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Clinical Pathology > Immunomodulation > Flashcards

Flashcards in Immunomodulation Deck (29):
1

What is immunomodulation?

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

2

What are the various mechanisms that can be used to bring about immunomodulation?

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

3

What are biologic immunomodulators?

Medicinal products produced using molecular biology techniques including recombinant DNA technology.

4

What are the main classes of biologic immunomodulators?

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

5

What is the problem with biologic immunomodulators?

Humans can develop autoantibodies against them.

6

What is is immunopotentiation?

Immunisation

7

What is the definition of passive immunisation?

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

8

What are the risks associated with passive immunisation?

- Risk of transmission of viruses
- Serum sickness

9

What types of passive immunisation are available?

- Pooled specific human immunoglobulin
- Animal sera (antitoxins an antivenins)

10

What are the clinical indications for passive immunisation?

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

11

What is the definition of active immunisation?

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

12

What kind of immunogenic material is used in vaccines?

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

13

What problems are associated with vaccination?

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

14

What is pooled human immunoglobulin used for?

Rx of antibody deficiency states

15

What are the various actions 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

16

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

17

What are the uses of corticosteroids?

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

18

What is calcineurin?

Calcineurin (CN) is a calcium and calmodulin dependent serine/threonine protein phosphatase. Activates T cells and stimulates growth and differentiation.

19

Name two calcineurin inhibitors.

- Ciclosporin A (CyA)
- Tacrolimus (FK506)

20

How does ciclosporin work?

- Binds to intracellular protein cyclophilin
- Prevents activation of NFAT
Factors which stimulate cytokines (i.e IL-2 and INFγ) gene transcription
- Reversible inhibition of T-cell activation, proliferation and clonal expansion

21

How does sirolimus work?

- Also binds to FKBP12 but different effects
- Inhibits mammalian target of rapamycin (mTOR)
- Inhibits response to IL-2
- Cell cycle arrest at G1-S phase

22

How does Azathioprine (AZA) work?

- Guanine anti-metabolite (i.e. purine analogue)
- Rapidly converted into 6-mercaptopurine
- Impaired T cell DNA production

23

How does Mycophenolate mofetil work?

- Non-competitive inhibitor of IMPDH
- Prevents production of guanosine triphosphate
- Interferes with proliferation of T and B cells

24

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

25

What are the features of anti-TNF drugs?

- 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

26

What are the features of IL-6 drugs?

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

27

What is rituximab?

- Chimeric mAb against CD20- B cell surface
- Can get rid of B cell producing autoreactive antibodies
- Used in:
- Lymphomas, leukaemias
- Transplant rejection
- Autoimmune disorders

28

What are the indications for allergen-specific immunotherapy?

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

29

What are the mechanisms behind allergen-specific immunotherapy?

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

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