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Immunotherapy

Prof Anura Weerasinghe

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Objectives What is immunotherapy? When is it used? Different strategies of immunomodulation

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Immunotherapy

Mode of therapy by which immune systemis mobilized or inhibited.

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When is it used? Immunization Allergic diseases Autoimmune diseases Cancers Immunodeficiency

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Immune response to immunization

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The aim of immunotherapy inallergy and autoimmunity is to

inhibit the immune response. Achieved by

- attempting to re-establish lymphocytenon-responsiveness (tolerance)- boosting suppressive mechanisms

eg; Regulatory T cells (T Reg cells)

- diverting the immune response to lessdamaging pathways

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Allergen desensitization Involves repeated injections of allergens Employed in

severe allergic rhinoconjunctivitis

Anaphylaxis to bee and wasp venom Allergic asthma

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Immunomodulatory therapy Corticosteroids Immunosuppressive drugs Cytokines

Monoclonal antibodies NSAIDs Antiallergic drugs

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Mechanisms of action ofcorticosteroids

Prevent the production of essentialcytokines and chemokines

Reduce lymphocyte activation andproliferation by preventing

Reduce inflammation through action onmacrophages and neutrophils

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Other immunosuppressive drugs Methotrexate Azathioprine Cyclosphorin Cyclophosphamide

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Cytokines Colony-stimulating factors

In Cytopenia associated with chemotherapyfor cancers

-interferon In viral hepatitis

IL-2 In renal cancers

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Monoclonal antibodies

Inhibit the effect of TNF- ( Eg; infliximab& etanercept) In Crohns and rheumatoid arthritis

Against B cell marker (CD20)(Eg; Rituximab)

In Lymphoma

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Anitinflammatory therapy

Corticosteroids Non-steroidal anti-inflammatory drugs

Side-effects of corticosteroids Alter fat and glucose metabolism Adrenal suppression

OsteoporosisHypertension

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NSAIDs Inhibit enzyme cyclo-oxygenase (COX)

and prevent synthesis of prostaglandins COX -1- gastric protection

COX -2 enzyme in macrophages Aspirin non-selective inhibitor Celecoxib Selective inhibitor of COX-2

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Other anti-inflammatory drugs Interfere with leukotrienes

Blocks production by the inhibition of lipo-oxygenase (Eg; Zileuton)

Leukotriene receptor blockers

(Eg; monteleukast and Zafirlukast)

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Antiallergic drugs Antihistamines

H1-histamine receptors on blood vessels andsmooth muscles

Sedative eg; Chlorphenaramine

Non-sedative eg; Cetrizine & fexofenadine H2-histamine receptors found mainly in

stomach (H2 blocker ranitidine)

Mast cell stabilizers Sodium chromoglycate

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