Immune Therapies Flashcards
What are the 7 classes of Immune therapies?
Anti- T cell monoclonal antibodies Anti Proliferative Agents Inhibitors of cell Signalling Corticosteroids Plasmapharesis Anti TNFalpha Monoclonal Antibodies Anti IL-12/23 Monoclonal Antibody
4 Examples of Anti T cell Monoclonal Antibodies
1) Muromonab-CD3
2) Basiliximab
3) Tocilizumab
4) Abatacept
What is the Method of action of Muromonab-CD3?
Blocks CD3 on T cells
What is Muromonab-CD3 used for?
For active rejection
What are the side effects of Muromonab-CD3?
Fever
Leucopenia
What is the method of action of Basiliximab?
Blocks CD25 (alpha chain of IL-2 Receptor)
What is Basiliximab used for?
Prevents rejection in Transplantation
What are the side effects of Basiliximab?
GI disturbances
What is the method of action of Tocilizumab?
Blocks IL-6 receptor
What is Tocilizumab used for?
Rheumatoid arthritis if Anti-TNF drugs have failed
What are the side effects of Tocilizumab?
Infections
What is the method of action of Abatacept?
Anti C TLA-4 Ig, Blocks Co stimulation of T cells
What is Abatacept used for?
Rheumatoid arthritis if Anti-TNF drugs have failed
What are the side effects of Abatacept?
Inections and cough
3 examples of Anti proliferative Agents?
1) Cyclophosphamide
2) Mycophenolate
3) Azathioprine
What is the method of action of Cyclophosphamide?
Alkylates guanine base of DNA. Affects B>T cells
What is Cyclophosphamide used for?
Muti-system connective tissue diseases (e.g. SLE) and Cancer
What are the side effects of Cyclophosphamide?
Hair Loss, Bone marrow suppression, Sterility, Haemorrhagic cystitis
What is the method of action of Mycophenolate?
Blocks de novo nucleotide synthesis. Affects T>B cells
What is Mycophenolate used for?
Autoimmune Disease, Vasculitis, Transplantation
What are the side effects of Mycophenolate?
Bone Marrow Suppression, Herpes
What is the method of action of Azathioprine?
Metabolised to 6-Mercaptopurine in the liver. Blocks de novo purine synthesis
What is Azathioprine used for?
Inflammatory and Autoimmune disease, Transplantation
What are the side effects of Azathioprine?
Bone Marrow Suppression (measure TPMT), Hepatotoxicity
Give 3 examples of immune Therapies that are ‘inhibitors of cell signalling’
1) Tacrolimus
2) Ciclosporin
3) Sirolimus
What is the method of action of Tacrolimus?
Inhibits Calcineurin which normally activated the transcription of IL-2 therefore decreased IL-2
What is Tacrolimus used for?
Mainly rejection prophylaxis in transplantation
What are the side effects of Tacrolimus?
Diabetes
What is the method of action of Ciclosporin?
Inhibits Calcineurin which normally activated the transcription of IL-2 therefore decreased IL-2
What is Ciclosporin used for?
Mainly rejection prophylaxis in transplantation
What are the side effects of Ciclosporin?
Gingival hypertrophy
What is the method of action of Sirolimus?
Blocks Clonal Proliferation
What is Sirolimus used for?
Mainly rejection prophylaxis in transplantation
What are the side effects of Sirolimus?
N/A
What is an example of a Corticosteroid?
Prednisolone
What is the method of action of Prednisolone?
Inhibits Phospholipase A2 causing a
- decrease in Platelet activating factors
- decreased Arachidonic Acid
- Decreased trafficking of phagocytes (hence transient increase in phagocyte count)
- Lymphopenia,
- Apoptosis of T+B cells
- Decreased Abs
What is Prednisolone used for?
used as anti-inflammatory and in autoimmune diseases
What are the side effects of Prednisolone?
Diabetes, Central obesity, Adrenal suppression, cataracts, glaucoma, Pancreatitis, osteoporosis, moon face, acne, hirtuism, neutrophilia.
What is Plasmapharesis?
Each time 50% of the patients plasma is replaces with a donors
What is Plasmapharesis used to treat?
Goodpastures, Myasthenia
Antibody mediated rejection
What are the side effects of Plasmapharesis?
Rebound antibody procution limits efficacy
What is an example of an Anti TNF alpha Monoclonal Antibody used for Immune Therapies?
Infliximab
What is an example of an Anti IL-12/23 Monoclonal Antibody used for Immune Therapies?
Ustekinumab
What is the method of action of Infliximab?
Binds to TNF alpha
What is the method of action of Ustekinumab?
Binds to p40 subunit of IL-12 and IL-23
What is Infliximab used to treat?
Psoraisis, Crohn’s, Rheumatoid Arthritis
What is Ustekinumab used to treat?
Psoriasis
What are the side effects of Infliximab?
TB, Lymphoma, Autoimmune phenomenon
What are the side effects of Ustekinumab?
Infections and cough
How does Rituximab work as a Immune Therapy?
Anti-CD20 and therefore decreased B cells (not plasma cells)
What is Rituximab used to treat?
Lymphoma and autoimmune diseases
How does Methotrexate work as an Immune Therapy?
Inhibits dihydrofolate reductase (DHFR) therefore decreases DNA synthesis
What is Methotrexate used to treat?
Autoimmune disorders e.g. RA, Psoriasis, Crohn’s
Chemotherapy and as an abortifacient
What are the side effects of Methotrexate?
Teratogenicity and hepatotoxicity
How does Alemtuzumab (campath) work as an Immune Therapy?
Monocolonal antibody that binds to CD52 found on lymphocytes resulting in depletion
What is Alemtuxumab used to treat?
CLL, MS
What are the side effects of Alemtuxumab?
Increased susceptibility to CMV infection
How does Natalizumab work as an Immune Therapy?
Anti alpha4 integrin
What is Natalizumab used to treat?
MS and Crohn’s
What is the Method for choosing an Immunosuppressive Regime to Suppress T-cells
Include on drug from each group
- Inhibitors of T cell signalling : Ciclosporin, Tacrolimus
- Anti Proliferative Agent : Azathioprine, Mycophenolate Mofetil, Methotrexate, Cyclophosphamide
- Blocker of Cytokine Production : Prednisolone
4 Methods to boost the immune system
vaccinations
Human Normal Immunoglobulin
Specific Immunoglobulin (passive vaccination)
Recombinant Cytokines
Human Normal Immunoglobulin as an Immune system Booster
From over 1000 donors (all screened for HIV and Hep b/c)
Contains preformed IgG vs full range of organisms
Given every 3-4 weeks, half life is 18days
Used for primary antibody deficiences (CVID, Brutons), secondary deficiencies (CLL and Multiple myeloma, BMT) and passive vaccination
What is Passive Vaccination (Specific Immunoglobulins) used for?
Rabies, Varicella Zoster, Hep B, Tetanus
Recombinant Cytokines as Immune system boosters, types and what they are used for.
Boosts immune response to cancer and some pathogens Interferon alpha - Hep B/C, Kaposi's Sacrcoma - Hairy cell leukaemia, chronic myelogenous leukaemia, malignant myeloma Interferon beta - Relapsing MS - Mechanism of action unknown Interferon gamma - Chronic granulomatous disease
Allergen Desensitization - how is it done?
Supervised administration of the allergen
Reduces clinical symptoms of mono allergic disorders
Good for - bee and wasp venom, grass pollen, house dust mites, NOT for food or latex
Given weekly, and then maintenance dose given monthly for 3-5 years
Costly, laborious and risk of seer adverse reaction
Only treatment that alters the natural course of the disease