Immunomodulation

Question 1

Immunomodulation

Answer 1

Use of gents to improve/suppress the IR
can be specific (tends to focus on just lymphocytes) or non-specific (refers to drugs or agents capable of inducing immunosuppression by affecting all cells involved in immune response)

Question 2

Non-specific immunosuppression: Radiation

Answer 2

Prevents cell division (so suppresses IR) by DNA damage (not only targeting lymphocytes- can be any cell
-cell cycle arrest (G1/S checkpoint)- checkpoint where cells with damaged DNA cant continue until they fix.
Will generate immune suppression but also a lot of other issues

Question 3

Non-specific immunosuppression: Corticosteroids

Answer 3

Stimulates synthesis of IkBa (an inhibitor of NF-kB- which is a transcription factor for cytokine production)
Blocks cytokine synthesis and T cell responses (and gene transcription as a whole)
Both anti inflammatory and immunosuppressive
When thinking about immunosuppression, usually thinking about lymphocytes or things produced by lymphocytes
At low doses coricosteroids have antiinflammatory effects
Higher doses= immmunosuppression

Lots of other immune system effects- like neutrophils, macrophages, lymphocytes, immunoglobulins.

Question 4

Non-specific immunosuppression: Cytotoxic drugs

Answer 4

Will block cell division
Alkylating agents (cyclophosphamide)- cross-link DNA preventing cell division- by preventing DNA from opening up for copying)
Folic acid antagonists (methotrexate)- blocks production of tetrahydrofolate, necessary for thymidine and purine nucleotides synthesis
DNA synthesis inhibitors (Azatiophrine)- inhibits DNA and RNA synthesis
Not really damaging DNA but are preventing multiplication

Question 5

Selective immunosuppression: Calcineurin inhibitors

Answer 5

Calcineurin- molecule involved in activation og genes responsible for IL-2 synthesis
Cyclosporine- forms complex with cyclophilin and blocks calcineurin
Tacrolimus- forms complex with immunophilin and blocks calcineurin

Inhibits IL-2 synthesis- cells without IL-2 cannot proliferate- so we are affecting T cell proliferation
-less effects on other cell lines

Question 6

Selective immunosuppression: Rapamycin (sirolimus)

Answer 6

Forms complex with immunophilin and blocks mTOR (mechanistinc target of Rapamycin)
mTOR is a regulator of cell metabolism, growth, proliferation, and survival
-cell cycle cant progress
-only T cells

Question 7

Selective immunosuppression: JAK (janus kinase) inhibitors

Answer 7

Could consider this non selective when all JAKs- when just 1 jak its selective
JAK-STAT signaling
-immunity
-cell division
-cell death
Targeting cytokine production more than other stuff

Apoquel- inhibits mainly JAK1
treatment for atopic dermatitis
JAK1 dependent cytokines: IL-2, IL-4, IL-6, IL-13, IL-31

Question 8

Stimulation of the immune system

Answer 8

Bacterial products

• bacill calmett-guerin (mycobacterium bovis)
• source of PAMPs, TLR stimulation, cytokine sysnthesis

Complex carbohydrates

• zymosan, glucans, lentinans, aminated polyglucose
• activates macrophages

Vitamins
-A, D, and E

Cytokines- these have specific effects and you can give these and know the effects that will take place
-IL-2, recombinant IFNs (a & y)- important in antiviral responses so can be used in antiviral treatment

Question 9

Trained immunity

Answer 9

BCG vaccine induces enhanced production of pro-inflammatory cytokines, such as IL-1B, TNF-a, and IL-6
Effects are accompanied by transcriptional, epigenetic and metabolic reprogramming of the myeloid cells in the BCG-vaccinated individuals