Immunotherapeutics - Immunomodulation Flashcards
Define: Immunomodulation
Manipulate immune system using immunomodulatory drugs –> immune response.
What 3 things can immunomodulation potentially lead to?
> Immunopotentiation (inc rate/prolong duration)
Immunosuppression
Induct immunological tolerance.
What are immunomodulators?
Medicinal products using molecular biology techniques (inc recombinant DNA tech).
What are the main classes of immunomodulators?
> Substances similar to body’s key signalling proteins
Monoclonal antibodies
Fusion proteins
What is passive immunity?
Transfer of high-titre antibody from donor to recipient . Short lasting immunity.
Problems of passive immunity?
> Transfer blood-bourne viruses
>Serum sickness- Anti’b overload can = inflam and cytokine release.
What are the different types of Ig?
> Pooled human immunoglobulin
> Animal sera –> makes antib’s.
How is animal sera given?
IV or IM.
What is active immunisation?
Stimulate development of protective immune response and immunological memory.
What is G-CSF/GM-CSF?
Acts on bone marrow –> stimulate neutrophil production.
What does IL-2 do?
Activates T cells
What is a-interferon used for?
Treat Hep C
What is B-interferon used for?
MS
What is y-interferon used for?
Chronic granulomatous disease, IL-12 deF.
What do Corticosteroids do in general?
Immunosuppression
What do Corticosteroids do specifically?
> Decreased neutrophil margination
Decreased cytokine production
Decreased T cell proliferation (toxic at high levels)
Decreased levels of lymphocytes
Inhibit phospholipase A2 (reduced arachidonic acid metabolite production).
What are the side effects of Corticosteroids?
> Reduced lipid/carbohydrate metabolism - slow down (Diabetes, Hyperlipidaemia) > Reduced protein synthesis > Osteoporosis > Glacucoma and eye problems > ~Anxiety
Corticosteroid uses?
> Allograft rejection
Malignancies - lymphoma
Inflam diseases
Autoimmune diseases
What are the four types of drugs targeting lymphocytes?
> M-TORS
IL-2 receptor monoclonal antibodies
Calcaneurin Inhibitors
Anti-metabolites
What is Calcaneurin?
A serine/threonine phosphatase protein that activates T cell production.`
What does CyA bind to?
CyA –> Cyclophillin (“CyA later PHIL mitchell”
What does Tacrolimus (FK506) bind to?
FKBP-12 (FK to FK)
What is the mode of action of Calcaneurin inhibitors?
Bind to NFAT- cytokine stimulation factors
What are the T cell effects of Calcaneurin?
Reversibly inhibit T-cell activation, proliferation and clonal expansion.
What type of lymphocyte drug is Sirolimus?
M-TOR inhibitor
What does Sirolimus bind to?
FKBP12 - Inhibit Rapamycin transcription factor
What are the T cell effects of Sirolimus?
Stops cell cycle at G1/S phase
What are Calcaneurin/MTOR side effects?
>Hypertension >Hirsutism >Nephro/neuro/hepatotoxicity >Opportunistic infections > Lymphomas
What do Antimetabolites inhibit?
PURINE SYNTHESIS (Adenosine and Guanine)
What is converted into 6-mercaptopurine by AZA?
Guanine
What does MMF inhibit?
IMPDH - stops GTP production
What does Methotrexate (MTX) inhibit?
Folate
What does cyclophosphamide stop?
DNA cross-linking
Cytoxic side effects?
> Bone marrow suppression
Gastric upset
Hepatitis
Infection susceptibility
Cyclophosphamide side effects?
Cystitis - bladder inflammation
Methotrexate side effects?
Pneumonitis - inflammed alveoli walls
What are the clinical uses of AZA/MMT?
> Allograft rejection
> Autoimmune diseases
What are the clinical uses of MTX?
> Rheumatoid arthritis, vasculitis, polymyolitis
> GvHD in bone marrow transplant.
What are the clinical uses of Cyclophosphamide?
Systemic Lupus Erythmatois, Vasculitis
What type of drug is Anti-TNF?
Anti-cytokine
What is Anti-TNF used for?
Crohn’s, Psoriasis, Ankylosing Spondylitis
What is Anti-IL6 used for?
Rheumatoid Disease,
What is Anti-IL1 used for?
AOSD and autoinflammatory syndromes.
What is Rituximab?
Chimeric mAb against CD20- B cell surface.
What type of B cells are cd20 only found on?
Blood B cells
What does Rituximab do?
Removes pool of autoreactive antibodies from blood.
What switches immune response from Th2 (allergic) to Th1 (non-allergic)?
Allergen specific immunotherapy
What route is used for allergen specific immunotherapy against aero-allergens?
Sub-lingual
