Immunomodulation and Immunosuppression Flashcards
What is immunomodulation?
The act of manipulating the immune system using immunomodulatory drugs to achieve a desired immune response.
A therapeutic effect of immunomodulation may lead to immunopotentiation, immunosuppression, or induction of immunological tolerance.
What are immunomodulators?
Medicinal products produced using molecular biology techniques including recombinant DNA technology
What are the main classes of immunomodulators?
- Substances that are (nearly) identical to the body’s own key signaling proteins
- Monoclonal antibodies
- Fusion proteins
Example of Human IgG1 monoclonal Ab –> Adalimumab
What is a chimeric antibody?
Chimeric antibodies are structural chimeras made by fusing variable regions from one species like a mouse, with the constant regions from another species such as a human being.
Define immunopotentiation?
Enhancement of immune responses.
3 examples of immunopotentiation?
- Immunisation (Active, Passive)
- Replacement therapies
- Immune stimulants
What is passive immunisation?
Transfer of specific, high-titre antibody (pre-formed antibodies) from donor to recipient. Provides immediate but transient protection.
Problems with passive immunisation?
- Transient protection
- Risk of transmission of viruses
- Serum sickness
3 types of passive immunisation?
- Convalescent plasma
- Pooled specific human immunoglobulin
- Animal sera (antitoxins an antivenins)
What is convalescent plasma?
Convalescent plasma is the antibody-rich plasma of someone who has recovered from an illness
What diseases is passive immunisation used in?
- COVID19, Hep B prophylaxis and treatment
- Botulism, VZV (pregnancy), diphtheria, snake bites
What is active immunisation?
To stimulate the development of a protective immune response and immunological memory
What material is involved in active immunisation?
- Weakened forms of pathogens
- Killed inactivated pathogens
- Purified materials (proteins, DNA, RNA)
- Adjuvants
Problems with active immunisation?
- Allergy to any vaccine component
- Limited usefulness in immunocompromised
- Delay in achieving protection
What is pooled human immunoglobulin? What is it used to treat?
Intravenous immunoglobulin (IVIG) contains the pooled immunoglobulin G (IgG) immunoglobulins from the plasma of approximately a thousand or more blood donors.
IVIGs are sterile, purified IgG products manufactured from pooled human plasma and typically contain more than 95% unmodified IgG, which has intact Fc-dependent effector functions and only trace amounts of immunoglobulin A (IgA) or immunoglobulin M (IgM).
Used to treat antibody deficiency states
What is G-CSF/GM-CSF? When would it be used?
A glycoprotein that acts on bone marrow to increase the production of mature neutrophils.
You might have G-CSF after chemotherapy to help your white blood cells recover after treatment.
What is IFN-γ?
IFN-γ is a cytokine critical to both innate and adaptive immunity, and functions as the primary activator of macrophages, in addition to stimulating natural killer cells and neutrophils.
What is IFN-γ used to treat?
Can be useful in treatment of certain intracellular infections (atypical mycobacteria), also used in chronic granulomatous disease and IL-12 deficiency
What drugs are used for immunosuppression?
- Corticosteroids
- Cytotoxic/ agents
- Anti-proliferative/activation agents
- DMARD’s
- Biological-DMARD’s
How do corticosteroids provide immunosuppression?
- Decreased neutrophil margination (Margination refers to the prolonged transit of neutrophils through specific organs)
- 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 corticosteroids used to treat?
- Autoimmune diseases
- CTD, vasculitis, RA
- Inflammatory diseases
- Crohn’s, sarcoid, GCA/polymyalgia rheumatica
- Malignancies
- Lymphoma
- Allograft rejection