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MIMM 214 > Dr. Cyr - Th2 Immunity > Flashcards

Dr. Cyr - Th2 Immunity Flashcards

1
Q

what type of pathogen is targeted in type 2 response?

A

helminth parasite

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2
Q

describe the evolution of the type 2 response

A

we evolved with parasites so we needed this special response for a large pathogen

now we experience less parasites, so when type 2 response is triggered and dysregulated, hard to bring it down and leads to inflammatory disease

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3
Q

what 4 types of innate cells are involved in type 2 response?

A
  1. ILC2
  2. Mast cell
  3. Basophil
  4. Eosinophil
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4
Q

what 2 types of adaptive cells are involved in type 2 response?

A
  1. Th2
  2. Tc2
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5
Q

patients with one Type 2 inflammatory disease have an increased risk of ________? why?

A

patients with one Type 2 inflammatory disease have an increased risk of developing other diseases driven by Type 2 inflammation

helminths infected everywhere so the immune response was all over body

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6
Q

what are 4 types of Type 2 inflammatory diseases?

A
  1. Atopic dermatitis
  2. Chronic rhinosinusitis with nasal polyps
  3. Allergic rhinitis
  4. Asthma
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7
Q

what are 6 common pathophysiological features of Type 2 inflammatory diseases?

A
  1. tissue remodeling
  2. epithelial barrier dysfunction
  3. sensitivity to environmental/microbial allergens
  4. reduced diversity of skin microbiota
  5. infiltration of immune cells (granulocytes) and IgE
  6. vascular permeability
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8
Q

describe the production of antibodies in the type 2 immune response

A
  • allergen breaches barrier
  • DC activates T cell to become TH2 (via IL-4)
  • IL-4 and IL-13 stimulate proliferation and B cell activation
  • B cell makes antibodies that respond to the allergen upon next exposure
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9
Q

describe the receptors of IL-4 and IL-13

A

Type I receptor –> for IL-4
Type II receptor –> for IL-4 and IL-13

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10
Q

what does the location of IL-4/IL-13 receptor determine?

A

determines the role of the cytokine

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11
Q

describe the roles of IL-4 and IL-13?

A

have overlapping and distinct roles for inflammation and skin barrier dysfunction

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12
Q

describe the itch-scratch cycle and its evolution

A

cytokines lower threshold of sensitization of skin –> gets itchy –> further damage barrier

evolved for physical removal of parasite

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13
Q

what are 3 targets that can be used for monoclonal antibodies against type 2 inflammation?

A
  1. IgE
  2. cytokines
  3. cytokine receptors
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14
Q

what is the function of DUPILUMAB?

A

monoclonal ab that binds IL-4Ralpha
- directly inhibits IL-4 in Type I receptor
- inhibits IL-13 via steric hindrance in Type II receptor

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15
Q

what are 4 results of dupilumab?

A
  1. reduced IgE-mediated response
  2. reduced decline of lung function
  3. reduced lung inflammation
  4. reduced lung infiltration
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16
Q

what are the 3 stages of Atopic Dermatitis and what happens at each stage?

A
  1. NON-LESIONAL STAGE
    - allergens breach bc of poor barrier
    - Th2 differentiates and proliferates
    - IL-4 and IL-13 released
  2. ACUTE STATE
    - IL-4 and IL-13 stimulate barrier disruption by suppressing differentiation and lipid metabolism
    - IL-4 and IL-13 induce itch via sensitization, leads to scratch and further disrupts barrier
  3. CHRONIC STATE
    - IL-4 and IL-13 causes barrier inhibition and epidermal hyperplasia
17
Q

how are the stages of atopic dermatitis affected by dupilumab?

A

since IL-4 and IL-13 are blocked, there is no barrier disruption, no itch/scratch, no barrier inhibition, no epidermal hyperplasia, etc.

18
Q

what are the approved and failed monoclonal targets for asthma?

A

approved: target IL-5, IL-4/IL-13, IgE
failed: target IL-13 alone

19
Q

what are the approved and failed monoclonal targets for atopic dermatitis?

A

approved: target IL-4/IL-13, IL-13 alone
failed: target IL-5, IgE

20
Q

how are human mouse antibodies produced in genetically engineered mice?

A

mouse antibody gene silenced, human antibody gene added

then injected with antigen and will produce fully human antibodies

21
Q

what is the upscaling process for producing monoclonal antibodies?

A

make cell lines from mice that produce the monoclonal antibodies and upscale the culture to industrial scale

22
Q

what is the downscaling process for monoclonal antibodies?

A

collect antibodies by centrifuge, filtration, etc. until therapeutic is packaged and can be injected into person

MIMM 214 (33 decks)

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