Immunotherapeutics Flashcards by Gemma Whyatt

Define immunomodulation

The act of manipulating the immune system using immunomodulatory drugs to achieve a desired immune response.

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What are some possible effects of immunomodulation?

A therapeutic effect of immunomodulation may lead to immunopotentiation, immunosuppression, or induction of immunological tolerance.

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What are some mechanisms of immunomodulation?

Immunization
Replacement therapy
Immune stimulants
Immune suppressants
Anti-inflammatory agents
Allergen immunotherapy (desentization)
Adoptive immunotherapy

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What are biologics- immunomodulators?

Medicinal products produced using molecular biology techniques including recombinant DNA technology

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What are the main classes of immunomodulators?

Substances that are (nearly) identical to the body’s own key signaling proteins
Monoclonal antibodies
Fusion proteins

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What is immunopotentiation?

Immunization
Active 
Passive
Replacement therapies
Immune stimulants

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What is passive immunisation?

transfer of specific, high-titre antibody from donor to recipient. Provides immediate but transient protection

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What are the risks of passive immunisation?

Risk of transmission of viruses

Serum sickness

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What are the types of passive immunisation?

Pooled specific human immunoglobulin
Animal sera (antitoxins an antivenins)

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What are the uses of passive immunisation?

Hep B prophylaxis and treatment

Botulism, VZV (pregnancy), diphtheria, snake bites

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Define active immunisation

To stimulate the development of a protective immune response and immunological memory

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What is immunogenic material?

Weakened forms of pathogens
Killed inactivated pathogens
Purified materials (proteins, DNA)
Adjuvants

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What are the problems with active immunisation

Allergy to any vaccine component
Limited usefulness in immunocompromised
Delay in achieving protection

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What does G-CSF/GM-CSF

do?

Acts on bone marrow to increase production of mature neutrophils

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What is α-interferon used for?

treatment of Hepatitis C

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What is β-interferon used for?

therapy of MS

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What is γ-interferon used for?

treatment of certain intracellular infections (atypical mycobacteria), also used in chronic granulomatous disease and IL-12 deficiency

What drugs cause immunosuppression?

Cortocosteroids
Cytotoxic/ agents
Anti-proliferative/activation  agents
DMARD’s
Biologic DMARD’s

What is the action of corticosteroids?

Decreased neutrophil margination
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 for?

Autoimmune diseases 
CTD, vasculitis, RA
Inflammatory diseases
Crohn’s, sarcoid, GCA/polymyalgia rheumatica
Malignancies
Lymphoma
Allograft rejection

What drugs target lymphocytes?

Antimetabolites

Azathioprine (AZA)
Mycophenolate mofetil (MMF)

Calcineurin inhibitors

Ciclosporin A (CyA)
Tacrolimus (FK506)

M-TOR inhibitors
- Sirolimus

IL-2 receptor mABs

Basiliximab
Daclizumab

How do caclineurin inhibitors work?

Prevents activation of NFAT

Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription

causing reversible inhibition of T-cell activation, proliferation and clonal expansion

How does sirolimus work?

Inhibits response to IL-2, causing cell cycle arrest at G1-S phase

What are the side effects of calcineurin?

``` Hypertension Hirsutism Nephrotoxicity Hepatotoxicity Lymphomas Opportunistic infections Neurotoxicity Multiple drug interactions (induce P450) ```

What are calcineurins used for?

Transplantation - Allograft rejection Autoimmune diseases

What do antimetabolites do?

Inhibit nucleotide (purine) synthesis, causing impaired DNA production which prevents the early stages of activated cells proliferation

What are the side effects of cytotoxics?

``` ALL Bone marrow suppression Gastric upset Hepatitis Susceptibility to infections Cylophosphamide Cystatis MTX pneumonitis ```

What are the clinical uses of cytotoxic drugs?

--AZA/MMF-- Autoimmune diseases (SLE, vasulitis, IBD) Allograft rejection --MTX-- RA, PsA, Polymyositis, vasculitis GvHD in BMT --Cyclophosphamide-- Vasculitis (Wagner’s, CSS) SLE

What are biologic DMARD's?

``` Anti-cytokines (TNF, IL-6 and IL-1) Anti-B cell therapies Anti-T cell activation Anti-adhesion molecules Complement inhibitors ```

What is anti-TNF?

anti-cytokine First biologics to be successfully used in therapy of RA (5 different agents now licensed) Used in a number of other inflammatory conditions (Crohn’s, psoriasis, ankylosing spondylitis) Caution: increase risk of TB

What is Anti-IL-6 (Tocilizumab)?

anti-cytokine Blocks IL-6 receptor Used in therapy of RA and AOSD May cause problems with control of serum lipids

What is Anti-IL-1?

anti-cytokine 3 different agents available (anakinra, rilonacept and canakinumab) Used in treatment of AOSD and autoinflammatory syndromes

What is rituximab?

Chimeric mAb against CD20- B cell surface Many uses: Lymphomas, leukaemias Transplant rejection Autoimmune disorders

What is adoptive immunotherapy?

Bone marrow transplant (BMT) Stem cell transplant (SCT) Uses - Immunodeficiencies (SCID) - Lymphomas and leukemias - Inherited metabolic disorders (osteopetrosis) - Autoimmune diseases

What immunomodulators are used in allergy?

Immune suppressants Allergen specific immunotherapy Anti-IgE monoclonal therapy Anti-IL-5 monoclonal treatment

What are the indications of allergen specific immunotherapy?

Allergic rhinoconjutivitis not controlled on maximum medical therapy Anaphylaxis to insect venoms

What are the mechanisms of allergen specific immunotherapy?

Switching of immune response from Th2 (allergic) to Th1 (non-allergic) Development of T reg cells and tolerance

What is omalizumab?

mAb against IgE Used in Rx of asthma Also useful in Rx of chronic urticaria and angioedema May cause severe systemic anaphylaxis

What is Mepolizumab?

mAb against IL-5 Prevents eosinophil recruitment and activation Limited effect on asthma No clinical efficacy in hypereosinophilic syndrome