Immunomodulation Flashcards
Definition of immunomodulation
Act of manipulation the immune system using immunomodulatory drug to achieve a desired immune response
Effects of immunomodulation
Immunopotentiation
Immunosuppression
Induction of immunological tolerance
Definition of immunomodulators
Medicinal products produced using molecular biology techniques including recombinant DNA technology
Main classes of immunomodulators
Substances (nearly) identical to the body’s own key signalling proteins
Monoclonal antibodies
Fusion proteins
Forms of immunopotentiation
Immunisation (both active and passive)
Replacement therapies
Immune stimulants
Passive immunisation
Transfer of antibodies e.g. naturally in breastmilk, or artificially from donor. Immediate but transient protection
Problems with passive immunisation
Risk of virus transmission Serum sickness (type III immune response)
Types of passive immunisation
Pooled specific human immunoglobulin Animal sera (antitoxins and antivenoms)
Uses of passive immunisation
Hep B prophylaxis and treatment
Botulism, VZV (pregnancy), diphtheria, snake bites
Active immunisation
Stimulation of the development of a protective immune reponse and immunological memory
Immunogenic material for active immunisation
Weakened pathogens
Killed inactivated pathogens
Purified materials (e.g protein, DNA)
Adjuvants
Problems with active immunisation
Allergy to any vaccine component
Limited usefulness in immunocompromised
Delay in achieving protection
Replacement therapies and immune stimulation
Pooled human immunoglobulin
G-SCF/GM-SCF
alpha-interferon
gamma-interferon
Pooled human immunoglobulin
Delivered IV or SC
Used in Rx of antibody deficiency states
G-CSF/GM-SCF
Act on bone marrow to increase production of mature neutrophils
alpha-interferon
Main use in treatment of Hep C, now superseded by new treatments
gamma-interferon
Can be useful in treatment of certain intracellular infection (atypical mycobacteria), also used in chronic granulomatous disease and IL-12 deficiency
Forms of immunosuppression
Corticosteroids Cytotoxic agents Anti-proliferative/activation agents DMARDSs Biological DMARDs
Action of corticosteroids
Decreased neutrophil margination
Reduced protection of inflammatory cytokines
Inhibition phospholipase A2 (reduced arachidionic acid metabolites production)
Lymphopenia
Decreased T cell proliferation
Reduced immunoglobulin production
Corticosteroid side effects
Carbohydrate and lipid metabolism (diabetes and hyperlipidaemia)
Reduced protein synthesis (poor wound healing)
Osteoporosis
Glaucoma and cataracts
Psychiatric complications
Uses of corticosteroids
Autoimmune diseases (CTD, vasculitis, RA)
Inflammatory diseases (Crohn’s, sarcoid, GCA/polymyalgia rheumatica)
Malignancies (lymphoma)
Allograft rejection
Drugs targeting lymphocytes
Antimetabolites (Azathioprine, Mycophenolate mofetil)
Calcineurin inhibitors (Cyclosporin A, Tacrolimus)
M-TOR inhibitors (Sirolimus)
IL-2 receptor mABs (Basiliximab, Daclizumab)
Calcineurin inhibitors
Prevents activation of NFAT (factors which stimulate cytokine gene transcription)
Reversibly inhibits T-cell activation, proliferation and clonal expansion
Clinical use of calcineurin inhibitors and mTORs
Allograft rejection after transplant
Autoimmune
