Immunotherapeutics Flashcards
define immunomodulation
The act of manipulating the immune system using immunomodulatory drugs to achieve a desired immune response.
what mechanisms can be used for immunomodulation
- Immunization
- Replacement therapy
- Immune stimulants
- Immune suppressants
- Anti-inflammatory agents
- Allergen immunotherapy (desentization)
- Adoptive immunotherapy
define immunomodulators.
medicinal products produced using molecular biology techniques including recombinant DNA technology, in order to modular the immune system,
What are the main classes of immunomodulators.
Monoclonal antibodies- made using specific technology and they target specific cell types.
fusion proteins- 2 proteins with different biological function.
Substances that are identical to body’s own signalling problems.
Give a example of an immunomodulator
TNF
define immunopotentiation
to encourage a immune response by administration of another product.
how is immunopotentiation carried out
immunisation
replacement therapies
immune stimulanats
define passive immunity
transfer of specific, high-titre antibody from donor to recipient. Provides immediate but transient protection
problems with passive immunity
Risk of transmission of viruses- as it is a blood product
Serum sickness- increased immunoglobulin, forms complex and activates complement.
uses of passive immunisation
Hep B prophylaxis and treatment
Botulism, VZV (pregnancy), diphtheria, snake bites
define active immunity
To stimulate the development of a protective immune response and immunological memory
what kinds of immune material are used in an active immunisation
weakened forms of the pathogen
killed inactivated pathogens
purified materials
components vaccines- e.g. bacterial cell wall.
adjuvants (substance added to vaccine to increase body’s immune response to it)
problems with active immunity
allergy to vaccine component
delay in protection
limited usefulness in the immunocompromised.
how is replacement therapy carried out
• Pooled human immunoglobulin (IV or SC)- plasma form lots of donors and therefore has lots of antibodies
how does immune stimulation take place (examples)
- G-CSF/GM-CSF – colony stimulating factor (specific to certain cells). Act on bone marrow to increase production of mature neutrophils.
- IL-2 (Stimulates T cell activation- rarely used).
- α-interferon (Main use in treatment of Hep C)
- β-interferon (Used in therapy of MS)
Names of drugs or molecules used in immunosuppression
- Cortocosteroids- majority
- Cytotoxic/ agents
- Anti-proliferative/activation agents
- DMARD’s
- Biologic DMARD’s
How do corticosteroids work
- Decreased neutrophil margination- so they don’t enter the tissue.
- Reduced production of inflammatory cytokines
- Inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
- Lymphopenia
- Decreased T cells proliferation- increased doses toxic to T cells
- Reduced immunoglobulins production – make T cells less likely to respond to proliferation.
main side effects of corticosteroids.
• Carbohydrate and lipid metabolism – Diabetes – Hyperlipidaemia • Reduced protein synthesis – Poor wound healing • Osteoporosis • Glaucoma and cataracts • Psychiatric complications
Uses of corticosteorids.
• Autoimmune diseases
– CTD, vasculitis, RA
– Used as induction agent- short term and long term in a cocktail of drugs.
• Inflammatory diseases
– Crohn’s, sarcoid, GCA/polymyalgia rheumatica
• Malignancies
– Lymphoma- corticosteroid toxic to T or B cell so can treat B/T cell lymphoma.
• Allograft rejection – transplantation
Name the drugs used in T cel targeted immunosuppression
Anti-IL-2 receptor mAbs, CyA, Tacrolimus, Sirolimus, Azathioprine MMF.
What types of drugs target lymphocytes
Antimetabolites- Azathioprine, MMF Calcineurin inhibitors (Ciclosporin A, tACROLIMUS M-TOR inhibitors- sirolimus IL2 receptor mABs- Basilximab Daclizumab
What is the function of calcineurin inhibitors
prevent T cell activation
interfere with initial signals after T cell receptor activation
mode of action of CyA and effect on T cell
– 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
mode of action tacrolimus and effect on T cell
– Binds to intracellular protein FKBP-12.
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
