Buxton: Asthma

Question 1

What causes wheezing in an asthma attack?

Answer 1

immune cells, in response to a type 1 hypersensitivity reaction, release chemicals that cause bronchoconstriction thus narrowing the airways in an asthma attack.

Question 2

What other problems might your asthmatic patient have?

Answer 2

Other type 1 hypersensitivity reactions i.e. eczema and hay fever; bronchiolitis as a baby

Question 3

Where are the genes located that are often in asthma and what do they produce?

Answer 3

Short arm of chromosome 5 (5q23-31)
Genes involved may regulate:
IgE production
IL-4, 5, 13 and g-IFN expression
Fc receptor expression on mast cells
Beta-2 adrenergic receptor expression on smooth muscle cells

Question 4

Describe how environmental elements can lead to asthma.

Answer 4

Irritants irritate the nerve ending on the bronchi, i.e. chemicals on the parents’ clothing, air pollution, smoke
Nerve endings are exposed.
Some chemical pollutants have been shown to promote allergic inflammation.
Examples:
- Release of cytokines from airway epithelial cells following exposure to NO2, O3,, diesel exhaust
- Aromatic hydrocarbons in diesel exhaust enhances IgE production by B cells in vitro
- Quinones in diesel exhaust induce secretion of RANTES from macrophages in vitro

Question 5

What are the three phases of type 1 hypersensitivity?

Answer 5

Sensitization, Immediate Reaction, and Late-Phase Response

Question 6

In asthma, what responds to an allergen to lead to an asthma attack?

Answer 6

Th2 cells respond and secrete cytokines that respond to mast cells, eosinophils, etc

Question 7

Overview of sensitization and immediate reaction

Answer 7

Sensitization is the first phase of the development of asthma. MP takes the allergen to lymph nodes; protein gets broken down/processing the protein on the way to the lymph node. Will go to the paracortex to activate the T cell. On the membrane of the MP is class 2 MHC. Tcell binds to the antigen. T cell is told to become a Th2 cell which will secrete IL4,5 to help a B cell interact with the antigen. (B cells are located in the cortex). B cell is also an APC. (like MP/dentritic cell). IL4 makes the B cell secrete IgE. (If no IL4, it will secrete IgM). IgE goes into the blood and goes to the mast cells (skin, mucosa). Fc epsilon are only for IgE. When an antigen comes in across the mucosa it can get snagged by the IgE on the surface of the mast cell. So it can take many seasons for the allergy to fully develop (4years?) More IgE is added to mast cells each season.
Early phase: first time there’s a reaction because there’s enough mast cells. The allergen bridges the 2 molecules. There has to be enough IgE on the surface of the mast cell for this to happen. Causes a signaling mechanism ->
3 things from the mast cell:
1. Immediate release of granule content (histamine – a weak bronchoconstrictor. This and TNF Causes endothelial cells to contract, which then get leaky. Sneezing, etc.
2. PG and LT also cause bC. (LT is very potent BC)
3. Genes activated for various cytokines (IL4, 13) for enhancement of mucus produciton and recruitment of eosinophils

Question 8

Early phase of allergen-induced airway reactivity leads to ______________________.

Answer 8

bronchoconstriction

Question 9

Late-phase response leads to infiltration of ________ and ________ into sites of mast cell degranulation.

Answer 9

eosinophils and neutrophils
(Bronchial walls. Eosinophils are loaded with granules that have toxic stuff for parasites so they end up damaging the airway) (repair of damaged tissue over time leads to airway remodeling)

Question 10

What are the 5 key reactions that are caused by cytokines released from Th2 cells?

Answer 10

1. Promote B cell class switching to IgE (IL-4)
2. Promote production of eosinophils in bone marrow (IL-5)
3. Attract and activate eosinophils (IL-5)
4. Induce bronchial hyperreactivity and airway remodeling (IL-5, 13, TNF)
5. Induce goblet cell hyperplasia (IL-4, IL-13)
   **Goblet cells produce mucus. So goblet cell hyperplasia is very bad.
   Mucus clumps together with pieces of destroyed epithelium (killed by eosinophils) and causes STATUS ASTHMATICUS -> deadly.

Question 11

How does desensitization/immunotherapy work as a treatment for asthma?

Answer 11

Allergy shot: by introducing the altered allergen, you teach imm system to respond my stimulating Th1 cells instead of Th2 cells. They make gamma-IFN, which downregulate Th2. More IgG made instead of IgE.