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Week 11 > Immunomodulation > Flashcards

Immunomodulation Flashcards

1
Q

Immunomodulation

what is it?
what are the 2 types?

A

Immunomodulation

  • Use of agents to improve/suppress the IR
  • Immunosuppression
  • Immunopotentiation
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2
Q

Immunomodulation

what are the 2 types of
immunosuppression?

A

Immunomodulation

  • Immunosuppression
    – Non-specific
    – Selective
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3
Q

Immunomodulation

What are the 3 kinds of non-specific immunosuppression?

A

Non-specific immunosuppression

  • Radiation
  • Corticosteroids
  • Cytotoxic drugs
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4
Q

Immunomodulation

Non-specific immunosuppression

  • Radiation
    Explain
A

– Prevents cell division

– DNA damage
* Cell cycle arrest
(G1/S checkpoint)

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5
Q

Immunomodulation

Non-specific immunosuppression

  • Corticosteroids
    Explain
A

– Stimulates synthesis of IκBα
(inhibitor of NF-κB)
– Blocks cytokines synthesis
and T cell responses
– Both anti inflammatory and
immunosuppressive

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6
Q

Immunomodulation

Non-specific immunosuppression

  • Effects of Corticosteroids on the IS

Neutrophils?
macrophages?
lymphocytes?
immunoglobulins?
Complement?

A

Neutrophils:
Neutrophilia
depressed chemotaxis
depressed margination
depressed phagocytosis
depressed ADCC
depressed bacterial activity
stabilization of membranes
inhibition of phospholipase A2

Macrophages:
depressed chemotaxis
depressed phagocytosis
depressed bacterial activity
depressed IL-1 and IL-6 production
depressed antigen processiong

Lymphocytes:
depressed proliferation
depressed T cell responses
Impaired T cell-mediated cytotoxicity
depressed IL-2 production
depressed lymphokine production

Immunoglobulins:
minimal decrease

Complement:
no effect

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7
Q

Immunomodulation

Non-specific immunosuppression

  • Cytotoxic drugs
    explain
A

– Alkylating agents (Cyclophosphamide)
* Cross-link DNA preventing cell division
– Folic acid antagonists (Methotrexate)
* Blocks production of tetrahydrofolate, necessary for
thymidine and purine nucleotides synthesis

– DNA synthesis inhibitors (Azatiophrine)
* Inhibits DNA and RNA synthesis

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8
Q

Selective immunosuppression

3 categories what are they?

A
  • Calcineurin inhibitors
  • Rapamycin (Sirolimus)
  • JAK (Janus kinase) inhibitors
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9
Q

Selective immunosuppression

  • Calcineurin inhibitors

2 types, what are they and what do they do?

A

– Cyclosporine
* Forms complex with cyclophilin
and blocks calcineurin

– Tacrolimus
* Forms complex with
immunophilin and blocks
calcineurin

– Inhibits IL-2 synthesis

**see slide for details

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10
Q

Selective immunosuppression

  • Rapamycin (Sirolimus)
    Explain
    what does it do
    how does it do it?
A
  • Rapamycin (Sirolimus)

– Forms complex with immunophilin
and blocks mTOR (mechanistic
Target Of Rapamycin)

– mTOR is a regulator of cell
metabolism, growth, proliferation
and survival

**see slide for details

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11
Q

Selective immunosuppression

  • JAK (Janus kinase) inhibitors

Explain:
* JAK-STAT signaling
* JAK (Janus kinase) inhibitors

A
  • JAK (Janus kinase) inhibitors
  • JAK-STAT signaling
  • Immunity
  • Cell division
  • Cell death
  • JAK (Janus kinase) inhibitors
  • Oclacitinib (Apoquel)
  • Inhibits mainly JAK1
  • Treatment for atopic dermatitis
  • JAK1 dependent cytokines:
  • IL-2, IL-4, IL-6, IL-13, IL-31

**see slide for details

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12
Q

Stimulation of the Immune System

What 4 catagories?

A

Stimulation of the Immune System
* Bacterial products
* Complex carbohydrates
* Vitamins
* Cytokines

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13
Q

Stimulation of the Immune System

Explain Bacterial products:

A

Stimulation of the Immune System

  • Bacterial products
    – Bacille Calmette-Guerin (Mycobacterium bovis)
    – Source of PAMPs, TLR stimulation, cytokine synthesis
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14
Q

Stimulation of the Immune System

Explain Complex Carbohydrates:

A

Stimulation of the Immune System

  • Complex carbohydrates
    – Zymosan, Glucans, Lentinans, aminated polyglucose
    – Activates macrophages
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15
Q

Stimulation of the Immune System

Explain Vitamins:

A

Stimulation of the Immune System
* Vitamins
– A, D, and E

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16
Q

Stimulation of the Immune System

Explain Cytokines

A

Stimulation of the Immune System

  • Cytokines
    – IL-2, recombinant INFs (α & γ)
17
Q

What is “trained Immunity”?

How do BCG vaccines work?

A

BCG vaccine induces enhanced
production of pro-inflammatory
cytokines, such as IL-1β,TNF-α, and
IL-6.

E ff e c t s a r e a c c o m p a n i e d b y
transcriptional, epigenetic and
metabolic reprogramming of the
myeloid cells in the BCG-vaccinated
individuals

“Trained immunity”

**see slide for details

18
Q

How do BCG vaccinations work?

A

BCG vaccination–> Epigenetic reprogramming of monocytes–>production of IL-1B, TNF, and IL-6 during subsequent viral infection–>

decreased RSV
decreased Influenza virus
Decreased HSV2
decreased SARS-COV-2?

19
Q

Explain innate immune response

A

primary challenge vaccine/infection–> peak of first response–> secondary infection –> peak of “trained” response (over time)

20
Q

How does recognition receptor work?

A

either it

1-Closed chromatin–>low response during primary challendge

2-metabolic reprogramming–>epigenetic enzyme–>histone modification–>open chromatin–>improved response during secondary challenge.

Week 11 (3 decks)

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