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MIMM 314 > Lecture 16 - Allergies > Flashcards

Lecture 16 - Allergies Flashcards

1
Q

6 types of allergic disease

A
  1. eczema
  2. allergic rhinitis
  3. asthma
  4. food allergy
  5. venom allergy
  6. drug allergy
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2
Q

difference btwn allergic rhinitis and asthma

A

allergic rhinitis occurs in upper airway, asthma occurs in lower airway

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3
Q

frequency of allergic disease

A

1/3 of ppl have 1 or more atopic disease

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4
Q

2 most prevalent respiratory allergies:

A
  1. allergic rhinitis
  2. asthma
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5
Q

what is the name of the immune response that occurs in allergy?

A

Type 2 response

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6
Q

when does an antigen become an allergen?

A

once it activates type 2 response

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7
Q

describe what happens in type 2 response for allergy

A
  1. IgE is produced and binds mast cell
  2. when IgE binds antigen, mast cell is activated and degranulates
  3. degranulation releases histamine, leukotrienes, IL4/IL13
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8
Q

is IgE alone sufficient to induce allergy?

A

no!!

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9
Q

where do allergic mediators act?

A

locally and systemically

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10
Q

symptoms induced by inflammatory mediators

A
  1. skin rash/itch
  2. sneezing
  3. itchy eyes
  4. coughing
  5. reactive airways
  6. increased intestinal motility
  7. edema
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11
Q

are IgE and mast cells required for asthma?

A

helps response, but not required to induce symptoms

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12
Q

2 factors that cause allergies to develop

A
  1. genetic
  2. environment
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13
Q

describe a baby’s immune system when it is born

A

exposed to many new microbes –> immune system must be fully regulatory so it can be calm

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14
Q

what happens to a baby’s immune system without FOXP3?

A

No Treg –> immune system cannot be calm, it goes crazy

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15
Q

how does atopic dermatitis develop on baby and how can this lead to food allergy?

A

once born, baby no longer moisturized in womb so it has a little atopic dermatitis with T2 activation

then food Ag touches skin where there’s atopic dermatitis –> T2 already activated so will develop T2 response against Ag

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16
Q

where in the body is T2 more common when you’re older?

A

T2 response in airways occurs later –> airways less exposed to Ag when young

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17
Q

what type of environment is best to develop tolerance?

A

complex Ag environment can help induce tolerance

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18
Q

what cells mainly mediate asthma? which cells are less involved?

A

mainly Th2, less mast cells (IgE)

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19
Q

what can asthma lead to?

A

fibrosis in the lungs

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20
Q

why is fibrosis in the lungs bad?

A

decreased elasticity = bad for lungs

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21
Q

besides genetics and environment, what is an example of something that can drive T2 response?

A

ex. viruses

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22
Q

describe how allergy becomes systemic

A

allergic sensitization may occur in 1 organ, but immune response can trigger a systemic inflammatory response

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23
Q

4 key cytokines

A
  1. TSLP
  2. IL4
  3. IL13
  4. IL5
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24
Q

2 less important cytokines

A
  1. IL33
  2. IL25
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25
Q

what 2 types of cells produce the key T2 cytokines

A
  1. DCs
  2. epithelial cells
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26
Q

what 2 types of cells are stimulated by T2 cytokines?

A
  1. TH2
  2. ILC2
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27
Q

where are ILC2?

A

airways

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28
Q

role of Th2 cells

A

cause B cells to class switch and form IgE plasma cells that produce allergen-specific IgE for binding to mast cells and basophils

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29
Q

difference btwn ppl who are allergic vs non-allergic

A

allergic: inflammatory T2 response

non-allergic: still takes Ag and presents it, then induces regulatory response

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30
Q

Th cells in non-allergic vs allergic

A

non-allergic: ANERGIC

allergic: Th2

31
Q

Tfh cells in non-allergic vs allergic

A

allergic: Tfh13 (make IL13)

32
Q

Treg cells in non-allergic vs allergic

A

non-allergic: has FOXP3 and also TGFbeta on surface that is inducible for peripheral tolerance

allergic: less TGFbeta

33
Q

Ab in non-allergic vs allergic

A

non-allergic: IgG

allergic: IgE

34
Q

role of innate immune system in non-allergic vs allergic

A

non-allergic: mainly regulatory

allergic: mainly pro-inflammatory

35
Q

what happens if you block T2 with treatment? why?

A

T1 becomes more prominent and inflammation still occurs –> bc all responses always induced, just magnitude matters

36
Q

what’s a better idea than just blocking a response?

A

REDIRECT the immune system

37
Q

5 methods of allergic disease treatment

A
  1. allergen avoidance
  2. symptom management
  3. targeted immune blockade
  4. immunotherapy
  5. prevention
38
Q

5 drugs for symptom management

A
  1. antihistamines
  2. corticosteroids
  3. antileukotrienes
  4. bronchodilators
  5. epinephrine
39
Q

what does Remibrutiniib do?

A

blocks BTK involved in mast cell degranulation –> no degranulation = no mast cell effect

40
Q

why might Remibrutiniib be better than antihistamines?

A

antihistamines only block His receptor but mast cell can still degranulate and anaphylaxis can still occur

41
Q

why might Remibrutiniib not be good?

A

BTK is involved in B cell maturation so would be bad idea to block this!

42
Q

issues with current targeted blockade treatments

A

only treat symptoms –> T2 still there and not redirected to regulatory –> don’t cure allergy

43
Q

what proportion of allergies improve/resolve over time?

A

1/5

44
Q

what 2 things happen with allergy as you age?

A
  1. allergy response becomes more severe
  2. threshold of allergen is lower
45
Q

why is it good to expose baby to complex Ag environment when they are young?

A

so their immune system can receive inputs to strengthen regulation –> need some inflammation to train immune system to have anti-inflammation

46
Q

describe immunomodulation

A

plasticity of T cell subsets: Th2 <–> Treg

47
Q

principle of immunotherapy for allergy

A

start with very low dose allergen and gradually build up so patients can start to tolerate their allergens

48
Q

how did immunotherapy for allergy start?

A

isolate bee venom to induce desensitization

49
Q

2 forms of immunotherapy for environmental allergens

A
  1. allergy shots
  2. sublingual
50
Q

describe the general idea of food immunotherapy

A

start with low amounts and gain tolerance

51
Q

describe food immunotherapy in adults

success rate?

A

can work but must eat specific amount of that food everyday to induce desensitization –> if you stop, will regain allergy

30%

52
Q

why can you regain allergy if you stop food immunotherapy in adult?

A

immune system is already developed in adults so baseline can’t be changed

53
Q

food immunotherapy success rate in kids under 2?

why does food immunotherapy work better in kids under 2?

A

95%

immune response / baseline is not fixed

54
Q

how does food immunotherapy work?

A

given amount of Ag below allergy threshold to “tickle” immune system –> induce regulatory response and lose inflammatory response

55
Q

what % of people will outgrow their food allergy?

A

20%

56
Q

what happens to IgE in ppl who naturally resolve their allergy?

A

IgE levels decrease

57
Q

how are immunotherapy-treated ppl different from ppl with tolerance / natural resolution?

A

immunotherapy-treated ppl still have some aspects of allergy response

58
Q

effect of immunotherapy on B cells

A

reduced drive for new B cells to make IgE –> but don’t know how long the existing B cells exist so it makes it hard when disease already exists

59
Q

4 limitations of immunotherapy

A
  1. risk of anaphylaxis
  2. therapy is YEARS
  3. no info on duration of non-responsiveness
  4. less successful in adults
60
Q

overall, what is the goal of immunotherapy

A

to immunomodulate the immune system

61
Q

what response is increased in immnotherapy?

A

REGULATORY

62
Q

what happens to cytokines with immunotherapy?

A

INCREASE in tolerant cytokines (TGFbeta and IL10)

DECREASE in T2 cytokines (IL4, IL13)

63
Q

4 modifiable environmental risk factors

A
  1. allergens, irritants in the home
  2. food introduction protocols
  3. supplements (vitamins, probiotics)
  4. infections, antibiotics
64
Q

mucosal contact = tolerizing or sensitizing?

A

mucosal = TOLERIZING

65
Q

skin contact = tolerizing or sensitizing?

A

skin = SENSITIZING

66
Q

what do ppl think asthma results from?

A

failure to tolerize mucosal immune system in early life

(bc non-allergic ppl have tolerant immune response when contact allergen)

67
Q

epidemiological evidence of urban vs. farm life affecting allergy?

A

exposure to farms, stables, and farm milk in early life and long-term is protective

68
Q

epidemiological evidence of birth order affecting allergy?

A

higher birth order is protective

69
Q

epidemiological evidence of daycare affecting allergy?

A

daycare gives best protection for asthma if <6 months old

70
Q

epidemiological evidence of pets affecting allergy?

A

exposure to pets is protective

71
Q

epidemiological evidence of cockroach allergen affecting allergy?

A

cockroach allergen is sensitizing which increase risk of asthma

72
Q

epidemiological evidence of early food introduction affecting allergy?

A

early introduction of complex antigenic foods reduces risk of food allergy

73
Q

how are oral vs skin exposures to food antigens different?

A

ORAL = reduced risk of allergy (mucosa is tolerizing)

SKIN = increased risk of allergy (skin is sensitizing)

MIMM 314 (23 decks)

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