Week 6 Flashcards
Type I Immunopathology
Allergic Hypersensitivity
IgE, Mast cells, eosinophil mediated
Role of IgG in Helminth infestation
Worm infestation → both IgE and IgG
IgG binds worm or its ova and activates complement → C3a, C5a attract neutrophils → BUT neutrophils lack helminthocidal mechanism…sad
Role of IgE, mast cells, and eosinophils in Helminth infestation
Worms shed antigens that mast cells bind on IgE receptors (cross link two IgE receptors)→ histamine secretion and later prostaglandin and leukotriene secretion
→ attract eosinophils in large numbers → kill helminth with Major Basic Protein (MBP) which is highly toxic to helminths
M2 macrophages in Helminth infestation
Th2 cells go out into body, find helminth antigens presented by APCs → attract BOTH eosinophils and M2 Macrophages (Th2 IL-4, IL-5, and IL-13 → M2)
M2 macrophages heal damage and wall off M1-resistant invaders
Eosinophilia indicative of parasitic disease or severe Type I immunopathology
General steps of Type I immunopathology: 4 steps
1) IgE binds strongly to FcER1 receptors on mast cells
2) 2 adjacent IgE molecules bound by mast cells and are cross-linked by allergen
3) → mast cell releases granules (histamine)
4) Histamine → local/systemic vasodilation, increased permeability, gut/bronchial smooth muscle contraction
Allergen
something that triggers an allergy, the “antigen”, plants/flowers, dust, animal dander, tobacco smoke
Anaphylaxis
severe, life-threatening Type I hypersensitivity reaction
Incidence of Atopic Disease
15% of general pop experience allergic symptoms at some time in their lives
35% in newborns with one allergic parent
65% in newborns with two allergic parents
Allergic seasonal rhinitis is the most common, food allergy, eczema in children and asthma.
Incidence of asthma nearly doubled from 1980 to 1995 (and the increase is REAL, not just better diagnostics).
Hypersensitivity Immediate Reaction (4 steps)
1) IgE binds to basophils or mast cells on IgE receptor (FcERI)
2) Reaction with allergens: IgE-loaded mast cells release contents of granules when two adjacent IgE molecules are cross-linked by allergen
3) Mediator release: histamine, heparin, enzymes, TNF pre-formed and released quickly from mast cells and basophils
4) Effects of mediators on target tissues and cells
Histamine → itch, blood vessel dilation, leakiness
½ life is 1 minute (transient reaction)
In order to activate mast cell release of granules, there must be …
Need 2 adjacent IgEs bound on mast cell specific for 2 epitopes on same allergenic protein
Pasma IgE and allergies
Plasma IgE usually very low because it binds so strongly to IgE receptor
Allergic people may have higher serum IgE
_______ can treat immediate hypersensitivity reaction but CANNOT treat late phase reaction
antihistamines
Late phase hypersensitivity reaction begins _________
4-10 hours post immediate reaction
Late phase hypersensitivity involves release of _______ and _______ which act as ________
Prostaglandins and leukotrienes
Eosinophil Chemotactic Factor of Anaphylaxis
______ and _____ attract eosinophils to a late phase hypersensitivity reaction
IL-4 (secreted by Th2) and ECF-A (PGE + LT)
Atopic Disease
characterized by abnormal IgE response to environmental antigen (mediated by Th2 cells)
_______ are common in atopic disease
cross reactions
Atopic State
prone to develop any range of allergic syndromes
Examples of Atopic Disease (4)
1) Allergic (Seasonal) Rhinitis (aka hay fever)
2) Eczema (atopic dermatitis)
3) Oral allergy Syndrome (OAS)
4) Asthma
Oral Allergy syndrome (OAS)
food allergy that occurs immediately when offending food put in mouth (antigens immediately passed to mast cells)
Tingling lips and tongue, itching, swelling of lips