Immunotherapeutics - Immunomodulation

Question 1

Define: Immunomodulation

Answer 1

Manipulate immune system using immunomodulatory drugs –> immune response.

Question 2

What 3 things can immunomodulation potentially lead to?

Answer 2

> Immunopotentiation (inc rate/prolong duration)
Immunosuppression
Induct immunological tolerance.

Question 3

What are immunomodulators?

Answer 3

Medicinal products using molecular biology techniques (inc recombinant DNA tech).

Question 4

What are the main classes of immunomodulators?

Answer 4

> Substances similar to body’s key signalling proteins
Monoclonal antibodies
Fusion proteins

Question 5

What is passive immunity?

Answer 5

Transfer of high-titre antibody from donor to recipient . Short lasting immunity.

Question 6

Problems of passive immunity?

Answer 6

> Transfer blood-bourne viruses

>Serum sickness- Anti’b overload can = inflam and cytokine release.

Question 7

What are the different types of Ig?

Answer 7

> Pooled human immunoglobulin

> Animal sera –> makes antib’s.

Question 8

How is animal sera given?

Answer 8

IV or IM.

Question 9

What is active immunisation?

Answer 9

Stimulate development of protective immune response and immunological memory.

Question 10

What is G-CSF/GM-CSF?

Answer 10

Acts on bone marrow –> stimulate neutrophil production.

Question 11

What does IL-2 do?

Answer 11

Activates T cells

Question 12

What is a-interferon used for?

Answer 12

Treat Hep C

Question 13

What is B-interferon used for?

Answer 13

MS

Question 14

What is y-interferon used for?

Answer 14

Chronic granulomatous disease, IL-12 deF.

Question 15

What do Corticosteroids do in general?

Answer 15

Immunosuppression

Question 16

What do Corticosteroids do specifically?

Answer 16

> Decreased neutrophil margination
Decreased cytokine production
Decreased T cell proliferation (toxic at high levels)
Decreased levels of lymphocytes
Inhibit phospholipase A2 (reduced arachidonic acid metabolite production).

Question 17

What are the side effects of Corticosteroids?

Answer 17

> Reduced lipid/carbohydrate metabolism - slow down (Diabetes, Hyperlipidaemia)
> Reduced protein synthesis 
> Osteoporosis 
> Glacucoma and eye problems 
> ~Anxiety

Question 18

Corticosteroid uses?

Answer 18

> Allograft rejection
Malignancies - lymphoma
Inflam diseases
Autoimmune diseases

Question 19

What are the four types of drugs targeting lymphocytes?

Answer 19

> M-TORS
IL-2 receptor monoclonal antibodies
Calcaneurin Inhibitors
Anti-metabolites

Question 20

What is Calcaneurin?

Answer 20

A serine/threonine phosphatase protein that activates T cell production.`

Question 21

What does CyA bind to?

Answer 21

CyA –> Cyclophillin (“CyA later PHIL mitchell”

Question 22

What does Tacrolimus (FK506) bind to?

Answer 22

FKBP-12 (FK to FK)

Question 23

What is the mode of action of Calcaneurin inhibitors?

Answer 23

Bind to NFAT- cytokine stimulation factors

Question 24

What are the T cell effects of Calcaneurin?

Answer 24

Reversibly inhibit T-cell activation, proliferation and clonal expansion.

Question 25

What type of lymphocyte drug is Sirolimus?

Answer 25

M-TOR inhibitor

Question 26

What does Sirolimus bind to?

Answer 26

FKBP12 - Inhibit Rapamycin transcription factor

Question 27

What are the T cell effects of Sirolimus?

Answer 27

Stops cell cycle at G1/S phase

Question 28

What are Calcaneurin/MTOR side effects?

Answer 28

``` >Hypertension >Hirsutism >Nephro/neuro/hepatotoxicity >Opportunistic infections > Lymphomas ```

Question 29

What do Antimetabolites inhibit?

Answer 29

PURINE SYNTHESIS (Adenosine and Guanine)

Question 30

What is converted into 6-mercaptopurine by AZA?

Answer 30

Guanine

Question 31

What does MMF inhibit?

Answer 31

IMPDH - stops GTP production

Question 32

What does Methotrexate (MTX) inhibit?

Answer 32

Folate

Question 33

What does cyclophosphamide stop?

Answer 33

DNA cross-linking

Question 34

Cytoxic side effects?

Answer 34

> Bone marrow suppression > Gastric upset > Hepatitis > Infection susceptibility

Question 35

Cyclophosphamide side effects?

Answer 35

Cystitis - bladder inflammation

Question 36

Methotrexate side effects?

Answer 36

Pneumonitis - inflammed alveoli walls

Question 37

What are the clinical uses of AZA/MMT?

Answer 37

> Allograft rejection | > Autoimmune diseases

Question 38

What are the clinical uses of MTX?

Answer 38

> Rheumatoid arthritis, vasculitis, polymyolitis | > GvHD in bone marrow transplant.

Question 39

What are the clinical uses of Cyclophosphamide?

Answer 39

Systemic Lupus Erythmatois, Vasculitis

Question 40

What type of drug is Anti-TNF?

Answer 40

Anti-cytokine

Question 41

What is Anti-TNF used for?

Answer 41

Crohn's, Psoriasis, Ankylosing Spondylitis

Question 42

What is Anti-IL6 used for?

Answer 42

Rheumatoid Disease,

Question 43

What is Anti-IL1 used for?

Answer 43

AOSD and autoinflammatory syndromes.

Question 44

What is Rituximab?

Answer 44

Chimeric mAb against CD20- B cell surface.

Question 45

What type of B cells are cd20 only found on?

Answer 45

Blood B cells

Question 46

What does Rituximab do?

Answer 46

Removes pool of autoreactive antibodies from blood.

Question 47

What switches immune response from Th2 (allergic) to Th1 (non-allergic)?

Answer 47

Allergen specific immunotherapy

Question 48

What route is used for allergen specific immunotherapy against aero-allergens?

Answer 48

Sub-lingual