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Clinical Pathology G > Immunotherapeutics > Flashcards

Flashcards in Immunotherapeutics Deck (40):
1

Define immunomodulation

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

2

What are some possible effects of immunomodulation?

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

3

What are some mechanisms of immunomodulation?

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

4

What are biologics- immunomodulators?

Medicinal products produced using molecular biology techniques including recombinant DNA technology

5

What are the main classes of immunomodulators?

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

6

What is immunopotentiation?

Immunization
Active
Passive
Replacement therapies
Immune stimulants

7

What is passive immunisation?

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

8

What are the risks of passive immunisation?

Risk of transmission of viruses
Serum sickness

9

What are the types of passive immunisation?

Pooled specific human immunoglobulin
Animal sera (antitoxins an antivenins)

10

What are the uses of passive immunisation?

Hep B prophylaxis and treatment
Botulism, VZV (pregnancy), diphtheria, snake bites

11

Define active immunisation

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

12

What is immunogenic material?

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

13

What are the problems with active immunisation

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

14

What does G-CSF/GM-CSF
do?

Acts on bone marrow to increase production of mature neutrophils

15

What is α-interferon used for?

treatment of Hepatitis C

16

What is β-interferon used for?

therapy of MS

17

What is γ-interferon used for?

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

18

What drugs cause immunosuppression?

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

19

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

20

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

21

What are corticosteroids used for?

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

22

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

23

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

24

How does sirolimus work?

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

25

What are the side effects of calcineurin?

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

26

What are calcineurins used for?

Transplantation
- Allograft rejection
Autoimmune diseases

27

What do antimetabolites do?

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

28

What are the side effects of cytotoxics?

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

29

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

30

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

31

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

32

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

33

What is Anti-IL-1?

anti-cytokine

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

34

What is rituximab?

Chimeric mAb against CD20- B cell surface

Many uses:
Lymphomas, leukaemias
Transplant rejection
Autoimmune disorders

35

What is adoptive immunotherapy?

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

Uses
-Immunodeficiencies (SCID)
-Lymphomas and leukemias
-Inherited metabolic disorders (osteopetrosis)
-Autoimmune diseases

36

What immunomodulators are used in allergy?

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

37

What are the indications of allergen specific immunotherapy?

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

38

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

39

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

40

What is Mepolizumab?

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