This essay covers all the content of lecture 5 of Immunology of Human Disease. It discusses Allergy and Asthma. The question is: Discuss the intricate immune mechanisms underlying IgE-mediated allergy, the diagnostic tests utilized for identifying this allergic condition, and the range of targeted ...
A. Discuss the intricate immune mechanisms underlying IgE-mediated allergy, the diagnostic
tests utilized for identifying this allergic condition, and the range of targeted therapies
employed in managing IgE-mediated allergies. Provide a detailed account in the following
subparts:
a. Explore the complex immune mechanisms involved in IgE-mediated allergy,
elucidating the role of IgE antibodies, mast cells, basophils, and the subsequent
cascade of events leading to allergic reactions.
b. Detail the sensitization phase, allergen exposure, and effector phase in the context
of IgE-mediated immune responses.
c. Examine the various diagnostic tools and methodologies used for detecting IgE-
mediated allergies.
d. Evaluate the array of targeted therapies available for managing IgE-mediated
allergic reactions. Discuss the efficacy, mechanisms of action, and limitations of
treatments.
Hypersensitivity is an adverse reaction to something, this can be allergic or non-allergic
intolerant reactions. Type I hypersensitivity or IgE-mediated hyper-sensitivity is a pathological
reaction mediated by IgE and caused by the release of mediators from mast cells and
basophils. The immediate-type allergic reaction involves symptoms like hive, sweating,
vomiting and hypertension. In this essay, we will discuss the intricate immune mechanisms
underlying IgE-mediated allergy, the diagnostic tests used to identify this allergic condition
and the range of targeted therapies.
Immune mechanisms
IgE hypersensitivity is mediated by IgE and the underlying immune mechanism involves
dendritic cells, Th2 cells, B cells producing IgE, mast cells and basophils effector cells of the
allergic reactions and eosinophils targeted to the site of inflammation in the late phase
reaction. Upon allergen exposure, the initial response includes the sensitisation phase where
the immune response develops until the secretion of IgE. Upon IgE secretion, the effector
phase begins with IgE causing apparent symptoms. The effector phase is marked by the
release of mediators by mast cells and basophils, recruiting eosinophils that release pro-
inflammatory mediators, contributing to the late phase reaction. Immediate mediators
include histamine, tryptase and kinase stored in granules and released immediately upon
allergen exposure. Proteoglycans are the next released with cytokines being released last.
Delving further into this immune mechanism, an antigen presenting cell captures the allergen
and migrates to the lymph node or lymphoid tissue to present it to naïve T cells’ TCR via its
MHC II. Conventional DCs type 2 will influence naïve T cells’ differentiation into Th2 cells. The
allergen is recognised via its PAMPs and TFs and other signals contribute to an effective
allergen presentation like CD86 binding CD80 and CD40 binding CD40L. These Th2 cells enter
the circulation and are characterised by IL-4, IL-5 and IL-13 cytokines. Tfh cells will influence
B cells’ differentiation and production of IgE and the secreted IgE will bind to receptors on
mast cells and basophils, causing sensitisation. Upon allergen exposure, if the individual is
allergic, the allergen cross-links to IgE on the surface of mast cells and basophils directly,
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