14 Lung Immunology and Allergic Disease Airway Flashcards
Q: Disease of upper airways? of bronchi? of alveoli?
A: Allergic rhinitis
asthma
allergic alveolitis
Q: What is hypersensitivity? 2 types?
A: exaggerated response
- immunological - “allergies”
- non immunological (no immune mechanism)
Q: 2 types of immunological hypersensitivity? 4 examples.
A: Non-IgE-mediated allergic diseases
(e.g. Farmers lung)
IgE-mediated = atopic diseases
- hayfever
- eczema
- asthma
Q: 3 types of non-immunological hypersensitivity? Example for each.
A: Intolerance (e.g.food)
Enzyme deficiency (e.g.lactase DH def)
Pharmacological e.g. Aspirin hypersensitivity
=> don’t have immune mechanism
Q: What is allergy?
A: Allergy is an exaggerated (inappropriate) immunological response to a foreign substance (allergen) which is either inhaled, swallowed, injected, or comes in contact with the skin or eye
hypersensitivity
Q: Allergy. Mechanism or disease?
A: Allergy is a mechanism (not a disease)
Allergic mechanisms play an important role in some diseases all the time, and in others for some of the time
Q: How can adaptive immunity generally be split? How is allergy referred to? What molecule does it revolve around?
A: Th1 and Th2
Th2 gone wrong / uneducated Th2 immunity
IgE
Q: Th1 mediated responses are launched against which 4 pathogens? Which cells are involved? (3) Which Ig? (3)
A: Viruses, bacteria, fungi, protozoa
Th17 cells, NK cells, cytotoxic T cells
IgM, IgA and IgG antibody subclasses
Q: Th2 mediated responses are launched against which 2 pathogens? Which cells are involved? (5) Which Ig? (2)
A: helminths (“worms”), ectoparasites (“ticks”) = multicellular
innate lymphoid cells, eosinophils, mast cells, basophils, activated macrophages
IgE and IgG1 antibodies epithelial barriers,
Q: What are the 2 phases of an allergic reaction? Describe each pathway.
A: acute and chronic phases of allergic reaction
- Allergen -> IgE antibody coating mast cell -> mast cell degranulation (and histamine produced) -> acute symptoms of allergy
- Same allergen -> APC -> Th2 cytokines and chemokines -> chronic symptoms of allergy
Q: How does an allergen produce acute symptoms of allergy? (7) How long do these symptoms last?
A: 1. if you’re allergic: identifies correctly as foreign but inappropriate response -> results in IgE production through help of Th2
- IgE will go in blood-> bind to granulocytes -> mast cells (in tissues- gut, lung, muscousal surfaces, skin) -> stay bound for long time)
MAST CELLS= EARLY PHASE
- and basophils (in periphery in blood)
- body will continue to make IgE antibody
- next time that specific antigen is encountered-> allergen will crosslink IgE on surface of mast cells
- -> mast cell undergoes immediate enzymatic reactions -> degranulate
- substance of granules made= responsible for acute symptoms of allergy that last minutes/hours (molecules locally effect eg by causing inflammation eg histamines)
Q: How does IgE bind to mast cells? How long do they stay bound?
A: IgE will bind to mast cells via receptor: high affinity receptor for IgE= FC epsilon R1 (FCER1) -> stay there for months (very long lasting)
Q: What happens the second time you encounter allergens? (3) Called? How long does it take?
A: 1. allergen coming 2nd time will also bind to other receptors and do other things
- APC activates Th2 cells -> replicates -> produces Th2 cytokines and chemokines
- -> Chronic symptoms of allergy (takes hours, days) = late allergic reaction
T CELL= LATE PHASE
Q: What do Th2 cells produce? (4) What do they each do? Which 2 are related to asthma?
A: IL-4 -> IgE synthesis (class switching of B cells to make IgE)
IL-5 -> Eosinophil development (can be a target for asthmatics)
IL-9 -> Mast cell development
IL-13 -> IgE synthesis + Airway Hyperresponsiveness + airway remodelling in asthma
Q: What does atopy mean? What is it? Name 3 atopic diseases.
A: Atopy means out of place (something inappropriate)
Atopy is the hereditary predisposition to produce IgE
antibodies against common environmental allergens
Q: Name 3 atopic diseases. Characterisation?
A: allergic rhinitis, asthma and atopic eczema
allergic tissue reactions (in atopic subjects) are
characterised by infiltration of Th2 cells and eosinophils
Q: Atopy and allergy. (3)
A: atopy just means there’s IgE in blood
allergy is the biological response/ outcome of atopy
can be atopic and not allergic
Q: What does the term allergic march describe? Process (4). What’s the idea? But?
A: describing the common progression of atopic diseases from atopic dermatitis to allergic asthma
- food allergy occurring in young infants
- could develop into atopic dermatitis
- or asthma
- or allergic rhinitis
idea if you stop food allergies when you’re young you can stop further diseases
The ’allergic march‘ is probably wrong,
observable at population level but not at an
individual level
Q: What is rhino-conjunctivitis? How many people does it affect? Also known as? General effect on?
A: (rhinitis)
allergic disease of the upper airway (nose and throat)
up to 17% of population
seasonal allergic conjunctivo-rhinitis: hay fever (pollens in summer etc.) -> vary allergen year round
QoL
Q: What are common causes of perennial allergic rhinitis
and asthma? (5)
A: -House dust mite
- cats
- dogs
- cockroach
- horses
Q: What is asthma? What percentage of the population is affected? Severity?
A: disease of lower airways: lungs, trachea, bronci/oles, alveoli (can manifest in whole lung)
8-12%
heterogeneous disease
Q: Symptoms of asthma? (5)
A: cough, shortness of breath, wheezing, chest tightness, secretions (more mucous)
Q: How is asthma clinically differentiated? 3 groups.
A: based on control and severity (lots of phenotypes) and symptoms
- Intermittent , mild, allergy frequently important
- Persistent, manageable, allergy often important
- Chronic severe, uncontrolled by treatment
Q: Asthma treatment (2).
A: bronchodilators
could be on steroids
Q: Another way to differentiate asthma not based on control? 3 groups. May not have?
A: looking at mechanisms behind it // Based on endotype or endo-phenotype
- allergic, atopic or eosinophilic asthma
- neutrophilic asthma
- exercise induced asthma
may not have evidence of eosinophils or Th2 pathway
Q: How do bronchi differ in healthy and asthmatic individuals? (6)
A: - bronchoconstriction- smooth muscle is contracted
- more smooth muscle due to remodelling (over long time)
- more mucous secreting cells (goblet)
- sometimes get denuded epithelium
- can get mucous plug and
- inflammation
Q: What is extrinsic allergic alveotitis? What percentage of the population is affected? Mechanism? (4)
A: disease of alveoli (and small airways)
0.1%
- all to do with inhaling small parts of allergen (less than 5 microns)
- penetrate to the distal airways and end up in alveoli
- allergen/antigen comes into contact with antibodies-> complex
- can enter pulmonary capillary and activate various parts of immune system
Q: Example of extrinsic allergic alveolitis? (5)
A: farmers lung (to do with mouldy hay)
Bird Fancier’s lung (Bird Droppings and feathers)
Air Conditioner lung (Air conditioner moulds)
Millers lung (infested flour)
Hot tub lung (Bacterial contamination)
Q: In what way can allergies manifest themselves in a serious way? (2) Symptoms? (8)
A: immediate/ general anaphylaxis
= a systemic allergic reaction
- dizziness, seizures, loss of consciousness
- lip, tongue swelling
- laryngeal oedema
- bronchoconstriction
- tingling in extremeties
- urticarial/ hives
- vomiting, diarrhoea, pain
- arrhythmia, anxiety
Q: What can cause anaphylaxis? (4)
A: -Drugs, such as penicillin
-Foods such as peanuts, tree nuts (walnuts, pecans)
milk, eggs, fish, shellfish, sesame seeds, soybeans,
celery, celeriac
-Insect stings from bees, wasps, hornets
-Latex
Q: Anaphylaxis treatment? result?
A: epinephrine pen (adrenaline)-> relieves lots of immediate symptoms
Q: Prevalence of allergic diseases? Why? Hypothesis.
A: on the increase
relationship between environment and genes (need both)
hygiene hypothesis:
- immunologically naive individual
- FACTOR A: genetic predispositon
- FACTOR B: germ free environment, no siblings, lots of antibiotics, vaccinations, industrialised society
- go on to have atopic Th2 response-> asthma
Q: What factors are associated with the changing incidence of asthma/allergy? Microbial (4).
A: Water sanitation (less oro-faecal water born infections)
Food quality (lack of fermenting bacteria, more processed foods)
Poverty (high asthma rates in the urban underprivileged)
Medical interventions (antibiotics in childhood, possibly certain vaccinations)
Q: What factors are associated with the changing incidence of asthma/allergy? Non-microbial (6).
A: Pollution (air, water, food) Diet and nutrition (lack of Vit D, fish oil, omega 3 fatty acids, trace elements) Obesity (may cause chronic inflammation) Climate change (high pollen counts) Stress (linked to chronic inflammation) Genetics/epigenetics
Q: What are the principles of treatment of allergic diseases?
A: - Allergen Avoidance
- Anti-allergic medication
- Immunotherapy (desensitisation/hyposensitisation)
Q: What does desentitisation involve in terms of treating allergies? Advantages? (2) Disadvantages? (3)
A: giving small doses of allergen in controlled manner and training immune system
Effective
Produces long lasting immunity
Occasional severe allergic reaction-> hence need controlled environment
Time consuming (low doses over time)
Standardisation problems
Q: Allergen-Specific Immunotherapy in the UK. (2)
A: Grass and tree pollen allergic rhinoconjunctivitis
uncontrolled by medication.
Bee or wasp sting anaphylaxis at risk for
repeated stings.
Q: Mechanism of Allergen-Specific Immunotherapy.
A: could be several mechanisms
- downregulation of Th2 response (less IgE, eosinophils etc)
- upregulation of Th1 response
- upregulation of regulatory T cells (act to do 1 and 2 either by direct contact or mediators eg IL-10)
