Immunomodulation Flashcards
What is immunomodulation?
The act of manipulating the immune system using immunomodulatory drugs to achieve
a desired immune response.
What are the various mechanisms that can be used to bring about immunomodulation?
- Immunization
- Replacement therapy
- Immune stimulants
- Immune suppressants
- Anti-inflammatory agents
- Allergen immunotherapy (desentization)
- Adoptive immunotherapy
What are biologic immunomodulators?
Medicinal products produced using molecular biology techniques including recombinant DNA technology.
What are the main classes of biologic immunomodulators?
- Substances that are (nearly) identical to the body’s own key signaling proteins
- Monoclonal antibodies
- Fusion proteins
What is the problem with biologic immunomodulators?
Humans can develop autoantibodies against them.
What is is immunopotentiation?
Immunisation
What is the definition of passive immunisation?
Transfer of specific, high-titre antibody from donor to recipient. Provides immediate but transient protection
What are the risks associated with passive immunisation?
- Risk of transmission of viruses
- Serum sickness
What types of passive immunisation are available?
- Pooled specific human immunoglobulin
- Animal sera (antitoxins an antivenins)
What are the clinical indications for passive immunisation?
Hep B prophylaxis and treatment
Botulism, VZV (pregnancy), diphtheria, snake bites
What is the definition of active immunisation?
To stimulate the development of a protective immune response and immunological memory.
What kind of immunogenic material is used in vaccines?
- Weakened forms of pathogens
- Killed inactivated pathogens
- Purified materials (proteins, DNA)
- Adjuvants
What problems are associated with vaccination?
- Allergy to any vaccine component
- Limited usefulness in immunocompromised
- Delay in achieving protection
What is pooled human immunoglobulin used for?
Rx of antibody deficiency states
What are the various actions of corticosteroids?
- Decreased neutrophil margination
- Reduced production of inflammatory cytokines
- Inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
- Lymphopenia
- Decreased T cells proliferation
- Reduced immunoglobulins production
What are the side-effects of corticosteroids?
- Carbohydrate and lipid metabolism
- Diabetes
- Hyperlipidaemia
- Reduced protein synthesis
- Poor wound healing
- Osteoporosis
- Glaucoma and cataracts
- Psychiatric complications
What are the uses of corticosteroids?
- Autoimmune diseases
- CTD, vasculitis, RA
- Inflammatory diseases
- Crohn’s, sarcoid, GCA/polymyalgia rheumatica
- Malignancies
- Lymphoma
- Allograft rejection
What is calcineurin?
Calcineurin (CN) is a calcium and calmodulin dependent serine/threonine protein phosphatase. Activates T cells and stimulates growth and differentiation.
Name two calcineurin inhibitors.
- Ciclosporin A (CyA)
- Tacrolimus (FK506)
How does ciclosporin work?
- Binds to intracellular protein cyclophilin
- Prevents activation of NFAT
Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription - Reversible inhibition of T-cell activation, proliferation and clonal expansion
How does sirolimus work?
- Also binds to FKBP12 but different effects
- Inhibits mammalian target of rapamycin (mTOR)
- Inhibits response to IL-2
- Cell cycle arrest at G1-S phase
How does Azathioprine (AZA) work?
- Guanine anti-metabolite (i.e. purine analogue)
- Rapidly converted into 6-mercaptopurine
- Impaired T cell DNA production
How does Mycophenolate mofetil work?
- Non-competitive inhibitor of IMPDH
- Prevents production of guanosine triphosphate
- Interferes with proliferation of T and B cells
What are the clinical uses of cytotoxic drugs?
- AZA/MMF
- Autoimmune diseases (SLE, vasulitis, IBD)
- Allograft rejection
- MTX
- RA, PsA, Polymyositis, vasculitis
- GvHD in BMT
- Cyclophosphamide
- Vasculitis (Wagner’s, CSS)
- SLE
