inflammatory cytokines
Inhibits phospholipase A2 (decreases production of arachidonic acid)
Lymphopenia
Decreased T cell proliferation-less likely to respond
Decreases immunoglobulin production
7
Side effects of corticosteroids
Carbohydrate and lipid metabolism (diabetes, dyperlipidaemia)
Decreased protein synthesis-poor wound healing
Osteoporosis
Glaucoma and cateracts
Psychiatric complications
8
Name 4 antimetabolites (T cell targeted immunosuppression)
Azathioprine
Mcophenolate Mofetil
Methotrexate
Cyclophosphamide
9
Name 4 types of T cell targeted immunosuppression
Antimetabolites
Calcineurin Inhibitors
M-Tor Inhibitors
Biological DMARDs
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Mechanism of action of antimetabolites
Inhibit nucleotide purine synthesis-prevents early stages of activated cells proliferation-will target any rapidly dividing cell.
Azathioprine is a guanine anti-metabolite
Mycophenolate Mofetil prevents the production of guanosine triphosphate
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Side effects of azathioprine and mycophenolate mofetil
Hepatotoxicity/hepatitis
Anaemia
Bone marrow suppression
12
Describe the mechanism of action of methotrexate and common side effect
Folate antagonist- pneumonitis
13
Describe the mechanism of action of cyclophosphamide and common side effect
X link DNA- cystitis
14
Mechanism of action of calcineurin inhibitors
Interfere with the initial T cell activation- prevent activation of NFAT-factors which stimulate cytokines i.e IL-2 and INF-y gene transcription. REVERSIBLE inhibition of T cell activation, proliferation and clonal expansion.
15
What are 2 calcineurin inhibitors
Ciclosporin A
Tacrolimus
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Mechanism of action of ciclosporin A
Binds to intracellular protien cylophilin.
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Mechanisms of action of tacrolimus
Bind to intracellular protein FKBP-12
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Give an example of an M-Tor inhibitor
Sirolimus (rapmycin)
Macrolide antibiotic-also binds to FKBP12 but different effects-inhibits response to IL-2, causes cell-cycle arrest at G1-S phase in T cell.
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Calcineurim/M-TOR side effects
Hypertension
Nephrotoxicity
Hepatotoxicity
Hirsutism-excessive hair growth
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Name the 2 main groups of biological DMARDs
Anticytokines
Anti B cells
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Anticytokines- Anti TNF
TNF activates macrophages, Used in treatment of RA, Crohn's, psoriasis, ankylosing spondylitis. Increases risk of TB
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Anti IL-6
Type of biological DMARD e.g. tocilizimab
Used in therapy of RA and AOSD (adult onset still's disease)
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Anti IL-1
Used in treatment of AOSD and other autoimmune conditions
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Anti B cells
Rifuximab (rufus shakespeare -BNOC)
mAb against CD20 on B cell surface. Used for treatment of lymphomas, leukaemias, transplant rejection and autoimmune disorders. Only targets B cells in the blood, not in the bone marrow or lympphoid tissue.
25
2 examples of adoptive immunotherapy
Bone marrow transplant
Stem cell transplant
26
Describe 4 immunomodulators used for the treatment of allergies
Immune suppressants e.g. steroids
Allergen-specific immunotherapy
Anti-IgE monoclonal therapy
Anti-IL5 monoclonal treatment
27
Mechanism of allergen specific immunotherap
Give a small amount of the allergen to switch off the immune response from Th2 (allergic) to Th1(non allergic) development of Treg cells and tolerance.
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