Immunomodulation and Immunosuppression Flashcards
Immunomodulation
Manipulating the immune system using immunomodulatory drugs to achieve a desired immune response.
Biologics- Immunomodulators
Products using molecular biologic techniques including recombinant DNA technology e.g. monoclonal antibodies, fusion proteins etc.
An example of a biologic immunomodulator
anti-TNF (pro-inflammatory cytokine) e.g. infliximab, etanercept
Passive immunisation is used for what infectious agents?
Hep B, botulism, VZV, antivenom
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
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
Side effects of corticosteroids
Carbohydrate and lipid metabolism (diabetes, dyperlipidaemia)
Decreased protein synthesis-poor wound healing
Osteoporosis
Glaucoma and cateracts
Psychiatric complications
Name 4 antimetabolites (T cell targeted immunosuppression)
Azathioprine
Mcophenolate Mofetil
Methotrexate
Cyclophosphamide
Name 4 types of T cell targeted immunosuppression
Antimetabolites
Calcineurin Inhibitors
M-Tor Inhibitors
Biological DMARDs
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
Side effects of azathioprine and mycophenolate mofetil
Hepatotoxicity/hepatitis
Anaemia
Bone marrow suppression
Describe the mechanism of action of methotrexate and common side effect
Folate antagonist- pneumonitis
Describe the mechanism of action of cyclophosphamide and common side effect
X link DNA- cystitis
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.
What are 2 calcineurin inhibitors
Ciclosporin A
Tacrolimus
Mechanism of action of ciclosporin A
Binds to intracellular protien cylophilin.
Mechanisms of action of tacrolimus
Bind to intracellular protein FKBP-12
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.
Calcineurim/M-TOR side effects
Hypertension
Nephrotoxicity
Hepatotoxicity
Hirsutism-excessive hair growth
Name the 2 main groups of biological DMARDs
Anticytokines
Anti B cells
Anticytokines- Anti TNF
TNF activates macrophages, Used in treatment of RA, Crohn’s, psoriasis, ankylosing spondylitis. Increases risk of TB
Anti IL-6
Type of biological DMARD e.g. tocilizimab
Used in therapy of RA and AOSD (adult onset still’s disease)
Anti IL-1
Used in treatment of AOSD and other autoimmune conditions
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.
2 examples of adoptive immunotherapy
Bone marrow transplant
Stem cell transplant
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
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.
mAB against IgE, used in the treatment of asthma, chronic urticaria and angioedema
Omalizumab
