Flashcards in Immunomodulation Deck (29):
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?
- 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?
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)
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)
- Decreased T cells proliferation
- Reduced immunoglobulins production
What are the side-effects of corticosteroids?
- Carbohydrate and lipid metabolism
- Reduced protein synthesis
- Poor wound healing
- Glaucoma and cataracts
- Psychiatric complications
What are the uses of corticosteroids?
- Autoimmune diseases
- CTD, vasculitis, RA
- Inflammatory diseases
- Crohn’s, sarcoid, GCA/polymyalgia rheumatica
- 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?
- Autoimmune diseases (SLE, vasulitis, IBD)
- Allograft rejection
- RA, PsA, Polymyositis, vasculitis
- GvHD in BMT
- Vasculitis (Wagner’s, CSS)
What are the features of anti-TNF drugs?
- First biologics to be successfully used in therapy of RA (5 different agents now licensed)
- Used in a number of other inflammatory conditions (Crohn’s, psoriasis, ankylosing spondylitis)
- Caution: increase risk of TB
What are the features of IL-6 drugs?
- Blocks IL-6 receptor
- Used in therapy of RA and AOSD
- May cause problems with control of serum lipids
What is rituximab?
- Chimeric mAb against CD20- B cell surface
- Can get rid of B cell producing autoreactive antibodies
- Used in:
- Lymphomas, leukaemias
- Transplant rejection
- Autoimmune disorders
What are the indications for allergen-specific immunotherapy?
- Allergic rhinoconjutivitis not controlled on maximum medical therapy
- Anaphylaxis to insect venoms