Saturday, June 28, 2014

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Summer Immunology- Block 3
Atopic Disease and Anaphylaxis
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Clinically oriented lecture so focus on treatments!!!

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IgE production:

produced by plasma cells in mucosa and lymph nodes
synthesis occurs in response to T-dependent Ag (MHC II)
Regulation:
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IL-4 induces Ab class switching to IgE (more likely to have allergies)

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IFNgamma inhibits class switching to IgE (less likely to have allergies)

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Atopy:

familial (genetic) tendency to become sensitized by natural exposure to common
environmental Ags
atopic individuals usually (but not always) have higher levels of circulating IgE Ab
than normal
route of Ag exposure dictates the site of the local reaction and nature of the allergic
(atopic) disease (ie, asthma, urticaria, etc)
IL-4, IL-13, and IL-5 (all 3 produced by TH2 cells) important in atopic events
Atopic diseases are considered TH2 disorders
REVIEW CYTOKINES TABLES (know which Ag--> which Ab--> which immune
cells--> which physiological response)
Immediate reactions:
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IgE mediated release of histamine and LTC4/D4 from basophils and mast cells
within the first 2-30 minutes

Saturday, June 28, 2014
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if strong, leads to secondary (ie, late phase) reaction

Late phase reactions:
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Appears 4-8 hours later at the site of the immediate reaction

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influx of eosinophils and IL-5 produced by T helper cells

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Anaphylaxis:

systemic reaction that is the most dramatic and catastrophic form of an allergic
reaction
caused by the release systemically of histamine and LTC4/D4 by basophils and
mast cells
REVIEW lecture slide of anaphylaxis graphs
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Anaphylactoid reactions:

anaphylaxis-like reaction
C3a, C5a, and contrast dye can produce a non-IgE mediated activation of basophil
and mast cell histamine and LTC4/D4 release
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Pharmacological treatment of allergic diseases:

4 pharm approaches to controlling allergic reactions:
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Inhibit mediator release:

Cromolyn selectively inhibits Ag-stimulated histamine release
Administered as an inhalant
MUST BE GIVEN PRIOR TO Ag EXPOSURE
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Block effects of histamine:

Anti-histamine compete for histamine receptors --> block histamine-mediated
effects on vascular smooth muscle
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Have negligible effects as an inhibitor of bronchospasm
ANTI-HISTAMINES DO NOT BLOCK HISTAMINE RELEASE
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Reverse effects of histamine and LTC4/D4:

Epinephrine only drug that can treat anaphylaxis
It is a potent alpha and beta-stimulating agonist
Administered IV to produce bronchodilation (via beta 2 receptors) and increase
blood pressure (via cardiac beta 1 and vascular alpha 1 receptors)
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Anti-inflammatory:

Corticosteroids can treat ONLY late stage allergic reactions
Also has anti-inflammatory effect in chronic allergic disease states
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Immunological treatment of allergic diseases:

Prevents or reduces severity of IMMEDIATE hypersensitivity reactions by reducing
interaction of Ag with the IgE Ab present on basophils and mast cell membranes.
2 immuno approaches to achieving previous goal:
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Desensitization:

Inject increasing concentrations of Ag (ie, penicillin or insulin) over a period of
8 hours
Cell-bound IgE gradually becomes saturated with monomeric Ag in a manner
that does not stimulate a significant mediator (ie, histamine) response
Desensitization must be maintained by immunotherapy
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Immunotherapy:

Minute concentrations of Ag are administered weekly or monthly to an atopic
individual via "allergy shots"
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Unknown mechanism of how it confers long term inhibition of mediator
response, but do know that it acts on TH2 cells somehow
Works best with injected allergens (ie, bee venom)