Immunomodulation Flashcards
Describe immunomodulation.
use of agents to improve/suppress the IR
1. Immunosuppression
-nonspecific
-selective
2. Immunopotentiation
-stim IS
Describe nonspecific immunosuppresion.
- Radiation
- Corticosteroids
- Cytotoxic drugs
>Alkylating agents = cyclophosphamide
>Folic acid antagonists = methotrexate
>DNA synthesis inhibitors = azatiophrine
Describe nonspecific immunosuppression - radiation.
-prevents cell division
-DNA damage
>cell cycle arrest (G1/S checkpoint)
Describe nonspecific immunosuppression - corticosteroids.
-stim synthesis of IkBa (inhibitor of NF-kB)
-blocks cytokine synthesis & T cell responses
-anti inflammatory & immunosuppressive
Describe nonspecific immunosuppression - cytotoxic drugs (alkylating agents = cyclophosphamide).
-cross link DNA preventing cell division
-cyclophosphamide is toxic for resting & dividing cells (esp for dividing immunocompetent cells)
-impaired B & T cell resp
-risk of bone marrow suppression
>leukopenia w predisposition to infection
>thrombocytopenia, anemia
Describe nonspecific immunosuppression - cytotoxic drugs (folic acid antagonists = methotrexate).
-blocks prod of tetrahydrofolate needed for thymidine & purine nucleotides syn
-treatment of rheumatoid arthritis
-chemotherapy against cancer
Describe nonspecific immunosuppression - cytotoxic drugs (DNA syn inhibitors = azatiophrine).
-suppress lymphocyte activation & mitosis
-inhibit DNA & RNA syn
-anti inflam
-toxic effects:
>bone marrow suppression (leukocytes only)
>acute pancreatitis
>gastroenteritis
Describe selective immunosuppresion.
- Calcineurin inhibitors
>cyclosporine
>tacrolimus - Rapamycin (sirolimus)
- JAK (Janus kinase) inhibitors
Describe selective immunosuppression calcineurin inhibitors - cyclosporine.
-forms complex w cyclophilin & blocks calcineurin
-inhibits signal transduction & blocks production of IL2 & IFNy by T cells
-block Th1 resp
-indirection suppressive effects on:
>macrophages, B cells, NK cells, neutrophils, eosinophils, mast cells
Describe selective immunosuppression calcineurin inhibitors - tacrolimus.
-forms complex w immunophilin & blocks calcineurin
-inhibits IL2, IL3, IL4, IL5, IFNy & TFNFa
-more potent than cyclosporine in inhibiting T & B cell resp
Describe selective immunosuppression rapamycin (sirolimus).
-forms complex w immunophilin & blocks mTOR (mechanistic target of rapamycin)
>mTOR = regulate T cell activation by integrating the signals received from antigens, costim receptors, & cytokines & directing the T cell differentiation into effector, regulatory, or memory pathways
Describe selective immunosuppression JAK inhibitors.
- JAK-STAT signaling
-immunity
-cell division
-cell death - JAK inhibitors = oclacitnib (Apoquel)
-inhibits JAK1
-treatment for atopic dermatitis
-JAK1 dependent cytokines:
>IL2, IL4, IL6, IL13, IL31
Describe the stimulation of the IS.
- Bacterial products
-bacille calmette-guerin
-source of PAMPs, TLR stim, cytokine syn - Complex carbohydrates
-zymosan, glucans, lentinans, aminated polyglucose
-activate macrophages - Vitamins
-A, D, & E - Cytokines
-IL2, recombinant INFs (a & y)
Describe trained immunity.
-BCG vaccine induces enhanced prod of pro-inflam cytokines like IL1B, TNFa, & IL6
-effects accompanied by transcriptional, epi genetic & metabolic reprogramming of myeloid cells in BCG vaccinated individuals