What is the role of IgG in helminth (worm) immunity?
- IgG binds the worm or its ova
- activates complement
- C3a & C5a attract neutrophils
- Neutrophils arrive and seize opsonized worms
- Neutrophils lack a helminthocidal mechanism so worms survive
We need IgE
What is the role of IgE in helminth (worm) immunity?
- Worms shed the IgG opsonin and diffuse to nearby mast cells
- FCeR of mast cells become loaded with anti-helminth IgE
- Worm antigen cross links the IgE causing mast cell degranulation -> histamine
- 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
What is the role of M2 macrophages in helminth (worm) immunity?
- 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
- Attracts M2 macrophages
- Secretes IL-4, IL-5, IL-13
M1 macrophages often are unable to kill most worms
What is the role of Eosinophils in helminth (worm) immunity?
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
- Release granules that contain Major Basic Protein (MBP)
Note: Eosinophils are also attracted by Th2
Eosinophillia in blood/sputum - often a sign of parasitic disease or Type I immunopathology
Define atopic
- 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
Define Immediate Hypersensitivity
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
Define Allergy
- 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
Define Allergen
- Allergen: refers to antigens in allergy studies
Define Anaphylaxis
- Anaphylaxis: Serious, rapid, allergic rxn that may cause death
Define Asthma
- Asthma: Reversible bronchocontrictive disease with progressive inflamation leading to fibrosis (which is not reversible)
- Requires close monitoring to prevent fibrosis
Define Hives
- Hives: Wheel and flare response
What is the incidence of atopic disease in
- General population?
- Individuals with allergic parents?
- 20% of all people have it
- 35% increased risk with 1 allergic parent;
- 65% increased risk with 2 allergic parents
What are the two phases of a Type I rxn and how do the treatments differ for each?
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
Explain pathophysiology Immediate Phase Rxn:
*Important concept*
- 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)
Explain the pathophysiology of a Late Phase Rxn
*Important Concept*
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)
Why do we lump Atopic disease together?
- 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.
What is the reasoning behind using glucocorticoids in asthma treatment?
- 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)
- Inhibit production of arachadonic acid from phospholipids
Intradermal Skin Test (tests allergen response)
- Reference the general procedure
- Safety concerns
- Is it specific?
- 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
- Safety: theoretical risk of a systemic response to allergen (low yeild if you ask me)
- 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
Immunotherapy of allergic disease (allergery shots)
- What is the general concept?
- What percent of pts receive significant allergy releif?
- Are there any risks? - Low yield question if you ask me
- 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
- 75% of patients claim they have an easier allergy season
- There is a theoretical risk of anaphylaxis, but he doesn’t touch on it in the PDF really
What is the time frame of:
- Immediate Phase Rxn
- Late Phase Rxn
- Immediate phase rxn: within 15 minutes
- Late phase rxn: 4-10hrs later
What is ECF-A really good at attracting?
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
