Immunomodulation Flashcards

1
Q

Describe immunomodulation.

A

use of agents to improve/suppress the IR
1. Immunosuppression
-nonspecific
-selective
2. Immunopotentiation
-stim IS

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2
Q

Describe nonspecific immunosuppresion.

A
  1. Radiation
  2. Corticosteroids
  3. Cytotoxic drugs
    >Alkylating agents = cyclophosphamide
    >Folic acid antagonists = methotrexate
    >DNA synthesis inhibitors = azatiophrine
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3
Q

Describe nonspecific immunosuppression - radiation.

A

-prevents cell division
-DNA damage
>cell cycle arrest (G1/S checkpoint)

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4
Q

Describe nonspecific immunosuppression - corticosteroids.

A

-stim synthesis of IkBa (inhibitor of NF-kB)
-blocks cytokine synthesis & T cell responses
-anti inflammatory & immunosuppressive

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5
Q

Describe nonspecific immunosuppression - cytotoxic drugs (alkylating agents = cyclophosphamide).

A

-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

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6
Q

Describe nonspecific immunosuppression - cytotoxic drugs (folic acid antagonists = methotrexate).

A

-blocks prod of tetrahydrofolate needed for thymidine & purine nucleotides syn
-treatment of rheumatoid arthritis
-chemotherapy against cancer

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7
Q

Describe nonspecific immunosuppression - cytotoxic drugs (DNA syn inhibitors = azatiophrine).

A

-suppress lymphocyte activation & mitosis
-inhibit DNA & RNA syn
-anti inflam
-toxic effects:
>bone marrow suppression (leukocytes only)
>acute pancreatitis
>gastroenteritis

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8
Q

Describe selective immunosuppresion.

A
  1. Calcineurin inhibitors
    >cyclosporine
    >tacrolimus
  2. Rapamycin (sirolimus)
  3. JAK (Janus kinase) inhibitors
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9
Q

Describe selective immunosuppression calcineurin inhibitors - cyclosporine.

A

-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

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10
Q

Describe selective immunosuppression calcineurin inhibitors - tacrolimus.

A

-forms complex w immunophilin & blocks calcineurin
-inhibits IL2, IL3, IL4, IL5, IFNy & TFNFa
-more potent than cyclosporine in inhibiting T & B cell resp

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11
Q

Describe selective immunosuppression rapamycin (sirolimus).

A

-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

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12
Q

Describe selective immunosuppression JAK inhibitors.

A
  1. JAK-STAT signaling
    -immunity
    -cell division
    -cell death
  2. JAK inhibitors = oclacitnib (Apoquel)
    -inhibits JAK1
    -treatment for atopic dermatitis
    -JAK1 dependent cytokines:
    >IL2, IL4, IL6, IL13, IL31
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13
Q

Describe the stimulation of the IS.

A
  1. Bacterial products
    -bacille calmette-guerin
    -source of PAMPs, TLR stim, cytokine syn
  2. Complex carbohydrates
    -zymosan, glucans, lentinans, aminated polyglucose
    -activate macrophages
  3. Vitamins
    -A, D, & E
  4. Cytokines
    -IL2, recombinant INFs (a & y)
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14
Q

Describe trained immunity.

A

-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

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