BL - Immunopathology Type I Allergy

Question 1

Roles of IgG, IgE, M2 macrophages, eosinophils in helminth immunity

Answer 1

IgG: binds worm or ova, activates complement, attracts neutrophils via C3a and C5a
IgE: worm antigens diffuse to nearby mast cells, loaded with anti-helminth IgE. Antigen crosslinks IgE and mast cells degranulate. Histamine causes smooth muscle contraction in gut leading to violent peristalsis
M2 macrophages: activated by Th2 producing IL-4, IL-5, IL-13. Heal damage and wall off M1-resistant invaders. Good in parasite infection, bad in asthma.
Eosinophils: engage opsonized worms and release contents of granules, including Major Basic Protein (MBP), which is highly toxic to worms

Question 2

Atopic

Answer 2

Prone to develop any of the range of allergic syndromes

Question 3

Immediate hypersensitivity

Answer 3

Allergic reaction provoked by re-exposure to an allergen, either by ingestion, inhalation, injection, or direct contact.

Question 4

Allergy

Answer 4

Inflammatory reaction mediated by IgE and mast cells; atypical immune response to environmental antigens, eventually becomes characterized by increased reactivity of end-organs to inflammatory mediators and irritants.
Widely misused to include Th1 cell-mediated reactions as well (ex. food “allergies”)

Question 5

Allergen

Answer 5

Antigen causing an allergy reaction

Question 6

Anaphylaxis

Answer 6

Acute allergic reaction to an antigen to which someone has become hypersensitive (ex. bee sting)

Question 7

Asthma

Answer 7

Both bronchoconstrictive and inflammatory. Goal of treatment is to maintain good control now to avoid future fibrosis

Question 8

Hives/wheal and flare reation

Answer 8

Urticaria: visible skin reaction to allergen exposure

Question 9

Approximate incidence of atopic disease in: 1) general population; 2) people with one allergic parent; 3) people with two allergic parents

Answer 9

1) 15% of general population
2) 35% of people with one allergic parent
3) 65% of people with two allergic parents

Question 10

Mechanism of IgE-mediated hypersensitivity in terms of IgE attachment to basophils or mast cells, reaction with allergens, mediator release, and effects of mediators on target tissues and cells

Answer 10

IgE attachment to basophils or mast cells: IgE binds main mast cell/basophil receptor with association constant of 10^-10 (off rate expressed in months) – meaning almost any secreted IgE is almost immediately bound by receptors.
reaction with allergens: adjacent IgE molecules are cross-linked by allergen, meaning allergen must be at least divalent
mediator release: binding of two IgE molecules to allergen causes IgE-loaded mast cells to release contents of granules, including histamine
effects of mediators on target tissues and cells: histamine release causes itch, blood vessel dilation, and leakiness. Half-life in tissues only a minute so effects are short-lived

Question 11

Reasoning for glucocorticoids as asthma treatment

Answer 11

Can help prevent fibrosis by controlling chronic inflammation mediated by Th2 cells in asthma. Good when kept local (inhaled to avoid systemic effects).
PK: Glucocorticoids inhibit production of arachidonic acid from phospholipids; block both PG and LT synthesis. Also induce apoptosis in eosinophils.

Question 12

Intradermal skin tests

Answer 12

Drop of allergen extract placed on forearm or back; hypodermic needle/lancet used to prick epidermis through the drop. Test areas observed at 15-20 minutes and results recorded as diameter of central raised wheal/diameter of flare (ex. 5/15mm).
Positive skin test does not mean symptoms are necessarily caused by that allergen; sensitivity level may be subclinical even with positive test, or symptoms may come from something that cross-reacts with test extract
Generally considered safe but should monitor patients for 20-30 minutes after testing to make sure no adverse reaction (i.e. anaphylaxis) develop

Question 13

Immunotherapy

Answer 13

Allergy shots - dilute solutions of allergen extracts, given once or twice a week with increasing concentration as tolerated. Shots given monthly when maximal dose is reached.
75% of patients with seasonal allergic rhinitis have an “easier season” after immunotherapy

Question 14

2 theories of mechanism of immunotherapy

Answer 14

1) Route of administration (as a shot) favors IgG production, which traps and clears antigen before IgE-loaded mast cells can be reached
2) Repeated Ag exposure desensitizes mast cells

Question 15

Immediate allergic reaction

Answer 15

Degranulation happens and wheal and flare/hive reaction visible within 15 minutes of ID injection in skin test. Histamine half-life is only a minute, so reaction is short-lived.
Due to histamine release and can be blocked by antihistamines

Question 16

Late-phase reaction

Answer 16

Begins 4-10 hours after exposure. Depends on PGs, LTs, and cytokines, so not affected by antihistamines.
Shows infiltration of Th2 cells and eosinophils (attracted by ECF-A from mast cells and IL-4 released by Th2 cells) on biopsy.
Ex. atopic dermatitis (eczema) is chronic late-phase Type I immunopathology