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Clinical Pathology G > Immunotherapeutics > Flashcards

Immunotherapeutics Flashcards

1
Q

Define immunomodulation

A

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

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2
Q

What are some possible effects of immunomodulation?

A

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

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3
Q

What are some mechanisms of immunomodulation?

A 
Immunization
Replacement therapy
Immune stimulants
Immune suppressants
Anti-inflammatory agents
Allergen immunotherapy (desentization)
Adoptive immunotherapy
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4
Q

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

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6
Q

What is immunopotentiation?

A 
Immunization
Active 
Passive
Replacement therapies
Immune stimulants
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7
Q

What is passive immunisation?

A

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

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8
Q

What are the risks of passive immunisation?

A

Risk of transmission of viruses

Serum sickness

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9
Q

What are the types of passive immunisation?

A 
Pooled specific human immunoglobulin
Animal sera (antitoxins an antivenins)
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10
Q

What are the uses of passive immunisation?

A

Hep B prophylaxis and treatment

Botulism, VZV (pregnancy), diphtheria, snake bites

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11
Q

Define active immunisation

A

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

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12
Q

What is immunogenic material?

A

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

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13
Q

What are the problems with active immunisation

A

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

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14
Q

What does G-CSF/GM-CSF

do?

A

Acts on bone marrow to increase production of mature neutrophils

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15
Q

What is α-interferon used for?

A

treatment of Hepatitis C

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16
Q

What is β-interferon used for?

A

therapy of MS

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17
Q

What is γ-interferon used for?

A

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

18
Q

What drugs cause immunosuppression?

A 
Cortocosteroids
Cytotoxic/ agents
Anti-proliferative/activation  agents
DMARD’s
Biologic DMARD’s
19
Q

What is the action of corticosteroids?

A

Decreased neutrophil margination
Reduced production of inflammatory cytokines
Inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
Lymphopenia
Decreased T cells proliferation
Reduced immunoglobulins production

20
Q

What are the side effects of corticosteroids?

A 
Carbohydrate and lipid metabolism
Diabetes
Hyperlipidaemia
Reduced protein synthesis
Poor wound healing
Osteoporosis
Glaucoma and cataracts
Psychiatric complications
21
Q

What are corticosteroids used for?

A 
Autoimmune diseases 
CTD, vasculitis, RA
Inflammatory diseases
Crohn’s, sarcoid, GCA/polymyalgia rheumatica
Malignancies
Lymphoma
Allograft rejection
22
Q

What drugs target lymphocytes?

A

Antimetabolites

  • Azathioprine (AZA)
  • Mycophenolate mofetil (MMF)

Calcineurin inhibitors

  • Ciclosporin A (CyA)
  • Tacrolimus (FK506)

M-TOR inhibitors
- Sirolimus

IL-2 receptor mABs

  • Basiliximab
  • Daclizumab
23
Q

How do caclineurin inhibitors work?

A

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

24
Q

How does sirolimus work?

A

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

25
Q

What are the side effects of calcineurin?

A 
Hypertension
Hirsutism
Nephrotoxicity
Hepatotoxicity
Lymphomas
Opportunistic infections
Neurotoxicity
Multiple drug interactions (induce P450)
26
Q

What are calcineurins used for?

A

Transplantation
- Allograft rejection
Autoimmune diseases

27
Q

What do antimetabolites do?

A

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

28
Q

What are the side effects of cytotoxics?

A 
ALL
Bone marrow suppression
Gastric upset
Hepatitis
Susceptibility to infections
Cylophosphamide
Cystatis
MTX
pneumonitis
29
Q

What are the clinical uses of cytotoxic drugs?

A

–AZA/MMF–
Autoimmune diseases (SLE, vasulitis, IBD)
Allograft rejection

–MTX–
RA, PsA, Polymyositis, vasculitis
GvHD in BMT

–Cyclophosphamide–
Vasculitis (Wagner’s, CSS)
SLE

30
Q

What are biologic DMARD’s?

A 
Anti-cytokines (TNF, IL-6 and IL-1)
Anti-B cell therapies
Anti-T cell activation
Anti-adhesion molecules 
Complement inhibitors
31
Q

What is anti-TNF?

A

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

32
Q

What is Anti-IL-6 (Tocilizumab)?

A

anti-cytokine

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

33
Q

What is Anti-IL-1?

A

anti-cytokine

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

34
Q

What is rituximab?

A

Chimeric mAb against CD20- B cell surface

Many uses:
Lymphomas, leukaemias
Transplant rejection
Autoimmune disorders

35
Q

What is adoptive immunotherapy?

A

Bone marrow transplant (BMT)
Stem cell transplant (SCT)

Uses

  • Immunodeficiencies (SCID)
  • Lymphomas and leukemias
  • Inherited metabolic disorders (osteopetrosis)
  • Autoimmune diseases
36
Q

What immunomodulators are used in allergy?

A

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

37
Q

What are the indications of allergen specific immunotherapy?

A

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

38
Q

What are the mechanisms of allergen specific immunotherapy?

A

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

39
Q

What is omalizumab?

A

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

40
Q

What is Mepolizumab?

A

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

Clinical Pathology G (23 decks)

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