Theme 2 Lecture 10: Immunomodulation and Immunosuppression Flashcards
What is immunomodulation?
-the act of manipulating the immune system using immunomodulatory drugs to achieve a desired immune response
What are immunomodulators?
medicinal products produced using molecular biology techniques including recombinant DNA technology
What are the 3 main classes of immunomodulators?
- substances that are (nearly) identical to the body’s own key signalling proteins
- monoclonal antibodies
- fusion proteins
What are 4 examples of immunomodulators?
- adalimumab
- infliximab
- etabercept
- cetrolizumab
Which cytokine to immunomodulators target?
TNF
What is immunopotentiation?
enhancement of the immune response by increasing the speed and extent of its development and by prolonging its duration
What is passive immunisation?
- the transfer of specific, high-titre antibody from donor to recipient
- provides immediate but transient protection
What are the problems of immunisation?
- risk of transmission of viruses
- serum sickness (type 3 hypersensitivity)
In what situations do we use immunisation?
- COVID-19
- HepB prophylaxis and treatment
- botulism
- diptheria
- snake bites
What is active immunisation?
to stimulate the development of a protective immune response and immunological memory
What are the 4 types of immunogenic material?
- weakened forms of pathogen
- killed inactivated pathogens
- purified materials (proteins, DNA, RNA)
- adjuvants
What are adjuvants?
chemicals that can stimulate a particular type of immune response
What are the problems with active immunisation?
- allergy to any vaccine component
- limited usefulness in immunocompromised
- delay in achieving protection
What are 3 examples of replacement therapies and immune stimulation?
- pooled human immunoglobulin
- G-CSF/ GM-CSF - act on bone marrow to increase production of mature neutrophils
- Y-interferon - used in CGD
Explain the action of corticosteroids
- immunosuppressive agent
- decreased neutrophil margination
- reduced production of inflammatory cytokines
- inhibition phospholipase A2
- lymphopenia
- decreased T cell proliferation
- reduced immunoglobulins production
What are the side effects of corticosteroids?
- carbohydrate and lipid metabolism - diabetes and hyperlipidaemia
- reduced protein synthesis - poor wound healing
- osteoporosis
- glaucoma and cataracts
- psychiatric complications
What are all the uses of corticosteroids?
- autoimmune diseases - CGD, RA, vasculitis
- inflammatory diseases - chron’s, sarcoid
- malignancies - lymphoma
- allograft rejection (prevention)
What are the 4 main categories of drugs that target lymphocytes and give an example of each?
- antimetabolites
- azathioprine (AZA)
- prevent T cell proliferation - calcineurin inhibitors
- ciclosporin A - M-TOR inhibitors
- sirolimus inhibits T cell activation - IL-2 receptor mABs
- basiliximab
How do calcineurin inhibitors work?
- CyA - bind to intracellular protein cyclophillin
- prevents activation of NFAT and therefore T cell stimulation
- reversible inhibition of T cell activation, proliferation and clonal expansion
What are the potential side effects of calcineurin?
- hypertension
- hirsutism
- nephrotoxicity
- hepatotoxicity
- lymphomas
- opportunistic infections
- neurotoxicity
What is the mode of action of sirolimus?
- inhibits response of IL-2
- cell cycle arrest at G1-S phase
What is the clinical use of calcineurin?
- transplantation - allograft rejection
- autoimmune disease
How do antimetabolites work?
- inhibit nucleotide (purine) synthesis
- azathioprine is a guanine anti-metabolite
- T and B cell effects - impaired NDA production, prevents early stages of activated cells proliferation
What is methotrexate?
folate antagonist
What are the side effects of cytotoxic drugs in general?
- target all dividing cells
- bone marrow suppression
- gastric upset
- hepatits
- susceptibility to infections
- cystitis (cylophosphamide)
- pneumonitis (methotrexate)
What is an allograft?
transplant of an organ from one individual to another of the same species with a different genotype
What is cyclophosphamide used to treat?
- vasculitis (Wagner’s, CSS)
- SLE
What do anti adhesion molecules do?
prevent migration of immune cells to sites of disease
What is Anti IL-6 and what is it used for?
- blocks IL-6 receptor
- used in therapy of RA and AOSD (rare form of arthiritis)
What is the risk of anti-TNF?
Increased risk of Tb
What is rituximab?
-chimeric (part mouse part human) mAb against CD20-B cell surface
What are the uses of rituximab?
- lymphomas, leukaemias
- transplant rejection
- autoimmune disorders
What is adoptive immunotherapy and when is it used?
- bone marrow transplant
- stem cell transplant
- essentially replace the immune system with a functioning one
- uses: immunodeficiencies (SCID), lymphomas and leukaemias, autoimmune diseases
Which classes of drugs can be used for treatment of allergies?
- immune suppressants
- allergen specific immunotherapy
- anti-IgE monoclonal therapy
- anti-IL-5 monoclonal treatment
What is omalizumab?
- mAB against IgE
- used in asthma
- chronic urticaria and angioedema
- may cause severe systemic anaphylaxis
