Asthma Flashcards
The pathogenetic process underlying allergic airway disease is initiated by __________ lymphocyte proliferation. How are these lymphocytes proliferated?
TH2
- An antigen is taken up by an antigen presenting cell
- The antigen is then presented to Th0, which can differentiate into either Th1 or Th2.
- Th0 is differentiated in Th1 in the presence of IL-12 and IL-18, IFN-gamma prevents the differentiation into Th2.
- The presence of IL-4 allows the differentiation into Th2.
- Th2 then release IL-3, IL-4, IL-5, IL-9, IL-10, IL-13
What happens once proliferation of Th2 is stimulated?
- Th2 releases IL-4 and IL-13, which stimulates production IgE from B lymphocytes.
- IL-3, IL-4, IL-6, IL-9, and Stem cell factor make IgE bind to basophils or mast cells.
- Th2 also releases IL-3, IL-5, and GM-CSF to stimulate eosinophil production and activity.
- Eosinophils, Basophils, and Mast cells release an array of mediators, cytokines, and chemokines.
What are the two signals required for class switching?
- The first signal is delivered from IL-4 or IL-13, which induce B cells to initiate transcription of germ-line emRNA for IgE antibodies.
- Signal 2 is the binding of Cd40 to the CD40 ligand, which causes gene rearrangement.
. Specific high-affinity receptors (___________) on mast cells, basophils, and Langerhans’ cells bind through the constant (Fc) region of IgE antibodies.
FcεRI
_________________- is the key event that launches the symptoms of the early allergic response.
Mast cell degranulation
What components do mast cells release? What effect does this have?
Mast cells release preformed mediators (especially histamine and proteases) and newly produced lipid mediators, including PGD2 and LTC4, that promote inflammation and are thought to be responsible for the smooth muscle contraction and airway mucosal edema that are seen in the acute response.
Mast cells can also produce many cytokines, such as IL-4 and IL-13, that can enhance IgE synthesis and contribute to the persistence of allergic inflammation and tissue remodeling.
The ____________ and the ____________are the major effector cells in allergic inflammation.
mast cell; eosinophil
-Interactions between the adhesion molecules (____________ and ____________) is important
for the cells to be able to enter the tissues.
VCAM; ICAM
What is asthma?
○ A chronic inflammatory disorder of the airways.
▪ Wheezing
▪ Chest tightness
▪ Dyspnea-shortness of breath
▪ Airway obstruction is reversible
There’s also increased bronchial hyper-responsiveness; meaning
their airways’ are twitchy, kind of like when someone blows
really hard and then starts coughing.
Type of hypersensitivity implicated in Asthma?
Type I (IgE)
Type IV (Delayed)
Different components are released from mast cells/ basophils at different times. What components are released at immediately, over minutes, and over hours?
Immediate release
- Granule contents (Histamine, TNFa, Proteases, Heparin)
Over Minutes
- Lipid Mediators (Prostaglandins, Leukotrienes)
Over Hours
- Cytokine production (IL-4 and IL-13)
Cells involved in asthma
Broncial epithelium
Th cells
Mast cells
Eosinophils
Neutrophils
Airway Smooth muscle
Airway remodeling is due to _________
Mucosal inflammation
Immunotherapy increase __________cells
IL10+ T
Strategies against ____________ameliorate asthma.
T lymphocytes
What is the role of immunotherapy?
Tolerance. Makes the body tolerant to the antigen.
Reduces IgE affinity
What does IL-10 do?
Blocks costimulation (B7 and CD28) and subsequent T cell signaling
Suppresses T cells along with TGFBeta
Effects of Leukotriene C
Bronchoconstriction
Vascular permeability
Mucous secretion
Chemotaxis
Effects of Histamine
Bronchoconstriction
Vascular permeability
Effects of Prostaglandin
Bronchoconstriction
Vascular permeability
Mucus Secretion
Effects of TNFa
Tissue injury
Cell recruitment
Effects of Proteases
Tissue Injury
Mucous Production
Mast Cell Tryptase in Asthma
Bronchoconstriction
Bronchial hyper-responsiveness
Stimulation of proliferation of fibroblast, smooth muscle, and epithelial cells
Generation of kinins
Stimulation of IL-8 release
Eosinophil chemotaxis
Monoclonal Antibodies
Mepolizumab
Reslizumab
Benralizumab
Tezepelumab
Gene related to asthma susceptibility related to the epithelial mesenchymal tropic unity
ADAM33
Possible side effects to Inhaled Corticosteriods
Bruising
Decreased bone density
Suppression of HPA-axis
Growth suppression
Dysphonia, thrush
Not appropriate for monotherapy
Beta2-agonists
If penicillin is given and within minutes the patients throat closes off, what type of reaction is that?
Type I
12 year old not controlled with allbutoron alone, what drug do add?
Inhaled corticosteriods
What medications would you use to mimic the effects of asthma that you could use diagnostically?
Methacholine
When does the delayed response occur?
6-8 hours or more
What cells are most important in causes anaphylaxis?
Mast cells
If you’re stung by a bee and you anaphylas, what cell type does the venom bind to?
Mast Cell
Anaphylactoid reactions
produce the same clinical picture with anaphylaxis but are not IgE mediated, occur through a direct nonimmune-mediated release of mediators from mast cells and/or basophils or result from direct complement activation.
