immunology/ bronchial asthma p.s. still it is pity that gifs don't open in this site.

1. Azerbaijan Medical University
Yuzbasheva Nihal 221
Creation Mechanisms of
Bronchial ASTHMA

2. • Asthma is a type-I allergic airway disease characterized by Th2 cells and IgE.
Episodes of bronchial inflammation, eosinophilic in nature and promoting
bronchoconstriction, may become chronic and lead to persistent respiratory
symptoms and irreversible structural airway changes.
• Asthma is caused by a combination of complex and incompletely understood
environmental and genetic interactions. These factors influence both its severity
and its responsiveness to treatment. It is believed that the recent increased rates
of asthma are due to changing epigenetics (heritable factors other than those
related to the DNA sequence) and a changing living environment. Onset before age
12 is more likely due to genetic influence, while onset after 12 is more likely due to
environmental influence.

3. • Peripheral blood cell generation of cytokines IFN-γ (TH1) and IL-5
(TH2) was used to evaluate the relationship of the balance of
TH1/TH2 cytokines to asthma persistence and severity in a 42-year,
longitudinal study.
• Chemokines, including thymus and activation-regulated chemokine,
are important to the regulation of inflammation and IgE synthesis.
Their potential role in asthma has also been evaluated.
• Finally, albuterol (R)- and (S)-enantiomers may have distinct effects
on airway relaxation and regulation of inflammation, suggesting the
possibility that monoisomeric therapy has therapeutic advantages.
• The potential contribution of genetic factors and mechanisms to
airway inflammation and remodeling also continues to be an area
of intense investigation.

4. • Allergic asthma is triggered by an immune-inflammatory
response driven by Th2 cells. This so-called “Th2-high” or
“Th2-like” subphenotype of asthma originates from a complex
interplay between the innate and adaptive branches of
immune system
• Differentiation of Th2 lymphocytes requires the cooperation
of several promoting factors, including costimulatory
molecules and cytokines expressed by dendritic cells and
inflammatory cells.

5. • Two of the cytokines secreted by Th2 cells or
by Tfh cells activated by the same antigen are
IL-4 and IL-13.
• These cytokines stimulate B lymphocytes to
switch to IgE-producing plasma cells.

6. • IgE antibody produced in response to an allergen
binds to high-affinity Fc receptors, specific for the ε
heavy chain, that are expressed on mast cells.
• The high-affinity receptor for IgE, called FcεRI
,consists of three polypeptide chains, one of which
binds the Fc portion of the ε heavy chain very
strongly, with a Kd of approximately 10−11 M. The
other two chains of the receptor are signaling
proteins.

7. • Mast cell activation results from binding of the allergen
to two or more IgE antibodies on the cell.
• When this happens, the FcεRI molecules that are
carrying the IgE are cross-linked, triggering biochemical
signals from the signal-transducing chains of FcεRI.
• The signals lead to three types of responses in the mast
cell: rapid release of granule contents (degranulation),
synthesis and secretion of lipid mediators, and
synthesis and secretion of cytokines.

8. • Bronchial asthma is form of respiratory allergy
in which inhaled allergens (often undefined)
stimulate bronchial mast cells to release
mediators, including leuko-trienes, which
cause repeated bouts of bronchial constriction
and airway obstruction.

9. • In chronic asthma, large numbers of eosinophils
accumulate in the bronchial mucosa, excessive
secretion of mucus occurs in the airways, and the
bronchial smooth muscle becomes hypertrophied
and hyper-reactive to various stimuli.
• Some cases of asthma are not associated with
IgE production, although all are caused by
mast cell activation.

10. 1. Development of mild asthma. A: On primary allergen exposure, DAMPs and/or PAMPs intrinsic to or accompanying the allergen activate DCs to become APCs
biased toward the induction of Th2 cells. As a result, immune sensitization featuring allergen-specific IgE and Th2 cells is generated. B: Activation of IgE-bearing innate
cells by inhaled allergen triggers the release of pro-inflammatory mediators such as histamine, leukotrienes, Th2-associated cytokines and chemokines, and reactive
oxygen species. The resulting early-phase allergic reaction is manifested by smooth muscle contraction, mucus hypersecretion, and increased airway responsiveness.
Inflammatory cell recruitment and activation leads to the production of a second wave of particularly Th2-associated inflammatory mediators such as IL-4, IL-5, IL-13,
eotaxins, RANTES, and others. This late-phase reaction occurs 6 to 9 hours after allergen inhalation and usually lasts for not more than a day.

11. • In studies, the scientists aimed to define the
mechanisms of what is referred to as immune tolerance
and to detail the role that dendritic cells play in the
process.
• To model the events that occur when an asthma sufferer
inhales a harmless allergen, the researchers exposed a
number of mice to an egg allergen known as ovalbumin,
or OVA. Within 24 hours of exposure to the allergen,
dendritic cells migrated to the lymph nodes and induced
the production of certain regulatory cells, as well as a
specific type of cytokine called IL-10. The regulatory cells
and IL-10 then worked to ensure that the innocent
substance wasn't attacked.

12. • By displaying the critical role of dendritic cells in maintaining
immune tolerance to certain antigens, the study points to the
possibility that defective dendritic cells may contribute to
asthma. If dendritic cells can't produce IL-10, for example, the
word might not get out that the foreign visitor is friendly, and
the immune system might launch an unwarranted attack.

13. Pathobiology of airway inflammation in asthma.

14. • Cellular inflammation of the airways with eosinophils
and neutrophils is a characteristic feature of asthma
and is considered relevant to the pathogenesis of the
disease.
• Eosinophilic asthma is a distinct phenotype of asthma
that is associated pathologically by thickening of the
basement membrane zone and pharmacologically by
corticosteroid responsiveness.
• In contrast, noneosinophilic asthma, a sizeable
subgroup of asthma that includes patients with severe
disease, is not characterized by thickening of the
basement membrane zone, and it appears to be
relatively corticosteroid resistant.

15. • Eosinophilic inflammation associated with
poor asthma control, increased branchodilator
response, lower lung function and
exacerbations in ICS treated patients
• Neutrophilic asthma seems to increase with
increasing severity ICS use

16. Distribution of sputum cellular phenotypes in severe asthma (n = 88). Eosinophilic
asthma (≥3% sputum eosinophils, <76% sputum neutrophils); Neutrophilic asthma (<3%
sputum eosinophils, ≥76% sputum neutrophils); Paucigranulocytic asthma (<3%
eosinophils and <76% neutrophils in induced sputum); Mixed granulocytic asthma (≥3%
eosinophils and ≥76% neutrophils in induced sputum).

18. Clinical Syndrome
•Bronchial
asthma
Clinical and
pathological
manifestations
• Airway obstruction
caused by bronchial
smooth muscle
hyperactivity;
• inflammation and tissue
injury caused by late-
phase reaction

19. Syndrome
Bronchial
Asthma
Therapy
Corticosteroids
Leukotriene
antagonists
Phosphodiesterase
inhibitors
Mechanism
of action
Reduce
inflammation
Relax bronchial
smooth muscle and
reduce inflammation
Relax bronchial
smooth muscles