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
Main classes of immunomodulators
- Monoclonal antibodies
- Fusion proteins
- Substances nearly identical to body proteins
What is immunopotentiation
Strengthening of the immune system:
- Immunisation
- Replacement therapies
- Immune stimulants
Passive immunisation
- Transfer of specific antibodies
- Risk of transmission of virus
Types of passive immunisation
- Convalescent plasma
- Pooled specific human immunoglobulin
- Animal sera
Active immunisation
To stimulate the development of a protective immune response and immunological memory
What is immunogenic material
- Weakened forms of pathogens
- Killed/inactivated pathogens
- Purified materials
- Adjuvants
Problems with secondary immunisation
- Allergy to vaccine
- no useful if immunocompromised
- Delay in achieving protection
Replacement therapies and immune stimulants for immunocompromised
- Pooled human immunoglobulin used in treatment of antibody deficiency states
- G-CSF/GM-CSF - increase production of mature neutrophils
Cytokines - immune stimulants
- IL-2 - stimulates T cell activation
- α-interferon - Hep C
- β-interferon - therapy of MS
- γ-interferon - chronic granulomatous disease
Immunosuppression methods
- Corticosteroids
- Cytotoxic agents
- DMARD’s
- Anti-proliferative/activation agents
Corticosteroids action
- Decreased neutrophil margination
- Reduced production of inflammatory cytokines
- Decrease T cell proliferation
- Inhibition phospholipase A2 released
Corticosteroids side effects
- Carbohydrate and lipid metabolism - Diabetes
- Reduced protein synthesis = poor wound healing
- Osteoporosis
- Glaucoma + cataracts
Corticosteroid uses
- Autoimmune disease
- Inflammatory diseases
- Malignancies
- Allograft rejection
Drugs targeting lymphocytes and the immune response
- Antimetabolites
- Calcineurin inhibitors
- M-TOR inhibitors
- IL-2 receptor mAB’s
Calcineurin inhibitors
- CyA - binds to intracellular protein cyclophilin
- Tacrolimus - binds to intracellular protein
- Prevents action of NFAT, less cytokine stimulation
Sirolimus (rapamycin) - M-TOR inhibitor
- A macrolide antibiotic
- Inhibits mammalian target of rapamycin
- Inhibits response to IL-2
- T cell cycle stops at G1-s phase
Calcineurin/mTOR side effects
- Hypertension
- Nephrotoxicity
- Hepatotoxicity
- Lymphomas
- Neurotoxicity
Antimetabolites
Inhibit purine synthesis
- Azathioprine - guanine metabolite
- Mycophenolate mofetil - prevents production of guanosine triphosphate
Cytotoxic drug effects
- Bone marrow suppression
- Gastric upset
- Hepatitis
- Susceptible to infections
AZA/MMF clinical uses
Autoimmune diseases - SLE, vasculitis
MTX clinical uses
RA, vasculitis, Polymyositis
Anti-cytokines
- Anti-TNF - used in therapy of RA - other inflammatory conditions
- Anti Il6 - blocks IL6 receptor
- Anti Il1 - used for autoinflammatory syndromes
Rituximab
Monoclonal antibody that acts on protein in B cell surface - used for lymphomas and transplant rejection
Adoptive immunotherapy
- Bone marrow transplant
- Stem cell transplant
Immunomodulators: Allergy
- Immune suppressants
- Allergen specific immunotherapy
- Anti-IgE monoclonal therapy
- Anti IL5 monoclonal treatments
Mechanism of allergen specific immunotherapy
Switching of immune response from TH2 (allergic) to TH1 (non-allergic)
Routes of allergen immunotherapy
sublingual
aero-allergens
Omalizumab
Antibody against IgE
- Used in reaction of asthma
- can cause severe systemic anaphylaxis
Mepolizumab
Antibody against IL-5
- Prevents eosinophil recruitment and activation
