Unit 4 Lec 5

Question 0

What is an unique feature of type I hypersensitivity?

Answer 0

Immediate response (seconds-minutes)

• IgE
• Cells with granules: Mast Cells, Basophils, Eosinophils
• Very common

Question 1

What is type I hypersensitivity?

Answer 1

Immediate hypersensitivity
IgE-mediated hypersensitivity
- Allergic disease

Question 2

What are allergens?

Answer 2

Immune response to nonmicrobial environmental antigens

• Allergic or Atopic disorders
• Most common 20%
• 2x increase prevalence in the past 15 years

Question 3

What has a strong genetic predisposition?

Answer 3

Allergic response
- If both parents are allergic child has 40-60% chance of developing allergy

• If neither parent has allergies then child has about a 10 percent chance of developing allergy

Question 4

What are allergens?

Answer 4

Proteins (chemicals bound to proteins to which the atopic individual is chronically exposed

• Proteins in pollen, house dust mites, animal dander, foods
• Chemicals (i.e. penicillin)

Question 5

What are some common features of allergens?

Answer 5

Glycosylated, low medium molecular weight highly soluble in body fluids
- Atopic individuals produce high levels of IgE in response to environmental allergens

• Highly soluble allows them to go through mucous membranes

Question 6

Why do we get allergic disease?

Answer 6

Genetic susceptibility of Environment

Question 7

What is the hygiene hypothesis?

Answer 7

Postulate that exposure to some infections and common environemntal microorganisms in infancy and childhood drives the immune system towards a general state of non-atopy

• But children with a genetic susceptibility to atopy and who live in an environment with low exposure to infectious disease are though to be more susceptible to the development of atopic/allergic disease

Question 8

What is the hallmark of allergic diseases?

Answer 8

Activation of Th2 cells and production of IgE

Question 9

What is the typical sequence of immediate hypersensitivity reactions?

Answer 9

Exposure to antigen– activate Th2 ells and B cells— production of IgE antibody– binding of antibody to Fc receptor of mast cells– triggering the mast cells by re exposure to the antigen resulting in release of mediators from mast cells and subsequent

Question 10

What is essential to the production of IgE?

Answer 10

Th2 cells through secretion of IL-4, IL-13 which stimulate B cells to undergo heavy chain isotype switching and produce IgE.

IL-5 activates eosinophils,

Question 11

What are the clinical manifestations of immediate hypersensitivity?

Answer 11

Vascular and smooth muscle reaction developing rapidly after repeated exposure to the allergen

Delayed inflammatory reation (

Question 12

What needs to occur to activate the release of granules?

Answer 12

Crosslinking of IgE on mast cells

Question 13

What are mast cells activated by?

Answer 13

Cross-linking of FceRI molecules’takes only seconds to go from cross linking to release of mast cell granules

Question 14

What are the effector cells of the immediate hypersensitivity reaction?

Answer 14

Mast cells, basophils, eosinophils
- Function are mediated by soluble molecules released upon activation of these cells
-

Question 15

What are the 3 common findings for 3 share common features?

Answer 15

Cytoplasmic granules whose contents are the major mediators of allergic reactions
- Lipid mediators and cytokines that induce inflammation

Question 16

What is major biogenic amine mediator in mast cells?

Answer 16

Histamine

- H1, H2, H3 blocked anti-histamine medications

Question 17

What is responsible for wheal and flare?

Answer 17

Histamine

Question 18

What are some lipid mediators of mast cell?

Answer 18

Arachidonic acid goes to cyclo oxygenase lipooxygenase

Membrane phosopholipids are hydrolyzed by phospholipase A2 (PLA2) to generate Arachidonic Acid, metabolized by the cyclooxygenase lipoxygenase pathways to produce lipid mediators

Question 19

What is stored in the granules of mast cells?

Answer 19

Mast cells and basophils mediators hold cytokines and lipid mediators that are newly synthesized on cell activation

Question 20

What do biogenic amines and lipid mediators induce?

Answer 20

Vascular leakage, bronchoconstriction, and intestinal hypermotility (all components of the immediate response)

Question 21

What do cytokines and lipid mediators contribute to?

Answer 21

Inflammation (late-phase) reaction

Question 22

What can enzymes of the activated mast cells contribute to?

Answer 22

Contribute to tissue damage

Question 23

What do activated eosinophils release?

Answer 23

Preformed cationic proteins as well as enzymes that are toxic to parasites and host cells

Question 24

How do immediate hypersensitivity reactions manifest?

Answer 24

Manifest in different ways
Depending on tissue affected (includes rashes, sinus congestion, bronchial constriction, abdominal pain, diarrhea, and systemic shock

Question 25

What is the most extreme form of immediate hypersensitivity?

Answer 25

Anaphylaxis (mast-cell) derived mediators

Question 26

How do CD4 T cells play a role in immediate hypersensitivity?

Answer 26

T cell independent antigens (polysaccharides) cannot eliciity reactions unless become attached to proteins

• Plays a role as some drugs (penicillin) react chemically with amino acid residues in self proteins to form hapten-carrier conjugates— stimulate Th2 and IgE production

Question 27

What does the regulation of IgE synthesis depend on?

Answer 27

Propensity of an individual to mount a Th2 response

- Influenced by genetic factors, nature of allergen, and history of allergen exposure

Question 28

What is IgE responsible for?

Answer 28

For sensitizing mast cells and provides recognition of antigen for immedediate hypersensitivyt reactions

• Binds high affinity IgE receptor FceRI on mast cells and basophils even in ABSENCE OF BOUND ALLERGEN
• Affinity higher than any other Fc receptor for its antibody ligand

Question 29

What does Th2 cells produce that activate components of hypersensitivity?

Answer 29

IL-4, IL-13 to activate B cells

IL-5 to activate Eosinophils (LATE PHASE)

Question 30

What is the immediate reaction to allergen?

Answer 30

Wheal and Flare

• Red (locally dilated blood vessels)
• Swells as a result of leaky endothelial cells (venules)= WHEAL
• BLood vessels at margins of wheal dilate and become engorged= FLARE

Question 31

What happens in Late Phase Reactions?

Answer 31

Accumulation of inflammatory WBCs
- Primary eosinophils, Th2 cells, and basophils, neutrophils can be present

• Clinically in patients with long term exposure to allergens
• Chronic allergic inflammation ensue
• Primarily mediated by Th2 cells
• Long term serious illness such as asthma

Question 32

What does allergen administration determine in the resulting type of IgE mediated allergic reaction

Answer 32

Route and dose determine the type of IgE mediated alergic reaction

Question 33

What are mast cells associated with?

Answer 33

Associated with vascularized connective tissue called connnective tissue mast cells

Associated with submucosal layers of the gut and respiratory tract are called mucosal mast cells

Question 34

What occurs in anaphylaxis?

Answer 34

Commonly caused by medicaitons
Symptoms from Urticaria to potentially fatal ANAPHYLACTIC SHOCK
- Anaphylaxis is a systemic immediate hypersensitivity reaction from the systemic presence of an allergen

Question 35

What happens in anaphylatic shock?

Answer 35

Massive release of histamine to become widespread and increase vascular permability decreases blood pressure to send person into SHOCK

• Rapidly fatal if not treated
• Epinephrine is life saving because reverses bronchoconstrictive and vasodilatory effects of mast cell mediators

Question 36

What is allergic asthma?

Answer 36

IgE mediated reaction to allergen exposure in lower respiratory tract
- Same allergens that cause allergic rhinitis/conjunctivitis
Shortness of breath, wheezing, cough (bronchial constriction)
- Asthmatic attacks can be life threatening

Question 37

What happens to repeated immediate hypersensitivity reactions effect on the lungs?

Answer 37

Intermittent and reversible airway obstruction
Bronchial smooth muscle hypertrophy and hyperreactivity
- eventually develop fibrosis

Question 38

What happens in chronic airway inflammation?

Answer 38

Mediators released by Th2, eosinophils, neutrophils
Airway tissue remodeling
Smooth muscle hypertrophy, thickening of airways
fibrosis

Airways become hyperactive and other factors can trigger asthma attacks

Question 39

How to treat allergic disease?

Answer 39

Trigger avoidance
Inhibition of effector pathway
- Treatment is palliative, rather than curative
- Frequently taken lifelong

Desensitization

Question 40

What would be a way to inhibit the effector mechanism?

Answer 40

Inhibit IgE (Omalizumab)

Block IL-5, IL-4, IL-13 (under trials

Question 41

What blocks histamines?

Answer 41

THe use of antihistamines i.e. H1 receptor antagonists

- There are sedating and non sedating

Question 42

How do you block lipid mediators?

Answer 42

NSAIDS against cyclo-oxygenase
Zileuton aginst lipo-oxygenase
Montelukast against LT B4, C4, D4, E4

Question 43

What treats inflammaiton?

Answer 43

Corticosteroids (systemic, inhaled, nasal)
Bronchodilators (beta agonists0
Epinephrine (acutely) (to treat acute vasodilation)

Question 44

What is desensitization immunotherapy?

Answer 44

Restore tolerance to the allergen by reducing its tendency to induce IgE production

Injections of escalating doses of the allergen starting with tiny amounts

Question 45

What are the mechanisms underlying desensitization?

Answer 45

Induction of regulatory T cells secreting IL-10 or TGF-B to skew the response away from IgE production

Treat for allergic rhinitis
Allergic asthma
Venom allergy
Drug Allergy