Immunomodulation and Immunotherapy L12 Flashcards
Describe HPV and its vaccine.
- Human papillomaviruses (HPV) is a sexually transmitted infection that invades epithelial cells
- There are at least 120 types of HPV and of these 18 are associated with cervical cancer. HPV16 and 18 cause 70% of cervical cancer
- HPV 6 and 11 cause 90% of cases of genital warts
- Merck and Co, Inc have developed a new vaccine against HPV 6, 11, 16 and 18 (Gardasil) which has been licensed in the UK. As do GSK
Describe DNA free virus like particles (VLP).
- DNA free virus like particles (VLP) have been manufactured in Saccharomyces cervisiae.
- These VLP express the major capsid antigen (L1) of HPV and induce a strong immune response.
- The neutralizing antibodies produced prevent infection of cells by HPV.
What are adjuvants?
- Adjuvants are inorganic or organic chemicals, macromolecules or entire cells of killed bacteria that can increase the immune response.
- They may be included in a vaccine to enhance the recipients immune response to the antigen or may be used in the production of antibodies from animals.
Describe the mechanisms of action of adjuvants.
a) Depot effect:
- soluble proteins converted to an insoluble form
- slower release of antigen
- more easily ingested and presented by APC
b) inducing inflammation (“danger” signal)
- additional microbial products induce co-stimulator molecules
c) Acting as a stabalizing agent
In adjuvants, the antigen is dispersed in ___1___ or adsorbed on ___2___ for slow release.
- Oil
2. Alum
Describe desensitization therapy in allergy.
- Only treatment that ‘cures’ allergies (Discovered 1911).
- Patients are given weekly injections with increasing doses aqueous allergen over 14-18 weeks. Once on a maintenance dose, intervals between injections are spaced out to 4-6 weeks for 3 years.
- Used in patients with anaphylactic responses to insect venoms, and rhinoconjunctivitis not controlled by oral steroids. Asthma may be amenable for treatment but carries a high risk.
- Mode of action is unknown
What are cytokines?
- Biological response modifiers secreted by a range of cells
- Multiple and diverse effects on immune function
- May feature in disease processes
- Cytokines or their antagonists can be used therapeutically
Include interleukins, interferons, colony-stimulating factors (CSF), others (TNF-alpha, TGF-beta etc)
What is Interferon alpha used to treat?
- Viral hepatitis
- Basal cell carcinoma
- External genital warts
- Wide range of lymphoma and leukemias
- Useful in treating some non-viral cancers (melanoma)
In cytokine therapy; what does IL2 do?
Stimulates T cells to divide.
In cytokine therapy; what does IL7 do?
Stimulates production of CD4 cells and B cells.
In cytokine therapy; what does IL15 do?
Preferentially stimulates the production of CD8 cells.
In cytokine therapy; what does IL1 do?
Binds to the receptor IL-1R as an antagonist.
Describe Antibody-based immunotherapies.
- For diseases affecting the immune system and for other types of disease e.g. cancers, allergies
- Antibodies to cell surface molecules may be used to interfere with molecular function or to kill cells
- Antibodies to cytokines, growth factors or antibodies may be used to prevent these molecules having their biological effect
- Used alone or in combination with other therapies
What is the side effect of anti-TNFalpha therapies?
Increased risk of infection, especially TB.
In antibody-based immunotherapies; what does anti-IgE do?
Used in allergic disease (particularly asthma but may be used in the treatment of allergic eczema).