Immune Therapies Flashcards by Daniel Hunt

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

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4 Examples of Anti T cell Monoclonal Antibodies

1) Muromonab-CD3
2) Basiliximab
3) Tocilizumab
4) Abatacept

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What is the Method of action of Muromonab-CD3?

Blocks CD3 on T cells

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What is Muromonab-CD3 used for?

For active rejection

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What are the side effects of Muromonab-CD3?

Fever

Leucopenia

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What is the method of action of Basiliximab?

Blocks CD25 (alpha chain of IL-2 Receptor)

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What is Basiliximab used for?

Prevents rejection in Transplantation

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What are the side effects of Basiliximab?

GI disturbances

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What is the method of action of Tocilizumab?

Blocks IL-6 receptor

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What is Tocilizumab used for?

Rheumatoid arthritis if Anti-TNF drugs have failed

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What are the side effects of Tocilizumab?

Infections

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What is the method of action of Abatacept?

Anti C TLA-4 Ig, Blocks Co stimulation of T cells

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What is Abatacept used for?

Rheumatoid arthritis if Anti-TNF drugs have failed

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What are the side effects of Abatacept?

Inections and cough

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3 examples of Anti proliferative Agents?

1) Cyclophosphamide
2) Mycophenolate
3) Azathioprine

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What is the method of action of Cyclophosphamide?

Alkylates guanine base of DNA. Affects B>T cells

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What is Cyclophosphamide used for?

Muti-system connective tissue diseases (e.g. SLE) and Cancer

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What are the side effects of Cyclophosphamide?

Hair Loss, Bone marrow suppression, Sterility, Haemorrhagic cystitis

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What is the method of action of Mycophenolate?

Blocks de novo nucleotide synthesis. Affects T>B cells

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What is Mycophenolate used for?

Autoimmune Disease, Vasculitis, Transplantation

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What are the side effects of Mycophenolate?

Bone Marrow Suppression, Herpes

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What is the method of action of Azathioprine?

Metabolised to 6-Mercaptopurine in the liver. Blocks de novo purine synthesis

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What is Azathioprine used for?

Inflammatory and Autoimmune disease, Transplantation

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What are the side effects of Azathioprine?

Bone Marrow Suppression (measure TPMT), Hepatotoxicity

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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