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Clinical Pathology > Immunotherapeutics > Flashcards

Immunotherapeutics Flashcards

1
Q

Define immunomodulation

A

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

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2
Q

What may a therapeutic effect of immunomodulation lead to?

A
  • immunosuppression
  • immunopotentiation
  • induction of immunological tolerance
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3
Q

What are mechanisms of immumodulation?

A
  • Immunisation
  • Replacement therapy
  • Immune stimulants
  • Immune suppressants
  • Anti-inflammatory agents
  • Allergen immunotherapy (desensitisation)
  • Adoptive immunotherapy
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4
Q

What are biological immunomodulators?

A

Medicinal products produced using molecular biology techniques including recombinant DNA technology

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5
Q

What are the main classes of immunomodulators?

A
  • Substances (nearly) identical to the body’s own key signalling proteins
  • Fusion proteins
  • Monoclonal antibodies
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6
Q

What are ways to achieve immunopotentiation?

A
  • Immunisation (active/passive)
  • Replacement therapies
  • Immune stimulants
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7
Q

Describe passive immunisation

A
  • Transfer of specific, high-titre antibody from donor to recipient
  • Provides immediate but transient protection
  • Used for Hep B, Botulism, VZV, snake bites, diphtheria
  • Problems: serum sickness, risk of transmission of viruses
  • Types: Animal sera, pooled specific human immunoglobulin
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8
Q

Describe active immunisation

A
  • Stimulate development of a protective immune response & memory
  • Weakened/killed/inactivated pathogens
  • Purified materials (DNA, proteins)
  • Adjuvants
  • Problems: allergy to vaccine, delay in achieving protection, limited usefulness in immunocompromised
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9
Q

What are replacement therapies?

A
  • Pooled human immunoglobulin
  • G-CSF/GM-CSF
  • IL-2
  • α-interferon
  • β-interferon
  • γ-interferon
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10
Q

How can immunosuppression be achieved?

A
  • Corticosteroids
  • Cytotoxic/agents
  • Anti-proliferative/activation agents
  • DMARDs
  • Biologic DMARDs
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11
Q

How do corticosteroids work?

A
  • Decreased neutrophil margination
  • Reduced production of inflammation cytokines
  • Inhibition phospholipase A2
  • Lymphopenia
  • Decreased T cell proliferation
  • Reduced immunoglobulins production
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12
Q

What are the side effects of corticosteroids?

A
  • Carbohydrate and lipid metabolism (diabetes, hyperlipidaemia)
  • Reduced protein synthesis (poor wound healing)
  • Osteoporosis
  • Glaucoma & cataracts
  • Psychiatric complications
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13
Q

What are the uses of corticosteroids?

A
  • Autoimmune diseases (CTD, RA, vasculitis)
  • Inflammatory diseases (Crohn’s, sarcoid, GCA)
  • Malignancies (lymphoma)
  • Allograft rejection
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14
Q

What drugs are used to target lymphocytes?

A
  • Antimetabolites (Azathioprine)
  • Calcineurin inhibitors (Ciclosporin A)
  • M-TOR
  • IL-2 receptor mABs
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15
Q

Describe Calcineurin inhibitors

A
  • CyA=Binds to intracellular protein cyclophilin
  • Tacrolimus=Binds to intracellular protein FKBP-12
  • Prevents activation of NFAT
  • Factors which stimulate cytokines gene transcription
  • Reversible inhibition of T-cell activation, proliferation & clonal expansion
  • Transplantation (allograft rejection), autoimmune diseases
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16
Q

Describe Sirolimus

A
  • AKA rapamycin
  • Inhibits response to IL-2
  • Cell cycle arrest at G1-S phase
  • Macrolide antibiotic also binds to FKBP12 but different effects, inhibits mammalian target of rapamycin
17
Q

What are the side effects of Calcineurin/mTOR

A
  • Hypertension
  • Hirsutism
  • Nephrotoxicity
  • Hepatotoxicity
  • Lymphomas
  • Opportunistic infections
  • Neurotoxicity
  • Multiple drug interactions (induce P450)
18
Q

Describe antimetabolites

A
  • Inhibit nucleotide (purine) synthesis
  • AZA= Guanine anti-metabolite, rapidly converted to 6-mercaptopurine
  • MMF= non-competitive inhibitors of IMPDH, prevents production of guanosine triphosphate
  • Impaired DNA production, prevents early stages of activated cells proliferation in T & B cells
19
Q

What are other antimetabolites & cytotoxic drugs?

A
  • Methotrexate= folate antagonist

- Cyclophosphamdie=cross-link DNA

20
Q

What are the side effects of cytotoxics?

A
  • Bone marrow suppression
  • Gastric upset
  • Hepatits
  • Susceptibility to infections
  • MTX= pneumonitis
  • Cyclophosphamide= Cystitis
21
Q

What are the clinical uses of cytotoxic?

A
  • AZA/MMF= autoimmune diseases, allograft rejetion
  • MTX= Polymyositis, vasculitis, RA, PsA, GvHD in BMT
  • Cyclophosphamide= SLE, vasculitis
22
Q

What are biologic DMARD’s

A
  • Anti-cytokines (TNF, IL-6, IL-1)
  • Anti-B cell therapies
  • Anti-T cell activation
  • Anti-adhesion molecules
  • Complement inhibitors
23
Q

Describe anti-cytokines

A
  • Anti-TNF= inc risk of TBused in inflammatory conditions- RA, Crohn’s, ankylosing spondylitis, psoriasis
  • Anti-IL-6= Blocks IL-6 receptors, used in RA & AOSD therapy, may cause problems with control of serum lipids
  • Anti-IL-1= used in treatment of AOSD 7 auto inflammatory syndromes
24
Q

Describe Rituximab

A
  • Chimeric mAb against CD20 B cell surface
  • Autoimmune disorders, transplant rejection, lymphomas, leukaemias
  • Treatment of chemotherapy resistant DLCL
25
Q

What are the uses of adoptive immunotherapy?

A
  • Immunodeficiencies (SCID)
  • Lymphomas & leukaemias
  • Autoimmune diseases
  • Inherited metabolic disorders (osteopetrosis)
26
Q

What are types of adoptive immunotherapy?

A
  • Bone marrow transplant

- Stem cell transplant

27
Q

What immunomodulators can be used in allergies?

A
  • Immune suppressants
  • Allergen specific immunotherapy
  • Anti-IgE monoclonal therapy
  • Anti-IL-5 monoclonal treatment
28
Q

What are the indications, side-effects, routes and mechanism for allergen specific immunotherapy?

A
  • M= Switching of immune response from Th2 to Th1
  • S= localised & systemic allergic reactions
  • R= SC/sublingual for aero-allergens
  • I=allergic rhinoconjutivitits not controlled on max medical therapy, anaphylaxis to insect venoms
29
Q

Describe Omalizumab

A
  • mAb against IgE
  • May cause severe systemic anaphylaxis
  • Used in asthma & chronic urticaria & angioedema
30
Q

Describe Mepolizumab

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

Clinical Pathology (56 decks)

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