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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
what 2 types of cells produce the key T2 cytokines
1. DCs 2. epithelial cells
26
what 2 types of cells are stimulated by T2 cytokines?
1. TH2 2. ILC2
27
where are ILC2?
airways
28
role of Th2 cells
cause B cells to class switch and form IgE plasma cells that produce allergen-specific IgE for binding to mast cells and basophils
29
difference btwn ppl who are allergic vs non-allergic
allergic: inflammatory T2 response non-allergic: still takes Ag and presents it, then induces regulatory response
30
Th cells in non-allergic vs allergic
non-allergic: ANERGIC allergic: Th2
31
Tfh cells in non-allergic vs allergic
allergic: Tfh13 (make IL13)
32
Treg cells in non-allergic vs allergic
non-allergic: has FOXP3 and also TGFbeta on surface that is inducible for peripheral tolerance allergic: less TGFbeta
33
Ab in non-allergic vs allergic
non-allergic: IgG allergic: IgE
34
role of innate immune system in non-allergic vs allergic
non-allergic: mainly regulatory allergic: mainly pro-inflammatory
35
what happens if you block T2 with treatment? why?
T1 becomes more prominent and inflammation still occurs --> bc all responses always induced, just magnitude matters
36
what's a better idea than just blocking a response?
REDIRECT the immune system
37
5 methods of allergic disease treatment
1. allergen avoidance 2. symptom management 3. targeted immune blockade 4. immunotherapy 5. prevention
38
5 drugs for symptom management
1. antihistamines 2. corticosteroids 3. antileukotrienes 4. bronchodilators 5. epinephrine
39
what does Remibrutiniib do?
blocks BTK involved in mast cell degranulation --> no degranulation = no mast cell effect
40
why might Remibrutiniib be better than antihistamines?
antihistamines only block His receptor but mast cell can still degranulate and anaphylaxis can still occur
41
why might Remibrutiniib not be good?
BTK is involved in B cell maturation so would be bad idea to block this!
42
issues with current targeted blockade treatments
only treat symptoms --> T2 still there and not redirected to regulatory --> don't cure allergy
43
what proportion of allergies improve/resolve over time?
1/5
44
what 2 things happen with allergy as you age?
1. allergy response becomes more severe 2. threshold of allergen is lower
45
why is it good to expose baby to complex Ag environment when they are young?
so their immune system can receive inputs to strengthen regulation --> need some inflammation to train immune system to have anti-inflammation
46
describe immunomodulation
plasticity of T cell subsets: Th2 <--> Treg
47
principle of immunotherapy for allergy
start with very low dose allergen and gradually build up so patients can start to tolerate their allergens
48
how did immunotherapy for allergy start?
isolate bee venom to induce desensitization
49
2 forms of immunotherapy for environmental allergens
1. allergy shots 2. sublingual
50
describe the general idea of food immunotherapy
start with low amounts and gain tolerance
51
describe food immunotherapy in adults success rate?
can work but must eat specific amount of that food everyday to induce desensitization --> if you stop, will regain allergy 30%
52
why can you regain allergy if you stop food immunotherapy in adult?
immune system is already developed in adults so baseline can't be changed
53
food immunotherapy success rate in kids under 2? why does food immunotherapy work better in kids under 2?
95% immune response / baseline is not fixed
54
how does food immunotherapy work?
given amount of Ag below allergy threshold to "tickle" immune system --> induce regulatory response and lose inflammatory response
55
what % of people will outgrow their food allergy?
20%
56
what happens to IgE in ppl who naturally resolve their allergy?
IgE levels decrease
57
how are immunotherapy-treated ppl different from ppl with tolerance / natural resolution?
immunotherapy-treated ppl still have some aspects of allergy response
58
effect of immunotherapy on B cells
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
4 limitations of immunotherapy
1. risk of anaphylaxis 2. therapy is YEARS 3. no info on duration of non-responsiveness 4. less successful in adults
60
overall, what is the goal of immunotherapy
to immunomodulate the immune system
61
what response is increased in immnotherapy?
REGULATORY
62
what happens to cytokines with immunotherapy?
INCREASE in tolerant cytokines (TGFbeta and IL10) DECREASE in T2 cytokines (IL4, IL13)
63
4 modifiable environmental risk factors
1. allergens, irritants in the home 2. food introduction protocols 3. supplements (vitamins, probiotics) 4. infections, antibiotics
64
mucosal contact = tolerizing or sensitizing?
mucosal = TOLERIZING
65
skin contact = tolerizing or sensitizing?
skin = SENSITIZING
66
what do ppl think asthma results from?
failure to tolerize mucosal immune system in early life (bc non-allergic ppl have tolerant immune response when contact allergen)
67
epidemiological evidence of urban vs. farm life affecting allergy?
exposure to farms, stables, and farm milk in early life and long-term is protective
68
epidemiological evidence of birth order affecting allergy?
higher birth order is protective
69
epidemiological evidence of daycare affecting allergy?
daycare gives best protection for asthma if <6 months old
70
epidemiological evidence of pets affecting allergy?
exposure to pets is protective
71
epidemiological evidence of cockroach allergen affecting allergy?
cockroach allergen is sensitizing which increase risk of asthma
72
epidemiological evidence of early food introduction affecting allergy?
early introduction of complex antigenic foods reduces risk of food allergy
73
how are oral vs skin exposures to food antigens different?
ORAL = reduced risk of allergy (mucosa is tolerizing) SKIN = increased risk of allergy (skin is sensitizing)

MIMM 314 (23 decks)

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