Type I Allergies

Question 1

What is the role of IgG in helminth (worm) immunity?

Answer 1

1. IgG binds the worm or its ova
2. activates complement
3. C3a & C5a attract neutrophils
4. Neutrophils arrive and seize opsonized worms
5. Neutrophils lack a helminthocidal mechanism so worms survive

We need IgE

Question 2

What is the role of IgE in helminth (worm) immunity?

Answer 2

1. Worms shed the IgG opsonin and diffuse to nearby mast cells
2. FCeR of mast cells become loaded with anti-helminth IgE
3. Worm antigen cross links the IgE causing mast cell degranulation -> histamine
4. Histamine - > GI smooth muscle contracts faster expeling worms

TL;DR - Worms attach to mast cells cross link IgE causing histamine release which induces the GI system to speed up contractions and expel the worm

Question 3

What is the role of M2 macrophages in helminth (worm) immunity?

Answer 3

• Th2 finds helminth antigens via APC
  
  • Secretes IL-4, IL-5, IL-13
    
    • Attracts M2 macrophages
      
      • Heal damage caused by worms
      • Wall off M1-resistant helminths

M1 macrophages often are unable to kill most worms

Question 4

What is the role of Eosinophils in helminth (worm) immunity?

Answer 4

Recall that IgG opsonizes the worms

• Eosinophils bind to opsinized worm with its Fc receptor for IgG
  
  • Release granules that contain Major Basic Protein (MBP)
    
    • MBP is toxic to helminths

Note: Eosinophils are also attracted by Th2

Eosinophillia in blood/sputum - often a sign of parasitic disease or Type I immunopathology

Question 5

Define atopic

Answer 5

• Atopic: prone to develop any of the range of allergic symptoms
  e. g. - you have atopic eczema; maybe you only have eczema but now you are prone to develop potentially asthma for example now that you have it

Question 6

Define Immediate Hypersensitivity

Answer 6

Also known as a Type I rxn, it is characterized by an immediate phase and late phase rxn

Occurs in people allergic to an allergen and they have previously been exposed to the allergen loading their mast cells with IgE

Question 7

Define Allergy

Answer 7

• An atypical immune response to environmental antigens
  
  • Eventually characterized by increased reactivity of the end-organs to inflammatory mediators and irritants
  • Hypersensitivity disorder of the immune system

Question 8

Define Allergen

Answer 8

• Allergen: refers to antigens in allergy studies

Question 9

Define Anaphylaxis

Answer 9

• Anaphylaxis: Serious, rapid, allergic rxn that may cause death

Question 10

Define Asthma

Answer 10

• Asthma: Reversible bronchocontrictive disease with progressive inflamation leading to fibrosis (which is not reversible)
  
  • Requires close monitoring to prevent fibrosis

Question 11

Define Hives

Answer 11

• Hives: Wheel and flare response

Question 12

What is the incidence of atopic disease in

1. General population?
2. Individuals with allergic parents?

Answer 12

1. 20% of all people have it
2. • 35% increased risk with 1 allergic parent;
   • 65% increased risk with 2 allergic parents

Question 13

What are the two phases of a Type I rxn and how do the treatments differ for each?

Answer 13

Recall: Type I rxn is an Immediate Hypersensitivity rxn

Two Phases

• Immediate Phase Rxn: Treatment is antihistamine
• Late-Phase Rxn: Treatment is antiinflamatory (glucocorticoid or leukotriene inhibitor - COX inhibitors (results in higher LT levels), and antihistamines are not indicated for late phase

Question 14

Explain pathophysiology Immediate Phase Rxn:

*Important concept*

Answer 14

• Initial phase of a Type I rxn

In an allergic person, mast cells are coated with IgE clones for that allergen

• This sensitizes them to that allergen
• Next time allergen binds 2 (divalent) of the IgE on a mast cell -> immune response involving degranulation of mast cells
  
  • Leads to release of histamine, heparin, TNF, and enzymes (all are rapid acting)

Question 15

Explain the pathophysiology of a Late Phase Rxn

*Important Concept*

Answer 15

Recall: Type 1 rxns have an immediate rxn that includes histamine release via degranualtion of mast cells

Activated mast cells also initiate the Arachidonic acid pathway

• PLA2 cleaves AA from membrane phospholipid
  
  • AA converted to prostaglandins via COX and leukotrienes via lipooxygenase pathways
  • Prostaglandins and leukotrienes together are called the eosinophil chemotactic factor of anaphylaxis (ECF-A)

Question 16

Why do we lump Atopic disease together?

Answer 16

• We lump atopic diseases together because cross rxns are common
  
  • Recall: atopic means prone to develop any of the range of allergic s/s

e.g. - Person with T cellmediated contact dermatitis to latex (gloves, catheters, condoms) may have symptoms of IgE-mediated oral allergy to avocados, bananas, or chestnuts, all of which contain a cross-reactive antigen.

Question 17

What is the reasoning behind using glucocorticoids in asthma treatment?

Answer 17

• Asthma treatments incorporate glucocorticoids to target the late-phase rxn component of Asthma (see “Define asthma” card for more detail on fibrosis)
• Glucocorticoids have 2 fxns
  
  • Inhibit production of arachadonic acid from phospholipids
    
    • This blocks PG and LT synth (essentially you are blocking the late phase rxn)
  • Induce apoptosis in eosinophils (recall late phase rxn -> ECF-A)

Question 18

Intradermal Skin Test (tests allergen response)

1. Reference the general procedure
2. Safety concerns
3. Is it specific?

Answer 18

1. A drop of allergen extract is place on forearm or back → using a hypodermic needle, prick the epidermis through the drop → in 15 minutes, record diameter of flare
2. Safety: theoretical risk of a systemic response to allergen (low yeild if you ask me)
3. A positive skin test does not necessarily mean that your symptoms are due to that allergen; your level of sensitivity may be subclinical even with a positive test, or your symptoms may come from something else that cross-reacts with the test extract

Question 19

Immunotherapy of allergic disease (allergery shots)

1. What is the general concept?
2. What percent of pts receive significant allergy releif?
3. Are there any risks? - Low yield question if you ask me

Answer 19

1. Give dilute allergen extracts via subcutaneous injection once or twice a week → increase in concentration as tolerated → reach maximum dosage is reached, give shot monthly
2. 75% of patients claim they have an easier allergy season
3. There is a theoretical risk of anaphylaxis, but he doesn’t touch on it in the PDF really

Question 20

What is the time frame of:

1. Immediate Phase Rxn
2. Late Phase Rxn

Answer 20

1. Immediate phase rxn: within 15 minutes
2. Late phase rxn: 4-10hrs later

Question 21

What is ECF-A really good at attracting?

Answer 21

Recall: ECF-A stands for Eosinophil Chemotactic (attractant) Factor of Anaphylaxis

Therefore

• ECF-A: is really good at attracting eosinophils in large numbers
• Glucocorticoids induce apoptosis in eosinophils