Asthma

Question 1

The pathogenetic process underlying allergic airway disease is initiated by __________ lymphocyte proliferation. How are these lymphocytes proliferated?

Answer 1

TH2

1. An antigen is taken up by an antigen presenting cell
2. The antigen is then presented to Th0, which can differentiate into either Th1 or Th2.
3. Th0 is differentiated in Th1 in the presence of IL-12 and IL-18, IFN-gamma prevents the differentiation into Th2.
4. The presence of IL-4 allows the differentiation into Th2.
5. Th2 then release IL-3, IL-4, IL-5, IL-9, IL-10, IL-13

Question 2

What happens once proliferation of Th2 is stimulated?

Answer 2

1. Th2 releases IL-4 and IL-13, which stimulates production IgE from B lymphocytes.
2. IL-3, IL-4, IL-6, IL-9, and Stem cell factor make IgE bind to basophils or mast cells.
3. Th2 also releases IL-3, IL-5, and GM-CSF to stimulate eosinophil production and activity.
4. Eosinophils, Basophils, and Mast cells release an array of mediators, cytokines, and chemokines.

Question 3

What are the two signals required for class switching?

Answer 3

1. 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.
2. Signal 2 is the binding of Cd40 to the CD40 ligand, which causes gene rearrangement.

Question 4

. Specific high-affinity receptors (___________) on mast cells, basophils, and Langerhans’ cells bind through the constant (Fc) region of IgE antibodies.

Answer 4

FcεRI

Question 5

_________________- is the key event that launches the symptoms of the early allergic response.

Answer 5

Mast cell degranulation

Question 6

What components do mast cells release? What effect does this have?

Answer 6

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.

Question 7

The ____________ and the ____________are the major effector cells in allergic inflammation.

Answer 7

mast cell; eosinophil

Question 8

-Interactions between the adhesion molecules (____________ and ____________) is important
for the cells to be able to enter the tissues.

Answer 8

VCAM; ICAM

Question 9

What is asthma?

Answer 9

○ 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.

Question 10

Type of hypersensitivity implicated in Asthma?

Answer 10

Type I (IgE)

Type IV (Delayed)

Question 11

Different components are released from mast cells/ basophils at different times. What components are released at immediately, over minutes, and over hours?

Answer 11

Immediate release

• Granule contents (Histamine, TNFa, Proteases, Heparin)

Over Minutes

• Lipid Mediators (Prostaglandins, Leukotrienes)

Over Hours

• Cytokine production (IL-4 and IL-13)

Question 12

Cells involved in asthma

Answer 12

Broncial epithelium

Th cells

Mast cells

Eosinophils

Neutrophils

Airway Smooth muscle

Question 13

Airway remodeling is due to _________

Answer 13

Mucosal inflammation

Question 15

Immunotherapy increase __________cells

Answer 15

IL10+ T

Question 16

Strategies against ____________ameliorate asthma.

Answer 16

T lymphocytes

Question 17

What is the role of immunotherapy?

Answer 17

Tolerance. Makes the body tolerant to the antigen.

Reduces IgE affinity

Question 18

What does IL-10 do?

Answer 18

Blocks costimulation (B7 and CD28) and subsequent T cell signaling

Suppresses T cells along with TGFBeta

Question 19

Effects of Leukotriene C

Answer 19

Bronchoconstriction

Vascular permeability

Mucous secretion

Chemotaxis

Question 20

Effects of Histamine

Answer 20

Bronchoconstriction

Vascular permeability

Question 21

Effects of Prostaglandin

Answer 21

Bronchoconstriction

Vascular permeability

Mucus Secretion

Question 22

Effects of TNFa

Answer 22

Tissue injury

Cell recruitment

Question 24

Effects of Proteases

Answer 24

Tissue Injury

Mucous Production

Question 25

Mast Cell Tryptase in Asthma

Answer 25

Bronchoconstriction Bronchial hyper-responsiveness Stimulation of proliferation of fibroblast, smooth muscle, and epithelial cells Generation of kinins Stimulation of IL-8 release Eosinophil chemotaxis

Question 26

Monoclonal Antibodies

Answer 26

Mepolizumab Reslizumab Benralizumab Tezepelumab

Question 27

Gene related to asthma susceptibility related to the epithelial mesenchymal tropic unity

Answer 27

ADAM33

Question 28

Possible side effects to Inhaled Corticosteriods

Answer 28

Bruising Decreased bone density Suppression of HPA-axis Growth suppression Dysphonia, thrush

Question 29

Not appropriate for monotherapy

Answer 29

Beta2-agonists

Question 30

If penicillin is given and within minutes the patients throat closes off, what type of reaction is that?

Answer 30

Type I

Question 31

12 year old not controlled with allbutoron alone, what drug do add?

Answer 31

Inhaled corticosteriods

Question 32

What medications would you use to mimic the effects of asthma that you could use diagnostically?

Answer 32

Methacholine

Question 33

When does the delayed response occur?

Answer 33

6-8 hours or more

Question 34

What cells are most important in causes anaphylaxis?

Answer 34

Mast cells

Question 35

If you're stung by a bee and you anaphylas, what cell type does the venom bind to?

Answer 35

Mast Cell

Question 36

Anaphylactoid reactions

Answer 36

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.